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CASE (Philadelphia, Pa.) May 2024
PubMed: 38947191
DOI: 10.1016/j.case.2024.03.002 -
Journal of Cell Communication and... Jun 2024Transmembrane-4 L-six family member-1 (TM4SF1) is an atypical tetraspanin that is highly and selectively expressed in proliferating endothelial cells and plays an...
Transmembrane-4 L-six family member-1 (TM4SF1) is an atypical tetraspanin that is highly and selectively expressed in proliferating endothelial cells and plays an essential role in blood vessel development. TM4SF1 forms clusters on the cell surface called TMED (TM4SF1-enriched microdomains) and recruits other proteins that internalize along with TM4SF1 via microtubules to intracellular locations including the nucleus. We report here that tumor growth and wound healing are inhibited in -heterozygous mice. Investigating the mechanisms of TM4SF1 activity, we show that 12 out of 18 signaling molecules examined are recruited to TMED on the surface of cultured human umbilical vein endothelial cells (HUVEC) and internalize along with TMED; notable among them are PLCγ and HDAC6. When TM4SF1 is knocked down in HUVEC, microtubules are heavily acetylated despite normal levels of HDAC6 protein, and, despite normal levels of VEGFR2, are unable to proliferate. Together, our studies indicate that pathological angiogenesis is inhibited when levels of TM4SF1 are reduced as in -heterozygous mice; a likely mechanism is that TM4SF1 regulates the intracellular distribution of signaling molecules necessary for endothelial cell proliferation and migration.
PubMed: 38946725
DOI: 10.1002/ccs3.12031 -
The Korean Journal of Pain Jul 2024Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in...
BACKGROUND
Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in South Korea.
METHODS
Pain physicians affiliated with the Korean Pain Society were asked to complete anonymous questionnaires regarding CEB between September and October 2022. The questionnaire consisted of 24 questions assessing the current status and methods of CEB in detail.
RESULTS
Of the 198 surveys collected, 171 physicians (86.4%) reported performing CEB. Among those, the majority (94.7%) used fluoroscopy during the procedure. The paramedian interlaminar (IL) approach was the most preferred method (50.3%). Respondents performing fluoroscopic-guided IL CEB were categorized into two groups based on clinical experience: those with ≤10 years of experience (≤10-year group, n = 91) and those with >10 years of experience (>10-year group, n = 71). The proportion of physicians obtaining informed consent in the ≤10-year group and >10-year group was 50.5% and 56.3%, respectively. When entering the epidural space during IL CEB, the contralateral oblique view was the second most frequently used in both groups (≤10-year group, 42.9%; >10-year group, 29.6%). In targeting the upper cervical lesions (C3-4), the proportion of respondents who used an IL space higher than C6-7 was 17.6% in the ≤10-year group and 29.5% in the >10-year experience group.
CONCLUSIONS
This study demonstrated variability in the CEB technique used by pain physicians in South Korea. The findings highlight the need for education on informed consent and techniques to enhance safety.
PubMed: 38946700
DOI: 10.3344/kjp.24087 -
The Korean Journal of Pain Jul 2024The application of ultrasound (US) in pain medicine has been a rapidly growing field since the 2000s. Musculoskeletal injections, peripheral nerve blocks, and neuraxial... (Review)
Review
The application of ultrasound (US) in pain medicine has been a rapidly growing field since the 2000s. Musculoskeletal injections, peripheral nerve blocks, and neuraxial injections under US guidance have been acknowledged for managing chronic pain. Although many studies on US-guided pain procedures have been published, there needs to be a classification system to evaluate which image device, the US or fluoroscopy, is clinically and technically better in various pain interventions. Therefore, this narrative review introduces the classification system for the US-guided pain procedures according to their clinical and technical outcomes and designates US-guided pain procedures into one of the four categories by reviewing previous prospective randomized comparative trials.
PubMed: 38946695
DOI: 10.3344/kjp.23358 -
The Korean Journal of Pain Jul 2024
PubMed: 38946694
DOI: 10.3344/kjp.24186 -
Advanced Science (Weinheim,... Jul 2024Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity....
Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
PubMed: 38946582
DOI: 10.1002/advs.202402086 -
Journal of Women's Health (2002) Jul 2024Military sexual trauma (MST) is more common among post-9/11 Veterans and women versus older Veterans and men. Despite mandatory screening, the concordance of electronic...
