A minimal physical model for curvotaxis driven by curved protein complexes at the cell's leading edge.

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed "curvotaxis." The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a "minimal cell" model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.

A Change of Paradigm in the Management of Acute Psychiatric Episodes? A Retrospective Cohort Study on Trajectories of Use of Clinical Resources After the Implementation of Intensive Home-Treatment.

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (pBonf = 0.018) and with previous hospitalizations (pBonf < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (pBonf = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.

Interplay of fibrinogen αEC globular domains and factor XIIIa cross-linking dictates the extensibility and strain stiffening of fibrin networks.

BACKGROUND: Fibrinogen is a plasma protein forming the fibrin scaffold of blood clots. Its mechanical properties therefore affect the risk of bleeding as well as thrombosis. There has been much recent interest in the biophysical mechanisms controlling fibrin mechanics; however, the role of molecular heterogeneity of the circulating fibrinogen in determining clot mechanical function remains poorly characterized. OBJECTIVES: By comparing 2 fibrinogen variants where the only difference is the Aα-chain length, with one variant having a globular domain at its C-terminus, this study aimed to reveal how the molecular structure impacts the structure and mechanics of fibrin networks. METHODS: We characterized the mechanical response to large shear for networks formed from 2 recombinant fibrinogen variants: the most prevalent variant in circulation with a molecular weight of 340 kDa (recombinant human fibrinogen [rFib] 340) and a minor variant with a molecular weight of 420 kDa (rFib420). RESULTS: We show that the elastic properties of the 2 variants are identical when fibrin is cross-linked with factor XIIIa but differ strongly in its absence. Uncross-linked rFib420 networks are softer and up to 3-fold more extensible than rFib340 networks. Electron microscopy imaging showed that the 2 variants formed networks with a comparable structure, except at 4 mg/mL, where rFib420 formed denser networks. CONCLUSION: We propose that the αEC domains of rFib420 increase the extensibility of uncross-linked fibrin networks by promoting protofibril sliding, which is blocked by FXIIIa cross-linking. Our findings can help explain the functional role of different circulating fibrinogen variants in blood clot mechanics and tissue repair.

Leveraging an implementation science partnership network to understand how Federally Qualified Health Centers operationalize and address health equity.

Health equity-focused implementation research requires using definitions and approaches that are relevant and meaningful to implementation partners. We examined how health equity was operationalized and addressed at Federally Qualified Health Centers (FQHCs). We conducted semi-structured interviews with leadership (n = 19) and staff (n = 12) at 10 FQHCs in an implementation science partnership network for cancer control equity to understand how they operationalized and addressed health equity. We performed rapid qualitative analysis and shared findings with a larger group of 13 community health centers (including the 10 FQHCs) at an Implementation Learning Community (ILC) to identify action areas for research and practice, followed by a second phase of synthesizing qualitative codes into themes and mapping themes onto a framework for advancing health equity in healthcare organizations. Participants defined health equity as central to the mission of FQHCs, and identified barriers (e.g. financing models) and facilitators (e.g. interpreter services) to advancing health equity at FQHCs. These findings resonated with ILC participants who emphasized the challenge of addressing root cause social determinants of inequities using limited available resources in FQHCs and the importance of developing meaningful collaboration with communities for data collection, data interpretation, data use, and data ownership. Themes captured recommendations to advance health equity in daily work at FQHCs, including investments in staffing, training, and resources. Mapping qualitative themes from health equity-centered interviews with FQHC partners onto a framework for advancing health equity in healthcare organizations can provide clear, context-specific direction for actions aimed at improving health and healthcare equity.

Health equity-focused implementation research requires using definitions and approaches that are relevant and meaningful to implementation partners. Toward this goal, our research team asked leadership and staff at Federally Qualified Health Centers (FQHCs) to share how they defined and addressed health equity at their practice settings. FQHC participants defined health equity as the essential mission of FQHCs as safety net organizations delivering care to medically underserved populations. In addition, key informants identified barriers (e.g. financing models) and facilitators (e.g. interpreter services) to advancing health equity at FQHCs. We presented these findings to a larger group of FQHC stakeholders who recommended that future implementation research and practice consider how FQHCs are challenged to address the root causes of healthcare inequities with limited resources. They also highlighted the importance of meaningful collaboration among researchers, FQHCs, and communities for data collection, data interpretation, data use, and data ownership to advance health equity. Conducting research to understand the perspectives and experiences of FQHC partners can provide clear, context-specific direction for actions to improve health equity and can inform future approaches to health equity-focused implementation research that ismeaningful to FQHC partners and the communities they serve.

Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

Cultural and translation challenges in assessing health literacy among immigrants from the former Soviet Union.

Health literacy is an important foundation for health promotion and an under-recognized risk factor for immigrant and refugee groups. Yet measuring health literacy among diverse ethnic and linguistic populations presents complex challenges. We describe cultural and translation challenges encountered in measuring health literacy among Russian-speaking immigrants to the USA and offer a mixed-methods approach to understanding them. The Rx-Health Literacy (RxHL) study used cross-sectional quantitative and qualitative data to examine health literacy and medication adherence among five cultural and four language groups (Latinx, Vietnamese, African-American, Russian-speaking immigrant and White American) who are patients at Caring Health Center, a federally qualified health center in Springfield, MA. We translated an existing health literacy scale into Russian and Vietnamese and examined item difficulty across cultural groups. We conducted qualitative cognitive interviews to learn more about Russian speakers' understandings of the scale. Health literacy scores varied by cultural group, and the range of correct responses was much greater among Russian speakers than in other groups. Percentage correct varied by 69.7% for Russian speakers, compared with 25.0-44.0% for other groups. These findings indicate greater variability in health literacy levels among this group compared with others. Cognitive interviews with Russian-speaking participants revealed multiple interpretations of several items, suggesting that the English version of the scale contained embedded meanings associated with an American health care context that were not captured in the translated instrument. Combining qualitative and quantitative research methods allows for greater insight into contextual and translation factors that may shape the results of translated instruments in unanticipated ways.

Implementation of evidence-based primary cancer prevention interventions in MA community health centers: an explanatory sequential mixed methods study.

BACKGROUND: More than half of cancers could be prevented by employing evidence-based interventions (EBIs), including prevention interventions targeting nutrition, physical activity, and tobacco. Federally qualified health centers (FQHCs) are the primary source of patient care for over 30 million Americans - making them an optimal setting for ensuring evidence-based prevention that advances health equity. The aims of this study are to (1) determine the degree to which primary cancer prevention EBIs are being implemented within Massachusetts FQHCs and (2) describe how these EBIs are implemented internally and via community partnerships. METHODS: We used an explanatory sequential mixed methods design to assess the implementation of cancer prevention EBIs. First, we collected 34 quantitative surveys from staff at 16 FQHCs across Massachusetts to determine the frequency of EBI implementation. We followed up with 12 qualitative one-on-one interviews among a sample of staff to understand how the EBIs selected on the survey were implemented. Exploration of contextual influences on implementation and use of partnerships was guided by the Consolidated Framework for Implementation Research (CFIR). Quantitative data were summarized descriptively, and qualitative analyses used reflexive, thematic approaches, beginning deductively with codes from CFIR, then inductively coding additional categories. RESULTS: All FQHCs indicated they offered clinic-based tobacco interventions, such as clinician-delivered screening practices and prescription of tobacco cessation medications. Quitline interventions and some diet/physical activity EBIs were available at all FQHCs, but staff perceptions of penetration were low. Only 38% of FQHCs offered group tobacco cessation counseling and 63% referred patients to mobile phone-based cessation interventions. We found multilevel factors influenced implementation across intervention types - including the complexity of intervention trainings, available time and staffing, motivation of clinicians, funding, and external policies and incentives. While partnerships were described as valuable, only one FQHC reported using clinical-community linkages for primary cancer prevention EBIs. CONCLUSIONS: Adoption of primary prevention EBIs in Massachusetts FQHCs is relatively high, but stable staffing and funding are required to successfully reach all eligible patients. FQHC staff are enthusiastic about the potential of community partnerships to foster improved implementation-providing training and support to build these relationships will be key to fulfilling that promise.

Social Risk Screening and Response Equity: Assessment by Race, Ethnicity, and Language in Community Health Centers.

