A mutualistic bacterium rescues a green alga from an antagonist.

Photosynthetic protists, known as microalgae, are key contributors to primary production on Earth. Since early in evolution, they coexist with bacteria in nature, and their mode of interaction shapes ecosystems. We have recently shown that the bacterium Pseudomonas protegens acts algicidal on the microalga Chlamydomonas reinhardtii. It secretes a cyclic lipopeptide and a polyyne that deflagellate, blind, and lyse the algae [P. Aiyar et al., Nat. Commun. 8, 1756 (2017) and V. Hotter et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2107695118 (2021)]. Here, we report about the bacterium Mycetocola lacteus, which establishes a mutualistic relationship with C. reinhardtii and acts as a helper. While M. lacteus enhances algal growth, it receives methionine as needed organic sulfur and the vitamins B1, B3, and B5 from the algae. In tripartite cultures with the alga and the antagonistic bacterium P. protegens, M. lacteus aids the algae in surviving the bacterial attack. By combining synthetic natural product chemistry with high-resolution mass spectrometry and an algal Ca2+ reporter line, we found that M. lacteus rescues the alga from the antagonistic bacterium by cleaving the ester bond of the cyclic lipopeptide involved. The resulting linearized seco acid does not trigger a cytosolic Ca2+ homeostasis imbalance that leads to algal deflagellation. Thus, the algae remain motile, can swim away from the antagonistic bacteria and survive the attack. All three involved genera cooccur in nature. Remarkably, related species of Pseudomonas and Mycetocola also act antagonistically against C. reinhardtii or as helper bacteria in tripartite cultures.

Oxidative Effects in Early Stages of Embryo Development Due to Alcohol Consumption.

Alcohol, a widely consumed drug, exerts significant toxic effects on the human organism. This review focuses on its impact during fetal development, when it leads to a spectrum of disorders collectively termed Fetal Alcohol Spectrum Disorders (FASD). Children afflicted by FASD exhibit distinct clinical manifestations, including facial dysmorphism, delayed growth, and neurological and behavioral disorders. These behavioral issues encompass diminished intellectual capacity, memory impairment, and heightened impulsiveness. While the precise mechanisms underlying alcohol-induced fetal damage remain incompletely understood, research indicates a pivotal role for reactive oxygen species (ROS) that are released during alcohol metabolism, inciting inflammation at the cerebral level. Ethanol metabolism amplifies the generation of oxidant molecules, inducing through alterations in enzymatic and non-enzymatic systems responsible for cellular homeostasis. Alcohol consumption disrupts endogenous enzyme activity and fosters lipid peroxidation in consumers, potentially affecting the developing fetus. Addressing this concern, administration of metformin during the prenatal period, corresponding to the third trimester of human pregnancy, emerges as a potential therapeutic intervention for mitigating FASD. This proposed approach holds promise for ameliorating the adverse effects of alcohol exposure on fetal development and warrants further investigation.

A cyclic lipopeptide produced by an antagonistic bacterium relies on its tail and transient receptor potential-type Ca2+ channels to immobilize a green alga.

The antagonistic bacterium Pseudomonas protegens secretes the cyclic lipopeptide (CLiP) orfamide A, which triggers a Ca2+ signal causing rapid deflagellation of the microalga Chlamydomonas reinhardtii. We performed chemical synthesis of orfamide A derivatives and used an aequorin reporter line to measure their Ca2+ responses. Immobilization of algae was studied using a modulator and mutants of transient receptor potential (TRP)-type channels. By investigating targeted synthetic orfamide A derivatives, we found that N-terminal amino acids of the linear part and the terminal fatty acid region are important for the specificity of the Ca2+ -signal causing deflagellation. Molecular editing indicates that at least two distinct Ca2+ -signaling pathways are triggered. One is involved in deflagellation (Thr3 change, fatty acid tail shortened by 4C), whereas the other still causes an increase in cytosolic Ca2+ in the algal cells, but does not cause substantial deflagellation (Leu1 change, fatty acid hydroxylation, fatty acid changes by 2C). Using mutants, we define four TRP-type channels that are involved in orfamide A signaling; only one (ADF1) responds additionally to low pH. These results suggest that the linear part of the CLiP plays one major role in Ca2+ signaling, and that orfamide A uses a network of algal TRP-type channels for deflagellation.

Stereoselective synthesis of S-norvaline and related amino acids through a common intermediate.

