Prevalence of Frank's sign in healthy young individuals, morphological characteristics, and its association with family history of chronic disease.

Frank's sign (FS, earlobe crease) is known to be associated with many chronic diseases i.e. coronary, cerebrovascular, and peripheral vascular diseases. The objective of this study is to investigate the presence and grade of FS in healthy, young-adult individuals aging between 18 and 25. Furthermore, to evaluate the relationship between FS and the chronic disease history of first-degree family members. 853 healthy people with a mean age of 20.09 years were imvolved in the research on a voluntary basis. Of 853 individuals, 85.3% (n:728) had no FS, whereas 14.7% (n:125) had. Of the 125 people observed FS, 41.6% (n:52) were female and 58.4% (n:73) were male. Of the 125 people diagnosed with FS, 32.8% (n:41) had no family history of any chronic disease, and 67.2% (n:84) had at least 1 family history of chronic disease as well. It was determined that there was a statistically significant (p < 0.05) relationship between FS identified in healthy individuals and familial chronic disease history. In this study, while no FS was observed in 85.3% of the participants, grade 1 was detected in 12.4% (n:105), grade 2a in 1.9% (n:16), grade 2b in 0.2% (n:2), and grade 3 in 0.2% (n:2). To the best of our knowledge, this study investigated the relationship between the presence and grade of FS in the healthy, young, Turkish population and the presence/absence of chronic disease in the first-degree relatives of individuals for the very first time. As a result of larger studies, being aware of the presence of FS, especially in young healthy individuals, may help predict some chronic diseases, and caution may be taken to avoid these diseases at an early age in at-risk individuals.

Early Versus Delayed Laparoscopic Cholecystectomy for Acute Cholecystitis: A Single Center Experience.

Introduction: Acute cholecystitis (AC) represents a public health problem, increasing hospitalization costs, especially determined by the surgical treatment of these patients. Laparoscopic cholecystectomy (LC) has become the therapeutic gold standard, the timing of the intervention: early (ELC) versus late (DLC), is still debated, impacting the results. The primary objective of the study was to compare postoperative outcomes between ELC and DLC. Secondary objectives assessed surgical outcomes from the pre-pandemic period with those from the Covid-19 pandemic. Material and methods: A retrospective observational study is presented of 266 patients diagnosed with AC who were admitted to Clinic I of General Surgery, County Emergency Clinical Hospital of T #226;rgu Mure #351;, from 2018 to 2022. They were classified into the ELC group ( 72 hours from the onset of symptoms) and DLC ( 72 hours from symptom onset) and were further stratified into prepandemic and pandemic cohorts. Data on clinical symptoms, paraclinical data, surgical details, and postoperative course were collected and analyzed. Discussion: The results confirm fewer conversions to open surgery and reduced hospitalization in the ELC group. The pandemic did not significantly alter the timing of surgeries or patient demographics. Conclusion: In conclusion, ELC for AC patients offers significant advantages, justifying its preference over DLC Despite the decrease in the incidence of AC hospitalizations during the pandemic, postoperative outcomes are comparable to those in the pre-pandemic period. Future multicenter studies are recommended for a broader analysis of the efficacy of laparoscopic surgery in emergency settings.

Comparison of the safety profile, conversion rate and hospitalization duration between early and delayed laparoscopic cholecystectomy for acute cholecystitis: a systematic review and meta-analysis.

Background: Although the past decade has witnessed unprecedented medical progress, no consensus has been reached on the optimal approach for patients with acute cholecystitis. Herein, we conducted a systematic review and meta-analysis to assess the differences in patient outcomes between Early Laparoscopic Cholecystectomy (ELC) and Delayed Laparoscopic Cholecystectomy (DLC) in the treatment of acute cholecystitis. Our protocol was registered in the PROSPERO database (registration number: CRD42023389238). Objectives: We sought to investigate the differences in efficacy, safety, and potential benefits between ELC and DLC in acute cholecystitis patients by conducting a systematic review and meta-analysis. Methods: The online databases PubMed, Springer, and the Cochrane Library were searched for randomized controlled trials (RCTs) and retrospective studies published between Jan 1, 1999 and Jan 1, 2022. Results: 21 RCTs and 13 retrospective studies with a total of 7,601 cases were included in this research. After a fixed-effects model was applied, the pooled analysis showed that DLC was associated with a significantly high conversion rate (OR: 0.6247; 95%CI: 0.5115-0.7630; z = -4.61, p < 0.0001) and incidence of postoperative complications (OR: 0.7548; 95%CI: 0.6197-0.9192; z = -2.80, p = 0.0051). However, after applying a random-effects model, ELC was associated with significantly shorter total hospitalization duration than DLC (MD: -4.0657; 95%CI: -5.0747 to -3.0566; z = -7.90, p < 0.0001). Conclusion: ELC represents a safe and feasible approach for acute cholecystitis patients since it shortens hospitalization duration and decreases the incidence of postoperative complications of laparoscopic cholecystectomy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=389238, identifier (CRD42023389238).