Electronic Health Record Concordance with Survey-Reported Military Sexual Trauma Among Younger Veterans: Associations with Health Care Utilization and Mental Health Diagnoses.
Military sexual trauma (MST) is more common among post-9/11 Veterans and women versus older Veterans and men. Despite mandatory screening, the concordance of electronic health record (EHR) documentation and survey-reported MST, and associations with health care utilization and mental health diagnoses, are unknown for this younger group. Veterans' Health Administration (VHA) EHR (2001-2021) were merged with data from the observational, nationwide WomenVeterans Cohort Study (collected 2016-2020, = 1058; 51% women). Experiencing MST was defined as positive endorsement of sexual harassment and/or assault. From the EHR, we derived Veterans' number of primary care and mental health visits in the initial two years of VHA care and diagnoses of posttraumatic stress disorder (PTSD), depression, and anxiety. First, the concordance of EHR MST screening and survey-reported MST was compared. Next, multivariate analyses tested the cross-sectional associations of EHR screening and survey-reported MST with Veterans' health care utilization, and compared the likelihood of PTSD, depression, and anxiety diagnoses by MST group, while covarying demographics and service-related characteristics. With few MST cases among men, multivariate analyses were only pursued for women. Overall, 29% of women and 2% of men screened positive for MST in the EHR, but 64% of women and 9% of men had survey-reported MST. Primary care utilization was similar between women with concordant, positive MST reports in the EHR and survey versus those with survey-reported MST only. Women with survey-reported MST only were less likely to have a PTSD or depression diagnosis than those with concordant, positive MST reports. There was no group difference in women's likelihood of anxiety. EHR MST documentation is discordant for many post-9/11 Veterans-both for men and women. Improving MST screening and better supporting MST disclosure are each critical to provide appropriate and timely care for younger Veterans, particularly women.
PubMed: 38946553
DOI: 10.1089/jwh.2023.0993 -
Circulation Research Jul 2024Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise...
BACKGROUND
Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism.
OBJECTIVE
To determine whether this mechanism broadly impacts diabetic complications, we investigated the role of ARRDC4 in the pathogenesis of diabetic cardiac and skeletal myopathy.
METHODS AND RESULTS
High glucose promoted translocation of MondoA into the nucleus, which upregulated transcriptional expression, increased lysosomal GLUT1 trafficking, and blocked glucose transport in cardiomyocytes, forming a feedback mechanism. This role of was confirmed in human muscular cells from type 2 diabetic patients. Prolonged hyperglycemia upregulated myocardial expression in multiple types of mouse models of diabetes. We then analyzed hyperglycemia-induced cardiac and skeletal muscle abnormalities in insulin-deficient mice. Hyperglycemia increased advanced glycation end-products and elicited oxidative and endoplasmic reticulum stress leading to apoptosis in the heart and peripheral muscle. However, deletion of augmented tissue glucose transport and mitochondrial respiration, protecting the heart and muscle from tissue damage. Stress hemodynamic analysis and treadmill exhaustion test uncovered that -knockout mice had greater cardiac inotropic/chronotropic reserve with higher exercise endurance than wild-type (WT) animals under diabetes. While multiple organs were involved in the mechanism, cardiac-specific overexpression (beyond levels observed during diabetes) using adenoassociated virus suggests that high levels of myocardial have the potential to contribute to exercise intolerance by interfering with cardiac metabolism through its interaction with GLUT1 in diabetes. Importantly, the mutation mouse line exhibited greater exercise tolerance, showing the potential therapeutic impact on diabetic cardiomyopathy by disrupting the interaction between ARRDC4 and GLUT1.
CONCLUSIONS
ARRDC4 serves as a regulator of hyperglycemia-induced toxicities toward cardiac and skeletal muscle, revealing a new molecular framework that connects hyperglycemia to cardiac/skeletal myopathy to exercise intolerance.
PubMed: 38946541
DOI: 10.1161/CIRCRESAHA.123.323158 -
Current Medical Research and Opinion Jul 2024Postoperative nausea and vomiting (PONV) occurs in up to 30% of patients and its pathophysiology and mechanisms have not been completely described. Hypotension and a...
