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Introduction: Medication management is an essential instrumental activity of daily living for older adults; however, 40–70% of older adults fail to take their medications correctly. Addressing medication management falls under the scope of occupational therapy, but there is a lack of evidence supporting occupational therapy interventions to improving medication management. This study’s primary aims are to examine the feasibility, acceptability, and preliminary efficacy of a Tailored Intervention for Medication Management delivered by occupational therapists to improve medication management. Method/Design: Single-blind, parallel-group randomized controlled equivalency trial, with two phases. Thirty community-dwelling older adults will be enrolled in this study. In Phase 1, participants in the treatment group will receive Tailored Intervention for Medication Management delivered remotely; those in the waitlist control will receive attention visits. In Phase 2, waitlist control participants will receive Tailored Intervention for Medication Management in person. The primary outcomes are feasibility and acceptability; secondary outcomes include preliminary efficacy of the intervention delivered by an occupational therapist remotely and in person. Additionally, the remote and in-person delivery methods will be compared to each other for equivalency. Discussion: Inability to manage medication and inappropriate polypharmacy are significant and prevalent problems that must be addressed so older adults can safely perform this essential instrumental activity of daily living. Trial Registration: ClinicalTrials.gov identifier NCT04717297.

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4′,6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46.66%. SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44.9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.

Fall from ladders is increasingly identified as a significant cause of injury and mortality, yet large-scale research into ladder fall outcomes and trends is limited.To explore the nature and severity of injuries resulting from ladder falls and to determine predictors of Injury Severity Score (ISS) and 6-month mortality.Data were obtained from the New South Wales (NSW) Trauma Registry, Admitted Patient Data Collection and Registry of Births, Deaths, and Marriages on patients aged 15 and over who had major trauma from a ladder fall and were admitted to hospital between January 1st, 2012, and July 31st, 2019. Data linkage and descriptive statistics were carried out alongside bivariate and multivariable regression analysis.963 patients injured after ladder falls were identified. The mean age was 61.9 years (SD 14.2), 91.0% were male, and 489 (50.8%) were born in Australia. The height of fall was between one and five meters in 827 (86.2%) patients, and the place of fall was home and residential places in 27.5%. The most common body areas injured were the head (26.5%), spine (21.2%) and thorax (20.6%), and the median injury severity score was 17. The median length of stay of patients' in-hospital and intensive care unit was six days and two days, respectively. Six months post-discharge mortality was 6.4%. The unadjusted association between the presence of comorbidities or socio-economic class and ISS or mortality was not statistically significant. Increasing ISS was found to be associated with increasing age (Estimate (Est), 15.2; 95% Confidence Interval (CI), 12.3-18.1) and a fall height greater than five metres (Est, 5.8; CI, 3.2-8.4). Mortality was found to be associated with increasing age (Odds ratio (OR), 1.06; CI, 1.03-1.08) and increasing ISS (OR, 1.19; CI, 1.15-1.24).People presenting to the hospital after falling from a ladder were predominately male, aged over 60 and had fallen in a residential setting. Increasing age and fall height are associated with more severe injuries.

We report the development of a label-, antibody-, enzyme-, and amplification-free ratiometric fluorescent biosensor for low-cost and rapid (less than 12 min) diagnosis of COVID-19 from isolated RNA samples. The biosensor is designed on the basis of cytosine-modified antisense oligonucleotides specific for either N gene or RdRP gene that can form silver nanoclusters (AgNCs) with both green and red emission on an oligonucleotide via a one-step synthesis process. The presence of the target RNA sequence of SARS-CoV-2 causes a dual-emission ratiometric signal transduction, resulting in a limit of detection of 0.30 to 10.0 nM and appropriate linear ranges with no need for any further amplification, fluorophore, or design with a special DNA fragment. With this strategy, five different ratiometric fluorescent probes are designed, and how the T/C ratio, the length of the stem region, and the number of cytosines in the loop structure and at the 3' end of the cluster-stabilizing template can affect the biosensor sensitivity is investigated. Furthermore, the effect of graphene oxide (GO) on the ratiometric behavior of nanoclusters is demonstrated and the concentration-/time-dependent new competitive mechanism between aggregation-caused quenching (ACQ) and aggregation-induced emission enhancement (AIE) for the developed ssDNA-AgNCs/GO nanohybrids is proposed. Finally, the performance of the designed ratiometric biosensor has been validated using the RNA extract obtained from more than 150 clinical samples, and the results have been confirmed by the FDA-approved reverse transcription-polymerase chain reaction (RT-PCR) diagnostic method. The diagnostic sensitivity and specificity of the best probe is more than90%, with an area under the receiver operating characteristic (ROC) curve of 0.978.

