Search

Background: The teaching of anatomy is a key component in the training of physicians, and the foundation of this teaching is the human body, which must be properly prepared to be used as a teaching aid. Due to a lack of modern literature on this topic, we decided to write a technical note discussing access to the carotid artery. Materials and methods: We pre-qualified 43 donor bodies for the study. The bodies had to meet standards such as no signs of post-mortem decomposition, preservation of body integrity, and the absence of known infections. Carotid artery access was performed based on descriptions of the types of vascular access performed in surgery and our own observations. Results: We consider carotid artery access to be a convenient option due to its ease of location. When performed correctly and with attention to the surrounding structures, it is relatively low in tissue trauma, which translates into a higher quality of preparation. Data analysis has revealed several factors that can have a significant impact on the success of the embalming procedure. Conclusions: Proper execution of minimally invasive access to the common carotid artery minimizes tissue damage and ensures a high success rate of the procedure. Knowledge of the types of vascular access is essential for preparing the highest quality specimens. [ABSTRACT FROM AUTHOR]

Summary: Despite low or undetectable plasma viral load, people living with HIV-2 (PLWH2) typically progress toward AIDS. The driving forces behind HIV-2 disease progression and the role of viremia are still not known, but low-level replication in tissues is believed to play a role. To investigate the impact of viremic and aviremic HIV-2 infection on target and bystander cell pathology, we used data-independent acquisition mass spectrometry to determine plasma signatures of tissue and cell type engagement. Proteins derived from target and bystander cells in multiple tissues, such as the gastrointestinal tract and brain, were detected at elevated levels in plasma of PLWH2, compared with HIV negative controls. Moreover, viremic HIV-2 infection appeared to induce enhanced release of proteins from a broader range of tissues compared to aviremic HIV-2 infection. This study expands the knowledge on the link between plasma proteome remodeling and the pathological cell engagement in tissues during HIV-2 infection.

Summary: Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active sACE2 (a-sACE2), with up to 1 μg/mL total sACE2 in moderate and severe patients. Fifty percent of COVID-19 sera inhibited ACE2 activity, in contrast to 1.3% of healthy donors and 4% of non-COVID-19 pneumonia patients. A mild inverse correlation of a-sACE2 with RBM-directed serum antibodies was observed. In silico, we show that sACE2 concentrations measured in COVID-19 sera can disrupt germinal center formation and inhibit timely production of high-affinity antibodies. We suggest that sACE2 is a biomarker for COVID-19 and that soluble receptors may contribute to immune suppression informing vaccine design.

Summary: Physiological and molecular processes including the transcriptome change across the 24-h day, driven by molecular circadian clocks and behavioral and systemic factors. It is not known how the temporal organization of the human transcriptome responds to a long-lasting challenge. This may, however, provide insights into adaptation, disease, and recovery.We investigated the human 24-h time series transcriptome in 20 individuals during a 90-day constant bed rest protocol. We show that the protocol affected 91% of the transcriptome with 76% of the transcriptome still affected after 10 days of recovery. Dimensionality-reduction approaches revealed that many affected transcripts were associated with mRNA translation and immune function. The number, amplitude, and phase of rhythmic transcripts, including clock genes, varied significantly across the challenge.These findings of long-lasting changes in the temporal organization of the transcriptome have implications for understanding the mechanisms underlying health consequences of conditions such as microgravity and bed rest.

" The COVID-19 pandemic significantly changed the way anatomy classes were carried out, depriving students of practical learning using real anatomical specimens. Once COVID restrictions were lifted and students returned to a normal class setting a randomized study was carried out to elevate effectiveness of practical anatomy didactics. " The aim of this study was to evaluate the impact of an anatomy workshop based on demonstrating anatomical structures delivered in a face-to-face format, and to compare it with a standard course based on online learning. " The randomization involved 350 students from whom 80 participants were drawn to form both a study and control group. " The study consisted of three parts: exam 1, workshop, exam 2. " The study group participated in all parts of the project, while the control group participated only in the exam. " The workshop was held by near peer teachers (NPT). Statistical analysis showed that participation in the workshop had an effect on the passing score of exam 2 (p=0.039). It was also shown that the difference in scores was significantly higher (p=0.049) in the study group compared to the control group. " The study proved that the workshops which were based on demonstrating anatomical structures by NPT significantly affected the scores obtained by trainees. In conclusion, the project confirmed the importance of student interaction with anatomical specimens and that online teaching is not a substitute for teaching in a dissecting room. Additionally, this study confirmed the high usefulness of NPT as a support for the didactic process conducted by experts. [ABSTRACT FROM AUTHOR]

Summary: Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.

