Effects of Tween 20 addition on electrokinetic transport in a polydimethylsiloxane microchannel.

Tween 20 is frequently added to particle suspensions for reducing the particle-wall adhesion and particle-particle aggregation in microfluidic devices. However, the influences of Tween 20 on the fluid and particle behaviors have been largely ignored. We present in this work the first experimental study of the effects of Tween 20 addition on the electrokinetic transport of fluids and particles in a polydimethylsiloxane microchannel. We find that adding 0.1% v/v Tween 20 to a buffer solution can significantly reduce the electroosmotic mobility as well as the electrokinetic and electrophoretic mobilities of polystyrene particles and yeast cells. Further increasing the Tween 20 concentration within the range typically used in microfluidic applications continues reducing these mobility values, but at a smaller rate. Our finding suggests that Tween 20 should be used with care in electrokinetic microdevices when the flow rate or particle/cell throughput is an important parameter.

Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology.

We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro, these agonists significantly induced secretion of cytokines IL-6, IL-1ß, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure-activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed.

Global Neurosurgery at the 76th World Health Assembly (2023): First Neurosurgery-Driven Resolution Calls for Micronutrient Fortification to Prevent Spina Bifida.

Since 2018, a neurosurgery delegation has been actively engaged and consistently present at the World Health Assembly. Recognizing the growing impact of neurosurgical diseases, the neurosurgery delegation participated in the 76th World Health Assembly in May 2023, advocating for timely, safe, and affordable global neurosurgical care. The delegation focused on forging new collaborations, strengthening the World Health Organization-World Federation of Neurosurgical Societies official relations, and actively supporting resolutions that impact the neurosurgical patients. However, there is a long advocacy journey ahead to address unmet neurosurgical needs. Patient-centered advocacy is an inherent task of our profession and the essence of the Global Neurosurgery Bogota Declaration of 2016. The highlight of the 76th World Health Assembly was the adoption of the first neurosurgery-driven resolution calling for micronutrient fortification to prevent spina bifida and other micronutrient deficiencies. For the last 4 years, the Global Alliance for Prevention of Spina Bifida, a group spearheaded by neurosurgeons, advocated for spina bifida prevention. This Alliance collaborated with many stakeholders, notably, the Colombian government to promote the resolution: "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." This is a proud milestone for the neurosurgical profession. There are many strategies available for neurosurgeons, when working together with elected leaders, other stakeholders, and allied professionals, to implement initiatives that can prevent future cases of spina bifida and other neurological disorders and reduce the burden of neurosurgical disease.

Neuroethics guidance documents: principles, analysis, and implementation strategies.

Innovations in neurotechnologies have ignited conversations about ethics around the world, with implications for researchers, policymakers, and the private sector. The human rights impacts of neurotechnologies have drawn the attention of United Nations bodies; nearly 40 states are tasked with implementing the Organization for Economic Co-operation and Development's principles for responsible innovation in neurotechnology; and the United States is considering placing export controls on brain-computer interfaces. Against this backdrop, we offer the first review and analysis of neuroethics guidance documents recently issued by prominent government, private, and academic groups, focusing on commonalities and divergences in articulated goals; envisioned roles and responsibilities of different stakeholder groups; and the suggested role of the public. Drawing on lessons from the governance of other emerging technologies, we suggest implementation and evaluation strategies to guide practitioners and policymakers in operationalizing these ethical norms in research, business, and policy settings.

Correction: Academic global surgical competencies: A modified Delphi consensus study.

[This corrects the article DOI: 10.1371/journal.pgph.0002102.].

Small area analysis methods in an area of limited mapping: exploratory geospatial analysis of firearm injuries in Port-au-Prince, Haiti.

