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Journal of Minimal Access Surgery Jul 2024Pancreaticojejunostomy have been studied and modified for more than a hundred years. We investigated a new method of pancreaticojejunostomy to explore its value in...
INTRODUCTION
Pancreaticojejunostomy have been studied and modified for more than a hundred years. We investigated a new method of pancreaticojejunostomy to explore its value in laparoscopic pancreaticoduodenectomy.
PATIENTS AND METHODS
A retrospective analysis was conducted on the clinical data of 93 patients who underwent laparoscopic pancreaticoduodenectomy with 'Shunt-block combined' pancreaticojejunostomy at Ningbo Medical Center Lihuili Hospital from April 2017 to February 2023.
RESULTS
All patients successfully completed the surgery, with two cases requiring conversion to open surgery. The average operation time was 328.5 (180-532) min, the average intraoperative blood loss was 182.9 (50-1000) mL and the average laparoscopic pancreaticojejunostomy time was 29.6 (20-39) min. There were no cases of grade C pancreatic fistula postoperatively, 10 cases of grade B pancreatic fistula, 43 cases of biochemical fistula and 40 cases without detected pancreatic fistula.
CONCLUSION
'Shunt-block combined' pancreaticojejunostomy was a safe and effective method for pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.
PubMed: 38958002
DOI: 10.4103/jmas.jmas_59_24 -
Photochemistry and Photobiology Jul 2024The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were...
The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were examined in this study. In silico analysis of CBD showed antioxidant capacity via proton donation and UV absorption at 209.09, 254.73, and 276.95 nm, according to the HAT and SPLET methodologies. FS-CBD protected against UVB-induced bacterial death for 30 min. FS-CBD protected against UVB-induced cell death by 42% (1.5 μg/mL) and 35% (3.5 μg/mL) in an in vitro keratinocyte cell model. An in vivo acute irradiated CD-1 mouse model (UVB-irradiated for 5 min) presented very low photoprotection when FS-CBD was applied cutaneously, as determined by histological analyses. In vivo skin samples showed that FS-CBD regulated inflammatory responses by inhibiting the inflammatory markers TGF-β1 and NLRP3. The docking analysis showed that the CBD molecule had a high affinity for TGF-β1 and NLRP3, indicating that protection against inflammation might be mediated by blocking these proinflammatory molecules. This result was corroborated by the docking interactions between CBD and TGF-β1 and NLRP3, which resulted in a high affinity and inhibition of both proteins The present work suggested a FS-CBD moderate photoprotective agent against UVB light-induced skin damage and that this effect is partially mediated by its anti-inflammatory activity.
PubMed: 38958000
DOI: 10.1111/php.13993 -
Circulation Research Jul 2024Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits....
BACKGROUND
Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear.
METHODS
Brain EC-specific CCM3-deficient () mice were generated by crossing mice with -CreER mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches.
RESULTS
Single-cell RNA-sequencing analyses from P10 0 mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier-associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6 0 brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins.
CONCLUSIONS
CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss-induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.
PubMed: 38957991
DOI: 10.1161/CIRCRESAHA.123.324015 -
Artificial Organs Jul 2024The Food and Drug Administration (FDA) blood pump is an open-source benchmark cardiovascular device introduced for validating computational and experimental performance...
BACKGROUND
The Food and Drug Administration (FDA) blood pump is an open-source benchmark cardiovascular device introduced for validating computational and experimental performance analysis tools. The time-resolved velocity field for the whole impeller has not been established, as is undertaken in this particle image velocimetry (PIV) study. The level of instantaneous velocity fluctuations is important, to assess the flow-induced rotor vibrations which may contribute to the total blood damage.
METHODS
To document these factors, time-resolved two-dimensional PIV experiments were performed that were precisely phase-locked with the impeller rotation angle. The velocity fields in the impeller and in the volute conformed with the previous single blade passage experiments of literature.
RESULTS
Depending on the impeller orientation, present experiments showed that volute outlet nozzle flow can fluctuate up to 34% during impeller rotation, with a maximum standard experimental uncertainty of 2.2%. Likewise, the flow fields in each impeller passage also altered in average 33.5%. Considerably different vortex patterns were observed for different blade passages, with the largest vortical structures reaching an average core radii of 7 mm. The constant volute area employed in the FDA pump design contributes to the observed velocity imbalance, as illustrated in our velocity measurements.
CONCLUSIONS
By introducing the impeller orientation parameter for the nozzle flow, this study considers the possible uncertainties influencing pump flow. Expanding the available literature data, analysis of inter-blade relative velocity fields is provided here for the first-time to the best of our knowledge. Consequently, our research fills a critical knowledge gap in the understanding of the flow dynamics of an important benchmark cardiovascular device. This study prompts the need for improved hydrodynamic designs and optimized devices to be used as benchmark test devices, to build more confidence and safety in future ventricular assist device performance assessment studies.