Summary: Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver.

Summary: Nucleocapsid (N) encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays key roles in the replication cycle and is a critical serological marker. Here, we characterize essential biochemical properties of N and describe the utility of these insights in serological studies. We define N domains important for oligomerization and RNA binding and show that N oligomerization provides a high-affinity RNA-binding platform. We also map the RNA-binding interface, showing protection in the N-terminal domain and linker region. In addition, phosphorylation causes reduction of RNA binding and redistribution of N from liquid droplets to loose coils, showing how N-RNA accessibility and assembly may be regulated by phosphorylation. Finally, we find that the C-terminal domain of N is the most immunogenic, based on antibody binding to patient samples. Together, we provide a biochemical description of SARS-CoV-2 N and highlight the value of using N domains as highly specific and sensitive diagnostic markers.

Summary: Critical limb ischemia (CLI) is a hazardous manifestation of atherosclerosis and treatment failure is common. Abnormalities in the arterioles might underlie this failure but the cellular pathobiology of microvessels in CLI is poorly understood. We analyzed 349 intramuscular arterioles in lower limb specimens from individuals with and without CLI. Arteriolar densities were 1.8-fold higher in CLI muscles. However, 33% of small (

Glyphosate is one of the most widely used herbicides globally, raising concerns about its potential impact on human health. Biomonitoring studies play a crucial role in assessing human exposure to glyphosate and providing valuable insights into its distribution and metabolism in the body. This review aims to summarize the current trends and future perspectives in biomonitoring of glyphosate and its major degradation product of aminomethylphosphonic acid (AMPA). A comprehensive literature search was conducted, focusing on studies published between January 2000 and December 2022. The findings demonstrated that glyphosate and AMPA have been reported in different human specimens with urine as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with liquid/gas chromatography-tandem mass spectrometry have achieved matrix elimination and accurate analysis. We also examined and compared the exposure characteristics of these compounds among different regions and various populations, with significantly higher levels of glyphosate and AMPA observed in Asian populations and among occupational groups. The median urinary concentration of glyphosate in children was 0.54 ng/mL, which was relatively higher than those in women (0.28 ng/mL) and adults (0.12 ng/mL). It is worth noting that children may exhibit increased susceptibility to glyphosate exposure or have different exposure patterns compared to women and adults. A number of important perspectives were proposed in order to further facilitate the understanding of health effects of glyphosate and AMPA, which include, but are not limited to, method standardization, combined exposure assessment, attention for vulnerable populations, long-term exposure effects and risk communication and public awareness. [Display omitted] • Human exposure to glyphosate and its metabolite AMPA was reviewed. • Urine was the major human specimen examined. • SPE and LLE coupled with HPLC-MS/MS assisted sample clean-up and analysis. • Higher levels of glyphosate and AMPA were observed in Asian and occupational populations. • Several perspectives were proposed for further research in biomonitoring of glyphosate and AMPA. [ABSTRACT FROM AUTHOR]

Despite low or undetectable plasma viral load, people living with HIV-2 (PLWH2) typically progress toward AIDS. The driving forces behind HIV-2 disease progression and the role of viremia are still not known, but low-level replication in tissues is believed to play a role. To investigate the impact of viremic and aviremic HIV-2 infection on target and bystander cell pathology, we used data-independent acquisition mass spectrometry to determine plasma signatures of tissue and cell type engagement. Proteins derived from target and bystander cells in multiple tissues, such as the gastrointestinal tract and brain, were detected at elevated levels in plasma of PLWH2, compared with HIV negative controls. Moreover, viremic HIV-2 infection appeared to induce enhanced release of proteins from a broader range of tissues compared to aviremic HIV-2 infection. This study expands the knowledge on the link between plasma proteome remodeling and the pathological cell engagement in tissues during HIV-2 infection., Competing Interests: The authors or their institutions declare no competing financial interests and did not at any time receive payment or services from a third party (government, commercial, private foundation, etc.) for any aspect of the submitted work (including data monitoring board, study design, manuscript preparation, statistical analysis, etc.). The authors have no patents, whether planned, pending, or issued, broadly relevant to the work., (© 2024 The Authors.)

Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active sACE2 (a-sACE2), with up to 1 μg/mL total sACE2 in moderate and severe patients. Fifty percent of COVID-19 sera inhibited ACE2 activity, in contrast to 1.3% of healthy donors and 4% of non-COVID-19 pneumonia patients. A mild inverse correlation of a-sACE2 with RBM-directed serum antibodies was observed. In silico , we show that sACE2 concentrations measured in COVID-19 sera can disrupt germinal center formation and inhibit timely production of high-affinity antibodies. We suggest that sACE2 is a biomarker for COVID-19 and that soluble receptors may contribute to immune suppression informing vaccine design., Competing Interests: The Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin have filed three patent applications in connection with this work on which M.L., F.K., L.E.S., and K.D.L.R. (EP21155584.2); C.V.G. and K.D.L.R. (EP22164013.9); and M.L., C.R., C.V.G., and K.D.L.R. (EP21194414.5) are inventors., (© 2024 The Authors.)

Physiological and molecular processes including the transcriptome change across the 24-h day, driven by molecular circadian clocks and behavioral and systemic factors. It is not known how the temporal organization of the human transcriptome responds to a long-lasting challenge. This may, however, provide insights into adaptation, disease, and recovery. We investigated the human 24-h time series transcriptome in 20 individuals during a 90-day constant bed rest protocol. We show that the protocol affected 91% of the transcriptome with 76% of the transcriptome still affected after 10 days of recovery. Dimensionality-reduction approaches revealed that many affected transcripts were associated with mRNA translation and immune function. The number, amplitude, and phase of rhythmic transcripts, including clock genes, varied significantly across the challenge. These findings of long-lasting changes in the temporal organization of the transcriptome have implications for understanding the mechanisms underlying health consequences of conditions such as microgravity and bed rest., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: The teaching of anatomy is a key component in the training of physicians, and the foundation of this teaching is the human body, which must be properly prepared to be used as a teaching aid. Due to a lack of modern literature on this topic, we decided to write a technical note discussing access to the carotid artery., Materials and Methods: We pre-qualified 43 donor bodies for the study. The bodies had to meet standards such as no signs of post-mortem decomposition, preservation of body integrity, and the absence of known infections. Carotid artery access was performed based on descriptions of the types of vascular access performed in surgery and our own observations., Results: We consider carotid artery access to be a convenient option due to its ease of location. When performed correctly and with attention to the surrounding structures, it is relatively low in tissue trauma, which translates into a higher quality of preparation. Data analysis has revealed several factors that can have a significant impact on the success of the embalming procedure., Conclusions: Proper execution of minimally invasive access to the common carotid artery minimizes tissue damage and ensures a high success rate of the procedure. Knowledge of the types of vascular access is essential for preparing the highest quality specimens.

Mutation targeted therapy in cystic fibrosis (CF) is still not eligible for all CF subjects, especially for cases carrying rare variants such as the CFTR genotype W57G/A234D (c.169T>G/c.701C>A). We performed in silico analysis of the effects of these variants on protein stability, which we functionally characterized using colonoids and reprogrammed nasal epithelial cells. The effect of mutations on cystic fibrosis transmembrane conductance regulator (CFTR) protein was analyzed by western blotting, forskolin-induced swelling (FIS), and Ussing chamber analysis. We detected a residual CFTR function that increases following treatment with the CFTR modulators VX661±VX445±VX770, correlates among models, and is associated with increased CFTR protein levels following treatment with CFTR correctors. In vivo treatment with VX770 reduced sweat chloride concentration to non-CF levels, increased the number of CFTR-dependent sweat droplets, and induced a 6% absolute increase in predicted FEV1% after 27 weeks of treatment indicating the relevance of theratyping with patient-derived cells in CF., Competing Interests: P.M. was paid for her expert testimony by Vertex Pharmaceuticals., (© 2023 The Author(s).)

Background and purpose Rupture risk of intracranial aneurysms is a major issue for public healthcare. A way to obtain an individual rupture risk assessment is a main objective of many research teams in the world. For many years, we have investigated the relationship between the mechanical properties of aneurysm wall tissues and the rupture risk. In this work, we try to go further and investigate rupture limit values. Methods Following surgical clipping, a specific conservation protocol was applied to aneurysmal tissues in order to preserve their mechanical properties. Thirty-nine intracranial aneurysms (27 females, 12 males) were tested using a uniaxial tensile test machine under physiological conditions, temperature, and saline isotonic solution. These represented 24 unruptured and 15 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a Yeoh hyperelastic model with 2 parameters. Moreover, uniaxial tensile tests were conducted until rupture of samples to obtain values of stress and strain rupture limit. Results The significant parameter a C 2 of the hyperelastic Yeoh model, allowed us to classify samples’ rigidity following the terminology we adopted in previous papers (Costalat et al., 2011; Sanchez et al., 2013 ): Soft, Stiff and Intermediate. Moreover, strain/stress rupture limit values were gathered and analyzed thanks to the tissue rigidity, the status of the aneurysm (initially ruptured or unruptured) and the gender of the patient. Conclusion Strain rupture limit was found quite stable around 20% and seems not to be correlated with the status of the aneurysm (initially ruptured or unruptured), neither with the gender of the patient. However, stretch and stress rupture limit seems not to be independent on the rigidity. The study confirms that ruptured aneurysms mainly present a soft tissue and unruptured aneurysms present a stiff material. [ABSTRACT FROM AUTHOR]

