Visualizing the Assembly Pathway of Nucleolar Pre-60S Ribosomes.

Eukaryotic 60S ribosomal subunits are comprised of three rRNAs and ∼50 ribosomal proteins. The initial steps of their formation take place in the nucleolus, but, owing to a lack of structural information, this process is poorly understood. Using cryo-EM, we solved structures of early 60S biogenesis intermediates at 3.3 Å to 4.5 Å resolution, thereby providing insights into their sequential folding and assembly pathway. Besides revealing distinct immature rRNA conformations, we map 25 assembly factors in six different assembly states. Notably, the Nsa1-Rrp1-Rpf1-Mak16 module stabilizes the solvent side of the 60S subunit, and the Erb1-Ytm1-Nop7 complex organizes and connects through Erb1's meandering N-terminal extension, eight assembly factors, three ribosomal proteins, and three 25S rRNA domains. Our structural snapshots reveal the order of integration and compaction of the six major 60S domains within early nucleolar 60S particles developing stepwise from the solvent side around the exit tunnel to the central protuberance.

The inhibiting effect of Aspirin Triggered-Resolvin D1 in non-canonical pyroptosis in rats with acute keratitis.

PURPOSE: To investigate the effect of Aspirin Triggered-Resolvin D1 (AT-RvD1) as an anti-pyroptosis and anti-inflammatory agent on lipopolysaccharide (LPS) induced acute keratitis in Wistar rats. METHODS: Acute keratitis in rats were induced by LPS stromal injection. Inflammatory reaction was measured by clinical score and histological observations. The non-canonical pyroptosis, the role of AT-RvD1 and Docosahexaenoic Acid (DHA) on non-canonical pyroptosis, were verified by quantification real-time PCR (qRT-PCR) and Western-blot. Besides, Human corneal epithelial cells (HCECs) primed with LPS, were stimulated with Nigericin, AT-RvD1 and necrosulfonamide (NSA), a Gasdermin-D (GSDMD) inhibitor separately. CCK-8 tests and flow cytometry were conducted to evaluate the cell viability and death ratio. And the marker of non-canonical pyroptosis were verified by Western blot. RESULTS: AT-RvD1 and DHA both alleviated the inflammation of rat cornea through inhibiting the expression of Caspase-11 and p30 which was triggered by LPS. Meanwhile, the activation of Caspase-4 and p30 were also significantly suppressed by AT-RvD1 in vitro, which is consistent with the results in rats. CONCLUSIONS: The non-canonical pyroptosis signaling pathways played an important role in rats with acute keratitis. In addition, AT-RvD1 can exert as an anti-inflammatory activity by inhibiting the non-canonical pyroptosis. Hence, it may be a promising and safe agent in treating acute keratitis.

Femoral neck shaft angle measurement on plain radiography: is standing or supine radiograph a reliable template for the contralateral femur?

INTRODUCTION: Neck-shaft angle (NSA) is of paramount importance to orthopedic surgeons due to its implications for various pathologies of the hip and femur. The primary aim of the study was to establish if NSA measurement may be affected by imaging position (standing and supine) and provide evidence regarding whether the contralateral NSA can be used as a template. The secondary aim was to determine a reference value and precisely understand the effects of sex on NSA measurement. MATERIALS AND METHODS: We measured bilateral NSA in a retrospective study of 200 standing and 200 supine anteroposterior pelvis radiographs that met the inclusion criteria, while paying special attention to bilateral hip symmetry. The overall inter-rater reliability was 0.688 (CI 0.128-0.851). Matching was performed according to sex (exact matching) and age. Paired t-test, Pearson correlation coefficient, and independent sample t-test were used (p < 0.01). RESULTS: A total of 400 pairs of femoral necks were reviewed, comprising of 200 males and 200 females. In the upright radiograph, the overall mean NSA was 131.21° ± 4.72°. There was no significant difference between right and left femur NSA among the patients (p = 0.95). On both sides, male NSA was higher than female NSA (p < 0.001). In supine radiograph, the overall mean NSA for the supine position was 133.06° ± 5.71°. There was a significant difference between NSA of the right and left femur among the patients in the supine position (p < 0.001). On supine radiographs there was no statistically significant difference between male and female NSA (p = 0.85). CONCLUSION: Our findings indicated no significant variability in upright radiographs between the right and left NSA. In contrast, significant asymmetry between the right and left NSA was found in the supine radiographs. However, this study does not provide definitive clinical evidence, and further clinical-oriented research is required. LEVEL OF EVIDENCE: Level III; retrospective comparative study.

Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels.

The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D2) expression and behavior (non-selective attention "NSA") in the mesocorticolimbic system of young healthy Sprague-Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D2 protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D2 expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.

RARE two-point Dixon with dual bandwidths.

PURPOSE: To investigate the impact of dual readout bandwidths (dBW) in a dual echo fat/water acquisition and describe a dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence where the concept is used to improve SNR by removing dead times between refocusing pulses and avoiding redundant Chemical-shift encoded. METHODS: Cramér-Rao bounds and Monte Carlo simulations were used to investigate a two-point fat/water model where the difference in bandwidths is incorporated. In vivo images were acquired at 1.5 and 3 T with the dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence. Typical bandwidth ratios were 1:2. SNR was compared with a single bandwidth sequence under identical scan parameters at 3T. RESULTS: Monte Carlo simulations and Cramér-Rao analysis demonstrate that number of signal averages can be improved with dual bandwidths compared to conventional single bandwidth acquisitions. The dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence can acquire images with high readout resolutions with well-conditioned sampling. An SNR improvement of 52% was measured, in line with the theoretical gain of 54%. CONCLUSIONS: The proposed dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence is a highly SNR-efficient two-point rapid acquisition relaxation enhanced, or turbo spin echo sequence without dead times, and can acquire images at higher resolutions than current vendor-supplied alternatives.

RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells.

Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin's cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin's anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin.

Challenges in the Australasian neurosurgery training program: who should be trained and where should they train?

OBJECTIVE: Neurosurgical training poses particular challenges in Australia and New Zealand, given the large landmass, small population, and widely separated, often small, neurosurgical units. Such factors have necessitated a move away from autonomous, single-institution-based training to the selection of trainees by a centralized binational process. The success of this system is based on rigorous standardized evaluation of candidates' academic achievements, anatomical knowledge, references, and interview performance. Similarly, the accreditation of hospitals to train successful candidates has been standardized. The authors review the evolution of trainee selection and the accreditation of training posts in Australia and New Zealand. METHODS: The records of the Neurosurgical Society of Australasia Surgical Education and Training Board were reviewed for documents pertaining to the selection of neurosurgical trainees and the accreditation of training posts. Application records and referee scores from 2014 to the present were reviewed to encompass process changes, in particular the change from written referee reports to standardized interviews of referees. Surgical logbook case numbers for 23 trainees completing training in 2016, 2017, and 2018 were collated and presented in an aggregated, de-identified form as a measure of adherence to accreditation standards. Written evaluations of the training experience were also sought from two trainees reflecting on the selection process, the quality of training posts, and training limitations. RESULTS: While a time-consuming process, the method of obtaining referee reports by interview has resulted in a wider spread of scores, more able to separate high- and low-scoring applicants than other components of the selection process. Review of the training post accreditation records for the last 2 years showed that adherence to standards has resulted in loss of accreditation for one unit and shortened periods of review for units with more minor deficiencies. Two applications for accreditation have been denied. Examination of caseload data showed that trainees more than fulfill minimum requirements in accredited training posts, confirming the robust nature of this aspect of unit accreditation. CONCLUSIONS: A key factor determining the success of neurosurgical training in Australia and New Zealand has been a willingness to evolve selection and other processes to overcome challenges as they become apparent. According to available analyses, the revised referee process and strict accreditation standards appear effective. The benefits and challenges of the current training system are discussed in the context of a paucity of international literature.

The Association Between Femoral Neck-Shaft Angle and Aging and Its Influence on the Performance of Functional Activity: A Cross-Sectional Investigation.

The purposes of this study were first to examine the association between aging and both the magnitude and asymmetry in the femoral neck-shaft angle (NSA). The second purpose was to determine the effects of both the magnitude and NSA asymmetry on the performance of functional activities in healthy individuals. Fifty-one subjects participated in this study. The femoral NSA was measured on computed tomography scout images. The participants performed four performance tests. Four hierarchical regression models were constructed to explore the effect of each predictor on the outcomes. Aging was associated with NSA asymmetry, but not with the degree of NSA. Age contributed significantly to the variability of all functional performance tests except the 10-m walking speed. The degree of the NSA did not contribute to the prediction of the functional performance tests. However, asymmetry in the NSA added significantly to the prediction of all functional performance tests except the 10-m walking speed.