A divergent, enantioselective synthetic strategy is reported to produce the non-proteinogenic, biologically active natural amino acids norvaline, 5-hydroxy-4-oxo-L-norvaline, and ɣ-oxonorvaline. These were synthesized in good yields (45-75%) from the common starting material (S)-allylglycine obtained by asymmetric transfer allylation of glycine Schiff base using the Corey catalyst derived from cinchonidine in more than 97% enantiomeric excess.

Evaluating pollution-related damage and restoration success in urban forests with participatory monitoring and digital tools.

Peri-urban forest monitoring requires indicators of vegetation damage. An example is the sacred fir (Abies religiosa) forests surrounding Mexico City, which have been heavily exposed to tropospheric ozone, a harmful pollutant, for over 4 decades. We developed a participatory monitoring system with which local community members and scientists generated data on ozone tree damage. Santa Rosa Xochiac rangers (13) used the digital tool KoboToolBox to record ozone damage to trees, tree height, tree ages, tree condition, tree position, and whether the tree had been planted. Thirty-five percent of the trees (n = 1765) had ozone damage. Younger trees had a lower percentage of foliage damaged by ozone than older trees (p < 0.0001), and asymptomatic trees tended to be younger (p < 0.0001). Symptomatic trees were taller than asymptomatic trees of the same age (R2 c  = 0.43, R2 m  = 0.27). Involving local communities facilitated forest monitoring and using digital technology improved data quality. This participatory system can be used to monitor forest condition change over time and thus aids restoration efforts driven by government or local communities' interests, facilitating local decision-making.

Evaluación del daño relacionado a la contaminación y del éxito de la restauración de los bosques urbanos con un monitoreo participativo y herramientas digitales Resumen El monitoreo de los bosques periurbanos requiere indicadores de daños en la vegetación. Un ejemplo son los bosques de abeto (Abies religiosa) que rodean la Ciudad de México, pues desde hace más de 4 décadas han estado expuestos al ozono troposférico, un contaminante nocivo. Desarrollamos un sistema de monitoreo participativo con el que miembros de la comunidad local y científicos generaron datos sobre los daños causados por el ozono en los árboles. Los guardabosques de Santa Rosa Xochiac (133) utilizaron la herramienta digital KoboToolBox para registrar los daños causados por el ozono en los árboles, su altura, edad, estado, posición y si eran árboles plantados. El 35% de los árboles (n = 1,765) presentó daños por ozono. Los árboles más jóvenes tenían un menor porcentaje de follaje dañado por el ozono que los árboles más viejos (p<0.0001), y los árboles asintomáticos tendían a ser más jóvenes (p<0.0001). Los árboles sintomáticos eran más altos que los asintomáticos de la misma edad (R2 c = 0.43, R2 m = 0.27). La participación de las comunidades locales facilitó el monitoreo forestal y el uso de tecnología digital mejoró la calidad de los datos. Este sistema participativo puede utilizarse para monitorear los cambios en el estado de los bosques a lo largo del tiempo y contribuir a los esfuerzos de restauración impulsados por el gobierno o las comunidades locales, facilitando la toma de decisiones a nivel local.

Quality improvement collaborative to optimize heart failure care in patients from a network of clinics in Argentina during the COVID-19 pandemic.

Heart failure (HF) is a major clinical and public health problem associated with significant mortality, morbidity, and health-care costs. Despite the existence of evidence-based guidelines for the optimal treatment of HF, the quality of care remains suboptimal. Our aim was to increase the use a care bundle in 50% of enrolled subjects during their hospitalization and discharge and to reduce their readmission for HF causes by 10%. We conducted an uncontrolled before-after study in eight hospitals in Argentina to evaluate the effect of a quality improvement intervention on the use of an HF care bundle in patients with HF New York Heart Association (NYHA) Class II-III. The HF bundle of care included medication, continuum of care, lifestyle habits, and predischarge examinations. Training and follow-up of multidisciplinary teams in each center were performed through learning sessions and plan-do-study-act improvement cycles. Data collectors reviewed bundle compliance in the health records of recruited patients after their hospital discharge and verified readmissions through phone calls to patients within 30-40 days after discharge. We recruited 200 patients (83 before and 127 during the intervention phase), and bundle compliance increased from 9.6% to 28.3% [odds ratio 3.71, 95% confidence interval (8.46; 1.63); P = .002]. Despite a slow improvement during the first months, bundle compliance gained momentum near the end of the intervention surpassing 80%. We observed a non-significant decreased readmission rate within 30 days of discharge due to HF in the postintervention period [8.4% vs. 5.5%, odds ratio 0.63, 95% CI (1.88; 0.21); P = .410]. Qualitative analysis showed that members of the intervention teams acknowledged the improvement of work organization and standardization of care, teamwork, shared mental model, and health record completeness as well as the utility of training fellows. Despite the challenges related to the pandemic, better care of patients with HF NYHA Class II-III was possible through simple interventions and collaborative work. Graphical abstract.