The use of neonicotinoid insecticides (NEOs) has been rising globally due to their broad-spectrum insecticidal activity, unique mode of neurotoxic action and presumed low mammalian toxicity. Given their growing ubiquity in the environment and neurological toxicity to non-target mammals, human exposure to NEOs is flourishing and now becomes a big issue. In the present work, we demonstrated that 20 NEOs and their metabolites have been reported in different human specimens with urine, blood and hair as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with high performance liquid chromatography-tandem mass spectrometry have successfully achieved matrix elimination and accurate analysis. We also discussed and compared exposure characteristics of these compounds among types of specimens and different regions. A number of important knowledge gaps were also identified in order to further facilitate the understanding of health effects of NEO insecticides, which include, but are not limited to, identification and use of neuro-related human biological samples for better elucidating neurotoxic action of NEO insecticides, adoption of advanced non-target screening analysis for a whole picture in human exposure, and expanding investigations to cover non-explored but NEO-used regions and vulnerable populations. [Display omitted] • Human exposure to neonicotinoid insecticides and their metabolites was reviewed. • Urine, blood and hair were the major human specimens tested. • SPE and LLE coupled with HPLC-MS/MS achieved matrix removal and accurate analysis. • Exposure characteristics were found among types of specimens and different regions. • Several major knowledge gaps were identified for further concerns. [ABSTRACT FROM AUTHOR]

Copyright of Wiener Medizinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background and purpose: Individual rupture risk assessment of intracranial aneurysms is a major issue in the clinical management of asymptomatic aneurysms. Aneurysm rupture occurs when wall tension exceeds the strength limit of the wall tissue. At present, aneurysmal wall mechanics are poorly understood and thus, risk assessment involving mechanical properties is inexistent. Aneurysm computational hemodynamics studies make the assumption of rigid walls, an arguable simplification. We therefore aim to assess mechanical properties of ruptured and unruptured intracranial aneurysms in order to provide the foundation for future patient-specific aneurysmal risk assessment. This work also challenges some of the currently held hypotheses in computational flow hemodynamics research. Methods: A specific conservation protocol was applied to aneurysmal tissues following clipping and resection in order to preserve their mechanical properties. Sixteen intracranial aneurysms (11 female, 5 male) underwent mechanical uniaxial stress tests under physiological conditions, temperature, and saline isotonic solution. These represented 11 unruptured and 5 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a 3-parameter (C 10, C 01, C 11) Mooney–Rivlin hyperelastic model. Each aneurysm was classified according to its biomechanical properties and (un)rupture status. Results: Tissue testing demonstrated three main tissue classes: Soft, Rigid, and Intermediate. All unruptured aneurysms presented a more Rigid tissue than ruptured or pre-ruptured aneurysms within each gender subgroup. Wall thickness was not correlated to aneurysmal status (ruptured/unruptured). An Intermediate subgroup of unruptured aneurysms with softer tissue characteristic was identified and correlated with multiple documented risk factors of rupture. Conclusion: There is a significant modification in biomechanical properties between ruptured aneurysm, presenting a soft tissue and unruptured aneurysms, presenting a rigid material. This finding strongly supports the idea that a biomechanical risk factor based assessment should be utilized in the to improve the therapeutic decision making. [Copyright &y& Elsevier]