While comorbidities and types of road users are known to influence survival in people hospitalised with injury, few studies have examined the association between comorbidities and survival in people injured in road traffic crashes. Further, few studies have examined outcomes across different types of road users with different types of pre-existing comorbidities. This study aims to examine differences in survival within 30 days of admission among different road user types with and without different pre-existing comorbidities.Retrospective cohort study using data for all major road trauma cases were extracted from the NSW Trauma Registry Minimum Dataset (1 January 2013 - 31 July 2019) and linked to the NSW Admitted Patient Data Collection, and the NSW Registry of Births, Deaths and Marriages - death dataset. Pre-existing comorbidities and road user types were identified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and Charlson Comorbidity Index in the Trauma Registry, hospital admission, and death datasets. Logistic regression was used to assess the associations between six types of road users (pedestrian, pedal cycle, two- and three-wheel motorcycle, car and pick-up truck, heavy vehicle and bus, and other types of vehicle) and death within 30 days of hospital admission while controlling for comorbidities. All models used 'car and pick-up truck driver/passenger' as the road user reference group and adjusted for demographic variables, injury severity, and level of impaired consciousness.Within 6253 traffic injury person-records (all aged ≥15 years old, ISS12), and in final models, injured road users with major trauma who had a history of cardiovascular diseases (including stroke), diabetes mellitus, and higher Charlson Comorbidity Index score, were more likely to die, than those without pre-existing comorbidities. Furthermore, in final models, pedestrians were more likely to die than car occupants (OR: 1.68 - 1.77, 95CI%: 1.26 - 2.29 depending on comorbidity type).This study highlights the need to prioritize enhanced management of trauma patients with comorbidities, given the increasing prevalence of chronic medical conditions globally, together with actions to prevent pedestrian crashes in strategies to reach Vision Zero.

ObjectiveTo investigate the impact of a road safety programme on adolescents’ willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest.MethodThebstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores.Results2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (−2.99, 95% CI −3.418 to −2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors.ConclusionsTrauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.

Personalized medicine is a novel frontier in health care that is based on each person’s unique genetic makeup. It represents an exciting opportunity to improve the future of individualized health care for all individuals. Pharmacogenomics, as the main part of personalized medicine, aims to optimize and create a more targeted treatment approach based on genetic variations in drug response. It is predicted that future treatments will be algorithm-based instead of evidence-based that will consider a patient’s genetic, transcriptomic, proteomic, epigenetic, and lifestyle factors resulting in individualized medication. A generative pretrained transformer (GPT) is an artificial intelligence (AI) tool that generates language resembling human-like writing enabling users to engage in a manner that is practically identical to speaking with a human being. GPT's predictive algorithms can respond to questions that have never been addressed. Chat Generative Pretrained Transformer (ChatGPT) is an AI chatbot's advanced with conversational capabilities. In the present study, Questions were asked from ChatGPT about the future of personalized medicine and pharmacogenomics. ChatGPT predicted both to be a promising approach with a bright future that holds great promises in improving patient outcomes and transforming the field of medicine.

Hemorrhage is a leading cause of preventable death in trauma. Prehospital medical teams can streamline access to massive transfusion and definitive hemorrhage control by alerting in-hospital trauma teams of suspected life-threatening bleeding in unstable patients. This study reports the initial experience of an Australian "Code Crimson" (CC) pathway facilitating early multidisciplinary care for these patients.This data-linkage study combined prehospital databases with a trauma registry of patients with an Injury Severity Score greater than 12 between 2017 and 2019. Four groups were created; prehospital CC activation with and without in-hospital links and patients with inpatient treatment consistent with CC, without one being activated. Diagnostic accuracy was estimated using capture-recapture methodology to replace the missing cell (no prehospital CC and Injury Severity Score12).Of 72 prehospital CC patients, 50 were linked with hospital data. Of 154 potentially missed patients, 42 had a prehospital link. Most CC patients were young men who sustained blunt trauma and required more prehospital interventions than non-CC patients. Code Crimson patients had more multisystem trauma, especially complex thoracic injuries (80%), while missed CC patients more frequently had single organ injuries (59%). Code Crimson patients required fewer hemorrhage control procedures (60% vs. 86%). Lower mortality was observed in CC patients despite greater hospital and intensive care unit length of stay. Despite a low sensitivity (0.49; 95% confidence interval [CI], 0.38-0.61) and good specificity (0.92; 95% CI, 0.86-0.96), the positive likelihood ratio was acceptable (6.42; 95% CI, 3.30-12.48).The initiation of a statewide CC process was highly specific for the need for hemorrhage control intervention in hospital, but further work is required to improve the sensitivity of prehospital activation. Patients who had a CC activation sustained more multisystem trauma but had lower mortality than those who did not. These results guide measures to improve this pathway.Therapeutic/Care Management; Level IV.