BACKGROUND: The city of Port-au-Prince, Haiti, is experiencing an epidemic of firearm injuries which has resulted in high burdens of morbidity and mortality. Despite this, little scientific literature exists on the topic. Geospatial research could inform stakeholders and aid in the response to the current firearm injury epidemic. However, traditional small-area geospatial methods are difficult to implement in Port-au-Prince, as the area has limited mapping penetration. Objectives of this study were to evaluate the feasibility of geospatial analysis in Port-au-Prince, to seek to understand specific limitations to geospatial research in this context, and to explore the geospatial epidemiology of firearm injuries in patients presenting to the largest public hospital in Port-au-Prince. RESULTS: To overcome limited mapping penetration, multiple data sources were combined. Boundaries of informally developed neighborhoods were estimated from the crowd-sourced platform OpenStreetMap using Thiessen polygons. Population counts were obtained from previously published satellite-derived estimates and aggregated to the neighborhood level. Cases of firearm injuries presenting to the largest public hospital in Port-au-Prince from November 22nd, 2019, through December 31st, 2020, were geocoded and aggregated to the neighborhood level. Cluster analysis was performed using Global Moran's I testing, local Moran's I testing, and the SaTScan software. Results demonstrated significant geospatial autocorrelation in the risk of firearm injury within the city. Cluster analysis identified areas of the city with the highest burden of firearm injuries. CONCLUSIONS: By utilizing novel methodology in neighborhood estimation and combining multiple data sources, geospatial research was able to be conducted in Port-au-Prince. Geospatial clusters of firearm injuries were identified, and neighborhood level relative-risk estimates were obtained. While access to neighborhoods experiencing the largest burden of firearm injuries remains restricted, these geospatial methods could continue to inform stakeholder response to the growing burden of firearm injuries in Port-au-Prince.

Academic global surgical competencies: A modified Delphi consensus study.

Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.

Global Neurosurgery: Progress and Resolutions at the 75th World Health Assembly.

Neurosurgical advocates for global surgery/neurosurgery at the 75th World Health Assembly gathered in person for the first time after the COVID-19 pandemic in Geneva, Switzerland, in May 2022. This article reviews the significant progress in the global health landscape targeting neglected neurosurgical patients, emphasizing high-level policy advocacy and international efforts to support a new World Health Assembly resolution in mandatory folic acid fortification to prevent neural tube defects. The process of developing global resolutions through the World Health Organization and its member states is summarized. Two new global initiatives focused on the surgical patients among the most vulnerable member states are discussed, the Global Surgery Foundation and the Global Action Plan on Epilepsy and other Neurological Disorders. Progress toward a neurosurgery-inspired resolution on mandatory folic acid fortification to prevent spina bifida-folate is described. In addition, priorities for moving the global health agenda forward for the neurosurgical patient as it relates to the global burden of neurological disease are reviewed after the COVID-19 pandemic.

South Africa and the Surgical Diaspora-A Hub for Surgical Migration and Training.

BACKGROUND: The shortage of trained surgeons, anesthesiologists, and obstetricians is a major contributor to the unmet need for surgical care in low- and middle-income countries, and the shortage is aggravated by migration to higher-income countries. METHODS: We performed a cross-sectional observational study, combining individual-level data of 43,621 physicians from the Health Professions Council of South Africa with data from the registers of 14 high-income countries, and international statistics on surgical workforce, in order to quantify migration to and from South Africa in both absolute and relative terms. RESULTS: Of 6670 surgeons, anesthesiologists, and obstetricians in South Africa, a total of 713 (11%) were foreign medical graduates, and 396 (6%) were from a low- or middle-income country. South Africa was an important destination primarily for physicians originating from low-income countries; 2% of all surgeons, anesthesiologists, and obstetricians from low- and middle-income countries were registered in South Africa, and 6% in the other 14 recipient countries. A total of 1295 (16%) South African surgeons, anesthesiologists, and obstetricians worked in any of the 14 studied high-income countries. CONCLUSION: South Africa is an important regional hub for surgical migration and training. A notable proportion of surgical specialists in South Africa were medical graduates from other low- or middle-income countries, whereas migration out of South Africa to high-income countries was even larger.

Health-Related Quality of Life After Single Ventricle Palliation or Tetralogy of Fallot Repair.

Single ventricle (SV) cardiac lesions and tetralogy of Fallot (TOF) are both common forms of cyanotic congenital heart disease. With advances in perioperative care and longitudinal follow-up, survival of these patients has dramatically improved and the majority survive to adulthood. This study compares health-related quality of life (HRQoL) of adult SV and TOF patients to each other and the general population. HRQoL of all surviving, non-transplanted SV and TOF patients 21 years of age and older at our institution was assessed with the SF-36 questionnaire via phone. Additional data including demographic parameters and information related to comorbidities and healthcare utilization were also analyzed. Among 81 eligible SV patients and 207 TOF patients, 33 (41%) and 75 (36%) completed the SF-36 phone survey, respectively. The mean age of SV patients was 32 vs. 38 years in the TOF group (p=0.01). SV patients reported more hepatic, pulmonary, and renal comorbidities. TOF patients were more likely to complete advanced degrees and more likely to have children (p=0.03). SV physical functioning scores were worse compared to TOF. In other domains of the SF-36 questionnaire, SV and TOF scores were similar. Compared to the general population, both groups reported worse bodily pain and mental health, but other aspects of psychosocial and general health were comparable. Overall HRQoL is good for both SV and TOF patients through early and mid-adulthood. Some QoL metrics were modestly worse in the SV patients. While these patients may have some physical limitations, psychosocial wellbeing appears preserved.

