APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children.

In brief: In light of the increasing age of first-time fathers, this article summarizes the current scientific knowledge base on reproductive aging in the male, including sperm quality and health impacts for the offspring. The emerging role of NAD decline in reproductive aging is highlighted. Abstract: Over the past decades, the age of first-time fathers has been steadily increasing due to socio-economic pressures. While general mechanisms of aging are subject to intensive research, male reproductive aging has remained an understudied area, and the effects of increased age on the male reproductive system are still only poorly understood, despite new insights into the potential dire consequences of advanced paternal age for the health of their progeny. There is also growing evidence that reproductive aging is linked to overall health in men, but this review mainly focuses on pathophysiological consequences of old age in men, such as low sperm count and diminished sperm genetic integrity, with an emphasis on mechanisms underlying reproductive aging. The steady decline of NAD levels observed in aging men represents one of the emerging concepts in that regard. Because it offers some mechanistic rationale explaining the effects of old age on the male reproductive system, some of the NAD-dependent functions in male reproduction are briefly outlined in this review. The overview also provides many questions that remain open about the basic science of male reproductive aging.

Access to legacy-oriented interventions at end of life for pediatric oncology patients: A decedent cohort review.

BACKGROUND: Legacy-oriented interventions have the potential to offer pediatric oncology patients and families comfort at end of life and during bereavement. Certified child life specialists often provide these services, and presently little is known about whether disparities exist in the provision of legacy-oriented interventions. METHODS: In this retrospective decedent cohort study, we examined demographic and clinical characteristics from a sample of 678 pediatric oncology patients who died between 2015 and 2019. Bivariate analysis assessed differences between patients who received any versus no legacy-oriented intervention. Uni- and multivariable logistic regression models assessed associations of baseline characteristics and likelihood of receiving legacy-oriented intervention. Further multivariable analysis explored joint effects of significant variables identified in the univariable analysis. RESULTS: Fifty-two percent of patients received a legacy-oriented intervention. Older adolescents (≥13 years) were less likely (odds ratio [OR]: 1.73, p = .007) to receive legacy-oriented interventions than younger ones. Patients with home/hospice deaths were also less likely (OR: 19.98, p < .001) to receive interventions compared to patients who passed away at SJCRH locations. Hispanic patients (OR: 1.53, p = .038) and those in palliative care (OR: 10.51, p < .001) were more likely to receive interventions. No significant race association was noted. CONCLUSION: All children and adolescents with cancer deserve quality care at end of life, including access to legacy-oriented interventions, yet nearly half of patients in this cohort did not receive these services. By identifying demographic and clinical characteristics associated with decreased odds of receiving legacy-oriented interventions, healthcare professionals can modify end-of-life care processes to improve access. Introducing legacy-oriented interventions early and increasing exposure in community spaces may enhance access to legacy-oriented interventions for pediatric oncology patients.

Turn-Off Fluorometric Determination of Bilirubin Using Facile Synthesized Nitrogen-Doped Carbon Dots as a Fluorescent Probe.

Bilirubin plays a significant role in human health management, particularly in the case of jaundice. Because of the need for the monitoring of bilirubin levels in jaundice patients, the development of a robust sensitive method becomes essential. Here, we describe the development of a highly sensitive and selective turn-off fluorometric detection method for bilirubin in blood serum samples using nitrogen-doped carbon dots (N-CDs). N-CDs was synthesized by the pyrolysis process, using citric acid and L-asparagine as the carbon and nitrogen sources, respectively. The prepared N-CDs solution showed highly intense blue emission with good stability. The HR-TEM image of N-CDs revealed spherical dot-like structures with an average size calculated to be 7.16 nm. Further, the surface functional groups of N-CDs were analyzed by FT-IR, Raman, XRD, and XPS techniques. Fluorescence spectra showed the maximum emission intensity at 443 nm (λex). The linear range of addition was performed from 1 to 150 µM, and the limit of detection (LOD) was determined to be 1.97 nM. The emission of N-CDs was quenched by Förster Resonance Energy Transfer (FRET) by adding bilirubin. These N-CDs showed extraordinary sensitivity and selectivity in the detection of bilirubin. Hence, this fluorescent probe has been proven successful in detecting the concentration of free bilirubin in human serum samples.

