Stopping the bleed when tourniquets cannot: a technique for Foley catheter balloon compression in trauma.

INTRODUCTION: Hemorrhage is a leading cause of death in trauma. Prehospital hemorrhage control techniques include tourniquet application for extremity wounds and direct compression; however, tourniquets are not effective in anatomic junctions, and direct compression is highly operator dependent. Balloon catheter compression has been employed previously in trauma care, but its use has been confined to the operating room and restricted to specific anatomic injuries. METHODS: In a single-center retrospective review, we describe a technique for balloon catheter compression for hemorrhage control that can be employed across the continuum of trauma care, from the prehospital setting to the trauma bay, the operating room, and postoperative period. RESULTS: Of 18,303 trauma patients in Venezuela, 45% of the 1757 patients with vascular injuries received Foley catheter compression for hemorrhage control. Of these catheters, the majority (75%) were placed in the emergency department, 5% in the prehospital setting, and 20% in the operating room. Over half (53.2%) of the balloon catheters were placed for hemorrhage control in non-compressible anatomic junctions. CONCLUSIONS: Foley catheter balloon compression is a useful addition to a provider's arsenal of hemorrhage control techniques, as it is effective in anatomic junctions, preserves collateral circulation through focused compression, and requires minimal active physical attention to maintain hemostasis.

Regulatory framework for genetically modified organisms in the Kingdom of Eswatini.

The Kingdom of Eswatini is a Party to the Convention on Biological Diversity and to the Cartagena Protocol on Biosafety. As Party, Eswatini has domesticated these agreements by passing the Biosafety Act, of 2012 to provide for the safe handling, transfer, and use of living modified organisms (LMOs) in the country. The Act regulates living modified organisms to be used for confined field trials, commercial release, import, export, and transit, and for food, feed, and processing. Guidance is provided for prospective applicants before any application is made to the Competent Authority. This framework also provides for the regulation of emerging technologies such as synthetic biology and genome editing. The regulatory framework for living modified organisms aims to provide an enabling environment for the precautionary use of modern biotechnology and its products in the country in order to safeguard biological diversity and human health.

Design and Synthesis of Polyphenolic Imidazo[4,5-c]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity.

TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure-function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation. In this work, we sought to address this issue through structural modifications in the agonists to enhance their adsorption capacity to the classic adjuvant alum. We selected a potent TLR7-selective agonist, BBIQ (EC50 = 0.85 µM), and synthesized polyphenolic derivatives to assess their TLR7 agonistic activity and adjuvant potential alone or in combination with alum. Most of the phenolic derivatives were more active than BBIQ and, except for 12b, all were TLR7 specific. Although the synthesized compounds were less active than resiquimod, the immunization data on combination with alum, specifically the IgG1, IgG2b and IgG2c responses, were superior in comparison to BBIQ as well as the reference standard resiquimod. Compound 12b was 5-fold more potent (EC50 = 0.15 µM in TLR7) than BBIQ and induced double the IgG response to SARS-CoV-2 and hepatitis antigens. Similarly, compound 12c (EC50 = 0.31 µM in TLR7) was about 3-fold more potent than BBIQ and doubled the IgG levels. Even though compound 12d exhibited low TLR7 activity (EC50 = 5.13 µM in TLR7), it demonstrated superior adjuvant results, which may be attributed to its enhanced alum adsorption capability as compared with BBIQ and resiquimod. Alum-adsorbed polyphenolic TLR7 agonists thereby represent promising combination adjuvants resulting in a balanced Th1/Th2 immune response.

Surgical capacity is disaster preparedness: A scoping review of how surgery and anesthesiology departments responded to COVID-19.

