Mucosa-penetrating liposomes for esophageal local drug delivery.

Local drug delivery to the esophagus is hampered by rapid transit time and poor permeability of the mucosa. If some strategies aimed to improve the residence time have been proposed, non-invasive approaches to increase the drug penetration in the mucosa have not been described so far. Herein, we designed mucosa-penetrating liposomes to favor the penetration and retention of curcumin (CURC) in the esophagus. A novel mucosa penetrating peptide (MPP), SLENKGP, was selected by Phage Display and conjugated to pegylated liposomes at different PEG and MPP's surface densities. Pegylation assured a long residence time of liposomes (at least 30 min) in the esophagus in vivo, but it did not favor the penetration of CURC in the mucosa. MPP-decorated liposomes instead delivered a significant higher amount of CURC in the mucosa compared to naked pegylated liposomes. Confocal microscopy studies showed that naked pegylated liposomes remain confined in the superficial layers of the mucosa whereas MPP-decorated liposomes penetrate the whole epithelium. In vitro, MPP reduced the interaction of PEG with mucin, meanwhile favoring the paracellular penetration of liposomes across epithelial cell multilayers. In conclusion, pegylated liposomes represent a valid approach to target the esophagus and the surface functionalization with MPP enhances their penetration in the mucosa.

A clinical observation algorithm for anterior abdominal stab wound is safe in an Australian setting.

INTRODUCTION: We previously published the outcomes associated with the use of diagnostic laparoscopy to determine peritoneal breach for AASW patients without an immediate indication for laparotomy. Although this pathway was 100% sensitive there was a 54% non-therapeutic laparotomy rate. Another option that has been extensively reported is the clinical observation algorithm (COA) however, majority of the data originate from high-volume centres. We hypothesized that a COA would also be a safe option in an Australian setting, and reduce the rate of non-therapeutic operative intervention in managing AASW. METHODS: This was a prospective cohort study examining patients with AASW admitted to a level 1 trauma centre in Sydney, Australia, between June 2021 and August 2023. Patient, injury, management and outcome data were collected from electronic medical records and the hospital trauma registry. Data were then analysed to determine the diagnostic accuracy of the COA, complication rates and median hospital length-of-stay (LOS). RESULTS: A total of 48 patients presented with AASW. Of these patients, 11 (22.9%) proceeded to immediate laparotomy. Seven patients had a contraindication to COA and underwent diagnostic laparoscopy. Thirty patients were managed with the COA, with three (10%) patients subsequently requiring a laparotomy. Only one patient (3.3%) underwent a non-therapeutic laparotomy. There were no missed injuries. The COA sensitivity was 100%, specificity 92.7%, PPV 50% and NPV 100%. Patients managed with COA had no complications. Overall median hospital LOS was 1 day (1.0-2.3). CONCLUSION: A COA is a safe approach for evaluating patients with AASW in an Australian setting with adequate resources. It reduces the rate of non-therapeutic operative intervention and has acceptable outcomes compared with a diagnostic laparoscopy pathway.

Poliovirus capsid protein VP3 can penetrate vascular endothelial cells.

The poliovirus (PV) enters the central nervous system (CNS) via the bloodstream, suggesting the existence of a mechanism to cross the blood-brain barrier. Here, we report that PV capsid proteins (VP1 and VP3) can penetrate cells, with VP3 being more invasive. Two independent parts of VP3 are responsible for this function. Both peptides can penetrate human umbilical cord vascular endothelial cells, and one peptide of VP3 could also penetrate peripheral blood mononuclear cells. In an in vitro blood-brain barrier model using rat-derived astrocytes, pericytes, and endothelial cells, both peptides were observed to traverse from the blood side to the brain side at 6 h after administration. These results provide insights into the molecular mechanisms underlying PV invasion into the CNS.

Wartime penetrating skull base trauma with unpredictable internal fragment ricochet and migration: illustrative case.