Inverse LGAD (iLGAD) Periphery Optimization for Surface Damage Irradiation.

Pixelated LGADs have been established as the baseline technology for timing detectors for the High Granularity Timing Detector (HGTD) and the Endcap Timing Layer (ETL) of the ATLAS and CMS experiments, respectively. The drawback of segmenting an LGAD is the non-gain area present between pixels and the consequent reduction in the fill factor. To overcome this issue, the inverse LGAD (iLGAD) technology has been proposed by IMB-CNM to enhance the fill factor and provide excellent tracking capabilities. In this work, we explore the use of iLGAD sensors for surface damage irradiation by developing a new generation of iLGADs, the periphery of which is optimized to improve the performance of irradiated sensors. The fabricated iLGAD sensors exhibit good electrical performances before and after X-ray irradiation.

Using de novo assembly to identify structural variation of eight complex immune system gene regions.

Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14+ monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31. We use this data to build a de novo assembly of eight genomic regions encoding four key components of the immune system, namely the human leukocyte antigen, immunoglobulins, T cell receptors, and killer-cell immunoglobulin-like receptors. Validation of our assembly using k-mer based and alignment approaches suggests that it has high accuracy, with estimated base-level error rates below 1 in 10 kb, although we identify a small number of remaining structural errors. We use the assembly to identify heterozygous and homozygous structural variation in comparison to GRCh38. Despite analyzing only a single individual, we find multiple large structural variants affecting core genes at all three immunoglobulin regions and at two of the three T cell receptor regions. Several of these variants are not accurately callable using current algorithms, implying that further methodological improvements are needed. Our results demonstrate that assessing haplotype variation in these regions is possible given sufficiently accurate long-read and associated data. Continued reductions in the cost of these technologies will enable application of these methods to larger samples and provide a broader catalogue of germline structural variation at these loci, an important step toward making these regions accessible to large-scale genetic association studies.

Brush-like Polyaniline with Optical and Electroactive Properties at Neutral pH and High Temperature.

In this research, a brush-like polyaniline (poly(2-acrylamide-2-methyl-1-propanesulfonate)-g-polyaniline)-b-poly(N-vinylcarbazole) (BL PAni) was developed as a strategy to overcome the limited processability and dedoping above pH 4 of conventional polyaniline (PAni). For the BL PAni synthesis, RAFT polymerization (homopolymer), RAFT-mediated surfactant-free emulsion polymerization (block copolymer), and interfacial oxidative polymerization were applied to graft the PAni chains. NMR and FT-IR spectroscopies were performed to confirm the structural elucidation of the reaction pathways, while the thermal properties were analyzed by TGA and DSC. Notably, the BL PAni presents absorption throughout the visible region and up to the near-infrared, showing dedoping resistance at up to 80 °C and at a neutral pH. The absorption range of the BL PAni, block copolymer, and homopolymer were studied by UV-Vis spectroscopy in solid-state and dispersion/solution, highlighting BL PAni and poly(anilinium 2-acrylamide-2-methyl-1-propanesulfonate)-b-poly(N-vinylcarbazole) (PAAMP-b-PVK) due to the π-stacking between the anilinium and carbazole groups. The cyclic voltammetry confirmed the persistence of electroactivity at a pH near 7.

A marine Chlamydomonas sp. emerging as an algal model.