OBJECTIVE: This study evaluated how surgical and anesthesiology departments adapted their resources in response to the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: This scoping review used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol, with Covidence as a screening tool. An initial search of PubMed, Embase, Web of Science, Global Index Medicus, and Cochrane Systematic Reviews returned 6,131 results in October 2021. After exclusion of duplicates and abstract screening, 415 articles were included. After full-text screening, 108 articles remained. RESULTS: Most commonly, studies were retrospective in nature (47.22 percent), with data from a single institution (60.19 percent). Nearly all studies occurred in high-income countries (HICs), 78.70 percent, with no articles from low-income countries. The reported responses to the COVID-19 pandemic involving surgical departments were grouped into seven categories, with multiple responses reported in some articles for a total of 192 responses. The most frequently reported responses were changes to surgical department staffing (29.17 percent) and task-shifting or task-sharing of personnel (25.52 percent). CONCLUSION: Our review reflects the mechanisms by which hospital surgical systems responded to the initial stress of the COVID-19 pandemic and reinforced the many changes to hospital policy that occurred in the pandemic. Healthcare systems with robust surgical systems were better able to cope with the initial stress of the COVID-19 pandemic. The well-resourced health systems of HICs reported rapid and dynamic changes by providers to assist in and ultimately improve the care of patients during the pandemic. Surgical system strengthening will allow health systems to be more resilient and prepared for the next disaster.

Amyloid precursor protein induces reactive astrogliosis.

AIM: Astrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis. METHODS: We investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors. RESULTS: Overexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI. CONCLUSIONS: The APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.

Beyond the Ivory Tower: Perception of academic global surgery by surgeons in low- and middle-income countries.

Interest in global surgery has surged amongst academics and practitioners in high-income countries (HICs), but it is unclear how frontline surgical practitioners in low-resource environments perceive the new field or its benefit. Our objective was to assess perceptions of academic global surgery amongst surgeons in low- and middle-income countries (LMICs). We conducted a cross-sectional e-survey among surgical trainees and consultants in 62 LMICs, as defined by the World Bank in 2020. This paper is a sub-analysis highlighting the perception of academic surgery and the association between practice setting and responses using Pearson's Chi-square test. Analyses were completed using Stata15. The survey received 416 responses, including 173 consultants (41.6%), 221 residents (53.1%), 8 medical graduates (1.9%), and 14 fellows (3.4%). Of these, 72 responses (17.3%) were from low-income countries, 137 (32.9%) from lower-middle-income countries, and 207 (49.8%) from upper-middle-income countries. 286 respondents (68.8%) practiced in urban areas, 34 (8.2%) in rural areas, and 84 (20.2%) in both rural and urban areas. Only 185 (44.58%) were familiar with the term "global surgery." However, 326 (79.3%) agreed that collaborating with HIC surgeons for research is beneficial to being a global surgeon, 323 (78.8%) agreed that having an HIC co-author improves likelihood of publication in a reputable journal, 337 (81.6%) agreed that securing research funding is difficult in their country, 195 (47.3%) agreed that their institutions consider research for promotion, 252 (61.0%) agreed that they can combine research and clinical practice, and 336 (82%) are willing to train HIC medical students and residents. A majority of these LMIC surgeons noted limited academic incentives to perform research in the field. The academic global surgery community should take note and foster equitable collaborations to ensure that this critical segment of stakeholders is engaged and has fewer barriers to participation.

Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

ABSTRACT: Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.

Efficacy of Purpureocillium lilacinum AUMC 10149 as biocontrol agent against root-knot nematode Meloidogyne incognita infecting tomato plant / Eficácia de Purpureocillium lilacinum AUMC 10149 como agente de biocontrole contra o nematoide Meloidogyne incógnita que infecta plantas de tomate

Abstract Root-knot nematode Meloidogyne incognita is among the biotic factors which has greatly affected both the yield and the quality of the tomato crop. The egg parasitic nematode, Purpureocillium lilacinum (Pl) is considered as one of the most promising agents in controlling and overcoming this plant pathogen. The nematicidal effect of the native isolate Pl AUMC 10149 on second stage juvenile's survival and egg hatching of M. incognita at different times of exposure was tested in vitro. The obtained data showed that Pl gave a maximum percentage of J2 mortality (97.6%) and egg hatching inhibition (79.8%) after 72 hours of exposure. The potentiality of Pl as well as Bio-Nematon to control M. incognita infecting tomato was conducted using different times of application in vivo. Nine treatments with five replicates were used for such bioagents compared with the nematicide Oxamyl. Each seedling was inoculated with 1000 J2s of nematode/pot and 10 mL of Pl (1x1010 CFU/mL) or Bio-Nematon spore suspension (1x108 CFU/mL) 10mL/pot. The results indicated that the most effective treatments in reducing nematode population, number of galls and egg masses of M. incognita in plant roots was performed with treatment by Pl pre-planting and post-infection with Pl (Rf 1.9) giving a significant enhancement in plant length (64.9%), fresh weight (72.52%) and shoot dry weight (163.41%) without negatively impacting environment. Therefore, the present study confirmed that using P. lilacinum AUMC 10149 can be used as a practical supplement to environmentally friendly disease management of root-knot nematodes in Egypt.

