-
Journal of Geriatric Cardiology : JGC May 2024The (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this fifth section of the report continues the dissection on...
The (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this fifth section of the report continues the dissection on the management of cardiovascular diseases (CVD). Cerebrovascular disease is the leading cause of death and loss of healthy life among Chinese residents. Based on the results of GBD 2019, from 1990 to 2019, the years of life lost due to premature death caused by stroke showed a decreasing trend, while the years lived with disability still increased continuously. At present, national mortality surveillance system can provide national and provincial representative annual death data on cerebrovascular disease, but the national representative data on some other important epidemiological indicators (such as incidence, prevalence, disability rate, and case fatality rate) are scarce in China. With the construction of large cohort population and extension of follow-up time, research on stroke-related risk factors is increasing, providing a basis for the prevention and control of risk factors. Due to limited large-scale population-based intervention studies, there is a lack of epidemiological evidence to transform into feasible intervention strategies and measures. In recent years, great progress in endovascular treatment for basilar-artery occlusion has been achieved in China, but there is still much room for improvement of guideline-based anticoagulant treatment and lipid-lowering treatment, as well as standardized diagnosis and treatment among patients with ischemic stroke.
PubMed: 38948893
DOI: 10.26599/1671-5411.2024.05.009 -
The effectiveness of selection in a species affects the direction of amino acid frequency evolution.BioRxiv : the Preprint Server For... Jun 2024Nearly neutral theory predicts that species with higher effective population size ( ) are better able to purge slightly deleterious mutations. We compare evolution in...
UNLABELLED
Nearly neutral theory predicts that species with higher effective population size ( ) are better able to purge slightly deleterious mutations. We compare evolution in high- vs. low- vertebrates to reveal which amino acid frequencies are subject to subtle selective preferences. We take three complementary approaches, two measuring flux and one measuring outcomes. First, we fit non-stationary substitution models of amino acid flux using maximum likelihood, comparing the high- clade of rodents and lagomorphs to its low- sister clade of primates and colugos. Second, we compare evolutionary outcomes across a wider range of vertebrates, via correlations between amino acid frequencies and . Third, we dissect the details of flux in human, chimpanzee, mouse, and rat, as scored by parsimony - this also enables comparison to a historical paper. All three methods agree on which amino acids are preferred under more effective selection. Preferred amino acids tend to be smaller, less costly to synthesize, and to promote intrinsic structural disorder. Parsimony-induced bias in the historical study produces an apparent reduction in structural disorder, perhaps driven by slightly deleterious substitutions. Within highly exchangeable pairs of amino acids, arginine is strongly preferred over lysine, and valine over isoleucine, consistent with more effective selection preferring a marginally larger free energy of folding. These two preferences match differences between thermophiles and mesophilic relatives. These results reveal the biophysical consequences of mutation-selection-drift balance, and demonstrate the utility of nearly neutral theory for understanding protein evolution.
SIGNIFICANCE STATEMENT
According to the nearly neutral theory of molecular evolution, selection is less able to distinguish between similar alleles in species with lower population size. We identify which amino acids are subject to such weak preferences - these tend to be smaller, to be less costly to make, to promote structural disorder of proteins, and to be enriched in thermophiles relative to mesophiles. The latter agrees with theories of marginal protein stability under mutation-selection-drift balance.
PubMed: 38948853
DOI: 10.1101/2023.02.01.526552 -
BioRxiv : the Preprint Server For... Jun 2024Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical...
Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical properties of the surrounding extracellular matrix modulate tubule deformation under constraints. These mechanical factors likely play a role in the pathophysiology of kidney diseases as exemplified by autosomal dominant polycystic kidney disease, in which pressure, flow and matrix stiffness have been proposed to modulate the cystic dilation of tubules with mutations. The lack of systems recapitulating the mechanical environment of kidney tubules impedes our ability to dissect the role of these mechanical factors. Here we describe a perfused kidney-on-chip with tunable extracellular matrix mechanical properties and hydrodynamic constraints, that allows a decoupling of shear stress and flow. We used this system to dissect how these mechanical cues affect tubule dilation. Our results show two distinct mechanisms leading to tubular dilation. For PCT cells (proximal tubule), overproliferation mechanically leads to tubular dilation, regardless of the mechanical context. For mIMCD-3 cells (collecting duct), tube dilation is associated with a squamous cell morphology but not with overproliferation and is highly sensitive to extracellular matrix properties and hydrodynamic constraints. Surprisingly, flow alone suppressed mIMCD-3 tubule dilation observed in static conditions, while the addition of luminal pressure restored it. Our model emulating nephron geometrical and mechanical organization sheds light on the roles of mechanical constraints in ADPKD and demonstrates the importance of controlling intraluminal pressure in kidney tubule models.