Efficacy of early laparoscopic cholecystectomy compared with percutaneous transhepatic gallbladder drainage in treating acute calculous cholecystitis in elderly patients.

BACKGROUND: Acute calculous cholecystitis is a common acute disease in elderly patients. This study aimed to evaluate the efficacy of early laparoscopic cholecystectomy (ELC) compared to percutaneous transhepatic gallbladder drainage (PTGD) for treating acute calculous cholecystitis in elderly patients. METHODS: This retrospective study compared the clinical outcomes of two groups of elderly patients treated with ELC (group A) and PTGD (group B) from January 2018 to December 2021. Preoperative clinical characteristics and postoperative treatment outcomes were analyzed for both groups. RESULTS: There were no statistically significant differences in preoperative clinical characteristics between the ELC and PTGD groups. ELC took longer to perform (69.8 ± 15.9 min vs. 29.6 ± 5.3 min, p < 0.001) but resulted in a significantly shorter duration of pain (1.9 ± 0.9 days vs. 3.9 ± 1.0 days, p < 0.001) and hospital stay (6.3 ± 2.5 days vs. 9.9 ± 3.6 days, p < 0.001), and a lower rate of sepsis (3.4% vs. 16.9%, p < 0.019). Time to soft diet was faster in the ELC group (1.5 ± 0.9 days vs. 3.0 ± 1.6 days, p < 0.001). Fewer patients in the ELC group experienced surgical reintervention than in the PTGD group (0% vs. 5.6%, p = 0.043). The incidence of postoperative complications and readmission rates in the ELC group were significantly lower than those in the PTGD group (ELC, 3.6%; PTGD, 25.4%, p = 0.001). CONCLUSIONS: ELC is an effective treatment option for acute calculous cholecystitis in elderly patients, and has the added benefits of low postoperative complication rates, rapid recovery, shorter duration of pain, and excellent curative effects as compared to PTGD.

Phosphorylation Mimetic of Myosin Regulatory Light Chain Mitigates Cardiomyopathy-Induced Myofilament Impairment in Mouse Models of RCM and DCM.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in essential (ELC, MYL3 gene) or regulatory (RLC, MYL2 gene) light chains of myosin. Phosphomimetic S15D-RLC was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild-type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by the S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted with fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared with those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM-treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

Methods for Communicating the Impact of Parameter Uncertainty in a Multiple-Strategies Cost-Effectiveness Comparison.

PURPOSE: Analyzing and communicating uncertainty is essential in medical decision making. To judge whether risks are acceptable, policy makers require information on the expected outcomes but also on the uncertainty and potential losses related to the chosen strategy. We aimed to compare methods used to represent the impact of uncertainty in decision problems involving many strategies, enhance existing methods, and provide an open-source and easy-to-use tool. METHODS: We conducted a systematic literature search to identify methods used to represent the impact of uncertainty in cost-effectiveness analyses comparing multiple strategies. We applied the identified methods to probabilistic sensitivity analysis outputs of 3 published decision-analytic models comparing multiple strategies. Subsequently, we compared the following characteristics: type of information conveyed, use of a fixed or flexible willingness-to-pay threshold, output interpretability, and the graphical discriminatory ability. We further proposed adjustments and integration of methods to overcome identified limitations of existing methods. RESULTS: The literature search resulted in the selection of 9 methods. The 3 methods with the most favorable characteristics to compare many strategies were 1) the cost-effectiveness acceptability curve (CEAC) and cost-effectiveness acceptability frontier (CEAF), 2) the expected loss curve (ELC), and 3) the incremental benefit curve (IBC). The information required to assess confidence in a decision often includes the average loss and the probability of cost-effectiveness associated with each strategy. Therefore, we proposed the integration of information presented in an ELC and CEAC into a single heat map. CONCLUSIONS: This article presents an overview of methods presenting uncertainty in multiple-strategy cost-effectiveness analyses, with their strengths and shortcomings. We proposed a heat map as an alternative method that integrates all relevant information required for health policy and medical decision making. HIGHLIGHTS: To assess confidence in a chosen course of action, decision makers require information on both the probability and the consequences of making a wrong decision.This article contains an overview of methods for presenting uncertainty in multiple-strategy cost-effectiveness analyses.We propose a heat map that combines the probability of cost-effectiveness from the cost-effectiveness acceptability curve (CEAC) with the consequences of a wrong decision from the expected loss curve.Collapsing of the CEAC can be reduced by relaxing the CEAC, as proposed in this article.Code in Microsoft Excel and R is provided to easily analyze data using the methods discussed in this article.