Resumo O nematoide-das-galhas Meloidogyne incognita está entre os fatores bióticos que afetaram enormemente a produção e a qualidade da cultura do tomate. O nematoide parasita de ovos, Purpureocillium lilacinum (Pl), é considerado um dos mais promissores agentes no controle e superação desse fitopatógeno. O efeito nematicida do isolado nativo Pl AUMC 10149 na sobrevivência de juvenis de segundo estágio e na eclosão dos ovos de M. incognita em diferentes momentos de exposição foi testado in vitro. Os dados obtidos mostraram que o Pl deu um percentual máximo de mortalidade de J2 (97.6%) e inibição da eclosão dos ovos (79.8%) após 72 horas de exposição. A potencialidade de Pl e de Bio-Nematon para controlar M. incognita infectando tomate foi conduzida em diferentes tempos de aplicação in vivo. Nove tratamentos com cinco repetições foram usados ​​para tais bioagentes em comparação com o nematicida Oxamyl. Cada muda foi inoculada com 1.000 J2s de nematoide / vaso e 10 mL de Pl (1×1010 CFU/mL). Ou suspensão de esporos Bio-Nematon (1×108 CFU/mL) 10mL/pot. Os resultados indicaram que os tratamentos mais eficazes na redução da população de nematoides, número de galhas e desovas de M. incognita nas raízes das plantas foram realizados com Pl pré-plantio e pós-infecção com Pl (Rf 1.9), dando um aumento significativo no comprimento da planta (64.9%), massa fresca (72.52%) e massa seca da parte aérea (163.41%) sem impactar negativamente o meio ambiente. Portanto, o presente estudo confirmou que o uso de P. lilacinum AUMC 10149 pode ser usado como um suplemento prático para o manejo ecologicamente correto de nematoides-das-galhas no Egito.

Efficacy of Purpureocillium lilacinum AUMC 10149 as biocontrol agent against root-knot nematode Meloidogyne incognita infecting tomato plant

Abstract Root-knot nematode Meloidogyne incognita is among the biotic factors which has greatly affected both the yield and the quality of the tomato crop. The egg parasitic nematode, Purpureocillium lilacinum (Pl) is considered as one of the most promising agents in controlling and overcoming this plant pathogen. The nematicidal effect of the native isolate Pl AUMC 10149 on second stage juveniles survival and egg hatching of M. incognita at different times of exposure was tested in vitro. The obtained data showed that Pl gave a maximum percentage of J2 mortality (97.6%) and egg hatching inhibition (79.8%) after 72 hours of exposure. The potentiality of Pl as well as Bio-Nematon to control M. incognita infecting tomato was conducted using different times of application in vivo. Nine treatments with five replicates were used for such bioagents compared with the nematicide Oxamyl. Each seedling was inoculated with 1000 J2s of nematode/pot and 10 mL of Pl (1x1010 CFU/mL) or Bio-Nematon spore suspension (1x108 CFU/mL) 10mL/pot. The results indicated that the most effective treatments in reducing nematode population, number of galls and egg masses of M. incognita in plant roots was performed with treatment by Pl pre-planting and post-infection with Pl (Rf 1.9) giving a significant enhancement in plant length (64.9%), fresh weight (72.52%) and shoot dry weight (163.41%) without negatively impacting environment. Therefore, the present study confirmed that using P. lilacinum AUMC 10149 can be used as a practical supplement to environmentally friendly disease management of root-knot nematodes in Egypt.