BACKGROUND: Transnasal transsphenoidal penetrating craniocerebral injury is very rare even in wartime. Cases with good outcomes are even less common. OBSERVATIONS: A 20-year-old male sustained multiple fragment wounds to his head and face from a landmine explosion. One metal fragment entered his right nostril, traversed the nasal septum and anterior sphenoid sinus, and ricocheted superiorly off the clivus. The fragment then traveled almost to the surface of the left parietal lobe. Subsequently, under its own weight, it migrated back down its original track. The patient suffered cerebrospinal fluid rhinorrhea, pneumocephalus, and right-sided hemiparesis. Digital subtraction angiography was followed by microscopic transnasal skull base reconstruction supplemented by external lumbar drainage. Follow-up brain computed tomogrpahy showed further metallic fragment migration through the ventricular system. The fragment was removed through a transcortical approach. The patient's neurological examination and brain magnetic resonance imaging results demonstrated good recovery. LESSONS: The absence of external signs of deep injuries does not exclude the presence of a penetrating craniocerebral injury. Metal fragments may undergo ricochet and internal migration in both the brain parenchyma and the ventricular system. Timely diagnosis including three-dimensional reconstruction of a projectile's trajectory may facilitate appropriate surgical planning in complex cases. Intraventricular fragment migration may necessitate microsurgical removal. https://thejns.org/doi/10.3171/CASE24128.

[Cell membrane-penetrating capacity of hPP10-Cu, Zn-SOD fusion protein and its antioxidant and anti-inflammatory activity].

OBJECTIVE: To investigate the cell membrane-penetrating capacity of human cell-penetrating peptide hPP10 carrying human antioxidant protein Cu-Zn superoxide dismutase (Cu, Zn-SOD) and assess the antioxidant and anti-inflammatory activity of these fusion proteins. METHODS: The fusion protein hPP10-Cu, Zn-SOD was obtained by genetic engineering and identified by Western blotting. The membrane-penetrating ability of the fusion protein was evaluated by immunofluorescence assay, fluorescence colocalization assay and Western blotting, its SOD enzyme activity was detected using a commercial kit, and its effect on cell viability was assessed with MTT assay. In a HEK293 cell model of H2O2-induced oxidative stress, the effect of hPP10-Cu, Zn-SOD on cell apoptosis was analyzed with flow cytometry and RT-qPCR, and its antioxidant effect was assessed using reactive oxygen species (ROS) assay; its anti-inflammatory effect was evaluated in mouse model of TPA-induced ear inflammation by detecting expression of the inflammatory factors using RT-qPCR, Western blotting and immunohistochemistry. RESULTS: The fusion protein hPP10-Cu, Zn-SOD was successfully obtained. Immunofluorescence assay confirmed obvious membrane penetration of this fusion protein in HEK293 cells, localized both in the cell membrane and the cell nuclei after cell entry. hPP10-Cu, Zn-SOD at the concentration of 5 µmol/L exhibited strong antioxidant activity with minimal impact on cell viability at the concentration up to 10 µmol/L. The fusion protein obviously inhibited apoptosis and decreased intracellular ROS level in the oxidative stress cell model and significantly reduced mRNA and protein expression of the inflammatory factors in the mouse model of ear inflammation. CONCLUSION: The fusion protein hPP10-Cu, Zn-SOD capable of penetrating the cell membrane possesses strong antioxidant and anti-inflammatory activities with only minimal cytotoxicity, demonstrating the value of hPP10 as an efficient drug delivery vector and the potential of hPP10-Cu, Zn-SOD in the development of skincare products.

Carotid artery penetrating trauma: Report of 4 cases and literature revision.

INTRODUCTION AND IMPORTANCE: In penetrating neck trauma, carotid artery penetrating trauma is considered one of the most complicated injuries to treat. Active bleeding, large hematomas, and rapid occlusion of the airways make the surgical approach to controlling bleeding and repairing the vessel much more complex, constituting an essential clinical challenge to every surgeon. CASE PRESENTATION: We present 4 cases of patients with carotid artery penetrating trauma. Two patients were treated with endovascular therapy, one with surgery, and the fourth one treated conservatively. None of the patients had posterior neurological impairment. CLINICAL DISCUSSION: Carotid artery penetrating trauma is uncommon yet is associated with high rates of mortality and neurological impairment. The common carotid artery is the most frequently injured, and gunshot wounds (GSW) are the most frequent trauma mechanism. Angiotomography (CTA) is the first-line exam for diagnosing these injuries. Treatment should be prompt and individualized and may include conservative techniques, endovascular therapy, and traditional surgical repair. CONCLUSION: Carotid artery penetrating trauma is an uncommon but complex injury that requires a timely diagnosis and treatment to avoid potentially devastating consequences, particularly in hemodynamically unstable patients. Traditionally, the treatment strategies for these injuries used to be limited to vascular repair or ligation. However, endovascular therapy and conservative management are viable alternatives, which have become more and more useful in selected patients, allowing less invasive approaches with fewer morbidity and acceptable results.

Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

A high hydrophobic moment arginine-rich peptide screened by a machine learning algorithm enhanced ADC antitumor activity.

Cell-penetrating peptides (CPPs) with better biomolecule delivery properties will expand their clinical applications. Using the MLCPP2.0 machine algorithm, we screened multiple candidate sequences with potential cellular uptake ability from the nuclear localization signal/nuclear export signal database and verified them through cell-penetrating fluorescent tracing experiments. A peptide (NCR) derived from the Rev protein of the caprine arthritis-encephalitis virus exhibited efficient cell-penetrating activity, delivering over four times more EGFP than the classical CPP TAT, allowing it to accumulate in lysosomes. Structural and property analysis revealed that a high hydrophobic moment and an appropriate hydrophobic region contribute to the high delivery activity of NCR. Trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, could improve its anti-tumor activity by enhancing targeted delivery efficiency and increasing lysosomal drug delivery. This study designed a new NCR vector to non-covalently bind T-DM1 by fusing domain Z, which can specifically bind to the Fc region of immunoglobulin G and effectively deliver T-DM1 to lysosomes. MTT results showed that the domain Z-NCR vector significantly enhanced the cytotoxicity of T-DM1 against HER2-positive tumor cells while maintaining drug specificity. Our results make a useful attempt to explore the potential application of CPP as a lysosome-targeted delivery tool.

Surgical outcome of pediatric abdominal trauma at Tertiary Hospital, Northwest Ethiopia, a 3-year retrospective study.

INTRODUCTION: Abdominal trauma in children is a significant health concern that often leads to severe complications and even death. Children experience trauma more frequently than adults, with approximately one in four pediatric patients suffering from serious abdominal injuries. Falls are the leading cause of such trauma among children, which is intriguing considering that most hospital admissions for pediatric abdominal injuries result from blunt force impacts. METHOD: A retrospective cross-sectional analysis of medical records was conducted to examine all patients under the age of 16 who underwent exploratory laparotomy for abdominal trauma between January 1, 2020, and January 1, 2023. The clinical data were gathered using a data extraction sheet from each patient's medical charts. Information on socio-demographic characteristics, injury mechanisms, clinical conditions at the initial presentation, intraoperative findings and complications, and patient outcomes were collected. RESULTS: The study involved a total of 90 patients, consisting of 72 males (80%) and 18 females (20%). The average age of the patients was 10, with a standard deviation of 4.7, ranging from 2 to 16 years. Half of the patients were below the age of 10, accounting for 46 individuals (51%). The causes of the injuries varied among patients below and above the age of 10. However, overall, bullet injuries were the most common cause, accounting for 28 cases (31%), followed by falls in 21 cases (23.3%), horse or donkey kicks in 10 cases (11.1%), stab injuries in 10 cases (11.1%), horn injuries in 7 cases (7.8%), and road traffic accidents in 6 cases (6.7%). Physical assault, blasts, and other types of injuries, such as hen bites and metal rod injuries, were observed in 8 cases (8.9%) of the patients. Fall accidents, horse or donkey kicks, and horn injuries were particularly more common among children below the age of 10, while bullet injuries and stab injuries were most common among those above the age of 10. CONCLUSION: Following abdominal trauma in children, a range of complications may arise, including immediate issues such as infections and hemorrhaging, as well as long-term consequences like impaired organ functionality and psychological distress. In our region, young children are particularly vulnerable to accidents involving falls, kicks from horses or donkeys, and injuries caused by horns. Therefore, it is crucial to educate parents about these hazards. Additionally, providing appropriate guidance on firearm safety is essential for individuals who possess such weapons.