Postoperative nausea and vomiting (PONV) occurs in up to 30% of patients and its pathophysiology and mechanisms have not been completely described. Hypotension and a decrease in cardiac output are suspected to induce nausea. The hypothesis that intraoperative hypotension might influence the incidence of PONV was investigated. The study was conducted as a retrospective large single center cohort study. The incidence of PONV was investigated until discharge from post anesthesia care unit (PACU). Surgical patients with general anesthesia during a 2-year period between 2018-2019 at a university hospital in Germany were included. Groups were defined based on the lowest documented mean arterial pressure (MAP) with group H50: MAP <50mmHg; group H60: MAP <60mmHg; group H70: MAP <70mmHg, and group H0: no MAP <70mmHg. Decreases of MAP in the different groups were related to PONV. Propensity-score matching was carried out to control for overlapping risk factors. In the 2-year period 18.674 patients fit the inclusion criteria. The overall incidence of PONV was 11%. Patients with hypotension had a significantly increased incidence of PONV (H0 vs. H50: 11.0% vs.17.4%, Risk Ratio (RR): 1.285 (99%CI: 1.102-1.498), p < 0.001; H0 vs. H60: 10.4% vs. 13.5%, RR: 1.1852 (99%CI: 1.0665-1.3172), p < 0.001; H0 vs. H70: 9.4% vs. 11.2%, RR: 1.1236 (99%CI: 1.013 - 1.2454); p = 0.0027). The study demonstrates an association between intraoperative hypotension and early PONV. A more severe decrease of MAP had a pronounced effect.
PubMed: 38946490
DOI: 10.1080/03007995.2024.2373885 -
European Review For Medical and... Jun 2024The mini-fluid challenge (MFC), which assesses the change in stroke volume index (SVI) following the administration of 100 mL of crystalloids, and the short-time low... (Observational Study)
Observational Study Comparative Study
Comparison of the ability of short time low PEEP challenge and mini fluid challenge to predict fluid responsiveness in patients undergoing open pancreaticoduodenectomy: an observational cohort study.
OBJECTIVE
The mini-fluid challenge (MFC), which assesses the change in stroke volume index (SVI) following the administration of 100 mL of crystalloids, and the short-time low positive end-expiratory pressure (PEEP) challenge (SLPC), which evaluates the temporary reduction in SVI due to a PEEP increment, are two functional hemodynamic tests used to predict fluid responsiveness in the operating room. However, SLPC has not been assessed in patients undergoing abdominal surgery, and there is no study comparing these two methods during laparotomy. Therefore, we aimed to compare the SLPC and MFC in patients undergoing open pancreaticoduodenectomy.
PATIENTS AND METHODS
All patients received a standard hemodynamic management. The study protocol evaluated the percentage change in SVI following the application of an additional 5 cmH2O PEEP (SVIΔ%-SLPC) and the infusion of 100 mL crystalloid (SVIΔ%-MFC). Challenges that resulted in an increase of more than 15% in SVI after the 500 ml of fluid loading were classified as positive challenges (PC). Areas under the receiver operating characteristics curves (ROC AUCs) were used for the comparison of the methods.
RESULTS
Thirty-three patients completed the study with 94 challenges. Fifty-five (58.5%) of them were PCs. The ROC AUC of SVIΔ%-MFC was observed to be significantly higher than that of SVIΔ%-SLPC (0.97 vs. 0.64, p < 0.001). The best cut-off value for SVIΔ%-MFC was 5.6%. If we had stopped the bolus fluid administration when SVIΔ%-MFC ≤ 5% was observed (lower limit of the gray zone), we would have postponed the fluid loading in 35 (89.7%) of 39 negative challenges. The amount of fluid deferred would have corresponded to up to 40% of the total fluid given.
CONCLUSIONS
SVIΔ%-MFC predicts fluid responsiveness with high diagnostic performance and is better than SVIΔ%-SLPC in patients undergoing open pancreatoduodenectomy. Additionally, the use of SVIΔ%-MFC has the potential to defer up to 40% of the total fluid given.
CLINICALTRIALS
gov: NCT05419570.
Topics: Humans; Pancreaticoduodenectomy; Fluid Therapy; Male; Female; Aged; Positive-Pressure Respiration; Middle Aged; Cohort Studies; Crystalloid Solutions; Stroke Volume
PubMed: 38946384
DOI: 10.26355/eurrev_202406_36463