INTRODUCTION: Little has previously been reported about the implementation of social risk screening across racial/ethnic/language groups. To address this knowledge gap, the associations between race/ethnicity/language, social risk screening, and patient-reported social risks were examined among adult patients at community health centers. METHODS: Patient- and encounter-level data from 2016 to 2020 from 651 community health centers in 21 U.S. states were used; data were extracted from a shared Epic electronic health record and analyzed between December 2020 and February 2022. In adjusted logistic regression analyses stratified by language, robust sandwich variance SE estimators were applied with clustering on patient's primary care facility. RESULTS: Social risk screening occurred at 30% of health centers; 11% of eligible adult patients were screened. Screening and reported needs varied significantly by race/ethnicity/language. Black Hispanic and Black non-Hispanic patients were approximately twice as likely to be screened, and Hispanic White patients were 28% less likely to be screened than non-Hispanic White patients. Hispanic Black patients were 87% less likely to report social risks than non-Hispanic White patients. Among patients who preferred a language other than English or Spanish, Black Hispanic patients were 90% less likely to report social needs than non-Hispanic White patients. CONCLUSIONS: Social risk screening documentation and patient reports of social risks differed by race/ethnicity/language in community health centers. Although social care initiatives are intended to promote health equity, inequitable screening practices could inadvertently undermine this goal. Future implementation research should explore strategies for equitable screening and related interventions.

Implementation of evidence-based primary cancer prevention interventions in MA community health centers: an explanatory sequential mixed methods study.

Background More than half of cancers could be prevented by employing evidence-based interventions (EBIs), including prevention interventions targeting nutrition, physical activity, and tobacco. Federally qualified health centers (FQHCs) are the primary source of patient care for over 30 million Americans - making them an optimal setting for ensuring evidence-based prevention that advances health equity. The aims of this study are to: 1) determine the degree to which primary cancer prevention EBIs are being implemented within Massachusetts FQHCs and 2) describe how these EBIs are implemented internally and via community partnerships. Methods We used an explanatory sequential mixed methods design to assess the implementation of cancer prevention EBIs. First, we used quantitative surveys of FQHC staff to determine the frequency of EBI implementation. We followed up with qualitative one-on-one interviews among a sample of staff to understand how the EBIs selected on the survey were implemented. Exploration of contextual influences on implementation and use of partnerships was guided by the Consolidated Framework for Implementation Research (CFIR). Quantitative data were summarized descriptively, and qualitative analyses used reflexive, thematic approaches, beginning deductively with codes from CFIR, then inductively coding additional categories. Results All FQHCs indicated they offered clinic-based tobacco interventions, such as clinician-delivered screening practices and prescription of tobacco cessation medications. Quitline interventions and some diet/physical activity EBIs were available at all FQHCs, but staff perceptions of penetration were low. Only 38% of FQHCs offered group tobacco cessation counseling and 63% referred patients to mobile phone-based cessation interventions. We found multilevel factors influenced implementation across intervention types - including the complexity of intervention trainings, available time and staffing, motivation of clinicians, funding, and external policies and incentives. While partnerships were described as valuable, only one FQHC reported using clinical-community linkages for primary cancer prevention EBIs. Conclusions Adoption of primary prevention EBIs in Massachusetts FQHCs is relatively high, but stable staffing and funding are required to successfully reach all eligible patients. FQHC staff are enthusiastic about the potential of community partnerships to foster improved implementation - providing training and support to build these relationships will be key to fulfilling that promise.

DisGUVery: A Versatile Open-Source Software for High-Throughput Image Analysis of Giant Unilamellar Vesicles.

Giant unilamellar vesicles (GUVs) are cell-sized aqueous compartments enclosed by a phospholipid bilayer. Due to their cell-mimicking properties, GUVs have become a widespread experimental tool in synthetic biology to study membrane properties and cellular processes. In stark contrast to the experimental progress, quantitative analysis of GUV microscopy images has received much less attention. Currently, most analysis is performed either manually or with custom-made scripts, which makes analysis time-consuming and results difficult to compare across studies. To make quantitative GUV analysis accessible and fast, we present DisGUVery, an open-source, versatile software that encapsulates multiple algorithms for automated detection and analysis of GUVs in microscopy images. With a performance analysis, we demonstrate that DisGUVery's three vesicle detection modules successfully identify GUVs in images obtained with a wide range of imaging sources, in various typical GUV experiments. Multiple predefined analysis modules allow the user to extract properties such as membrane fluorescence, vesicle shape, and internal fluorescence from large populations. A new membrane segmentation algorithm facilitates spatial fluorescence analysis of nonspherical vesicles. Altogether, DisGUVery provides an accessible tool to enable high-throughput automated analysis of GUVs, and thereby to promote quantitative data analysis in synthetic cell research.