The freshwater microalga Chlamydomonas reinhardtii, which lives in wet soil, has served for decades as a model for numerous biological processes, and many tools have been introduced for this organism. Here, we have established a stable nuclear transformation for its marine counterpart, Chlamydomonas sp. SAG25.89, by fusing specific cis-acting elements from its Actin gene with the gene providing hygromycin resistance and using an elaborated electroporation protocol. Like C. reinhardtii, Chlamydomonas sp. has a high GC content, allowing reporter genes and selection markers to be applicable in both organisms. Chlamydomonas sp. grows purely photoautotrophically and requires ammonia as a nitrogen source because its nuclear genome lacks some of the genes required for nitrogen metabolism. Interestingly, it can grow well under both low and very high salinities (up to 50 g · L-1 ) rendering it as a model for osmotolerance. We further show that Chlamydomonas sp. grows well from 15 to 28°C, but halts its growth at 32°C. The genome of Chlamydomonas sp. contains some gene homologs the expression of which is regulated according to the ambient temperatures and/or confer thermal acclimation in C. reinhardtii. Thus, knowledge of temperature acclimation can now be compared to the marine species. Furthermore, Chlamydomonas sp. can serve as a model for studying marine microbial interactions and for comparing mechanisms in freshwater and marine environments. Chlamydomonas sp. was previously shown to be immobilized rapidly by a cyclic lipopeptide secreted from the antagonistic bacterium Pseudomonas protegens PF-5, which deflagellates C. reinhardtii.

Depressive symptoms in child caregivers of very old Mexican Americans.

OBJECTIVE: To study the effects of disability, cognitive impairment, and neuropsychiatric disturbance among older Mexican Americans on depressive symptoms in their children caregivers. METHODS: This study utilizes data from Wave 7 (2010-2011) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE). The final sample included 200 adult children caregivers that provided direct personal care with activities of daily living (ADL) (e.g. bathing, toileting, dressing, etc.) to their older parents (average age = 87). We analyzed the influence of ADL disability, cognition (MMSE), and neuropsychiatric symptoms (NPI) of the care recipient on depressive symptoms of the adult child caregiver. A cross-sectional multivariable linear regression analysis was conducted to examine the effect of neuropsychiatric disturbance on caregiver depressive symptoms. RESULTS: Presence of care recipient NPI symptoms was associated with higher depressive symptoms for caregivers. Additional characteristics associated with caregiver depressive symptoms were not being married, and higher perceived social stress. ADL disability of the care recipient, cognitive functioning of the care recipient, or caregiver health status alone did not have a significant effect on depressive symptoms of the caregiver. CONCLUSIONS: In a Mexican American familistic culture, disability and cognitive impairment might be better tolerated by families but neuropsychiatric behavioral symptoms related to dementia may take an increased toll on family member caregivers. The need to provide respite services, mental health resources and community services for caregivers of care recipients with neuropsychiatric symptoms is of paramount importance to alleviate depressive symptoms and burden among caregivers.

Disease-Associated Tau Phosphorylation Hinders Tubulin Assembly within Tau Condensates.

Cellular condensation of intrinsically disordered proteins (IDPs) through liquid-liquid phase separation (LLPS) allows dynamic compartmentalization and regulation of biological processes. The IDP tau, which promotes the assembly of microtubules and is hyperphosphorylated in Alzheimer's disease, undergoes LLPS in solution and on the surface of microtubules. Little is known, however, about the influence of tau phosphorylation on its ability to nucleate microtubule bundles in conditions of tau LLPS. Herein, we show that unmodified tau as well as tau phosphorylated at disease-associated epitopes condense into liquid-like droplets. Although tubulin partitioned into and reached high concentrations inside all tau droplets, it was unable to grow into microtubules form the inside of droplets formed by tau phosphorylated at the AT180 epitope (T231/S235). In contrast, neither phosphorylation of tau in the repeat domain nor at its tyrosine residues inhibited the assembly of tubulin from tau droplets. Because LLPS of IDPs has been shown to promote different types of cytoskeletal assembly, our study suggests that IDP phosphorylation might be a broadly used mechanism for the modulation of condensate-mediated cytoskeletal assembly.

Colon capsule endoscopy versus CT colonography in FIT-positive colorectal cancer screening subjects: a prospective randomised trial-the VICOCA study.