Background: Extracranial carotid atherosclerosis has been variably associated with dementia. Prior studies have focused on the association of carotid intima media thickness or carotid stenosis; however, there is evidence that carotid plaque may contribute to dementia, perhaps via microembolic phenomena. Objectives: We sought to evaluate the role of carotid plaque in contributing to cognitive impairment by performing a systematic review and meta-analysis to summarize the association between extracranial carotid plaque and cognitive dysfunction and dementia. Methods: We performed a comprehensive literature search evaluating the association of extracranial carotid plaque with cognition. We included studies measuring carotid plaque on ultrasound, computed tomography, or MR and also evaluated cognition through neuropsychological testing. Meta-analyses with assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model. Results: After screening 1,674 studies, we included 40 for systematic review and 16 and 7 studies for two meta-analyses with a total of 19,029 and 27,325 patients, respectively. We found a positive relationship between the presence of extracranial carotid plaque and cognitive dysfunction with a pooled random-effects odds ratio (OR) of 1.83 (95% CI, 1.50, 2.24) and a pooled random-effects hazard ratio (HR) of 1.47 (95% CI, 1.15, 1.89), respectively. A sensitivity analysis of only longitudinal studies found a persistent positive association. Measures of heterogeneity showed moderate heterogeneity in each meta-analysis, respectively (I-squared statistic = 57% and 70%). Conclusion: The presence of extracranial carotid plaque is significantly associated with cognitive dysfunction and dementia in both cross-sectional and longitudinal analyses. After further confirmation, our results support carotid plaque being a potentially modifiable risk factor in the development of dementia.

Vaginal inflammation increases the risk for sexual HIV-1 transmission but underlying mechanisms remain unclear. In this study we assessed the impact of immune activation on HIV-1 susceptibility of primary human vaginal Langerhans cells (LCs). Vaginal LCs isolated from human vaginal tissue expressed a broad range of TLRs and became activated after exposure to both viral and bacterial TLR ligands. HIV-1 replication was restricted in immature vaginal LCs as only low levels of infection could be detected. Notably, activation of immature vaginal LCs by bacterial TLR ligands increased HIV-1 infection, whereas viral TLR ligands were unable to induce HIV-1 replication in vaginal LCs. Furthermore, mature vaginal LCs transmitted HIV-1 to CD4 T cells. This study emphasizes the role for vaginal LCs in protection against mucosal HIV-1 infection, which is abrogated upon activation. Moreover, our data suggest that bacterial STIs can increase the risk of HIV-1 acquisition in women.

How prevalent is spontaneous thrombosis (ST) in intracranial aneurysms (IAs) for an all-size pop- ulation? How can we calibrate computational models of thrombosis based on published data from size-specific aneurysms cohorts? How does ST differ in normo- and hypertensive subjects? We ad- dress the first question by a thorough analysis of published that provide ST rates across different patient demographics and aneurysm characteristics. This analysis provides data for a subgroup of the gen- eral population, viz. large and giant aneurysms (>10 mm). Based on these observed ST rates, our novel computational modelling platform enables the first in-silico observational study of ST prevalence across a broader set of IA phenotypes. We generate 109 virtual patients and use a novel approach to calibrate two trigger thresholds: residence time (RT) and shear rate (SR), thus addressing the second question. We then address the third question by utilising this calibrated thrombosis model to provide new insights on the effects of hypertension on ST. We demonstrate how a mechanistic ST model calibrated on a reduced IA cohort can help esti- mate ST prevalence in a broader IA population. This study was enabled through a comprehensive and fully automatic multi-scale modeling pipeline. We use an emerging property, viz. ST, as an indirect population-level validation of a complex computational modeling framework. Furthermore, our frame- work allows exploration of the influence of hypertension in ST. This lays the foundation for in-silico clinical trials of cerebrovascular devices in high-risk populations, e.g. assessing the performance of flow diverters in cerebral aneurysms for hypertensive patients.