Resumo O nematoide-das-galhas Meloidogyne incognita está entre os fatores bióticos que afetaram enormemente a produção e a qualidade da cultura do tomate. O nematoide parasita de ovos, Purpureocillium lilacinum (Pl), é considerado um dos mais promissores agentes no controle e superação desse fitopatógeno. O efeito nematicida do isolado nativo Pl AUMC 10149 na sobrevivência de juvenis de segundo estágio e na eclosão dos ovos de M. incognita em diferentes momentos de exposição foi testado in vitro. Os dados obtidos mostraram que o Pl deu um percentual máximo de mortalidade de J2 (97.6%) e inibição da eclosão dos ovos (79.8%) após 72 horas de exposição. A potencialidade de Pl e de Bio-Nematon para controlar M. incognita infectando tomate foi conduzida em diferentes tempos de aplicação in vivo. Nove tratamentos com cinco repetições foram usados para tais bioagentes em comparação com o nematicida Oxamyl. Cada muda foi inoculada com 1.000 J2s de nematoide / vaso e 10 mL de Pl (1×1010 CFU/mL). Ou suspensão de esporos Bio-Nematon (1×108 CFU/mL) 10mL/pot. Os resultados indicaram que os tratamentos mais eficazes na redução da população de nematoides, número de galhas e desovas de M. incognita nas raízes das plantas foram realizados com Pl pré-plantio e pós-infecção com Pl (Rf 1.9), dando um aumento significativo no comprimento da planta (64.9%), massa fresca (72.52%) e massa seca da parte aérea (163.41%) sem impactar negativamente o meio ambiente. Portanto, o presente estudo confirmou que o uso de P. lilacinum AUMC 10149 pode ser usado como um suplemento prático para o manejo ecologicamente correto de nematoides-das-galhas no Egito.

Exploring the Pathophysiology of Delirium: An Overview of Biomarker Studies, Animal Models, and Tissue-Engineered Models.

Delirium is an acute brain disorder associated with disorganized thinking, difficulty focusing, and confusion that commonly follows major surgery, severe infection, and illness. Older patients are at high risk for developing delirium during hospitalization, which may contribute to increased morbidity, longer hospitalization, and increased risk of institutionalization following discharge. The pathophysiology underlying delirium remains poorly studied. This review delves into the findings from biomarker studies and animal models, and highlights the potential for tissue-engineered models of the brain in studying this condition. The aim is to bring together the existing knowledge in the field and provide insight into the future direction of delirium research.

Cardiac Resynchronisation with Conduction System Pacing.

To date, biventricular pacing (BiVP) has been the standard pacing modality for cardiac resynchronisation therapy. However, it is non-physiological, with the activation spreading between the left ventricular epicardium and right ventricular endocardium. Up to one-third of patients with heart failure who are eligible for cardiac resynchronisation therapy do not derive benefit from BiVP. Conduction system pacing (CSP), which includes His bundle pacing and left bundle branch area pacing, has emerged as an alternative to BiVP for cardiac resynchronisation. There is mounting evidence supporting the benefits of CSP in achieving synchronous ventricular activation and repolarisation. The aim of this review is to summarise the current options and outcomes of CSP when used for cardiac resynchronisation in patients with heart failure.

Developmental and reproductive safety of Advax-CpG55.2™ adjuvanted COVID-19 and influenza vaccines in mice.

SpikoGen® is a recombinant spike protein vaccine against COVID-19 that obtained marketing authorization in the Middle East on October 6th, 2021, becoming the first adjuvanted protein-based COVID-19 vaccine of its type to achieve approval. SpikoGen® vaccine utilizes a unique adjuvant Advax-CpG55.2, which comprises delta inulin and CpG55.2 oligonucleotide, a synthetic human toll-like receptor (TLR)-9 agonist. As part of a safety assessment, developmental and reproductive toxicity (DART) studies were undertaken in mice of Advax-CpG55.2 adjuvanted formulations including SpikoGen®, a H7 hemagglutinin influenza vaccine (rH7HA), the bivalent combination of SpikoGen® and rH7HA, and a next-generation quadrivalent spike protein vaccine. In the first study, vaccines were administered intramuscularly to pregnant dams on gestation days (GD) 6.5 and 12.5, and in the second two doses were given in the pre-mating period with a further two doses during gestation. The doses used in the pregnant mice were 250-1000 times the usual human doses on a weight for weight basis. Strong serum antibody responses with neutralizing activity against the relevant virus were seen in the immunized dams and also at the time of weaning in the sera of their pups, consistent with robust maternal antibody transfer. No adverse effects of any of the vaccine formulations were observed in the immunized dams or their pups. Notably, there were no adverse effects of any of the Advax-CpG55.2 adjuvanted vaccines on female mating performance, fertility, ovarian or uterine parameters, embryo-fetal or postnatal survival, fetal growth, or neurofunctional development. No evidence of antigen interference was observed when SpikoGen® vaccine was mixed and co-administered with influenza hemagglutinin vaccine to pregnant dams. Together with the strong safety profile of SpikoGen® vaccine seen in adults and children in human trials, this DART study data supports the safety of Advax-CpG55.2 adjuvanted COVID-19 and influenza vaccine in women of childbearing potential including during pregnancy.