BACKGROUND: Colon capsule endoscopy (CCE) and CT colonography (CTC) are minimally invasive techniques for colorectal cancer (CRC) screening. Our objective is to compare CCE and CTC for the identification of patients with colorectal neoplasia among participants in a CRC screening programme with positive faecal immunochemical test (FIT). Primary outcome was to compare the performance of CCE and CTC in detecting patients with neoplastic lesions. METHODS: The VICOCA study is a prospective, single-centre, randomised trial conducted from March 2014 to May 2016; 662 individuals were invited and 349 were randomised to CCE or CTC before colonoscopy. Endoscopists were blinded to the results of CCE and CTC. RESULTS: Three hundred forty-nine individuals were included: 173 in the CCE group and 176 in the CTC group. Two hundred ninety individuals agreed to participate: 147 in the CCE group and 143 in the CTC group. In the intention-to-screen analysis, sensitivity, specificity and positive and negative predictive values for the identification of individuals with colorectal neoplasia were 98.1%, 76.6%, 93.7% and 92.0% in the CCE group and 64.9%, 95.7%, 96.8% and 57.7% in the CTC group. In terms of detecting significant neoplastic lesions, the sensitivity of CCE and CTC was 96.1% and 79.3%, respectively. Detection rate for advanced colorectal neoplasm was higher in the CCE group than in the CTC group (100% and 93.1%, respectively; RR = 1.07; p = 0.08). Both CCE and CTC identified all patients with cancer. CCE detected more patients with any lesion than CTC (98.6% and 81.0%, respectively; RR = 1.22; p = 0.002). CONCLUSION: Although both techniques seem to be similar in detecting patients with advanced colorectal neoplasms, CCE is more sensitive for the detection of any neoplastic lesion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02081742 . Registered: September 16, 2013.

Simultaneous Sulfite Electrolysis and Hydrogen Production Using Ni Foam-Based Three-Dimensional Electrodes.

The electrochemical oxidation of sulfite ions offers encouraging advantages for large-scale hydrogen production, while sulfur dioxide emissions can be effectively used to obtain value-added byproducts. Herein, the performance and stability during sulfite electrolysis under alkaline conditions are evaluated. Nickel foam (NF) substrates were functionalized as the anode and cathode through electrochemical deposition of palladium and chemical oxidation to carry out the sulfite electro-oxidation and hydrogen evolution reactions, respectively. A combined analytical approach in which a robust electrochemical flow cell was coupled to different in situ and ex situ measurements was successfully implemented to monitor the activity and stability during electrolysis. Overall, satisfactory sulfite conversion and hydrogen production efficiencies (>90%) at 10 mA·cm-2 were mainly attributed to the use of NF in three-dimensional electrodes with a large surface area and enhanced mass transfer. Furthermore, stabilization processes associated with electrochemical dissolution and sulfur crossover through the membrane induced specific changes in the chemical and physical properties of the electrodes after electrolysis. This study demonstrates that NF-based electrocatalysts can be incorporated in an efficient electrochemical flow cell system for sulfite electrolysis and hydrogen production, with potential applications at a large scale.

Evaluating Different Methodologies for Bioprospecting Actinomycetes in Canary Islands Soils.

Actinomycetes are a wide group of Gram positive prokaryotes, the soil being their most characteristic habitat, where they play important ecological functions. Their immense biotechnological potential as producers of bioactive molecules of great commercial and industrial interest is exemplified by most antibiotics for clinical use being derived from this group of bacteria. In this work several methodologies and culture media were tested for the isolation of actinomycetes in soils from three different edafoclimatic areas of Tenerife (Canary Islands, Spain): an arid zone of the southeast coast of the island, a humid area in the laurel forest and the Canary high mountain. The results of this work evidenced that just an air drying of the sample during 7 days (pretreatment) produces high counts of actinomycetes versus non-actinomycetes in the three soils and in any of the culture media studied, making unnecessary post physical and chemical treatments. However, the only method that produced an exclusive isolation of actinomycetes was the use of 0.22-µm filters as a physical barrier, and hence being a tool of unquestionable utility to estimate actinomycetes populations in soil.The analysis by BOX rep-PCR determined that the richness and genetic diversity of the isolates of these localities are very high. The greatest similarities were, with one exception, found between strains from the same locations. Izaña was one that obtained the highest diversity. Regarding the biotecnology potential as antibiotic produces isolates from Güimar soils are the most promising as 7 out of 10 isolates showed some antibiotic activity.

A Musashi Splice Variant and Its Interaction Partners Influence Temperature Acclimation in Chlamydomonas.