Breast cancer is the most common malignancy in women worldwide. Administration of oncolytic viruses is one of the novel promising cancer therapy approaches. Replication of these viruses is usually limited to cancer cells that have interferon (IFN) signaling defects. However, Interferon signaling is not completely impaired in all cancer cells which may limit the benefits of virotherapy. Identification of realistic IFN-mediated biomarkers to identify patients who most likely respond to virotherapy would be helpful. In this study, eight patients-derived primary tumor cultures were infected with an ICP34.5 deleted oHSV, then the rate of infectivity, cell survival, and expression of the gene involved in IFN pathway were analyzed. Data showed that mRNA expressions of Myeloid differentiation primary response protein (Myd88) is significantly higher in tumors whose primary cultures showed less cell death and resistance to oHSV infectivity (P-value

To describe the characteristics of major injury and identify determinants of long-term unplanned readmission and mortality after self-inflicted and non-self-inflicted injury to inform potential readmission screening. A retrospective cohort study of 11,269 individuals aged ≥ 15 years hospitalised for a major injury during 2013–2017 in New South Wales, Australia. Unplanned readmission and mortality up to 27-month post-injury were examined. Logistic regression was used to examine predictors of unplanned readmission. During the 27-month follow-up, 2700 (24.8%) individuals with non-self-inflicted and 98 (26.1%) with self-inflicted injuries had an unplanned readmission. Individuals with an anxiety-related disorder and a non-self-inflicted injury who were discharged home were three times more likely (OR: 3.27; 95%CI 2.28–4.69) or if they were discharged to a psychiatric facility were four times more likely (OR: 4.11; 95%CI 1.07–15.80) to be readmitted. Compared to individuals aged 15–24 years, individuals aged ≥ 65 years were 3 times more likely to be readmitted (OR 3.12; 95%CI 2.62–3.70). Individuals with one (OR 1.60; 95%CI 1.39–1.84) or ≥ 2 (OR 1.88; 95%CI 1.52–2.32) comorbidities, or who had a drug-related dependence (OR 1.88; 95%CI 1.52–2.31) were more likely to be readmitted. The post-discharge age-adjusted mortality rate following a self-inflicted injury (35.6%; 95%CI 29.9–41.8) was higher than for individuals with a non-self-inflicted injury (11.0%; 95%CI 10.4–11.8). Unplanned readmission after injury is associated with injury intent, age, and comorbid health. Screening for anxiety and drug-related dependence after major injury, accompanied by service referrals and post-discharge follow-up, has potential to prevent readmission.

Objective This study aimed to identify factors associated with 90-day mortality in older patients with a severe head injury. Methods A data linkage study was performed with the New South Wales Trauma Registry, Admitted Patient Data Collection and Registry of Births Deaths and Marriages to identify patients aged ≥75 years with isolated severe head injury presenting to trauma hospitals between 2012 and 2016. The primary outcome was all-cause mortality at 90 days. Results In all, 2045 patients were included in the analysis. The mean (±s.d.) age was 84.5 ± 5.6 years. Falls accounted for 93.7% of this cohort. In-hospital mortality was 28.2% and 90-day mortality was 60.7%. Clinical variables associated with increased 90-day mortality were a Glasgow Coma Scale (GCS) score

Dimethylformamide (DMF) vapor is a toxic compound that has many industrial applications. In this article, a DMF gas sensor was developed using cadmium-doped nickel manganese ferrite/cadmium oxide nanoparticles based on the co-precipitation method. A study of response/recovery characteristics in a temperature range of 50 °C–300 °C revealed that the best operating temperature is 250 °C. At this temperature, a fast response/recovery time and a high response magnitude were achieved. The sensor was highly selective at this temperature for DMF among other toxic gases. The sensor also showed a very low drift of less than 2% in its response magnitude over 15 days.

Diffusion-weighted imaging (DWI) is a well-established MRI sequence for diagnosing early stroke and provides therapeutic implications. However, DWI yields pertinent information in various other brain pathologies and helps establish a specific diagnosis and management of other central nervous system disorders. Some of these conditions can present with acute changes in neurological status and mimic stroke. This review will focus briefly on diffusion imaging techniques, followed by a more comprehensive description of the utility of DWI in common neurological entities beyond stroke.

Aims: Without any doubt, vaccination was the best choice for Coronavirus disease 2019 (COVID-19) pandemic control. According to the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO), people with cancer or a history of cancer have a higher risk of dying from Covid-19 than ordinary people; hence, they should be considered a high-priority group for vaccination. On the other hand, the effect of the Covid-19 vaccination on cancer is not transparent enough. This study is one of the first in vivo studies that try to show the impact of Sinopharm (S) and AstraZeneca (A) vaccines on breast cancer, the most common cancer among women worldwide. Materials and methods: Vaccination was performed with one and two doses of Sinopharm (S1/S2) or AstraZeneca (A1/A2) on the 4T1 triple-negative breast cancer (TNBC) mice model. The tumor size and body weight of mice were monitored every two days. After one month, mice were euthanized, and the existence of Tumor-infiltrating lymphocytes (TILs) and expression of the important markers in the tumor site was assessed. Metastasis in the vital organs was also investigated. Key findings: Strikingly, all of the vaccinated mice showed a decrease in tumor size and this decrease was highest after two vaccinations. Moreover, we observed more TILs in the tumor after vaccination. Vaccinated mice demonstrated a decrease in the expression of tumor markers (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, and metastasis to the vital organs. Significance: Our results strongly suggest that COVID-19 vaccinations decrease tumor growth and metastasis.