Differential requirement for DICER1 activity during the development of mitral and tricuspid valves.

Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. Here, we specifically inactivated Dicer1 in the endocardium during cardiogenesis and found that Dicer1 deletion caused congenital mitral valve stenosis and regurgitation, whereas it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. We thus reveal miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.

An Umbrella Review With Meta-Analysis of Chest Computed Tomography for Diagnosis of COVID-19: Considerations for Trauma Patient Management.

Background: RT-PCR testing is the standard for diagnosis of COVID-19, although it has its suboptimal sensitivity. Chest computed tomography (CT) has been proposed as an additional tool with diagnostic value, and several reports from primary and secondary studies that assessed its diagnostic accuracy are already available. To inform recommendations and practice regarding the use of chest CT in the in the trauma setting, we sought to identify, appraise, and summarize the available evidence on the diagnostic accuracy of chest CT for diagnosis of COVID-19, and its application in emergency trauma surgery patients; overcoming limitations of previous reports regarding chest CT accuracy and discussing important considerations regarding its role in this setting. Methods: We conducted an umbrella review using Living Overview of Evidence platform for COVID-19, which performs regular automated searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and more than 30 other sources. The review was conducted following the JBI methodology for systematic reviews. The Grading of Recommendations, Assessment, Development, and Evaluation approach for grading the certainty of the evidence is reported (registered in International Prospective Register of Systematic Reviews, CRD42020198267). Results: Thirty studies that fulfilled selection criteria were included; 19 primary studies provided estimates of sensitivity (0.91, 95%CI = [0.88-0.93]) and specificity (0.73, 95%CI = [0.61; 0.82]) of chest CT for COVID-19. No correlation was found between sensitivities and specificities (ρ = 0.22, IC95% [-0.33; 0.66]). Diagnostic odds ratio was estimated at: DOR = 27.5, 95%CI (14.7; 48.5). Evidence for sensitivity estimates was graded as MODERATE, and for specificity estimates it was graded as LOW. Conclusion: The value of chest CT appears to be that of an additional screening tool that can easily detect PCR false negatives, which are reportedly highly frequent. Upon the absence of PCR testing and impossibility to perform RT-PCR in trauma patients, chest CT can serve as a substitute with increased value and easy implementation. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42020198267].

Factors associated with left ventricular hypertrophy in children with sickle cell disease: results from the DISPLACE study.

Cardiopulmonary complications remain a leading cause of morbidity and mortality in sickle cell disease (SCD). The overall goals of this study were to evaluate the relationship between left ventricular hypertrophy (LVH) and laboratory markers of hemolysis and determine the association between LVH and SCD-specific therapies (hydroxyurea and chronic red cell transfusion). Data from the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study cohort was used. LVH was defined based on the left ventricular mass indexed to the body surface area as left ventricular mass index >103.0 g/m2 for males and >84.2 g/m2 for females. There were 1,409 children included in the analysis and 20.3% had LVH. Results of multivariable analysis of LVH showed baseline hemoglobin levels were associated with the lower odds of having LVH (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.60- 0.84). The odds of LVH increases for every 1-year increase in age (OR: 1.07, 95% CI: 1.02-1.13). Similarly, the odds of LVH were lower among males than females (OR: 0.59, 95% CI: 0.38-0.93). The odds of LVH were higher among those on hydroxyurea compared to no therapy (OR: 1.83, 95% CI: 1.41-2.37). Overall results of the study showed that LVH occurs early in children with SCD and the risk increases with increasing age and with lower hemoglobin. Further, we found higher use of hydroxyurea among those with LVH, suggesting that the need for hydroxyurea conveys a risk of cardiovascular remodeling.

Inherited regulation for advanced ARTs: comparing jurisdictions' applications of existing governance regimes to emerging reproductive technologies.