Midterm survival after aortic repair versus conservative treatment in patients with penetrating aortic ulcer.

Background: The clinical outcomes and survival of patients with penetrating aortic ulcers (PAU) were evaluated in a tertiary care hospital, comparing those who underwent aortic repair to those treated conservatively. Patients and methods: A retrospective single-centre analysis included all patients that underwent a computed tomography angiography (CT-A) scan with the diagnosis of a PAU between January 2009 and May 2019. "PAU" was identified in 1,493 of 112,506 CT-A scan reports in 576 patients. Clinical and angiomorphological data were collected. The primary outcome was overall survival (OS), with secondary outcomes focusing on identifying risk factors for poor OS. Survival probabilities were analysed by the Kaplan-Meier method using the log-rank test. A Cox hazard model using survival as dependent variable with stepwise backward eliminations based on the likelihood ratios was employed. Results: 315 PAUs were identified in 278 patients. The prevalence in the cohort was 0.8%. The mean age of the patients was 74.4 years, and they were predominantly male (n = 208, 74.8%). The mean ulcer depth was 11.8 mm (range 2-50 mm). Out of the patients, 232 were asymptomatic (83.5%). Among 178 PAUs (56.5%), high-risk factors, such as ulcer depth >10 mm, aortic diameter >40 mm, and ulcer length >20 mm, were observed. Aortic repair was associated with a better mean OS compared to conservatively managed patients (72.6 versus 32.2 months, p = 0.001). The Cox hazard model showed that ulcer depth >1 mm was associated with poor OS (HR 0.67, p = 0.048), while aortic repair was related to a better OS (HR 4.365, p<0.013). Conclusions: Aortic repair is associated with better OS, but this finding should be interpreted with caution because of differences in age and comorbidities between the groups. Further evaluation is warranted through prospective studies with randomized groups. Further assessment for angiomorphological parameters is recommended to identify patients at increased risk for poor OS.

Variable data structures and customized deep learning surrogates for computationally efficient and reliable characterization of buried objects.

In this study, in order to characterize the buried object via deep-learning-based surrogate modeling approach, 3-D full-wave electromagnetic simulations of a GPR model have been used. The task is to independently predict characteristic parameters of a buried object of diverse radii allocated at different positions (depth and lateral position) in various dispersive subsurface media. This study has analyzed variable data structures (raw B-scans, extracted features, consecutive A-scans) with respect to computational cost and accuracy of surrogates. The usage of raw B-scan data and the applications for processing steps on B-scan profiles in the context of object characterization incur high computational cost so it can be a challenging issue. The proposed surrogate model referred to as the deep regression network (DRN) is utilized for time frequency spectrogram (TFS) of consecutive A-scans. DRN is developed with the main aim being computationally efficient (about 13 times acceleration) compared to conventional network models using B-scan images (2D data). DRN with TFS is favorably benchmarked to the state-of-the-art regression techniques. The experimental results obtained for the proposed model and second-best model, CNN-1D show mean absolute and relative error rates of 3.6 mm, 11.8 mm and 4.7%, 11.6% respectively. For the sake of supplementary verification under realistic scenarios, it is also applied for scenarios involving noisy data. Furthermore, the proposed surrogate modeling approach is validated using measurement data, which is indicative of suitability of the approach to handle physical measurements as data sources.

A novel multitargeted self-assembling peptide-siRNA complex for simultaneous inhibition of SARS-CoV-2-host cell interaction and replication.

Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and restrict SARS-CoV-2 replication. Cell-penetrating peptides is a robust method for siRNA delivery, enhancing siRNA stability and targeting specific receptors. We developed a peptide HE25 that blocks SARS-CoV-2 replication by various mechanisms, including the binding of multiple receptors involved in the virus's internalization, such as ACE2, integrins and NRP1. HE25 not only acts as a vehicle to deliver the SARS-CoV-2 RNA-dependent RNA polymerase siRNA into cells but also facilitates their internalization through endocytosis. Once inside endosomes, the siRNA is released into the cytoplasm through the Histidine-proton sponge effect and the selective cleavage of HE25 by cathepsin B. These mechanisms effectively inhibited the replication of the ancestral SARS-CoV-2 and the Omicron variant BA.5 in vitro. When HE25 was administered in vivo, either by intravenous injection or inhalation, it accumulated in lungs, veins and arteries, endothelium, or bronchial structure depending on the route. Furthermore, the siRNA/HE25 complex caused gene silencing in lung cells in vitro. The SARS-CoV-2 siRNA/HE25 complex is a promising therapeutic for COVID-19, and a similar strategy can be employed to combat future emerging viral diseases.