Purpura fulminans can result in significant full-thickness wounds, posing a challenge in the pediatric population, given the paucity of donor sites for reconstruction. The authors present the case of an 11-month-old patient for whom a split-thickness skin allograft (TheraSkin) was successfully implemented as a temporizing measure for a large leg wound.

Bacteriophages (BP) are viruses that invade bacteria and propagate inside them, leading to the lysis of the bacterial cells. The aim of this study was to investigate the effect of adding BP to the broiler’s diet and its effect on the performance, morphology and bacterial population of the gut, some immune responses and expression of some intestinal genes. Accordingly, dietary treatments were as follows: basal diet (control), and control + 0.3 g/kg colistin or 0.5, 1 and 1.5 g BP/kg of diet. BP increased the body weight gain and reduced the feed conversion ratio (FCR), as compared to the colistin treatment, in the finisher and overall period (P 0.05). European efficiency factor was significantly higher in 1.5 g BP-fed birds, as compared to the control and colistin treatments. meanwhile, bacteriophage and colistin-fed birds had higherLactobacillusand lowered coliform bacteria counts, as compared to the control treatment (P 0.05). Cecal concentrations of propionate in the 1.5 g BP-fed birds were higher than those in the control treatment (P 0.05). BP-fed birds had a significantly increased villus height to crypt depth ratio, as compared to the control treatment. BP increased the serum concentrations of the total antibody, immunoglobulin (Ig) M, and IgG, as compared to the control treatment (P 0.05). In the ileum, the expression of the Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) gene was decreased by dietary BP supplementation (P 0.05). Furthermore, Toll-like receptor 4 (TLR4) gene expression was down-regulated in the BP-fed birds, whereas Interleukin 10 (IL-10) gene expression was up-regulated (P 0.05). Overall, the use of BP may be a promising alternative to growth-promoting antibiotics in broilers by altering the gastrointestinal tract microbiota, enhancing immunological responses and improving the gut's morphology.

The role of scaffolds in bone regeneration is of great importance. Here, the electrospun scaffolds of poly (3-hydroxybutyrate)-keratin (PHB-K)/nanohydroxyapatite (nHA) with different morphologies (long nanorods (HAR) and very short nanorods (HAP)) and weight percentages (up to 10 w/w%) of nHA were fabricated and characterized. The fibers integrity, the porosity of above 80%, and increase in pore size up to 16 μm were observed by adding nHA. The nanofibers crystallinity increased by 13.5 and 22.8% after the addition of HAR and HAP, respectively. The scaffolds contact angle decreased by almost 20° and 40° after adding 2.5 w/w% HAR and HAP, respectively. The tensile strength of the scaffolds increased from 2.99 ± 0.3 MPa for PHB-K to 6.44 ± 0.16 and 9.27 ± 0.04 MPa for the scaffolds containing 2.5 w/w% HAR and HAP, respectively. After immersing the scaffolds into simulated body fluid (SBF), the Ca concentration decreased by 55% for HAR- and 73% for HAP-containing scaffolds, showing the bioactivity of nHA-containing scaffolds. The results of cell attachment, proliferation, and viability of MG-63 cells cultured on the nanocomposites showed the positive effects of nHA. The results indicate that the nanocomposite scaffolds, especially HAP-containing ones, can be suitable for bone tissue engineering applications.

Idiopathic intracranial hypertension (IIH) represents a clinical disease entity without a clear etiology, that if left untreated, can result in severe outcomes, including permanent vision loss. For this reason, early diagnosis and treatment is necessary. Historically, the role of cross-sectional imaging has been to rule out secondary or emergent causes of increased intracranial pressure, including tumor, infection, hydrocephalus, or venous thrombosis. MRI and MRV, however, can serve as valuable imaging tools to not only rule out causes for secondary intracranial hypertension but can also detect indirect signs of IIH resultant from increased intracranial pressure, and demonstrate potentially treatable sinus venous stenosis. Digital subtraction venographic imaging also plays a central role in both diagnosis and treatment, providing enhanced anatomic delineation and temporal flow evaluation, quantitative assessment of the pressure gradient across a venous stenosis, treatment guidance, and immediate opportunity for endovascular therapy. In this review, we discuss the multiple modalities for imaging IIH, their limitations, and their contributions to the management of IIH.

Background High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. Methods We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. Results No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). Conclusion Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. Trial registration: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947.