PubMed: 38957988
DOI: 10.1111/aor.14811 -
Arteriosclerosis, Thrombosis, and... Jul 2024Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the...
BACKGROUND
Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the biological mechanism involved in cellular communication among these cells and whether this biological mechanism can be used to treat atherosclerosis remain unknown. We hypothesized that endothelial autophagy mediates the cellular communication in vascular tissue through exosome-mediated delivery of atherosclerosis-related genes.
METHODS
Rapamycin and adeno-associated virus carrying short hairpin RNA under the Tie (TEK receptor tyrosine kinase) promoter were used to activate and inhibit vascular endothelial autophagy in high-fat diet-fed mice, respectively. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue were used to explore the effects of endothelial autophagy on endothelial function and atherosclerosis and its molecular mechanisms. Quantitative polymerase chain reaction and miRNA sequencing were performed to determine changes in miRNA expression in exosomes. Immunofluorescence and exosome coculture experiments were conducted to examine the role of endothelial autophagy in regulating the communication between endothelial cells and smooth muscle cells (SMCs) via exosomal miRNA.
RESULTS
Endothelial autophagy was inhibited in thoracic aortas of high-fat diet-fed mice. Furthermore, rapamycin alleviated high-fat diet-induced atherosclerotic burden and endothelial dysfunction, while endothelial-specific depletion aggravated the atherosclerotic burden. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue analysis revealed that miR-204-5p was significantly increased in endothelial cells after high-fat diet exposure, which directly targeted to regulate endothelial cell apoptosis. Importantly, endothelial autophagy activation decreased excess miR-204-5p by loading miR-204-5p into multivesicular bodies and secreting it through exosomes. Moreover, exosomal miR-204-5p can effectively transport to SMCs, alleviating SMC calcification by regulating target proteins such as RUNX2.
CONCLUSIONS
Our study revealed the exosomal pathway by which endothelial autophagy protects atherosclerosis: endothelial autophagy activation transfers miR-204-5p from endothelial cells to SMCs via exosomes, both preventing endothelial apoptosis and alleviating SMC calcification.
REGISTRATION
URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2200064155.
PubMed: 38957984
DOI: 10.1161/ATVBAHA.123.319993 -
Journal of Burn Care & Research :... Jul 2024Burn injury contributes to significant morbidity and mortality in the United States. Despite an increased focus on racial and ethnic disparities in healthcare, there...
Burn injury contributes to significant morbidity and mortality in the United States. Despite an increased focus on racial and ethnic disparities in healthcare, there remains a critical knowledge gap in our understanding of the effect of these disparities on complications experienced by burn patients. The American Burn Association's National Burn Repository data were reviewed from 2010-2018. Information regarding demographics, burn mechanism and severity, complications, and clinical outcomes were recorded. Data analysis was performed using 1:1 propensity-score-matching and logistic regression modeling. A separate analysis of Hispanic and non-Hispanic patients was performed using Chi squared tests. Among 215,071 patients, racial distribution was 65.16% white, 19.13% black, 2.18% Asian, 0.74% American Indian/Alaskan Native, and 12.78% other. Flame injuries were the most common cause (35.2%), followed by scald burns (23.3%). All comparisons were made in reference to the white population. Black patients were more likely to die (OR: 1.28; 95%CI: 1.17-1.40), experience all (OR: 1.08; 95%CI: 1.03-1.14), cardiovascular (OR: 1.24; 95%CI: 1.08-1.43), or infectious (OR: 1.64; 95%CI: 1.40-1.91) complications, and less likely to experience airway complications (OR: 0.83; 95%CI: 0.74-0.94). American Indian/Alaskan Native patients were more likely to experience any complication (OR: 1.33; 95%CI: 1.05-1.70). All minority groups had increased length of hospital stay. Black, Asian, and other patients had longer length of ICU stay. Black patients had longer ventilator duration. Among 82,775 patients, 24,075 patients were identified as Hispanic and 58,700 as non-Hispanic. Statistically significant differences were noted between groups in age, TBSA, proportion of 2nd degree burn, and proportion of 3rd degree burn (p<0.01). These findings highlight the need for further work to determine the etiology of these disparities to improve burn care for all patients.
PubMed: 38957983
DOI: 10.1093/jbcr/irae126 -
Journal of Histotechnology Jul 2024H vessels are an essential link in angiogenic-osteogenic coupling and orchestrate the process of bone healing. H vessels are critically deficient in the setting of...