On-Off-On Fluorometric Detection of Hg(II) and L-Cysteine Using Red Emissive Nitrogen-Doped Carbon Dots for Environmental and Clinical Sample Analysis.

This research introduces a novel fluorescence sensor 'on-off-on' employing nitrogen-doped carbon dots (N-CDs) with an 'on-off-on' mechanism for the selective and sensitive detection of Hg(II) and L-cysteine (L-Cys). N-CDs was synthesized using citric acid as the carbon precursor and urea as the nitrogen source in dimethylformamide (DMF) solvent, resulting in red emissive characteristics under UV light. Comprehensive spectroscopic analyses, including UV-Vis, fluorescence, FT-IR, XRD, XPS, Raman, and Zeta potential techniques, validated the structural and optical characteristics of the synthesized N-CDs. The maximum excitation and emission of N-CDs were observed at 548 and 622 nm, respectively. The quantum yield of N-CDs was calculated to be 16.1%. The fluorescence of N-CDs effectively quenches upon the addition of Hg(II) due to the strong coordination between Hg(II) and the surface functionalities of N-CDs. Conversely, upon the subsequent addition of L-Cys, the fluorescence of N-CDs was restored. This restoration can be attributed to the stronger affinity of the -SH group in L-Cys towards Hg(II) relative to the surface functionalities of N-CDs. This dual-mode response enabled the detection of Hg(II) and L-Cys with impressive detection limits of 15.1 nM and 8.0 nM, respectively. This sensor methodology effectively detects Hg(II) in lake water samples and L-Cys levels in human urine, with a recovery range between 99 and 101%. Furthermore, the N-CDs demonstrated excellent stability, high sensitivity, and selectivity, making them a promising fluorescence on-off-on probe for both environmental monitoring of Hg(II) and clinical diagnostics of L-Cys.

Changes in the gut microbiota of rats after exposure to the fungicide Mancozeb.

Mancozeb is a fungicide commonly used in pest control programs, especially to protect vineyards. Its toxicity has already been evidenced in several studies. However, its influence on the composition and diversity of the gut microbiota remains unknown. In this work, the adverse impact of Mancozeb on the intestinal microbiota was investigated using a rodent model. Adult male Sprague Dawley rats were randomized into three groups: Control (standard diet), MZ1 (Mancozeb dose: 250 mg/kg bw/day), and MZ2 (Mancozeb dose: 500 mg/kg bw/day). After 12 weeks of experiment, animals were euthanized, and feces present in the intestine were collected. After fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ System. Alpha and beta diversity analysis showed significant differences between Control and Mancozeb groups (MZ1 e MZ2), but no difference between MZ1 and MZ2 was observed. Seven genera significantly increased in abundance following Mancozeb exposure, while five genera decreased. Co-occurrence analyses revealed that the topological properties of the microbial networks, which can be used to infer co-occurrence interaction patterns among microorganisms, were significantly lower in both groups exposed to Mancozeb when compared to Control. In addition, 23 differentially abundant microbial metabolic pathways were identified in Mancozeb-treated groups mainly related to a change in energy metabolism, LPS biosynthesis, and nucleotide biosynthesis. In conclusion, the exposure to Mancozeb presented side effects by changing the composition of the microbiota in rats, increasing bacterial diversity regardless of the dose used, reducing the interaction patterns of the microbial communities, and changing microbial metabolic pathways.

Postpartum long-acting reversible contraceptive use among active-duty, female US Army soldiers.