An Advax-CpG55.2 adjuvanted recombinant hemagglutinin vaccine provides immunity against H7N9 influenza in adult and neonatal mice.

There is a major unmet need for strategies to improve the immunogenicity and effectiveness of pandemic influenza vaccines, particularly in poor responder populations such as neonates. Recombinant protein approaches to pandemic influenza offer advantages over more traditional inactivated virus approaches, as they are free of problems such as egg adaptation or need for high level biosecurity containment for manufacture. However, a weakness of recombinant proteins is their low immunogenicity. We asked whether the use of an inulin polysaccharide adjuvant (Advax) alone or combined with a TLR9 agonist (CpG55.2) would enhance the immunogenicity and protection of a recombinant hemagglutinin vaccine against H7N9 influenza (rH7HA), including in neonatal mice. Advax adjuvant induced predominantly IgG1 responses against H7HA, whereas Advax-CpG55.2 adjuvant also induced IgG2a, IgG2b and IgG3 responses, consistent with the TLR9 agonist component inducing a Th1 bias. Advax-CpG55.2 adjuvanted rH7HA induced high serum neutralizing antibody titers in adult mice. In newborns it similarly overcame immune hypo-responsiveness and enhanced serum anti-rH7HA IgG levels in 7-day-old BALB/C and C57BL/6 mice. Immunized adult mice were protected against a lethal H7N9 virus challenge. When formulated with Advax-CpG55.2 adjuvant, greater protection was seen with rH7HA than with inactivated H7 whole virus antigen. Advax-CpG55.2 adjuvanted rH7HA represents a promising influenza vaccine platform for further development.

A systematic review and meta-analysis of pathogen reduction in onsite sanitation systems.

The safe management of fecal sludge from the 3.4 billion people worldwide that use onsite sanitation systems can greatly reduce the global infectious disease burden. However, there is limited knowledge about the role of design, operational, and environmental factors on pathogen survival in pit latrines, urine diverting desiccation toilets, and other types of onsite toilets. We conducted a systematic literature review and meta-analysis to characterize pathogen reduction rates in fecal sludge, feces, and human excreta with respect to pH, temperature, moisture content, and the use of additives for desiccation, alkalinization, or disinfection. A meta-analysis of 1,382 data points extracted from 243 experiments described in 26 articles revealed significant differences between the decay rates and T99 values of pathogens and indicators from different microbial groups. The overall median T99 values were 4.8 days, 29 days, >341 days, and 429 days for bacteria, viruses, protozoan (oo)cysts, and Ascaris eggs, respectively. As expected, higher pH values, higher temperatures, and the application of lime all significantly predicted greater pathogen reduction rates but the use of lime by itself was more effective for bacteria and viruses than for Ascaris eggs, unless urea was also added. In multiple lab-scale experiments, the application of urea with enough lime or ash to reach a pH of 10 - 12 and a sustained concentration of 2,000 - 6,000 mg/L of non-protonated NH3-N reduced Ascaris eggs more rapidly than without urea. In general, the storage of fecal sludge for 6 months adequately controls hazards from viruses and bacteria, but much longer storage times or alkaline treatment with urea and low moisture or heat is needed to control hazards from protozoa and helminths. More research is needed to demonstrate the efficacy of lime, ash, and urea in the field. More studies of protozoan pathogens are also needed, as very few qualifying experiments were found for this group.