Microalgae contribute significantly to carbon fixation on Earth. Global warming influences their physiology and growth rates. To understand algal short-term acclimation and adaptation to changes in ambient temperature, it is essential to identify and characterize the molecular components that sense small temperature changes as well as the downstream signaling networks and physiological responses. Here, we used the green biflagellate alga Chlamydomonas reinhardtii as a model system in which to study responses to temperature. We report that an RNA recognition motif (RRM)-containing RNA-binding protein, Musashi, occurs in 25 putative splice variants. These variants bear one, two, and three RRM domains or even lack RRM domains. The most abundant Musashi variant, 12, with a molecular mass of 60 kD, interacts with two clock-relevant members of RNA metabolism, the subunit C3 of the RNA-binding protein CHLAMY1 and the 5'-3' exoribonuclease XRN1. These proteins are able to integrate temperature information by up- or down-regulation of their protein levels in cells grown at low (18°C) or high (28°C) temperature. We further show that the 60-kD Musashi variants with three RRM domains can bind to (UG)7 repeat-containing RNAs and are up-regulated in cells grown at a higher temperature during early night. Intriguingly, the 60-kD Musashi variant 12, as well as C3 and XRN1, confer thermal acclimation to C. reinhardtii, as shown with mutant lines. Our data suggest that these three proteins of the RNA metabolism machinery are key members of the thermal signaling network in C. reinhardtii.

Biological and toxicological evaluation of Rhus trilobata Nutt. (Anacardiaceae) used traditionally in mexico against cancer.

BACKGROUND: Rhus trilobata Nutt. (Anacardiaceae) (RHTR) is a plant of Mexico that is traditionally used as an alternative treatment for several types of cancer. However, the phytochemical composition and potential toxicity of this plant have not been evaluated to support its therapeutic use. Therefore, this study aimed to evaluate the biological activity of RHTR against colorectal adenocarcinoma cells, determine its possible acute toxicity, and analyze its phytochemical composition. METHODS: The traditional preparation was performed by decoction of stems in distilled water (aqueous extract, AE), and flavonoids were concentrated with C18-cartridges and ethyl acetate (flavonoid fraction, FF). The biological activity was evaluated by MTT viability curves and the TUNEL assay in colorectal adenocarcinoma (CACO-2), ovarian epithelium (CHO-K1) and lung/bronchus epithelium (BEAS-2B) cells. The toxicological effect was determined in female BALB/c mice after 24 h and 14 days of intraperitoneal administration of 200 mg/kg AE and FF, respectively. Later, the animals were sacrificed for histopathological observation of organs and sera obtained by retro-orbital bleeding for biochemical marker analysis. Finally, the phytochemical characterization of AE and FF was conducted by UPLC-MSE. RESULTS: In the MTT assays, AE and FF at 5 and 18 µg/mL decreased the viability of CACO-2 cells compared with cells treated with vehicle or normal cells (p ≤ 0.05, ANOVA), with changes in cell morphology and the induction of apoptosis. Anatomical and histological analysis of organs did not reveal important pathological lesions at the time of assessment. Additionally, biochemical markers remained normal and showed no differences from those of the control group after 24 h and 14 days of treatment (p ≤ 0.05, ANOVA). Finally, UPLC-MSE analysis revealed 173 compounds in AE-RHTR, primarily flavonoids, fatty acids and phenolic acids. The most abundant compounds in AE and FF were quercetin and myricetin derivates (glycosides), methyl gallate, epigallocatechin-3-cinnamate, ß-PGG, fisetin and margaric acid, which might be related to the anticancer properties of RHTR. CONCLUSION: RHTR exhibits biological activity against cancer cells and does not present adverse toxicological effects during its in vivo administration, supporting its traditional use.

Novel Acetabular Cup for Revision THA Improves Hip Center of Rotation: A Radiographic Evaluation.