BACKGROUND: Postpartum use of long-acting reversible contraception has been found to be effective at increasing interpregnancy intervals, reducing unintended pregnancies, and optimizing health outcomes for mothers and babies. Among female active-duty military service members, reproductive planning may be particularly important, yet little is known about postpartum long-acting reversible contraceptive use among active-duty soldiers. OBJECTIVE: This study aimed to (1) quantify postpartum uptake of long-acting reversible contraception among active-duty female US Army soldiers and (2) identify demographic and military-specific characteristics associated with use. STUDY DESIGN: This retrospective cohort study used longitudinal data of all digitally recorded health encounters for active-duty US Army soldiers from 2014 to 2017. The servicewomen included in our analysis were aged 18 to 44 years with at least one delivery and a minimum of 4 months of total observed time postdelivery within the study period. We defined postpartum long-acting reversible contraception use as initiation of use within the delivery month or in the 3 calendar months following delivery and identified likely immediate postpartum initiation via the proxy of placement recorded during the same month as delivery. We then evaluated predictors of postpartum long-acting reversible contraception use with multivariable logistic regression. RESULTS: The inclusion criteria were met by 15,843 soldiers. Of those, 3162 (19.96%) initiated the use of long-acting reversible contraception in the month of or within the 3 months following delivery. Fewer than 5% of these women used immediate postpartum long-acting reversible contraception. Among women who initiated postpartum long-acting reversible contraceptive use, 1803 (57.0%) received an intrauterine device, 1328 (42.0%) received an etonogestrel implant, and 31 received both (0.98%). Soldiers of younger age, self-reported White race, and those who were married or previously married were more likely to initiate long-acting reversible contraception in the postpartum period. Race-stratified analyses showed that self-reported White women had the highest use rates overall. When compared with these women, the adjusted odds of postpartum use among self-reported Black and Asian or Pacific Islander women were 18% and 30% lower, respectively (both P<.001). There was also a trend of decreasing postpartum use with increasing age within each race group. Differences observed between age groups and race identities could partially be attributed to differential use of permanent contraception (sterilization), which was found to be significantly more prevalent among both women aged 30 years or older and among women who identified as Black. CONCLUSION: Among active-duty US Army servicewomen, 1 in 5 used postpartum long-acting reversible contraception, and fewer than 5% of these women used an immediate postpartum method. Within this population with universal healthcare coverage, we observed relatively low rates of use and significant differences in the uptake of effective postpartum long-acting contraceptive methods across self-reported race categories.

Association of intraplacental oxygenation patterns on dual-contrast MRI with placental abnormality and fetal brain oxygenation.

OBJECTIVES: Most human in-vivo placental imaging techniques are unable to distinguish and characterize various placental compartments, such as the intervillous space (IVS), placental vessels (PV) and placental tissue (PT), limiting their specificity. We describe a method that employs T2* and diffusion-weighted magnetic resonance imaging (MRI) data to differentiate automatically placental compartments, quantify their oxygenation properties and identify placental lesions (PL) in vivo. We also investigate the association between placental oxygenation patterns and fetal brain oxygenation. METHODS: This was a prospective study conducted between 2018 and 2021 in which dual-contrast clinical MRI data (T2* and diffusion-weighted MRI) were acquired from patients between 20 and 38 weeks' gestation. We trained a fuzzy clustering method to analyze T2* and diffusion-weighted MRI data and assign placental voxels to one of four clusters, based on their distinct imaging domain features. The new method divided automatically the placenta into IVS, PV, PT and PL compartments and characterized their oxygenation changes throughout pregnancy. RESULTS: A total of 27 patients were recruited, of whom five developed pregnancy complications. Total placental oxygenation level and T2* did not demonstrate a statistically significant temporal correlation with gestational age (GA) (R2 = 0.060, P = 0.27). In contrast, the oxygenation level reflected by T2* values in the placental IVS (R2 = 0.51, P = 0.0002) and PV (R2 = 0.76, P = 1.1 × 10-7 ) decreased significantly with advancing GA. Oxygenation levels in the PT did not show any temporal change during pregnancy (R2 = 0.00044, P = 0.93). A strong spatial-dependent correlation between PV oxygenation level and GA was observed. The strongest negative correlation between PV oxygenation and GA (R2 = 0.73, P = 4.5 × 10-7 ) was found at the fetal-vessel-dominated region close to the chorionic plate. The location and extent of the placental abnormality were automatically delineated and quantified in the five women with clinically confirmed placental pathology. Compared to the averaged total placental oxygenation, placental IVS oxygenation level best reflected fetal brain oxygenation level during fetal development. CONCLUSION: Based on clinically feasible dual-MRI, our method enables accurate spatiotemporal quantification of placental compartment and fetal brain oxygenation across different GAs. This information should improve our knowledge of human placenta development and its relationship with normal and abnormal pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Modern trends in minimally invasive versus open hepatectomy for colorectal liver metastasis: an analysis of ACS-NSQIP.