Over the past 5 years, advanced assisted reproductive technologies (ARTs), such as mitochondrial replacement therapies (MRTs) and heritable human genome editing (HHGE), have raised global policy concerns and fears of 'unregulated' proliferation. Yet, few innovations are ever truly unregulated and more often fall within the scope of one or more pre-existing regulatory regimes, a process referred to as 'inherited regulation'. While the United Kingdom has enacted new legislation to specifically authorize and closely regulate MRTs, many jurisdictions will likely default to current oversight systems to manage advanced ARTs. This article evaluates and compares how several jurisdictions have already used four types of inherited regulatory regimes to manage MRTs and HHGE. Cases are drawn from jurisdictions where inherited regulatory interventions on advanced ARTs have taken place (USA, Greece, Ukraine, China, and Russia) and include jurisdictions closely connected with those cases (Mexico and Spain). When accounting for political, cultural, and religious contexts, many of these inherited regimes offer promise as starting points for governance of advanced ARTs, yet each will require further adjustments and tailoring to adequately manage the benefits and risks of these powerful innovations.

Preoperative Quadratus Lumborum Block Reduces Opioid Requirements in the Immediate Postoperative Period Following Hip Arthroscopy: A Randomized, Blinded Clinical Trial.

PURPOSE: To examine acute postoperative opioid consumption in patients undergoing hip arthroscopy and randomized to either receive a preoperative lateral quadratus lumborum block or sham injection. METHODS: This trial randomized 46 subjects undergoing hip arthroscopy with a single surgeon to receive a preoperative lateral quadratus lumborum block (40 mL, ropivacaine 0.25%) or sham injection. The primary outcome was postoperative opioid consumption in patients with and without a block. All opioid medications were converted to morphine milligram equivalents for comparisons. Categorical data were compared with χ2 tests and Fisher exact tests where appropriate. Continuous data were compared with 2-sided t-test and Wilcoxon rank-sum tests. RESULTS: Forty-six subjects scheduled for elective hip arthroscopy were successfully consented and randomized. Demographic and clinical characteristics did not differ. Postoperative opioid consumption decreased 28.3% in patients who received a preoperative lateral quadratus lumborum block (P = .04). Total perioperative opioid consumption (intraoperative and postoperative combined) was reduced 20% in the block group; however, this did not achieve statistical significance (P = .05). Three subjects in the sham group (12.5%) required unblinding for a rescue block in the postoperative anesthetic care unit (PACU) for uncontrolled pain despite systemic analgesics. While cold sensation was decreased postoperatively over the abdomen (P < .001) and anterior thigh (P = .03) in the block group, other PACU variables did not differ, including VAS pain scores, motor function, side effects, PACU duration, and patient satisfaction. CONCLUSIONS: Opioid consumption was reduced in patients who received a preoperative lateral quadratus lumborum block combined with a standardized, multimodal protocol as compared with patients who did not receive a block. Our findings support the growing evidence that quadratus lumborum blocks are an effective component of multimodal analgesia options for patients undergoing elective hip arthroscopy. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Primary stroke prevention worldwide: translating evidence into action.

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

The Health Determinants of Accessibility to Clubfoot Treatment in LMICs: A Global Exploration of Barriers and Solutions.

BACKGROUND: Clubfoot or Congenital Talipes Equinovarus (CTEV) treatment in newborn infants involves simple, non-invasive manipulation and is primarily managed non-surgically if identified early. In low- and middle-income countries (LMICs), less than 15% of patients with CTEV access treatment. This cross-sectional questionnaire study conducted descriptive and regression analysis of institutional reasons for CTEV management in LMICs. METHODS: A cross-sectional study was undertaken of 1,489 medical institutions in 62 LMICs. Data were evaluated from the "World Health Organization Situation Analysis tool" database. We analyzed characteristics of institutions that manage and did not manage CTEV. With the use of a multivariate linear regression model, we identified a set of factors linked to referral for non-management of CTEV. RESULTS: A total of 72.7% (1,083/1,395) of institutions surveyed did not manage CTEV. The most common reason cited for not managing CTEV was a lack of sufficient skills, 92.1% (668/725, P<0.001). A total of 39.4% (286/725) of institutions also cited a lack of functioning equipment as a reason. Multivariate linear regression analysis showed lack of training, lack of supplies, and lack of functioning equipment were most closely related to non-management of CTEV. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: We identified that failure to manage CTEV may result from a lack of skills and medical equipment. Increasing the capacity of sustainable training programs may reduce the presently available skill deficit in treating CTEV in LMICs and provide improved health outcomes for those with CTEV. While considerable progress has been made in building capacity for the treatment and management of CTEV in LMICs, structured training programs that support conservative manipulative methods to manage CTEV should be initiated globally.