Association Between Intravenous to Oral Opioid Transition Time and Length of Hospital Stay After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

BACKGROUND: Transitioning from intravenous (IV) to oral opioids after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is necessary during the postoperative course. However, few studies have assessed the effects of longer transition times on hospital length of stay (LOS). This study investigated the impact of longer IV to oral opioid transition times on LOS after PSF for AIS. METHODS: The medical records of 129 adolescents (10-18 years old) with AIS undergoing multilevel PSF at a major academic institution from 2013 to 2020 were reviewed. Patients were categorized by IV to oral opioid transition time: normal (≤2 days) vs prolonged (≥3 days). Patient demographics, comorbidities, deformity characteristics, intraoperative variables, postoperative complications, and LOS were assessed. Multivariate analyses were used to determine odds ratios for risk-adjusted extended LOS. RESULTS: Of the 129 study patients, 29.5% (n = 38) had prolonged IV to oral transitions. Demographics and comorbidities were similar between the cohorts. The major curve degree (P = 0.762) and median (interquartile range) levels fused (P = 0.447) were similar between cohorts, but procedure time was significantly longer in the prolonged cohort (normal: 6.6 ± 1.2 hours vs prolonged: 7.2 ± 1.3 hours, P = 0.009). Postoperative complication rates were similar between the cohorts. Patients with prolonged transitions had significantly longer LOS (normal: 4.6 ± 1.3 days vs prolonged: 5.1 ± 0.8 days, P < 0.001) but similar discharge disposition (P = 0.722) and 30-day readmission rates (P > 0.99). On univariate analysis, transition time was significantly associated with extended LOS (OR: 2.0, 95% CI [0.9, 4.6], P = 0.014), but this assocation was not significant on multivariate analysis (adjusted OR: 2.1, 95% CI [1.3, 4.8], P = 0.062). CONCLUSIONS: Longer postoperative IV to oral opioid transitions after PSF for AIS may have implications for hospital LOS.

2D-Self-Assembled Organic Materials in Undoped Hole Transport Bilayers for Efficient Inverted Perovskite Solar Cells.

Interfaces between photoactive perovskite layer and selective contacts play a key role in the performance of perovskite solar cells (PSCs). The properties of the interface can be modified by the introduction of molecular interlayers between the halide perovskite and the transporting layers. Herein, two novel structurally related molecules, 1,3,5-tris(α-carbolin-6-yl)benzene (TACB) and the hexamethylated derivative of truxenotris(7-azaindole) (TTAI), are reported. Both molecules have the ability to self-assemble through reciprocal hydrogen bond interactions, but they have different degrees of conformational freedom. The benefits of combining these tripodal 2D-self-assembled small molecular materials with well-known hole transporting layers (HTLs), such as PEDOT:PSS and PTAA, in PSCs with inverted configuration are described. The use of these molecules, particularly the more rigid TTAI, enhanced the charge extraction efficiency and reduced the charge recombination. Consequently, an improved photovoltaic performance was achieved in comparison to the devices fabricated with the standard HTLs.

Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation.

Introduction: Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity. Cohorts: To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses - in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other. Results: We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation - in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03. Discussion: Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.

Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus.

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

Second Primary Malignancies of the Bones and Joints: More Common than Expected in Osteosarcoma Patients.

BACKGROUND: Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults. Second primary malignancies (SPMs) are a potential serious long-term event that can occur in osteosarcoma survivors. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database was queried for all osteosarcoma cases from 2000 through 2015. Standardized incidence ratio (SIR) and absolute excess risk (AER) of SPM per 10,000 persons (AER) relative to representative population-level data were calculated across for various anatomic locations. RESULTS: In total, 3438 patients with osteosarcoma were identified. Of these patients, 79 (2.3%) developed SPMs, with an SIR of 2.84 (95% confidence interval [CI] 2.35 to 3.39, P < 0.0001) and an AER of 44.96. The most common SPMs were tumors of the bones or joints (SIR 73.07, CI, 38.90 to 124.94, P < 0.0001, AER 7.48), tumors of soft tissues including the heart (SIR 15.19, CI, 5.58 to 33.07, P < 0.0001, AER 3.27), and leukemia (SIR 22.28, CI, 15.03 to 31.80, P < 0.0001, AER 16.74). CONCLUSION: The overall incidence of SPMs in osteosarcoma survivors was significantly higher than would otherwise be expected for this population. Considering the occurrence and targeting surveillance for SPM in the osteosarcoma patient population is warranted.