BACKGROUND: Surgical resection of colorectal liver metastasis (CRLM) provides the best opportunity for prolonged survival. Eligibility for metastasectomy has expanded with technical advancements including parenchymal-sparing hepatectomy (PSH). Meanwhile, enthusiasm for minimally invasive surgery (MIS) has increased, though this approach may be preferentially utilized for technically straightforward cases. The purpose of this study is to characterize modern trends in open versus MIS approaches to partial hepatectomy and anatomic hepatectomy for CRLM within a nationwide cohort. METHODS: The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) was used to investigate trends in MIS versus open hepatectomy for CRLM from 2015 to 2019. We examined baseline clinicopathologic and disease-related characteristics and compared trends in treatments over the study period. RESULTS: A total of 7457 patients undergoing hepatectomy for CRLM were identified (1367 MIS, 6090 open). Patients had similar clinicopathologic features between the two groups. Patients undergoing MIS resection less frequently received neoadjuvant therapy (51.1% vs 64.0%, p < 0.001) or concurrent intraoperative ablation (15.0% vs 21.3%, p < 0.001). Patients with tumors < 2 cm (34.9% vs 26.8%, p < 0.001) or only one to two tumors (82.8% vs 65.0%, p < 0.001) more commonly underwent MIS. MIS and open partial hepatectomies both significantly increased over the study period, but open partial hepatectomy increased at a greater rate than MIS (p < 0.001). Rates of anatomic resections have remained the same, with a greater proportion performed using an open approach (34.9% vs 16.4%, p < 0.001). Rates of operations consisting of > 1 concurrent partial hepatectomy are stable, but significantly more likely to be performed open (p < 0.001). CONCLUSIONS: Hepatectomy for CRLM has increased from a rise in partial hepatectomy, potentially translating to increased use of PSH. Current trends suggest MIS approaches appear to be increasing, but selectively implemented for patients with less technically demanding disease characteristics. Educational efforts should be directed towards increased dissemination of parenchymal-sparing MIS techniques for more complex resections.

The effects of preconception and early gestation SARS-CoV-2 infection on pregnancy outcomes and placental pathology.

OBJECTIVE: To evaluate if peri-pregnancy timing of a PCR+ test for SARS-CoV-2 RNA affects pregnancy outcomes and placental pathology. METHODS: This is a retrospective cohort study conducted in a tertiary center. Pregnancy outcomes and placental pathology were compiled for women who tested positive for SARS-CoV-2 RNA from a nasopharyngeal swab assessed by RT-PCR. The population comprised four groups that were PCR+ preconception (T0) or in the 1st (T1), 2nd (T2), or 3rd (T3) trimester of pregnancy. A fifth, control group (TC) tested PCR- for SARS-CoV-2 before delivery. RESULTS: Seventy-one pregnancies were studied. The T0 group exhibited lower gestational ages at delivery, had infants with the lowest birth weights, the highest rate of pregnancy loss before 20 weeks. Features of maternal vascular malperfusion and accelerated villous maturation were prominent findings in the histopathology of placentas from women PCR+ for SARS-CoV-2 RNA, especially in the T0 and the T1 groups. CONCLUSION: Women at highest risk for pregnancy complications are those who test PCR+ for viral RNA preconception or during first trimester of pregnancy.