Mutational Analysis of the Nsa2 N-Terminus Reveals Its Essential Role in Ribosomal 60S Subunit Assembly.

The ribosome assembly factor Nsa2 is part of the Rea1-Rsa4-Nsa2 interconnected relay on nuclear pre-60S particles that is essential for 60S ribosome biogenesis. Cryo-EM structures depict Nsa2 docked via its C-terminal ß-barrel domain to nuclear pre-60S particles, whereas the extended N-terminus, consisting of three α-helical segments, meanders between various 25S rRNA helices with the extreme N-terminus in close vicinity to the Nog1 GTPase center. Here, we tested whether this unappreciated proximity between Nsa2 and Nog1 is of functional importance. Our findings demonstrate that a conservative mutation, Nsa2 Q3N, abolished cell growth and impaired 60S biogenesis. Subsequent genetic and biochemical analyses verified that the Nsa2 N-terminus is required to target Nsa2 to early pre-60S particles. However, overexpression of the Nsa2 N-terminus abolished cytoplasmic recycling of the Nog1 GTPase, and both Nog1 and the Nsa2-N (1-58) construct, but not the respective Nsa2-N (1-58) Q3N mutant, were found arrested on late cytoplasmic pre-60S particles. These findings point to specific roles of the different Nsa2 domains for 60S ribosome biogenesis.

Nop-7-associated 2 (NSA2) is required for ribosome biogenesis and protein synthesis.

Ribosome biogenesis is a fundamental cellular process and occurs mainly in the nucleolus in eukaryotes. The process is exceptionally complex and highly regulated by numerous ribosomal and non-ribosomal factors. A recent discovery strengthened the link between ribosome biogenesis and malignant transformation. Here, we determined that Nop-7-associated 2 (NSA2) is a nucleolar protein required for ribosome biogenesis. NSA2 knockdown reduced the rate of rRNA synthesis, diminishing the 60S ribosomal subunit. Moreover, we demonstrated that depletion of NSA2 suppressed protein synthesis. To investigate the signaling pathway affected by NSA2, NSA2 was depleted, which triggered the inactivation of the mTOR signaling pathway. Taken together, our findings reveal a novel function of NSA2 and provide insight into the regulation of ribosome biogenesis by NSA2.

The femoral neck-shaft angle on plain radiographs: a systematic review.

OBJECTIVE: The femoral neck-shaft angle (NSA) is an important measure for the assessment of the anatomy of the hip and planning of operations. Despite its common use, there remains disagreement concerning the method of measurement and the correction of hip rotation and femoral version of the projected NSA on conventional radiographs. We addressed the following questions: (1) What are the reported values for NSA in normal adult subjects and in osteoarthritis? (2) Is there a difference between non-corrected and rotation-corrected measurements? (3) Which methods are used for measuring the NSA on plain radiographs? (4) What could be learned from an analysis of the intra- and interobserver reliability? MATERIAL AND METHODS: A systematic literature search was performed including 26 publications reporting the measurement of the NSA on conventional radiographs. RESULTS: The mean NSA of healthy adults (5,089 hips) was 128.8° (98-180°) and 131.5° (115-155°) in patients with osteoarthritis (1230 hips). The mean NSA was 128.5° (127-130.5°) for the rotation-corrected and 129.5° (119.6-151°) for the non-corrected measurements. CONCLUSION: Our data showed a high variance of the reported neck-shaft angles. Notably, we identified the inconsistency of the published methods of measurement as a central issue. The reported effect of rotation-correction cannot be reliably verified.

The role of nitroaromatic compounds (NACs) in constraining BrC absorption in the Indo-Gangetic Plain (IGP).