Background. Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system, capable of killing viral-infected and cancerous cells. NK cell-mediated immunotherapy has remarkably changed the current paradigm of cancer treatment in recent years. It emerged as a safe and effective therapeutic approach for patients with advanced-stage leukemia. Several immune-escape mechanisms can be enacted by cancer cells to avoid NK-mediated killing. Exosomes released by NK cells that carry proteins and miRNAs can exert an antitumor effect. In the present study, we hypothesized that maybe exosomes derived from trained natural killer cells show more antitumor effect in comparison to non-trained one. Methods. PBMC was separated by the Ficoll method and cultured with IL-2 for 21 days to expand NK cells. The NK cells were co-cultured with K562 for 72 hours and exosome-derived co-cultured (as trained) and natural killer cell-derived exosomes (as non-trained) were extracted by Exo kit. The exosomes were confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM), flow cytometry, and western blotting. The K562 cells were separately treated by trained and non-trained exosomes and MTT assay, apoptosis, and real-time PCR were performed. Results. Based on flow cytometry, CD56 marker was 89.7% and 40.1% for NK cells and NK-derived exosomes, respectively. CD63 and CD9 were positive for exosomes by western blotting. The morphology of exosome was confirmed by TEM. Treated K562 cells by trained exosomes indicated the diminished cell viability and higher apoptosis. Furthermore, the trained exosomes showed up-regulation in both P53 and caspase3 genes as compared with non-trained sample. Discussion. Trained Exos showed a potent inhibitory effect on proliferation and induced apoptosis on K562 cell lines compared to the same dose of non-trained Exos. According to the results of qRT-PCR, trained Exos exerted an antitumor activity through up-regulation of caspase 3 and P53 in the apoptotic signaling pathway in tumor cells. Our findings indicate an effective action of trained Exos against cancer cells.

In this study, static analysis of functionally graded (FG) sandwich plates is performed using the finite strip method based on the refined plate theory (RPT). Two types of common FG sandwich plates are considered. The first sandwich plate is composed of two FG material (FGM) face sheets and a homogeneous ceramic or metal core. The second one consists of two homogeneous fully metal and ceramic face sheets at the top and bottom, respectively, and a FGM core. Differential equations of FG sandwich plates are obtained using Hamilton's principle and stiffness and force matrices are formed using the finite strip method. The central deflection and the normal stress values are obtained for a sinusoidal loaded FG sandwich plate and the accuracy of the results are verified against those obtained from other theories such as the classical plate theory (CPT), the first-order shear deformation theory (FSDT), and the higher order shear deformation theory (HSDT). For the first time, this study presents a finite strip formulation in conjunction with the RPT to analyze FG Sandwich plates. While the proposed method is fast and simple, it is capable of modeling a variety of boundary conditions.

Peripheral nerve injuries of the upper extremity can result from a wide array of etiologies, with the two most common being compression neuropathy and traumatic injuries. These types of injuries are common and can be psychologically, functionally, and financially devastating to the patient. A detailed preoperative evaluation is imperative for appropriate management. Traumatic injuries can typically be treated with local burial techniques, targeted muscle reinnervation, and regenerative peripheral nerve interfaces. Median nerve compression is frequently managed with complete release of the antebrachial fascia/transverse carpal ligament and/or use of flap coverage such as the hypothenar fat pad flap and local muscle flaps. Ulnar nerve compression is commonly managed via submuscular transposition, subcutaneous transposition, neurolysis, and nerve wrapping. In this review, we discuss the preoperative evaluation, surgical techniques, and advantages and disadvantages of each treatment modality for patients with compressive and traumatic upper extremity nerve injuries.

Scars pose a complex challenge to the reconstructive surgeon in the variability of their presentation and their effect on cosmesis and function. Numerous surgical and nonsurgical options exist for scar management, each with their respective advantages and disadvantages. Each treatment modality should be tailored to the patient to ensure enhanced outcomes. In this review, we discuss different scar presentations, scar management options, and the benefits and risks with undergoing these various treatment modalities.

This paper is focused on the application of a novel reproducing kernel particle finite strip method (RKP-FSM) for the static, mechanical and thermal buckling, and free vibration analyses of rectangular functionally graded (FG) plates with different boundary conditions and internal supports. Conventional reproducing kernel particle method (RKPM) is incorporated into the finite strip method (FSM), and the governing equations are derived based on the first-order shear deformation theory (FSDT). As a convenient approach, boundary conditions are imposed using a simple method based on the RKPM correction function and the essence of the FSDT displacement field. Several examples are studied using this method, and the results are compared to those obtained from other numerical methods. The proposed method is also extended to consider different support geometries and complex inner conditions, and the results are validated using COMSOL finite element software. The shear-locking error, which occurs when considering C0 plate theories, is noticeably reduced by considering the RKPM parameters in the finite strip formulation.