PubMed: 38948811
DOI: 10.1101/2024.06.18.599137 -
BioRxiv : the Preprint Server For... Jun 2024Genome-wide CRISPR-Cas9 screens have untangled regulatory networks and revealed the genetic underpinnings of diverse biological processes. Their success relies on...
Genome-wide CRISPR-Cas9 screens have untangled regulatory networks and revealed the genetic underpinnings of diverse biological processes. Their success relies on experimental designs that interrogate specific molecular phenotypes and distinguish key regulators from background effects. Here, we realize these goals with a generalizable platform for CRISPR interference with barcoded expression reporter sequencing (CiBER-seq) that dramatically improves the sensitivity and scope of genome-wide screens. We systematically address technical factors that distort phenotypic measurements by normalizing expression reporters against closely-matched control promoters, integrated together into the genome at single copy. To test our ability to capture post-transcriptional and post-translational regulation through sequencing, we screened for genes that affected nonsense-mediated mRNA decay and Doa10-mediated cytosolic protein decay. Our optimized CiBER-seq screens accurately capture the known components of well-studied RNA and protein quality control pathways with minimal background. These results demonstrate the precision and versatility of CiBER-seq for dissecting the genetic networks controlling cellular behaviors.
PubMed: 38948701
DOI: 10.1101/2024.06.21.600132 -
Frontiers in Veterinary Science 2024This study investigated the description and feasibility of a surgical procedure for enucleation-exenteration of the equine eye via the supraorbital fossa. A preliminary...
This study investigated the description and feasibility of a surgical procedure for enucleation-exenteration of the equine eye via the supraorbital fossa. A preliminary study was performed on both eyes of four cadaveric heads of native breed donkeys () to describe the surgical anatomy and demonstrate a new supraorbital enucleation surgical approach. For the clinical study, eight donkeys were admitted for unilateral enucleation. All procedures were performed in a lateral recumbent position under the influence of inhalation anesthesia in combination with a retrobulbar nerve block. A semi-circular incision was made in the skin and fascia of the supraorbital fossa to gain access into the orbital cavity, after which the periorbital fat was dissected and removed. Bleeding was controlled by electrocautery and large blood vessels were ligated, then the eyeball was dissected sharply and freed from its bony attachment. The procedure was successfully accomplished in all clinical cases, and no significant complications occurred during or throughout the postoperative follow-up period. The initial results suggest the feasibility and safety of the supraorbital enucleation technique described in this study for equine eye enucleation. This new technique seems promising due to its feasibility, safety, and positive outcomes observed in both cadaveric and clinical studies.
PubMed: 38948677
DOI: 10.3389/fvets.2024.1379151 -
Journal of Family Medicine and Primary... May 2024Malignant phyllodes, along with ductal carcinoma, is known as metaplastic cancer of the breast. This tumor is additionally known as breast carcinosarcoma. Malignant...
Malignant phyllodes, along with ductal carcinoma, is known as metaplastic cancer of the breast. This tumor is additionally known as breast carcinosarcoma. Malignant phyllodes in conjunction with ductal carcinoma is a rare finding in routine clinical practice. We describe the case report of a 47-year-old female patient who arrived with a large right breast mass. A core biopsy was performed, and histopathological examination indicated that the tumor was a malignant phyllodes tumor. A positron emission tomography (PET) scan revealed hyper-metabolic and hypo-metabolic tumors with perilesional stranding and satellite nodularity. There were a few metastatic right axillary nodes visible. There was no indication of distant metastases. Due to the presence of both components, a modified radical mastectomy surgery with axillary dissection was undertaken for this patient. Histopathological analysis of paraffin sections revealed ductal carcinoma (DCIS) comedo-epithelial component and spindle-shaped cells with hyper-chromatic oval nuclei and scanty cytoplasm.
PubMed: 38948622
DOI: 10.4103/jfmpc.jfmpc_983_23 -
Frontiers in Surgery 2024This study aimed to compare the short-term outcomes of surgical treatment for acute type A aortic dissection between patients undergoing cardiopulmonary arrest at the...
BACKGROUND
This study aimed to compare the short-term outcomes of surgical treatment for acute type A aortic dissection between patients undergoing cardiopulmonary arrest at the time of entry into the operating room and patients who received successful preoperative cardiopulmonary resuscitation before entering the operating room or patients who had cardiopulmonary arrest on the operating room table after entering the operating room without cardiopulmonary arrest. In the present study, we focused on the circulatory status at the time of entering the operating room because it is economically and emotionally difficult to cease intervention once the patient has entered the operating room, where surgeons, anesthesiologists, nurses, and perfusionists are already present, all necessary materials are packed off and cardiopulmonary bypass have already been primed.