Rates of Lapidus Procedures in the US Military Before and After the Advent of and Advocacy for Tri-Plane Lapidus Corrective Surgery.

Tri-plane corrective Lapidus surgery has been described as advantageous with respect to its anatomic basis and outcomes. Because the procedure has been broadly publicized, changes in overall Lapidus procedure rates due to increased numbers of patients opting for the tri-plane approach could have occurred. Data supporting this possibility appears lacking. We employed official personnel and health records of the total active-duty US military to conduct a retrospective cohort study of Lapidus surgery rates before and after the advent of the tri-plane corrective Lapidus procedure. Least-squares and locally-weighted scatterplot smoother regression functions were used to confirm time trends. Sociodemographic and occupational traits of Lapidus patients were compared using 2-sided t tests and chi square tests. Lapidus surgery rates among hallux valgus patients decreased during 2014 to 2016 and increased during 2017 to 2021. While multiple factors might explain these trends, they coincide with the advent of and advocacy for tri-plane Lapidus surgery. The results support the possibility that its rise influenced overall Lapidus rates in this population. As these findings represent limited evidence of such an influence, further research is required to confirm a causal link. If such a link is found, and if the ongoing research suggests that superior outcomes are associated with tri-plane Lapidus surgery, substantial implications could exist for this population. Benefits might include enhanced medical readiness due to the importance of lower extremity function during military duties. Additional research is needed to confirm the impact of the procedure and to determine whether Lapidus surgery rate patterns in civilian populations mirror these findings.

Leading indicators of readiness among the general Army and Special Operations Forces: Predictive and psychometric analysis of the Global Assessment Tool.

Self-assessments are commonly used to track Army readiness in specialized communities, but they are rarely analyzed for reliability and predictive validity. Before introducing new assessments, existing ones should be reevaluated. We examined the Global Assessment Tool (GAT), an annual Army-required self-assessment with multiple psychosocial and health behavior short scales. Psychometric analyses on nine scales included item response theory (IRT) and measurement invariance models across total Army (n = 743,057) and special operations forces (SOF; n = 3,478) cohorts. Predictive analyses examined demographic-adjusted associations between GAT scales and one-year incident medical non-readiness (MNR). Most scales had adequate reliability, although some exhibited highly skewed distributions, which likely increased measurement error. Most scales exhibited metric and scalar measurement equivalence across total Army and SOF groups. Scores from scales measuring positive characteristics were associated with lower odds of MNR (good coping, flexibility, optimism, positive affect, work engagement, friendship, organization trust; adjusted odds ratios ≤ 0.75); scores from scales measuring negative characteristics were associated with increased odds of MNR (poor sleep, depression, negative affect, loneliness; adjusted odds ratios ≥ 1.4). Associations were similar across Army and SOF cohorts. In conclusion, self-report data can potentially contribute to command surveillance, but iterative quality-checks are necessary after deployment.

Structural insight into the membrane targeting domain of the Legionella deAMPylase SidD.