BACKGROUND: Bone loss in patients undergoing revision THA poses a considerable challenge for orthopaedic surgeons. Often, to achieve better fixation in remaining bone, larger diameter acetabular components and reaming superiorly may be necessary. However, this is likely to raise the hip center of rotation, which may lead to altered biomechanics, specifically, insufficiency of the abductor muscles, altered gait, and increased risk of dislocation from impingement. More recently, a newer acetabular shell has been designed to more closely replicate the native hip center of rotation in these circumstances while maintaining adequate fixation. QUESTIONS/PURPOSES: The purpose of this study was to compare the radiographic parameters of this newer design with conventional hemispheric cups in revision THA. Specifically, we assessed the differences in (1) vertical center of rotation (COR) displacement and (2) horizontal COR displacement. METHODS: Between January 2016 and April 2016, five reconstructive surgeons at five institutions utilized a newer highly porous acetabular shell designed with peripheral screw holes and vertically eccentric COR to allow for restoration of center of hip rotation in revision THA. We included all patients who received this device. During this time, the general indications at these sites for using the new device included Paprosky Stage IIA, IIB, IIC, or IIIA acetabular defects. This yielded 29 patients who were subsequently matched (one to two) by cup size and sex to a cohort who underwent revision THA with conventional hemispheric cups between January 2015 and May 2016. To determine hip COR, radiographic measurements were performed. A circle contiguous to the acetabulum was drawn and the center was determined as the hip COR. All measurements were made from the interteardrop line for both the revised and native hips. A line through the teardrops was used for all horizontal measurements. Center position adjustments were made based on the manufacturer-specified values. Comparisons were performed using chi-square tests for categorical and t-tests for continuous variables. There was no difference in the severity of bone loss before the revision in the groups, as evidenced by Paprosky staging of preoperative radiographs. RESULTS: The mean vertical COR displacement was smaller in patients who had the novel cup (3.5 mm; range, -12 to 15 mm; mean difference, -7.3 mm; 95% confidence interval [CI], -13.2 to -1.5) as compared with those who had the conventional cup (10.5 mm; range, -4 to 50 mm; mean difference, 7.3 mm; 95% CI, -12.5 to -2.2; p = 0.003). There was no difference in mean horizontal displacement between the two groups (-0.06 ± 6.1 versus 1.7 ± 7.1; mean difference, -1.8; p = 0.903). CONCLUSIONS: Although hip COR was improved based on radiographic measurements with the use of this novel acetabular design, and although this may improve hip biomechanics, more studies are required before its widespread adoption for revision cases of this nature can be recommended. Both implant costs and the risks associated with using a new design in practice will have to be justified by studies that evaluate fixation, clinical function and implant survival, and patient-reported outcome scores, all of which were beyond the scope of this preliminary report. LEVEL OF EVIDENCE: Level III, therapeutic study.

Current Practices of Measuring and Reference Range Reporting of Free and Total Testosterone in the United States.

PURPOSE: The evaluation and management of male hypogonadism should be based on symptoms and on serum testosterone levels. Diagnostically this relies on accurate testing and reference values. Our objective was to define the distribution of reference values and assays for free and total testosterone by clinical laboratories in the United States. MATERIALS AND METHODS: Upper and lower reference values, assay methodology and source of published reference ranges were obtained from laboratories across the country. A standardized survey was reviewed with laboratory staff via telephone. Descriptive statistics were used to tabulate results. RESULTS: We surveyed a total of 120 laboratories in 47 states. Total testosterone was measured in house at 73% of laboratories. At the remaining laboratories studies were sent to larger centralized reference facilities. The mean ± SD lower reference value of total testosterone was 231 ± 46 ng/dl (range 160 to 300) and the mean upper limit was 850 ± 141 ng/dl (range 726 to 1,130). Only 9% of laboratories where in-house total testosterone testing was performed created a reference range unique to their region. Others validated the instrument recommended reference values in a small number of internal test samples. For free testosterone 82% of laboratories sent testing to larger centralized reference laboratories where equilibrium dialysis and/or liquid chromatography with mass spectrometry was done. The remaining laboratories used published algorithms to calculate serum free testosterone. CONCLUSIONS: Reference ranges for testosterone assays vary significantly among laboratories. The ranges are predominantly defined by limited population studies of men with unknown medical and reproductive histories. These poorly defined and variable reference values, especially the lower limit, affect how clinicians determine treatment.

Correlates of depression in self-neglecting older adults: A cross-sectional study examining the role of alcohol abuse and pain in increasing vulnerability.

Self-neglect among older adults results in increased morbidity and mortality rates. Depression is strongly linked to self-neglect and when untreated, severely complicates management of health and functional outcomes. The study aims to identify factors correlated with depression to inform approaches to service recruitment and retention that improve long-term outcomes. The sample included urban community-dwelling older adults (n = 96) 65 years of age and older with Adult Protective Services-substantiated self-neglect. All participants completed a range of validated cognitive, functional, and self-report demographic and clinical measures around health and mental health functioning. A secondary data analysis using multivariable logistic regression revealed that a positive screen for alcohol abuse, low self-rated health, and higher self-reported pain were associated with significantly higher odds of self-reported depression. Further research is needed to understand the temporality between these correlates and depression and to inform prevention and intervention practices for self-neglecting older adults.