METHODS
Twenty (5.5%) of 362 patients who underwent surgical treatment for acute type A aortic dissection between January 2016 and March 2022 had preoperative cardiopulmonary arrest. To compare the early operative outcomes, the patients were divided into the spontaneous circulation group ( = 14, 70.0%) and the non-spontaneous circulation group ( = 6, 30.0%) based on the presence or absence of spontaneous circulation upon entering the operating room. The primary endpoint was postoperative 30-day mortality. The secondary endpoints included in-hospital complications and persistent neurological disorders.
RESULTS
Thirty-day mortality was 65% ( = 13/20) in the entire cohort; 50% ( = 7/14) in the spontaneous circulation group and 100% ( = 6/6) in the non-spontaneous circulation group. The major cardiopulmonary arrest causes were aortic rupture and cardiac tamponade ( = 16; 80.0%), followed by coronary malperfusion ( = 4; 20.0%). Seven patients (50.0%) survived in the spontaneous circulation group, and none survived in the non-spontaneous circulation group (= .044). Five survivors walked unaided and were discharged home; the remaining two were comatose and paraplegic.
CONCLUSIONS
The outcomes were extremely poor in patients with acute type A aortic dissection who had preoperative cardiopulmonary arrest and received ongoing cardiopulmonary resuscitation at entry into the operating room. Therefore, surgical treatment might be contraindicated in such patients.
PubMed: 38948478
DOI: 10.3389/fsurg.2024.1404825 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women...
OBJECTIVE
Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy, revealing a potential association between hyperandrogenism in women and PE. To explore the causal relationship between hyperandrogenism and PE, this study selected total testosterone (TT), bioavailable testosterone (BIOT), and sex hormone binding globulin (SHBG) as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes. Two-sample Mendelian randomization (MR) analyses were used to genetically dissect the causal relationships between the three exposure factors (TT, BIOT, and SHBG) and the outcomes of PE and chronic hypertension with superimposed PE.
METHODS
Two independent genome-wide association study (GWAS) databases were used for the two-sample MR analysis. In the GWAS data of female participants from the UK Biobank cohort, single nucleotide polymorphisms (SNPs) associated with TT, BIOT, and SHBG were analyzed, involving 230454, 188507, and 188908 samples, respectively. GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP, involving 3556 PE cases and 114735 controls, as well as 38 cases of chronic hypertension with superimposed PE and 114735 controls. To meet the assumptions of instrumental relevance and independence in MR analysis, SNPs associated with exposure were identified at the genome-wide level (<5.0×10), and those in linkage disequilibrium interference were excluded based on clustering thresholds of <0.001 and an allele distance greater than 10000 kb. Known confounding factors, including previous PE, chronic kidney disease, chronic hypertension, diabetes, systemic lupus erythematosus, or antiphospholipid syndrome, were also identified and the relevant SNPs were removed. Finally, we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS, integrating exposure and outcome data, and removing palindromic sequences. Five genetic causal analysis methods, including inverse variance-weighted method (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method, were used to infer causal relationships. In the IVW, it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect. IVW was consequently used as the primary analysis method in this study. Considering the potential heterogeneity among the instrumental variables, random-effects IVW was used for MR analysis. The results were interpreted using odds ratios (OR) and the corresponding 95% confidence interval (CI) to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE. If the CI did not include 1 and had a value less than 0.05, the difference was considered statistically significant. Sensitivity analysis was conducted to assess heterogeneity and pleiotropy. Heterogeneity was examined using Cochran's test, and pleiotropy was assessed using MR-Egger intercept analysis. Additionally, leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations. To further validate the findings, MR analyses were performed using the same methods and outcome variables, but with different exposure factors, including waist-to-hip ratio adjusted for BMI (WHRadjBMI) and 25-hydroxyvitamin D levels, with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls.
RESULTS
According to the criteria for selecting genetic instrumental variables, 186, 127, and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT, BIOT, and SHBG. MR analysis did not find a causal relationship between the TT, BIOT, and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE. The IVW method predicted that genetically predicted TT (OR [95% CI]=1.018 [0.897-1.156], =0.78), BIOT (OR [95% CI]=1.11 [0.874-1.408], =0.392), and SHBG (OR [95% CI]=0.855 [0.659-1.109], =0.239) were not associated with PE. Similarly, genetically predicted TT (OR [95% CI]=1.222 [0.548-2.722], =0.624), BIOT (OR [95% CI]=1.066 [0.242-4.695], =0.933), and SHBG (OR [95% CI]=0.529 [0.119-2.343], =0.402) were not significantly associated with chronic hypertension with superimposed PE. Additionally, MR analysis using the MR-Egger method, weighted median method, simple mode method, and weighted mode method yielded consistent results, indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE. Heterogeneity was observed for SHBG in the analysis with PE (Cochran's test, =0.01), and pleiotropy was detected for BIOT in the analysis with PE (MR-Egger intercept analysis, =0.014), suggesting that the instrumental variables did not affect PE through BIOT. Other instrumental variables did not show significant heterogeneity or pleiotropy. Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables. Consistent with previous MR studies, the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study.