AMPylation, the post-translational modification with adenosine monophosphate (AMP), is catalyzed by effector proteins from a variety of pathogens. Legionella pneumophila is thus far the only known pathogen that, in addition to encoding an AMPylase (SidM/DrrA), also encodes a deAMPylase, called SidD, that reverses SidM-mediated AMPylation of the vesicle transport GTPase Rab1. DeAMPylation is catalyzed by the N-terminal phosphatase-like domain of SidD. Here, we determined the crystal structure of full length SidD including the uncharacterized C-terminal domain (CTD). A flexible loop rich in aromatic residues within the CTD was required to target SidD to model membranes in vitro and to the Golgi apparatus within mammalian cells. Deletion of the loop (Δloop) or substitution of its aromatic phenylalanine residues rendered SidD cytosolic, showing that the hydrophobic loop is the primary membrane-targeting determinant of SidD. Notably, deletion of the two terminal alpha helices resulted in a CTD variant incapable of discriminating between membranes of different composition. Moreover, a L. pneumophila strain producing SidDΔloop phenocopied a L. pneumophila ΔsidD strain during growth in mouse macrophages and displayed prolonged co-localization of AMPylated Rab1 with LCVs, thus revealing that membrane targeting of SidD via its CTD is a critical prerequisite for its ability to catalyze Rab1 deAMPylation during L. pneumophila infection.

Structure dependence and species sensitivity of in vivo hepatobiliary toxicity with lysophosphatidic acid receptor 1 (LPA1) antagonists.

BMS-986020, BMS-986234 and BMS-986278, are three lysophosphatidic acid receptor 1 (LPA1) antagonists that were or are being investigated for treatment of idiopathic pulmonary fibrosis (IPF). Hepatobiliary toxicity (elevated serum AST, ALT, and ALP, plasma bile acids [BAs], and cholecystitis) was observed in a Phase 2 clinical trial with BMS-986020, and development was discontinued. In dogs and rats, the species used for the pivotal toxicology studies, there was no evidence of hepatobiliary toxicity in the dog while findings in the rat were limited to increased plasma BAs levels (6.1× control), ALT (2.9×) and bilirubin (3.4×) with no histopathologic correlates. Since neither rats nor dogs predicted clinical toxicity, follow-up studies in cynomolgus monkeys revealed hepatobiliary toxicity that included increased ALT (2.0× control) and GLDH (4.9×), bile duct hyperplasia, cholangitis, cholestasis, and cholecystitis at clinically relevant BMS-986020 exposures with no changes in plasma or liver BAs. This confirmed monkey as a relevant species for identifying hepatobiliary toxicity with BMS-986020. In order to assess whether the toxicity was compound-specific or related to LPA1 antagonism, two structurally distinct LPA1 antagonists (BMS-986234 and BMS-986278), were evaluated in rat and monkey. There were no clinical or anatomic pathology changes indicative of hepatobiliary toxicity. Mixed effects on plasma BAs in both rat and monkey has made this biomarker not a useful predictor of the hepatobiliary toxicity. In conclusion, the nonclinical data indicate the hepatobiliary toxicity observed clinically and in monkeys administered BMS-986020 is compound specific and not mediated via antagonism of LPA1.

Seasonality of temperate forest photosynthesis and daytime respiration.

Terrestrial ecosystems currently offset one-quarter of anthropogenic carbon dioxide (CO2) emissions because of a slight imbalance between global terrestrial photosynthesis and respiration. Understanding what controls these two biological fluxes is therefore crucial to predicting climate change. Yet there is no way of directly measuring the photosynthesis or daytime respiration of a whole ecosystem of interacting organisms; instead, these fluxes are generally inferred from measurements of net ecosystem-atmosphere CO2 exchange (NEE), in a way that is based on assumed ecosystem-scale responses to the environment. The consequent view of temperate deciduous forests (an important CO2 sink) is that, first, ecosystem respiration is greater during the day than at night; and second, ecosystem photosynthetic light-use efficiency peaks after leaf expansion in spring and then declines, presumably because of leaf ageing or water stress. This view has underlain the development of terrestrial biosphere models used in climate prediction and of remote sensing indices of global biosphere productivity. Here, we use new isotopic instrumentation to determine ecosystem photosynthesis and daytime respiration in a temperate deciduous forest over a three-year period. We find that ecosystem respiration is lower during the day than at night-the first robust evidence of the inhibition of leaf respiration by light at the ecosystem scale. Because they do not capture this effect, standard approaches overestimate ecosystem photosynthesis and daytime respiration in the first half of the growing season at our site, and inaccurately portray ecosystem photosynthetic light-use efficiency. These findings revise our understanding of forest-atmosphere carbon exchange, and provide a basis for investigating how leaf-level physiological dynamics manifest at the canopy scale in other ecosystems.