H vessels are an essential link in angiogenic-osteogenic coupling and orchestrate the process of bone healing. H vessels are critically deficient in the setting of radiation-induced fractures, which have been reported to occur in up to 25% of patients undergoing radiotherapy. By increasing H-vessel proliferation, Deferoxamine (DFO) revitalizes the physiologic response to skeletal injury and accelerates irradiated fracture repair. H-vessel quantification is therefore an important outcome measure in histologic analysis of bone healing. However, an optimized protocol for staining H vessels in formalin-fixed paraffin-embedded (FFPE) tissue sections has not been reported. With this protocol, we describe a method of staining FFPE bone samples with minimal background fluorescence and high signal-to-noise ratio. We examined mandibular specimens in a rat model of bone healing from a range of fracture conditions, including healthy bone (Fx), irradiated bone (XFx), and irradiated bone with DFO treatment (XFx-DFO). Quantitative analysis revealed a significant increase of H vessels in the XFxDFO group compared to both the Fx and XFx groups. By optimizing immunofluorescent staining of H vessels in FFPE samples across a range of fracture conditions, we offer investigators an efficacious means of producing reliable imaging for quantitative analysis of H vessels in an irradiated fracture callus.
PubMed: 38957981
DOI: 10.1080/01478885.2024.2371060 -
American Journal of Epidemiology Jul 2024The 1918-20 influenza pandemic devastated Alaska's Indigenous populations. We report on quantitative analyses of pandemic deaths due to pneumonia and influenza (P&I)...
The 1918-20 influenza pandemic devastated Alaska's Indigenous populations. We report on quantitative analyses of pandemic deaths due to pneumonia and influenza (P&I) using information from Alaska death certificates dating between 1915 and 1921 (n=7,147). Goals include a reassessment of pandemic death numbers, analysis of P&I deaths beyond 1919, estimates of excess mortality patterns overall and by age using intercensal population estimates based on Alaska's demographic history, and comparisons between Alaska Native (AN) and non-AN residents. Results indicate that ANs experienced 83% of all P&I deaths and 87% of all-cause excess deaths during the pandemic. AN mortality was 8.1 times higher than non-AN mortality. Analyses also uncovered previously unknown mortality peaks in 1920. Both subpopulations showed characteristically high mortality of young adults, possibly due to imprinting with the 1889-90 pandemic virus, but their age-specific mortality patterns were different: non-AN mortality declined after age 25-29 and stayed relatively low for the elderly, while AN mortality increased after age 25-29, peaked at age 40-44, and remained high up to age 64. This suggests a relative lack of exposure to H1-type viruses pre-1889 among AN persons. In contrast, non-AN persons, often temporary residents, may have gained immunity before moving to Alaska.
PubMed: 38957978
DOI: 10.1093/aje/kwae173 -
Surgical Infections Jul 2024Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is...
Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is substantially higher in cesarean section procedures. Approximately 8% of women who undergo cesarean sections are susceptible to infection. Although the body of evidence supporting the regular pre-operative utilization of prophylactic antibiotic treatment is steadily expanding, its usefulness in cesarean sections has not yet been standardized, and post-partum infection is still a serious medical challenge. We aimed to retrospectively assess the prophylactic effectiveness of cefazolin in combination with other antibiotic agents in cesarean sections. Both uni-variable and multi-variable analyses were conducted to identify factors that may affect cefazolin pre-operative antibiotic prophylaxis in elective cesarean section operations. The uni-variable analysis included timing of administration, operation duration, body mass index (BMI), and wound type. A multi-variable logistic regression model was then created to determine which variables provide independent information in the context of other variables. Time of administration did not affect prophylactic cefazolin efficacy. However, prophylactic cefazolin was 1.43 and 1.77 times more effective when the operation lasted for 45 minutes or more, compared with operations that were shorter than 45 minutes. Patients with a BMI ranging from 18 to 29 kg/m showed increased efficacy of prophylactic cefazolin compared with obese patients with a BMI exceeding 30 kg/m. The effectiveness of prophylactic cefazolin decreased by 95% in patients with clean-contaminated surgical incisions compared with those with clean surgical incisions. Our findings demonstrate that administering pre-operative prophylactic antibiotic agents to women undergoing cesarean section resulted in a reduction in post-partum infections, thereby reducing maternal mortality. Furthermore, optimal timing of administration, re-dosing if necessary, length of prophylactic medication, and dosing adjustments for obese patients are crucial factors in preventing surgical site infections and promoting antimicrobial stewardship.
PubMed: 38957977
DOI: 10.1089/sur.2024.048 -
Hypertension (Dallas, Tex. : 1979) Jul 2024Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who...
BACKGROUND
Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.
METHODS
In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.
RESULTS
Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; =0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively.
CONCLUSIONS
In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.
PubMed: 38957975
DOI: 10.1161/HYPERTENSIONAHA.124.22876