We present here the first measurements of nitroaromatic compounds (NACs) including nitrophenols (NPs), nitrocatechols (NCs) and nitrosalicylic acids (NSAs) from the Indian subcontinent and their role in constraining brown carbon (BrC) absorption. NACs at a rural receptor site in the eastern Indo-Gangetic Plain (IGP) (annual average: 185 ± 94 ng m-3) was dominated by NSAs (135 ± 77 ng m-3), followed by NPs (29 ± 11 ng m-3) and NCs (17 ± 16 ng m-3), with notable enrichments during nighttime and during the biomass burning seasons. An equilibrium absorption partitioning model estimated that >90 % of NSAs and NCs were in the particle-phase, suggesting lower degradation rates via oxidation and photolysis potentially due to year-round high relative humidity. While the contribution of NACs to organic aerosol mass was only 0.42 ± 0.23 %, their contribution to BrC absorption in the 300-450 nm range was higher by an order of magnitude (8 ± 4 %), with NCs and NSAs contributing almost equally in the low-visible (400-450 nm) range as at 365 nm. Despite having mass concentrations lower than NPs by factors of ∼2, contribution of NCs to BrC absorption at λ ≥ 400 nm was comparable to that by NPs, indicating the importance of the absorption efficiency of chromophores. The receptor model positive matrix factorization (PMF) quantified three major NAC sources: fossil fuel combustion (49 ± 15 %; annual average), secondary formation (40 ± 12 %), and biomass burning (11 ± 9 %), with variable contributions on seasonal and day-night bases. In summary, the study uncovered the significant role of NACs in constraining BrC absorption in the IGP, which stresses the importance for molecular-level characterization of BrC chromophores.

Does early stable fixation reduce complications in paediatric femoral neck fractures?

The primary objective of this study was to juxtapose the union rate and incidence of complications in paediatric patients presenting early (≤ 7 days) following injury with children presenting later (> 7 days) with femoral neck fractures. This critical appraisal evaluated 15 patients according to their timing of presentation and surgery from the initial day of injury (Group A: operated ≤ 7 days or Group B: > 7 days of injury). Patients with traumatic femoral neck fractures with Delbet 1 to 4 subtypes who were skeletally immature (age ≤ 16 years) were included in the study. Pathological fractures and post-infective fractures were not included. Each patient's secondary loss of reduction was calculated by measuring the Neck shaft angle (NSA) on the immediate post-operative radiograph and at the union. A change in NSA of ≥ 5 degrees was considered a significant loss of reduction. Ratliff's Criteria was used to analyze the final result, and a thorough record of complications was kept. There were no significant variations in the two groups' with respect to distributions of age, sex, injury mechanism, or fracture pattern. The most frequent injury culprit in both groups was falling from a height. Type II fracture pattern (54.54%) was more common in group A, while Type III and Type II fracture pattern was equally distributed in group B. In group A, the mean operation time was 55 ± 8.25 minutes, whereas in group B, it was 65 ± 15 minutes (p-value > 0.05). In group A, 90.9% of patients underwent CCS fixation, and in group B, 75% underwent fixation by CCS. The quality of reduction in post-operative radiographs was anatomical in 10 (90.9%) patients and unacceptable in 1 (9.1%) patient. In group B, 2 (50%) patients had an anatomical reduction, while 2 (50%) patients had an unacceptable reduction. Timing of reduction and its association with complications showed that early stable reduction and fixation decrease the occurrence of complications in femoral neck fractures (p-value = 0.033). Fracture union was seen in all our patients in both groups and none of our patients underwent non-union. The mean union time was 11.11 ± 7.06 weeks in group A and 16.5 ± 2.59 weeks in group B (p-value = 0.0189). In group A, only 1 (9.1%) patient developed coxa vara. In group B, out of 4 patients, the femoral head of one patient underwent avascular necrosis, one patient exhibited coxa vara, and 1 patient developed premature physeal closure with limb length inequality. Management of femoral neck fractures in children is challenging because of the paediatric bone's peculiar anatomic and physiological considerations. In our study, patients operated within 7 days developed fewer complications as compared to patients who were operated after 7 days, which was statistically significant. Although AVN is a frequent adverse consequence of pediatric femoral neck fractures, early reduction and stable fixation lowers AVN rates, as observed in our study. Our short-term functional and radiological results using the Ratliff scoring system were comparable to previous studies owing to stable anatomic reduction. Based on our findings and the existing literature, we emphasize long-term follow-up and recommend an early stable anatomic reduction in the treatment of paediatric femoral neck fractures.

Multi-level structural damage characterization using sparse acoustic sensor networks and knowledge transferred deep learning.