Aiding the prescriber: developing a machine learning approach to personalized risk modeling for chronic opioid therapy amongst US Army soldiers.

The opioid epidemic is a major policy concern. The widespread availability of opioids, which is fueled by physician prescribing patterns, medication diversion, and the interaction with potential illicit opioid use, has been implicated as proximal cause for subsequent opioid dependence and mortality. Risk indicators related to chronic opioid therapy (COT) at the point of care may influence physicians' prescribing decisions, potentially reducing rates of dependency and abuse. In this paper, we investigate the performance of machine learning algorithms for predicting the risk of COT. Using data on over 12 million observations of active duty US Army soldiers, we apply machine learning models to predict the risk of COT in the initial months of prescription. We use the area under the curve (AUC) as an overall measure of model performance, and we focus on the positive predictive value (PPV), which reflects the models' ability to accurately target military members for intervention. Of the many models tested, AUC ranges between 0.83 and 0.87. When we focus on the top 1% of members at highest risk, we observe a PPV value of 8.4% and 20.3% for months 1 and 3, respectively. We further investigate the performance of sparse models that can be implemented in sparse data environments. We find that when the goal is to identify patients at the highest risk of chronic use, these sparse linear models achieve a performance similar to models trained on hundreds of variables. Our predictive models exhibit high accuracy and can alert prescribers to the risk of COT for the highest risk patients. Optimized sparse models identify a parsimonious set of factors to predict COT: initial supply of opioids, the supply of opioids in the month being studied, and the number of prescriptions for psychotropic medications. Future research should investigate the possible effects of these tools on prescriber behavior (e.g., the benefit of clinician nudging at the point of care in outpatient settings).

Receipt of Electroconvulsive Therapy and Subsequent Development of Amyotrophic Lateral Sclerosis: A Cohort Study.

We investigated the potential relationship between receipt of electroconvulsive therapy (ECT) and development of amyotrophic lateral sclerosis (ALS). We conducted a cohort study using a sample of more than one million beneficiaries enrolled in the U.S. Medicare health insurance program from 1997 to 2017. Using time-varying proportional hazard modeling, we compared ALS occurrence among patients diagnosed with psychiatric conditions who received ECT to ALS occurrence among patients diagnosed with psychiatric conditions but who did not receive ECT. We observed moderately increased, but imprecise, hazard ratios (HR) for ALS following ECT (HR = 1.39, 95% confidence interval [CI]: 0.69-2.80). A statistically significant increase in the HR of ALS was observed among those who received more than 10 ECT treatments (>10 treatments, HR = 2.24, 95% CI: 1.00-5.01), compared to those receiving no ECT, with an even stronger association observed among subjects older than 65 years (HR = 3.03, 95% CI: 1.13-8.10). No monotonic exposure-response relationship was detected in categorical analyses. Our results provide weak support for the hypothesis that receipt of ECT increases the risk of developing ALS. Additional studies in larger populations, or in populations where ECT is more common, will be needed to refute or confirm an association between receipt of ECT and subsequent development of ALS. Bioelectromagnetics. 43:81-89, 2022. © 2021 Bioelectromagnetics Society.

Antifungal and antiocratoxigenic potential of Alpinia speciosa and Cymbopogon flexuosus essential oils encapsulated in poly(lactic acid) nanofibres against Aspergillus fungi.