Crystal structure of the yeast Rad7-Elc1 complex and assembly of the Rad7-Rad16-Elc1-Cul3 complex.

Nucleotide excision repair (NER) is a versatile system that deals with various bulky and helix-distorting DNA lesions caused by UV and environmental mutagens. Based on how lesion recognition occurs, NER has been separated into global genome repair (GGR) and transcription-coupled repair (TCR). The yeast Rad7-Rad16 complex is indispensable for the GGR sub-pathway. Rad7-Rad16 binds to UV-damaged DNA in a synergistic fashion with Rad4, the main lesion recognizer, to achieve efficient recognition of lesions. In addition, Rad7-Rad16 associates with Elc1 and Cul3 to form an EloC-Cul-SOCS-box (ECS)-type E3 ubiquitin ligase complex that ubiquitinates Rad4 in response to UV radiation. However, the structure and architecture of the Rad7-Rad16-Elc1-Cul3 complex remain unsolved. Here, we determined the structure of the Rad7-Elc1 complex and revealed key interaction regions responsible for the formation of the Rad7-Rad16-Elc1-Cul3 complex. These results provide new insights into the assembly of the Rad7-Rad16-Elc1-Cul3 complex and structural framework for further studies.

Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics.

Cardiac ventricular myosin (ßmys) translates actin by transducing ATP free energy into mechanical work during muscle contraction. Unitary ßmys translation of actin is the step-size. In vitro and in vivo ßmys regulates contractile force and velocity autonomously by remixing three different step-sizes with adaptive stepping frequencies. Cardiac and skeletal actin isoforms have a specific 1 : 4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) upregulate skeletal actin in ventriculum probably compensating the diseased muscle's inability to meet demand by adjusting ßmys force-velocity characteristics. ßmys force-velocity characteristics were compared for skeletal versus cardiac actin substrates using ensemble in vitro motility and single myosin assays. Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing single ßmys mechanics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads probably by the unique cardiac essential light chain (ELC) N-terminus/cardiac actin contact at Glu6/Ser358. It modifies ßmys force-velocity by stabilizing the ELC N-terminus/cardiac actin association. Uneven onset of the high-force regime for skeletal versus cardiac actin modulates force-velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle.

Mechanics and regulation of cytokinesis in budding yeast.

Cytokinesis is essential for the survival of all organisms. It requires concerted functions of cell signaling, force production, exocytosis, and extracellular matrix remodeling. Due to the conservation in core components and mechanisms between fungal and animal cells, the budding yeast Saccharomyces cerevisiae has served as an attractive model for studying this fundamental process. In this review, we discuss the mechanics and regulation of distinct events of cytokinesis in budding yeast, including the assembly, constriction, and disassembly of the actomyosin ring, septum formation, abscission, and their spatiotemporal coordination. We also highlight the key concepts and questions that are common to animal and fungal cytokinesis.

Neurocognitive outcomes in congenital diaphragmatic hernia survivors: a cross-sectional prospective study.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) survivors may have persistent neurocognitive delays. We assessed neurodevelopmental outcomes in CDH survivors from infancy to late teenage years. METHODS: A cross-sectional study was conducted on 37 CDH survivors to examine neurocognitive functioning. Overall cognitive score was tested with the early learning composite (ELC) of Mullen Scales of Early Learning (n=19), and Full Scale IQ (FSIQ) of Wechsler Intelligence Scale for Children-Fourth Edition (n=18). RESULTS: ELC was 85.7±16.4, lower than the expected norm of 100, P=0.004, and 6 survivors had moderate, and 3 severe delay, which is not greater than expected in the general population (P=0.148). FSIQ was 99.6±19.1, consistent with the expected norm of 100, P=0.922, and 3 survivors had moderate and 2 severe delay, which is greater than expected (P=0.048). Although ELC was lower than FSIQ (P=0.024), within each testing group overall cognitive ability was not associated with participant age (ELC, P=0.732; FSIQ, P=0.909). Longer hospital stay was the only factor found to be consistently associated with a worse cognitive score across all participants in our cohort. CONCLUSIONS: A high percentage of survivors with CDH have moderate to severe cognitive impairment suggesting that these subjects warrant early testing with implementation of therapeutic and educational interventions.

Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains.