Standard structural health monitoring techniques face well-known difficulties for comprehensive defect diagnosis in real-world structures that have structural, material, or geometric complexity. This motivates the exploration of machine-learning-based structural health monitoring methods in complex structures. However, creating sufficient training data sets with various defects is an ongoing challenge for data-driven machine (deep) learning algorithms. The ability to transfer the knowledge of a trained neural network from one component to another or to other sections of the same component would drastically reduce the required training data set. Also, it would facilitate computationally inexpensive machine learning based inspection systems. In this work, a machine-learning-based multi-level damage characterization is demonstrated with the ability to transfer trained knowledge within the sparse sensor network. A novel network spatial assistance and an adaptive convolution technique are proposed for efficient knowledge transfer within the deep learning algorithm. Proposed structural health monitoring method is experimentally evaluated on an aluminum plate with artificially induced defects. It was observed that the method improves the performance of knowledge transferred damage characterization by 50 % during localization and 24 % during severity assessment. Further, experiments using time windows with and without multiple edge reflections are studied. Results reveal that multiply scattered waves contain rich and deterministic defect signatures that can be mined using deep learning neural networks, improving the accuracy of both identification and quantification. In the case of a fixed sensor network, using multiply scattered waves shows 100 % prediction accuracy at all levels of damage characterization.

An efficient method for organic acetylation and use of DL-phosphinothricin as a negative selection agent in argE transgenic rice.

We present an efficient method for the production of N-acetyl-L-phosphinothricin (N-AcPt) from commercial DL-phosphinothricin (DL-PPT) by organic acetylation for use as a negative selection agent (NSA) that induces cell death in argE transgenic rice. DL-PPT was efficiently converted into N-AcPt with tetrahydrofuran (THF) and acetic anhydride (Ac2O). Chemical changes were confirmed using NMR and ATR-FTIR analyses. DL-PPT was toxic but N-AcPt did not show cytotoxic effects on leaf discs or seed germination of wild-type rice. Conversely, in argE-hpt transgenic rice, non-toxic N-AcPt showed the negative selection (NS) effect by inducing cell destruction in leaf discs and restricting seed germination. For inducing NS, ≥0.1 mg ml(-1) and ≥0.5 mg ml(-1) of N-AcPt were effective in leaf and seed assays, respectively. Further, the NS effect occurred faster in the leaf assay compared with the seed germination assay, again indicating the leaf assay was a more sensitive indicator of N-AcPt as an NSA to argE transgenic rice than the seed germination assay. This negative selection approach could be useful for the development of selectable marker free transgenic plants in the economically important monocot species and its commercialization for multiple gene transformation.

Optimal cutoff scores of the Chinese version of 15-item negative symptom assessment that indicate prominent negative symptoms of schizophrenia.

Objective: The Chinese version of 15-item negative symptom assessment (NSA-15) is an instrument with a three-factor structure specifically validated for assessing negative symptoms of schizophrenia. To provide a reference for future practical applications in the recognition of schizophrenia patients with negative symptoms, this study aimed to determine an appropriate NSA-15 cutoff score regarding negative symptoms to identify prominent negative symptoms (PNS). Methods: A total of 199 participants with schizophrenia were recruited and divided into the PNS group (n = 79) and non-PNS group (n = 120) according to scale for assessment of negative symptoms (SANS) scores. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal NSA-15 cutoff score for identifying PNS. Results: The optimal cutoff NSA-15 score for identifying PNS was 40. Communication, emotion and motivation factors in the NSA-15 had cutoffs of 13, 6, and 16, respectively. The communication factor score had slightly better discrimination than scores on the other two factors. The discriminant ability of the global rating of the NSA-15 was not as good as that of the NSA-15 total score (area under the curve (AUC): 0.873 vs. 0.944). Conclusion: The optimal NSA-15 cutoff scores for identifying PNS in schizophrenia were determined in this study. The NSA-15 provides a convenient and easy-to-use assessment for identifying patients with PNS in Chinese clinical situations. The communication factor of the NSA-15 also has excellent discrimination.

Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study.

Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients.

Ferroptosis model system by the re-expression of BACH1.

Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation. The heme-responsive transcription factor BTB and CNC homology 1 (BACH1) promotes ferroptosis by repressing the transcription of genes involved in glutathione (GSH) synthesis and intracellular labile iron metabolism, which are key regulatory pathways in ferroptosis. We found that BACH1 re-expression in Bach1-/- immortalized mouse embryonic fibroblasts (iMEFs) can induce ferroptosis upon 2-mercaptoethanol removal, without any ferroptosis inducers. In these iMEFs, GSH synthesis was reduced, and intracellular labile iron levels were increased upon BACH1 re-expression. We used this system to investigate whether the major ferroptosis regulators glutathione peroxidase 4 (Gpx4) and apoptosis-inducing factor mitochondria-associated 2 (Aifm2), the gene for ferroptosis suppressor protein 1, are target genes of BACH1. Neither Gpx4 nor Aifm2 was regulated by BACH1 in the iMEFs. However, we found that BACH1 represses AIFM2 transcription in human pancreatic cancer cells. These results suggest that the ferroptosis regulators targeted by BACH1 may vary across different cell types and animal species. Furthermore, we confirmed that the ferroptosis induced by BACH1 re-expression exhibited a propagating effect. BACH1 re-expression represents a new strategy for inducing ferroptosis after GPX4 or system Xc- suppression and is expected to contribute to future ferroptosis research.

Physicochemical, rheological, and emulsification properties of nonenyl succinic anhydride (NSA) modified quinoa starch.

Nonenyl succinic anhydride (NSA) modification could be an alternative to octenyl succinic anhydride (OSA) modification of starch to obtain a range of physicochemical and rheological properties and for emulsification applications. A series of NSA-modified quinoa starches in granular form with different degrees of substitution (DS) (0.0080, 0.0175, 0.0359, and 0.0548) were prepared. The NSA modifications reduced the gelatinization temperatures and frequency dependence of storage modulus (G'), while increasing the peak viscosity, gel hardness, and G'. The NSA-modified quinoa starches with medium DS were the most effective in stabilising Pickering emulsions. The droplet size of Pickering emulsions decreased first with increasing DS before increasing at the highest DS. Modified starch with a DS of 0.0359 had the highest emulsifying capacity. Apart from the commonly used octenyl succinic anhydride (OSA) modification, the NSA-modified starches could be potential candidates as efficient Pickering emulsion stabilizers.

Similar optimal distalization and lateralization angles can be achieved with different reverse shoulder arthroplasty implant designs.

BACKGROUND: Optimal postoperative distalization (DSA) and lateralization (LSA) shoulder angles have been described as radiological measurements correlated with function after reverse shoulder arthroplasty (RSA). The proposed optimal values are DSA between 40° and 65° and LSA between 75° and 95°; however, whether these values can be reached with different implant designs is unclear. AIM: To determine which RSA implant could achieve higher rates of optimal DSA and LSA, to determine any association between each implant and optimal DSA and LSA, and to assess the correlation of the preoperative critical shoulder angle (CSA) and acromial index (AI) with the DSA and LSA. METHODS: This was a retrospective comparative study of all patients who underwent primary RSA for rotator cuff arthropathy. Three RSA implant designs were included, based on which patients were divided into three groups: group 1 (FH Arrow™; 16 patients) comprised onlay implants with a 135° neck-shaft angle (NSA); group 2 (Biomet Comprehensive™; 20 patients) comprised onlay implants with a 147° NSA; group 3 (Mathys Affinis™; 15 patients) comprised inlay implants with a 155° NSA. The AI and CSA were measured on preoperative radiographs. The DSA and LSA were measured on true AP postoperative radiographs. RESULTS: The mean DSAs were 44°, 46°, and 46° (P = 0.671) and the mean LSAs were 92°, 91°, and 82° for groups 1, 2, and 3, respectively (P = 0.003). Group 3 had lower LSA than groups 1 (-10°; P = 0.005) and 2 (-9°; P = 0.002). Optimal DSA and LSA were achieved in 71% and 73% of all arthroplasties, respectively. No association between implant designs and achieving an optimal DSA or LSA was observed. None of the implant designs had DSA >65°. The most common cause of failure to reach an optimal LSA in onlay implants was a combination of LSA >95° and DSA <40°. The most common cause of failure in group 3 was DSA <40°. The DSA was negatively correlated with the AI (-0.384; P = 0.006) and CSA (-0.305; P = 0.033). No correlation was observed between the LSA and AI (P = 0.312) or CSA (P = 0.137). CONCLUSION: The LSA is lower with the Mathys Affinis™ implant than with the Biomet Comprehensive™ and FH Arrow™ implants; however, most LSAs are in the optimal ranges, and no association is observed between different implant designs and optimal DSA and LSA. Implant design, CSA, and AI should be considered during preoperative planning to achieve optimal DSA and LSA.