Essential oils encapsulated in a polymeric matrix can be used as an alternative method to control fungi and mycotoxins. The essential oils were extracted by hydrodistillation and characterized by gas chromatography. The nanofibres were produced from poly (acid lactic) (PLA) containing essential oils by the Solution Blow Spinning method. The antifungal and antimicotoxygenic properties were evaluated against Aspergillus ochraceus and Aspergillus westerdijkiae by the fumigation method. Terpinen-4-ol (20·23%), sabinene (20·18%), 1·8-cineole (16·69%) and γ-terpinene (11·03%) were the principal compounds present in the essential oil from Alpinia speciosa, whereas citral (97·67%) was dominant from Cymbopogon flexuosus. Microscopy images showed that the addition of essential oils caused an increase in the diameter of the nanofibres. The infrared spectroscopy results indicated the presence of essential oils in the PLA nanofibres. Differential scanning calorimetry curves also indicated the existence of interactions between the essential oils and polymeric macromolecules through their plasticizing action. The hydrophobic character of nanofibres was revealed by the contact angle technique. An antifungal effect was observed, the mycelial growths (3·25-100%) and the synthesis of ochratoxin A (25·94-100%) were inhibited by the presence of the nanofibres. The results suggest that bioactive nanofibres hold promise for application to control toxigenic fungi.

Antifungal activity of poly(ε-caprolactone) nanoparticles incorporated with Eucalyptus essential oils against Hemileia vastatrix.

Coffee (Coffea L.) is one of the main crops produced globally. Its contamination by the fungus Hemileia vastatrix Berkeley and Broome has been economically detrimental for producers. The objective of this work was to extract and characterize the essential oils from Eucalyptus citriodora Hook, Eucalyptus camaldulensis Dehn and Eucalyptus grandis Hill ex Maiden, produce and characterize nanoparticles containing these essential oils and evaluate the in vivo and in vitro antifungal activity of free and nanoencapsulated essential oils. The principal constituent of the essential oil from E. citriodora was citronellal; that from E. grandis was α-pinene; and that from E. camaldulensis was 1,8-cineol. The in vitro antifungal activity against the fungus H. vastatrix was 100% at a concentration of 1000 µl l-1 for all the oils and nanoparticles containing these natural products. The sizes of the nanoparticles produced with the essential oils from E. citriodora, E. camaldulensis and E. grandis were 402·13 nm, 275·33 nm and 328·5 nm, respectively, with surface charges of -11·8 mV, -9·24 mV and - 6·76 mV, respectively. Fourier transform infrared analyses proved that the encapsulation of essential oils occurred in the polymeric matrix of poly(ε-caprolactone). The incorporation of essential oils into biodegradable poly(ε-caprolactone) nanoparticles increased their efficiency as biofungicides in the fight against coffee rust, decreasing the severity of the disease by up to 90·75% after treatment with the nanoparticles containing the essential oil from E. grandis.

Histopathology of Third Trimester Placenta from SARS-CoV-2-Positive Women.

Background: This study aims to investigate whether maternal SARS-CoV-2 status affects placental pathology. Methods: A retrospective case-control study was conducted by reviewing charts and slides of placentas delivered between April 1 to July 24, 2020. Clinical history of "COVID-19" was searched in Pathology Database (CoPath). Controls were matched with SARS-CoV-2-negative women with singleton deliveries in the 3rd-trimester. Pathological features were extracted from placental pathology reports. Results: Twenty-one 3rd trimester placentas from SARS-CoV-2-positive women were identified and compared to 20 placentas from SARS-CoV-2-negative women. There were no significant differences in individual or group gross or microscopic pathological features. Within the SARS-CoV-2+ group, there are no differences between symptomatic and asymptomatic women. Conclusion: Placentas from SARS-CoV-2-positive women do not demonstrate a specific pathological pattern. Pregnancy complicated with COVID-19 during the 3rd trimester does not have a demonstrable effect on placental structure and pathology.