Copyright of Journal of Orofacial Orthopedics/Fortschritte der Kieferorthopadie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Orofacial Orthopedics/Fortschritte der Kieferorthopadie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Study Design: Biomechanical., Objective: This study evaluates the biomechanical properties of lag-screws used in vertebral pincer fractures at the thoracolumbar junction., Methods: Pincer fractures were created in 18 bisegmental human specimens. The specimens were assigned to three groups depending on their treatment perspective, either bolted, with the thread positioned in the cortical or cancellous bone, or control. The specimens were mounted in a servo-hydraulic testing machine and loaded with a 500 N follower load. They were consecutively tested in 3 different conditions: intact, fractured, and bolted/control. For each condition 10 cycles in extension/flexion, torsion, and lateral bending were applied. After each tested condition, a computed tomography (CT) scan was performed. Finally, an extension/flexion fatigue loading was applied to all specimens., Results: Biomechanical results revealed a nonsignificant increase in stiffness in extension/flexion of the fractured specimens compared with the intact ones. For lateral bending and torsion, the stiffness was significantly lower. Compared with the fractured specimens, no changes in stiffness due to bolting were discovered. CT scans showed an increasing fracture gap during axial loading both in extension/flexion, torsion, and lateral bending in the control specimens. In bolted specimens, the anterior fragment was approximated, and the fracture gap nullified. This refers to both the cortical and the cancellous thread positions., Conclusion: The results of this study concerning the effect of lag-screws on pincer fractures appear promising. Though there was little effect on stiffness, CT scans reveal a bony contact in the bolted specimens, which is a requirement for bony healing.

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

The force experienced while inserting an 18-gauge Tuohy needle into the epidural space or dura is one of only two feedback components perceived by an anaesthesiologist to deduce the needle tip position in a patient's spine. To the best of the authors knowledge, no x-ray validated measurements of these forces are currently available to the public. A needle insertion force recording during an automated insertion of an 18-gauge Tuohy needle into human vertebral segments of four female donors was conducted. During the measurements, x-ray images were recorded simultaneously. The force peaks due to the penetration of the ligamentum supraspinale and ligamentum flavum were measured and compared to the measurements of an artificial patient phantom for a hybrid patient simulator. Based on these force peaks and the slope of the ligamentum interspinale, a mathematical model was developed. The model parameters were used to compare human specimens and artificial patient phantom haptics. The force peaks for the ligamenta supraspinale and flavum were 7.55 ± 3.63 N and 15.18 ± 5.71 N, respectively. No significant differences were found between the patient phantom and the human specimens for the force peaks and four of six physical model parameters. The patient phantom mimics the same resistive force against the insertion of an 18-gauge Tuohy needle. However, there was a highly significant (p < 0.001, eff size = 0.949 and p < 0.001, eff size = 0.896) statistical difference observed in the insertion depth where the force peaks of the ligamenta supraspinale and flavum were detected between the measurements on the human specimens and the patient phantom. Within this work, biomechanical evidence was identified for the needle insertion force into human specimens. The comparison of the measured values of the human vertebral segments and the artificial patient phantom showed promising results. [ABSTRACT FROM AUTHOR]

Nucleocapsid (N) encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays key roles in the replication cycle and is a critical serological marker. Here, we characterize essential biochemical properties of N and describe the utility of these insights in serological studies. We define N domains important for oligomerization and RNA binding and show that N oligomerization provides a high-affinity RNA-binding platform. We also map the RNA-binding interface, showing protection in the N-terminal domain and linker region. In addition, phosphorylation causes reduction of RNA binding and redistribution of N from liquid droplets to loose coils, showing how N-RNA accessibility and assembly may be regulated by phosphorylation. Finally, we find that the C-terminal domain of N is the most immunogenic, based on antibody binding to patient samples. Together, we provide a biochemical description of SARS-CoV-2 N and highlight the value of using N domains as highly specific and sensitive diagnostic markers., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Critical limb ischemia (CLI) is a hazardous manifestation of atherosclerosis and treatment failure is common. Abnormalities in the arterioles might underlie this failure but the cellular pathobiology of microvessels in CLI is poorly understood. We analyzed 349 intramuscular arterioles in lower limb specimens from individuals with and without CLI. Arteriolar densities were 1.8-fold higher in CLI muscles. However, 33% of small (<20 μm) arterioles were stenotic and 9% were completely occluded. The lumens were closed by bulky, re-oriented endothelial cells expressing abundant N-cadherin that uniquely localized between adjacent and opposing endothelial cells. S100A4 and SNAIL1 were also expressed, supporting an endothelial-to-mesenchymal transition. SMAD2/3 was activated in occlusive endothelial cells and TGFβ1 was increased in the adjacent mural cells. These findings identify a microvascular closure process based on mesenchymal transitions in a hyper-TGFß environment that may, in part, explain the limited success of peripheral artery revascularization procedures., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The article discusses a study which investigates and compares the mechanical behavior of human cerebral arteries at various locations in the Willis circle. The study shows the nonlinear elastic behavior of the cerebral arteries and significant difference of stiffness between the locations. It concludes that the arterial mechanical properties is dependent on the location on the circle of Willis and that mechanical behavior varies between longitudinal and circumferential directions.