Currently only two alloplastic temporomandibular joint (TMJ) total joint replacement (TJR) systems are available in the United States. The aim of this study was to define variables that determine whether a Biomet stock prosthesis could have been used to reconstruct a TMJ previously reconstructed with a TMJ Concepts patient-fitted prosthesis. All of the TMJ Concepts prostheses placed between 2010 and 2018 at the University of Texas - Health at San Antonio were analyzed retrospectively. There were 128 cases (241 joints) with intact stereolithographic models analyzed for successful adaptation of the Biomet stock TMJ prosthesis. Anatomical, demographic, etiological, and perioperative data were gathered for each joint to investigate possible causes of failure of stock adaptation. The majority of joints, 74% (178/241), could have had a stock prosthesis adapt. All joints with ≥40mm gap arthroplasty failed stock prosthesis adaptation. Only 50% (32/64) of the joints with at least one previous open TMJ surgery and 60% (58/96) of the joints with concomitant orthognathic surgery could have had a stock TMJ prosthesis. The stock prosthesis could not be adapted for any of the patients requiring TMJ replacement for congenital disorders or those requiring TMJ salvage. Overall, the majority of cases treated with a patient-specific TMJ TJR could have been treated with a stock prosthesis.

Transport incidents are among the major causes of trauma and injury in Australia and worldwide. While improving infrastructure can decrease the rate of incidents, the required construction imposes challenges regarding simultaneous public use of the relevant road sections. This study focused on construction zones along the New South Wales (NSW) Pacific Highway. We aimed to investigate if the rate of people who had major trauma as a result of a transport incident in a construction zone was higher than the rate of people with similar incidents at other times. This was a retrospective study, conducted by screening the data of patients admitted to the trauma services, or who died due to traffic incidents on the NSW Pacific Highway 2011-2016. We identified 35 causalities who experienced a traffic incident within a construction zone, 19 of these incidents occurred during the construction dates and 16 before or after those dates. The rate of casualty in construction periods was 2.21 per 1000 days, which is significantly higher than the rate in non-construction periods (1.2 per 1000 days, p-value: 0.037). There was no significant difference between the age, injury severity score and mortality rate of casualties who had an incident during the construction dates and those who had an incident in non-construction periods. This study indicated that the rate of incidents increased at NSW Pacific Highway construction zones during construction periods. More investigation is needed to improve the safety of road users during highway road constructions.

To investigate the impact of a road safety programme on adolescents' willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest.The2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (-2.99, 95% CI -3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors.Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.

Objectiveinvestigate the impact of a road-safety program on adolescent willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest.Methodbstreetsmart is a road-safety program delivered to around 25,000 adolescent students annually in New South Wales. Using a smart phone-based app, student and teacher participation incentives, students were surveyed before and after program attendance. Mixed methods linear regression analysed pre-post modified Behaviour of Young Novice Driver (BYNDS_M) scores.Results2360 and 1260 students completed pre- and post-event surveys respectively. Post-event BYNDS_M scores were around 3 points lower than pre-event scores (−2.99, 95%CI - 3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622-2.011), identifying as non-binary gender (20.8, 95% CI 8.795 to 40.852), adjusting for other predictors.ConclusionsTrauma-informed, reality-based injury prevention programs are effective in changing short term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multi-pronged to address the many factors influencing their behaviour.What is already known on this topicRoad traffic injuries are the leading cause of death for adolescents in most developed countries globally. Injury prevention action must be multi-pronged to address the many factors influencing their behaviourWhat this study addsThe bstreetsmart injury prevention intervention which incorporates trauma informed, CBT influence and reality-based road safety information to around 25,000 students annually, showed significant short-term impact on the stated willingness of the study population to engage in risky driving behaviour when obtaining their probationary licence. Adolescents are strongly influenced by examples of risky road behaviours among their closest adult drivers.How this study might affect research, practice, or policyInterventions such as bstreetsmart hold a positive place in the multi-pronged approach needed to address the difficult issue of novice drivers.

In this paper, a coupling of improved element-free Galerkin with the finite strip (IEFG-FS) is used to investigate the buckling analysis of cold-formed steel (CFS) channel-section beam with web holes. For this purpose, three sections of the CFS channel are considered under bending loading. These sections are divided into two sub-domains in which the IEFG method is used in sub-domain with openings, and the finite strip (FS) method is applied for another sub-domain. In the IEFG domain, the boundary conditions are enforced using the Lagrange multiplier method. In the following, hole size effects are investigated on the moment buckling load of sections. The results show that the IEFG-FS is an efficient method for buckling analysis of channel-section beams. Moreover, the presence of holes in CFS channel section reduces the moment buckling load, so that the decrease in the local buckling is more than the distortional and global buckling loads.