A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma.

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43266-283. Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43266-283 may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43266-283 correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43266-283 correlated with shorter survival, supporting its use in clinical trials.

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP.

We have designed cell-penetrating peptides that target the leucine zipper transcription factors ATF5, CEBPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. Though such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell context-dependent manner (in about two-thirds of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin-interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell context-dependent manner that in turn suppresses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

Applying enhanced recovery principles to emergency laparotomy in penetrating abdominal trauma: a case-matched study.

PURPOSE: The implementation of enhanced recovery after surgery programs (ERPs) has significantly improved outcomes within various surgical specialties. However, the suitability of ERPs in trauma surgery remains unclear. This study aimed to (1) design and implement an ERP for trauma laparotomy patients; (2) assess its safety, feasibility, and efficacy; and (3) compare the outcomes of the proposed ERP with conventional practices. METHODS: This case-matched study prospectively enrolled hemodynamically stable patients undergoing emergency laparotomy after penetrating trauma. Patients receiving the proposed ERP were compared to historical controls who had received conventional treatment from two to eight years prior to protocol implementation. Cases were matched for age, sex, injury mechanism, extra-abdominal injuries, and trauma scores. Assessment of intervention effects were modelled using regression analysis for outcome measures, including length of hospital stay (LOS), postoperative complications, and functional recovery parameters. RESULTS: Thirty-six consecutive patients were enrolled in the proposed ERP and matched to their 36 historical counterparts, totaling 72 participants. A statistically significant decrease in LOS, representing a 39% improvement in average LOS was observed. There was no difference in the incidence of postoperative complications. Opioid consumption was considerably lower in the ERP group (p < 0.010). Time to resumption of oral liquid and solid intake, as well as to the removal of nasogastric tubes, urinary catheters, and abdominal drains was significantly earlier among ERP patients (p < 0.001). CONCLUSION: The implementation of a standardized ERP for the perioperative care of penetrating abdominal trauma patients yielded a significant reduction in LOS without increasing postoperative complications. These findings demonstrate that ERPs principles can be safely applied to selected trauma patients.

Risk factors for corneal graft rejection after penetrating keratoplasty for keratoconus.

PURPOSE: To evaluate the association between donor-related factors and the risk of rejection in patients undergoing penetrating keratoplasty (PKP) for keratoconus. METHODS: A retrospective review was performed of keratoconus patients with no corneal neovascularization who underwent PKP from November 2014 to December 2016 and completed at least two years of follow-up. Preoperative, donor, operative, and postoperative data were collected and analyzed to identify factors leading to corneal graft rejection. RESULTS: A total of 201 eyes (of 201 patients) that underwent PKP for keratoconus were included. Of these, 22.9% (95% CI 17.6-29.2%) had an episode of graft rejection. The overall graft survival rate was 98.5%. Receipts with a history of corneal transplant in the fellow eye (IRR 1.69, 95% CI 1.01, 2.80; p = 0.044) and those with postoperative stromal neovascularization (IRR 2.51, 95% CI 1.49, 4.21; p = 0.001) had a significantly higher incidence of rejection than those without these features. In univariate analysis, death-to-surgery time and death-to-excision time (DET) showed a weak association with graft rejection (p 0.05 and 0.08 respectively); However, in the multivariable analysis, this significance was lost. Grafts with a death-to-excision time (DET) greater than 8 h had a 0.53X lower risk of rejection compared with grafts with DET within 8 h or less (p = 0.05). Rejection was higher in patients receiving grafts with a preservation time within 7 days or less compared with preservation time greater than 7 days (30.6% vs. 21.2%, respectively, p = 0.291). CONCLUSION: In the multivariable analysis, none of the donor-related factors were significantly associated with graft rejection; however, short death-to-surgery time may be associated with rejection after PKP. Recipients with a history of PKP in the fellow eye and those who developed corneal neovascularization were also at increased risk of developing rejection after keratoplasty.

Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs).

Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on RNA as a molecular biomarker. In this regard, FLJ22447 lncRNA is an RNA biomarker that is over-expressed in ovarian cancer (OC) and in cancer-associated fibroblasts (CAFs). CAFs appear early on in OC as they provide a metastatic niche for OC progression. FIT-PNAs (forced intercalation-peptide nucleic acids) are DNA analogs that are designed to fluoresce upon hybridization to their complementary RNA target sequence. In recent studies, we have shown that the introduction of cyclopentane PNAs into FIT-PNAs (cpFIT-PNA) results in superior RNA sensors. Herein, we report the design and synthesis of cpFIT-PNAs for the detection of this RNA biomarker in living OC cells (OVCAR8) and in CAFs. cpFIT-PNA was compared to FIT-PNA and the cell-penetrating peptide (CPP) of choice was either a simple one (four L-lysines) or a CPP with enhanced cellular uptake (CLIP6). The combination of CLIP6 with cpFIT-PNA resulted in a superior sensing of FLJ22447 lncRNA in OVCAR8 cells as well as in CAFs. Moreover, incubation of CLIP6-cpFIT-PNA in OVCAR8 cells leads to a significant decrease (ca. 60%) in FLJ22447 lncRNA levels and in cell viability, highlighting the potential theranostic use of such molecules.

Risk factors for stroke in penetrating cerebrovascular injuries.

OBJECTIVE: Penetrating cerebrovascular injuries (PCVI) are associated with a high incidence of mortality and neurological events. The optimal treatment strategy of PCVI, especially when damage control measures are required, remains controversial. The aim of this study was to describe the management of PCVI and patient outcomes at a level 1 trauma center where vascular injuries are managed predominantly by trauma surgeons. METHODS: An institutional trauma registry was queried for patients with PCVI from 2011 to 2021. Patients with common carotid artery (CCA), internal carotid artery (ICA), or vertebral artery injuries were included for analysis. The primary outcome was in-hospital stroke. The secondary outcomes were in-hospital mortality and in-hospital stroke or death. A subgroup analysis was completed of arterial repair (primary repair or interposition graft) vs ligation or embolization vs temporary intravascular shunting at the index procedure. RESULTS: We analyzed 54 patients with PCVI. Overall, the in-hospital stroke rate was 17% and in-hospital mortality was 26%. Twenty-one patients (39%) underwent arterial interventions for PCVI. Ten patients underwent arterial repair, six patients underwent ligation or embolization, and five patients underwent intravascular shunting as a damage control strategy with a plan for delayed repair. The rate of in-hospital stroke was 30% after arterial repair, 0% after arterial ligation or embolization, and 80% after temporary intravascular shunting. There was a significant difference in the stroke rate between the three subgroups (P = .015). Of the 32 patients who did not have an intervention to the CCA, ICA, or vertebral artery, 1 patient with ICA occlusion and 1 patient with CCA intimal injury developed in-hospital stroke. The mortality rate was 0% after arterial repair, 50% after ligation or embolization, and 60% after intravascular shunting. The rate of stroke or death was 30% in the arterial repair group, 50% in the ligation or embolization group, and 100% in the temporary intravascular shunting group. CONCLUSIONS: High rates of stroke and mortality were seen in patients requiring damage control after PCVI. In particular, temporary intravascular shunting was associated with a high incidence of in-hospital stroke and a 100% rate of stroke or death. Further investigation is needed into the factors related to these finding and whether the use of temporary intravascular shunting in PCVI is an advisable strategy.

Intravenous Administration of Anti-CD47 Antibody Augments Hematoma Clearance, Mitigates Acute Neuropathology, and Improves Cognitive Function in a Rat Model of Penetrating Traumatic Brain Injury.