CONCLUSION
The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT, BIOT, and SHBG levels and the development of PE and chronic hypertension with superimposed PE. This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.
Topics: Humans; Female; Polymorphism, Single Nucleotide; Pregnancy; Pre-Eclampsia; Genome-Wide Association Study; Hyperandrogenism; Sex Hormone-Binding Globulin; Mendelian Randomization Analysis; Testosterone; Hypertension
PubMed: 38948277
DOI: 10.12182/20240560106 -
Bio-protocol Jun 2024All aerial organs in plants originate from the shoot apical meristem, a specialized tissue at the tip of a plant, enclosing a few stem cells. Understanding developmental...
All aerial organs in plants originate from the shoot apical meristem, a specialized tissue at the tip of a plant, enclosing a few stem cells. Understanding developmental dynamics within this tissue in relation to internal and external stimuli is of crucial importance. Imaging the meristem at the cellular level beyond very early stages requires the apex to be detached from the plant body, a procedure that does not allow studies in living, intact plants over longer periods. This protocol describes a new confocal microscopy method with the potential to image the shoot apical meristem of an intact, soil-grown, flowering Arabidopsis plant over several days. The setup opens new avenues to study apical stem cells, their interconnection with the whole plant, and their responses to environmental stimuli. Key features • Novel dissection and imaging method of the shoot apical meristem of . • Procedure performed with intact, soil-grown, flowering plants. • Possibility of long-term live imaging of the shoot apical meristem. • Protocol can be adapted to different plant species.
PubMed: 38948259
DOI: 10.21769/BioProtoc.5015 -
PeerJ 2024Eagle syndrome is caused by an elongated styloid process affecting carotid arteries and cranial nerves. Pain, dysphagia, tinnitus, paresthesia (classic subtype), and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Eagle syndrome is caused by an elongated styloid process affecting carotid arteries and cranial nerves. Pain, dysphagia, tinnitus, paresthesia (classic subtype), and neurovascular events (vascular subtype) may be triggered by head movements or arise spontaneously. However, Eagle syndrome remains underappreciated in the neurological community. We aimed to determine the most common neurological and non-neurological clinical presentations in patients with Eagle syndrome and to assess the clinical outcome post-surgical resection in comparison to non-surgical therapies.
METHODOLOGY
We conducted a systematic review of patient-level data on adults with Eagle syndrome, following PRISMA guidelines. We extracted data on demographics, presenting symptoms, neurological deficits, radiological findings, and treatments, including outcomes and complications, from studies in multiple indexing databases published between 2000 and 2023. The study protocol is registered with PROSPERO.
RESULTS
In total, 285 studies met inclusion criteria, including 497 patients with Eagle syndrome (mean age 47.3 years; 49.8% female). Classical Eagle (370 patients, 74.5%) was more frequent than vascular Eagle syndrome (117 patients, 23.5%, < 0.0001). Six patients (1.2%) presented with both variants and the subvariant for four patients (0.8%) was unknown. There was a male preponderance (70.1% male) in the vascular subtype. A history of tonsillectomy was more frequent in classic (48/153 cases) than in vascular (2/33 cases) Eagle syndrome (Odds Ratio 5.2, 95% CI [1.2-22.4]; = 0.028). By contrast, cervical movements as trigger factors were more prevalent in vascular (12/33 cases) than in classic (7/153 cases) Eagle syndrome (Odds Ratio 7.95, 95% CI [2.9-21.7]; = 0.0001). Headache and Horner syndrome were more frequent in vascular Eagle syndrome and dysphagia and neck pain more prominent in classic Eagle syndrome (all < 0.01). Surgically treated patients achieved overall better outcomes than medically treated ones: Eighty-one (65.9%) of 123 medically treated patients experienced improvement or complete resolution, while the same applied to 313 (97.8%) of 320 surgical patients (Odds Ratio 1.49, 95% CI [1.1-2.0]; = 0.016).
CONCLUSIONS
Eagle syndrome is underdiagnosed with potentially serious neurovascular complications, including ischemic stroke. Surgical treatment achieves better outcomes than conservative management. Although traditionally the domain of otorhinolaryngologist, neurologist should include this syndrome in differential diagnostic considerations because of the varied neurological presentations that are amenable to effective treatment.
Topics: Female; Humans; Male; Middle Aged; Ossification, Heterotopic; Phenotype; Temporal Bone; Treatment Outcome
PubMed: 38948209
DOI: 10.7717/peerj.17423