In this study we aimed to provide an in-depth proteomic analysis of differentially expressed proteins in the hearts of transgenic mouse models of pathological and physiological cardiac hypertrophy using tandem mass tag labeling and liquid chromatography tandem mass spectrometry. The Δ43 mouse model, expressing the 43-amino-acid N-terminally truncated myosin essential light chain (ELC) served as a tool to study the mechanisms of physiological cardiac remodeling, while the pathological hypertrophy was investigated in A57G (Alanine 57 â†’ Glycine) ELC mice. The results showed that 30 proteins were differentially expressed in Δ43 versus A57G hearts as determined by multiple pair comparisons of the mutant versus wild-type (WT) samples with P < 0.05. The A57G hearts showed differential expression of nine mitochondrial proteins involved in metabolic processes compared to four proteins for ∆43 hearts when both mutants were compared to WT hearts. Comparisons between ∆43 and A57G hearts showed an upregulation of three metabolically important mitochondrial proteins but downregulation of nine proteins in ∆43 hearts. The physiological model of cardiac hypertrophy (∆43) showed no changes in the levels of Ca(2+)-binding proteins relative to WT, while the pathologic model (A57G) showed the upregulation of three Ca(2+)-binding proteins, including sarcalumenin. Unique differences in chaperone and fatty acid metabolism proteins were also observed in Δ43 versus A57G hearts. The proteomics data support the results from functional studies performed previously on both animal models of cardiac hypertrophy and suggest that the A57G- and not ∆43- mediated alterations in fatty acid metabolism and Ca(2+) homeostasis may contribute to pathological cardiac remodeling in A57G hearts.

Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans.

The transcription factor hypoxia-inducible factor 1 (HIF-1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF-1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc-1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc-1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc-1 RNA interference increased lifespan and protein homeostasis by upregulating HIF-1. The roles of elongin C and HIF-1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF-1 in complex metazoans.

Flexibility within the heads of muscle myosin-2 molecules.

We show that negative-stain electron microscopy and image processing of nucleotide-free (apo) striated muscle myosin-2 subfragment-1 (S1), possessing one light chain or both light chains, is capable of resolving significant amounts of structural detail. The overall appearance of the motor and the lever is similar in rabbit, scallop and chicken S1. Projection matching of class averages of the different S1 types to projection views of two different crystal structures of apo S1 shows that all types most commonly closely resemble the appearance of the scallop S1 structure rather than the methylated chicken S1 structure. Methylation of chicken S1 has no effect on the structure of the molecule at this resolution: it too resembles the scallop S1 crystal structure. The lever is found to vary in its angle of attachment to the motor domain, with a hinge point located in the so-called pliant region between the converter and the essential light chain. The chicken S1 crystal structure lies near one end of the range of flexion observed. The Gaussian spread of angles of flexion suggests that flexibility is driven thermally, from which a torsional spring constant of ~23 pN·nm/rad² is estimated on average for all S1 types, similar to myosin-5. This translates to apparent cantilever-type stiffness at the tip of the lever of 0.37 pN/nm. Because this stiffness is lower than recent estimates from myosin-2 heads attached to actin, we suggest that binding to actin leads to an allosteric stiffening of the motor-lever junction.

Oligomerization of rice granule-bound starch synthase 1 modulates its activity regulation.

Granule-bound starch synthase 1 (GBSS1) is responsible for amylose synthesis in cereals, and this enzyme is regulated at the transcriptional and post-transcriptional levels. In this study, we show that GBSS1 from Oryza sativa L. (OsGBSS1) can form oligomers in rice endosperm, and oligomerized OsGBSS1 exhibits much higher specific enzymatic activity than the monomer. A monomer-oligomer transition equilibrium for OsGBSS1 occurs in the endosperm during development. Redox potential is a key factor affecting the oligomer percentage as well as the enzymatic activity of OsGBSS1. Adenosine diphosphate glucose, the direct donor of glucose, also impacts OsGBSS1 oligomerization in a concentration-dependent manner. OsGBSS1 oligomerization is influenced by phosphorylation status, which was strongly enhanced by Mitogen-activated protein kinase (MAPK) and ATP treatment and was sharply weakened by protein phosphatase (PPase) treatment. The activity of OsGBSS1 affects the ratio of amylose to amylopectin and therefore the eating quality of rice. Understanding the regulation of OsGBSS1 activity may lead to the improvement of rice eating quality.

Gene cloning and expression of human chemokine ELC / 第三军医大学学报

Objective To clone human chemokine ELC and express the ELC fusion protein. Methods Total RNA from human inflammatory tonsil was extracted and the cDNA was generated with reverse transcription. Mature ELC gene was amplified with PCR and NcoⅠand EcoRⅠ sites were added to the 5′ and 3′ terminal respectively, and then cloned into pET32a(+). E.coli DH5? was transformed with the recombinant plasmid, and positive clones were selected. The inserted DNA was verified by enzyme digestion and DNA sequencing. The fusion expression vector of mature ELC was formed with deletion mutation. ELC expression was analyzed by SDS-PAGE and Western blotting and the ELC fusion protein was purified. Results Human chemokine ELC was successfully cloned and the fusion protein was expressed and purified. Conclusion The ELC fusion protein was expressed with solubility.