This paper presents the static and mechanical buckling analyses of thick functionally graded (FG) plates. For this purpose, Carrera’s unified formulation (CUF) and the principle of virtual displace...

Mechanical and thermal buckling of corrugated-core sandwich plates is investigated in this study. To consider the effect of shear deformations, the first-order shear deformation theory is applied to the finite strip method. The validity of the proposed method is evaluated by comparing the results with those presented by previous research. Various boundary conditions and different loading types, as well as the geometric parameters affecting the buckling loads and critical temperatures are explored and evaluated. To the authors' best knowledge, investigation of the effective geometric parameters, convergence process and different boundary conditions are discussed for the first time using finite strip method.

The objective of the present study was the fabrication of a wound dressing membrane based on RGD modified polybutylene adipate-co-terephthalate (PBAT)/gelatin nanofibrous structures loaded with dox...

This study investigates the effect of hydronium ions (H3O+) on the structure and dynamics of water at the interface of a phospholipid bilayer using molecular dynamics simulations of a POPC bilayer in the presence and absence of H3O+ ions. From these simulations, the survival probability, hydrogen bond lifetimes, orientation relaxation, and angular distribution of interfacial water, at increasing distances from the membrane surface, were calculated. Simulations of POPC in the absence of H3O+ ions reproduce previously reported deviations of interfacial water from the properties of bulk water. Our results show that in the presence of H3O+, these deviations are even more pronounced with the strongest effects seen in the survival probability and orientation relaxation. To further investigate the effect of the H3O+-induced reduction of area per lipid on interfacial water, we carried out simulations where H3O+ ions were removed, but the area per lipid was fixed to the values seen in the presence of H3O+. The combined findings from our study suggest that the presence of H3O+ ions affects the properties of interfacial water, accentuates the deviation from bulk properties, and extends the long-range effect of these deviations further away from the membrane surface.

The use of cricoid pressure (CP) to prevent aspiration during rapid sequence induction (RSI) has become controversial, although CP is considered central to the practice of RSI. There is insufficient research to support its efficacy in reducing aspiration, and emerging concerns it reduces the first-pass success (FPS) of intubation. This systematic review aims to assess the safety and efficacy of CP during RSI in EDs by investigating its effect on FPS and the incidence of complications, including gastric regurgitation and aspiration. A systematic review of four databases was performed for all primary research investigating CP during RSI in EDs. The primary outcome was FPS; secondary outcomes included complications such as gastric regurgitation, aspiration, hypoxia, hypotension and oesophageal intubation. After screening 4208 citations, three studies were included: one randomised controlled trial (n = 54) investigating the incidence of aspiration during the application of CP and two registry studies (n = 3710) comparing the rate of FPS of RSI with and without CP. The results of these individual studies are not sufficient to draw concrete conclusions but do suggest that aspiration occurs regardless of the application of CP, and that FPS is not reduced by the application of CP. There is insufficient evidence to conclude whether applying CP during RSI in EDs affects the rate of FPS or the incidence of complications such as aspiration. Further research in the ED, including introducing CP usage into other existing airway registries, is needed.

In the case of the COVID-19 early diagnosis, numerous tech innovations have been introduced, and many are currently employed worldwide. But, all of the medical procedures for the treatment of this disease, up to now, are just limited to chemical drugs. All of the scientists believe that the major challenge toward the mortality of the COVID-19 patients is the out-of-control immune system activation and the subsequent cytokine production. During this process, the adaptive immune system is highly activated, and many of the lymphocytes start to clonally expand; hence many cytokines are also released. So, any attempt to harness this cytokine storm and calm down the immune outrage is appreciated. While the battleground for the immune hyperactivation is the lung ambient of the infected patients, the only medical treatment for suppressing the hypercytokinemia is based on the immunosuppressor drugs that systemically dampen the immunity with many unavoidable side effects. Here, we applied the alternating electric field to suppress the expansion of the highly activated lymphocytes, and by reducing the number of the renewed cells, the produced cytokines were also decreased. Applying this method to the blood of the COVID-19 patients in vitro showed ∼33% reduction in the average concentration of the three main cytokines after 4 days of stimulation. This method could carefully be utilized to locally suppress the hyperactivated immune cells in the lung of the COVID-19 patients without any need for systemic suppression of the immune system by the chemical drugs.

Additional file 1: Table S1. Vital signs of 20 enrolled patients with COVID-19 beforeintervention (0) and 1 day after intervention (+1).