Traumatic brain injury (TBI)-induced intracerebral hematoma is a major driver of secondary injury pathology such as neuroinflammation, cerebral edema, neurotoxicity, and blood-brain barrier dysfunction, which contribute to neuronal loss, motor deficits, and cognitive impairment. Cluster of differentiation 47 (CD47) is an antiphagocytic cell surface protein inhibiting hematoma clearance. This study was designed to evaluate the safety and efficacy of blockade of CD47 via intravenous (i.v.) administration of anti-CD47 antibodies following penetrating ballistic-like brain injury (PBBI) with significant traumatic intracerebral hemorrhage (tICH). The pharmacokinetic (PK) profile of the anti-CD47 antibody elicited that antibody concentration decayed over 7 days post-administration. Blood tests and necropsy analysis indicated no severe adverse events following treatment. Cerebral hemoglobin levels were significantly increased after injury, however, anti-CD47 antibody administration at 0.1 mg/kg resulted in a significant reduction in cerebral hemoglobin levels at 72 h post-administration, indicating augmentation of hematoma clearance. Immunohistochemistry assessment of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) demonstrated a significant reduction of GFAP levels in the lesion core and peri-lesional area. Based on these analyses, the optimal dose was identified as 0.1 mg/kg. Lesion volume showed a reduction following treatment. Rotarod testing revealed significant motor deficits in all injured groups but no significant therapeutic benefits. Spatial learning performance revealed significant deficits in all injured groups, which were significantly improved by the last testing day. Anti-CD47 antibody treated rats showed significantly improved attention deficits, but not retention scores. These results provide preliminary evidence that blockade of CD47 using i.v. administration of anti-CD47 antibodies may serve as a potential therapeutic for TBI with ICH.

Unsafe Practices of Motorcycle Riders in El Petén, Guatemala: A Community Observational Study and a Retrospective Institutional Review.

INTRODUCTION: Outcomes from trauma at the major referral hospital [Hospital Nacional de San Benito (HNSB)] in El Petén, Guatemala, have not been analyzed. Empirical evidence demonstrated a high number of motorcycle accidents (MAs). We hypothesized a large incidence of head trauma with poor outcomes in MAs compared to all other forms of blunt trauma. METHODS: Our hypothesis was tested by performing a community observational study and a retrospective chart review in El Petén, Guatemala. An independent observer catalogued 100 motorcycle riders on the streets of El Petén for riding practices as well as helmet utilization. HNSB does not have electronic medical records. For this study, we performed a retrospective chart review of randomly selected nonconsecutive trauma admission at HNSB between March 2018 and June 2023. Blunt trauma was compared between MAs versus all others. Variables were examined by parametric and nonparametric tests as well as contingency table analyses. RESULTS: Most motorcycles riders involved multiple individuals (2.61 ± 0.79/motorcycle). Seventy riders included children (median = 1.0 [Q1-Q3 range = 1.0-3.0]/motorcycle). Overall, only three riders were wearing helmets. Forty-one were women. Of patients presenting to HNSB with trauma, 91 charts were reviewed (33.0 [20.0-37.0] y old; male 89%), 76.7% were blunt, and 23.3% were penetrating trauma. Within blunt trauma, 57.1% were MAs versus 42.9% all others; P = 0.13. MAs were younger (29.5 [20.0-37.0] versus 34.0 [21.8-45.8] y old; P < 0.05) and of similar gender (male 82.5% versus 96.6%; P = 0.1). More MAs had a computed tomography (70.0% versus 30.0%; P < 0.01) and they were more likely to present with head trauma (72.5% versus 46.7%; P = 0.04) but similar Glasgow Coma Scale (15.0 [13.5-15.0] versus 15.0 [12.5-15.0]; P = 0.7). MAs were less likely to require surgical intervention (37.5% versus 56.7%; P = 0.05) but had similar hospital length of stay (4.0 [2-6] versus 4.0 [2-10.5] d; P = 0.5). CONCLUSIONS: Unsafe motorcycle practices in El Petén are staggering. Most trauma at HNSB is blunt, and likely from MAs. More patients with MAs presented with head trauma. However, severe trauma might be transferred to higher level hospitals or mortality might occur on scene, which will need further investigations. Assessment of mortality from trauma admissions is ongoing. These findings should lead to enforcement of safe motorcycle practices in El Petén, Guatemala.