Fístula arteriovenosa post-TIPS, un reto diagnóstico: reporte de caso / Post-TIPS arteriovenous fistula, a diagnostic challenge: case report

La hipertensión portal es una de las principales complicaciones de la cirrosis. El papel de la derivación portosistémica transyugular intrahepática (TIPS, por sus siglas en inglés), ha ganado aceptación como tratamiento efectivo en la hipertensión portal. En los últimos años su técnica se ha ido perfeccionando, disminuyendo la morbimortalidad relacionada con este procedimiento. Describimos un caso de un paciente masculino con cirrosis Child-Pugh 8 y MELD 16, con antecedente de descompensación por sangrado variceal recurrente y trombosis parcial de la vena porta, con un gradiente de presión venosa hepática (GPVH) de 20 mmHg, por lo que es llevado a TIPS como profilaxis secundaria, con un gradiente final post-TIPS de 6 mmHg. Posterior al procedimiento, presentó evolución tórpida con deterioro de las pruebas de bioquímica hepática. Se realizó una angiografía demostrando permeabilidad del TIPS sin progresión de la trombosis portal, y hallazgos anormales inespecíficos de la arteria hepática. Se decidió realizar una arteriografía selectiva, demostrando un pseudoaneurisma de la rama derecha de la arteria hepática y una fístula arteriovenosa de la arteria hepática a las colaterales portales. Se realizó embolización selectiva de la fístula con evolución satisfactoria del paciente.

Portal hypertension is a life-threatening complication of cirrhosis. The role of transyugular intrahepatic portosystemic shunt (TIPS) has gained acceptance as an effective treatment for portal hypertension. In the past few years, its technique has been improved, decreasing the mortality related with the procedure. We describe a case of a male with Child-Pugh 8 and MELD 16 cirrhosis, with previous decompensation of recurrent variceal bleeding and partial thrombosis of the portal vein. TIPS was performed due to a hepatic venous pressure gradient (HVPG) of 20 mmHg. The final measure showed HVPG of 6 mmHg. After the procedure, he presented a torpid evolution with deterioration of liver function tests. An angiography was performed demonstrating patency of the TIPS without progression of portal thrombosis and nonspecific abnormal findings of the hepatic artery. Selective arteriography was performed and revealed a pseudoaneurysm of the right branch of the hepatic artery and an arteriovenous fistula (AVF) from the hepatic artery to portal collaterals. Embolization was performed to treat the fistula with satisfactory evolution of the patient.

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Cross-Sectional Associations: Social Risks and Diabetes Care Quality, Outcomes.

INTRODUCTION: Social risks (e.g., food/transportation insecurity) can hamper type 2 diabetes mellitus (T2DM) self-management, leading to poor outcomes. To determine the extent to which high-quality care can overcome social risks' health impacts, this study assessed the associations between reported social risks, receipt of guideline-based T2DM care, and T2DM outcomes when care is up to date among community health center patients. METHODS: A cross-sectional study of adults aged ≥18 years (N=73,484) seen at 186 community health centers, with T2DM and ≥1 year of observation between July 2016 and February 2020. Measures of T2DM care included up-to-date HbA1c, microalbuminuria, low-density lipoprotein screening, and foot examination, and active statin prescription when indicated. Measures of T2DM outcomes among patients with up-to-date care included blood pressure, HbA1c, and low-density lipoprotein control on or within 6‒12 months of an index encounter. Analyses were conducted in 2021. RESULTS: Individuals reporting transportation or housing insecurity were less likely to have up-to-date low-density lipoprotein screening; no other associations were seen between social risks and clinical care quality. Among individuals with up-to-date care, food insecurity was associated with lower adjusted rates of controlled HbA1c (79% vs 75%, p<0.001), and transportation insecurity was associated with lower rates of controlled HbA1c (79% vs 74%, p=0.005), blood pressure (74% vs 72%, p=0.025), and low-density lipoprotein (61% vs 57%, p=0.009) than among those with no reported need. CONCLUSIONS: Community health center patients received similar care regardless of the presence of social risks. However, even among those up to date on care, social risks were associated with worse T2DM control. Future research should identify strategies for improving HbA1c control for individuals with social risks. TRIAL REGISTRATION: This study is registered at www. CLINICALTRIALS: gov NCT03607617.

Plasma and Whole Blood Taurine Concentrations in Dogs May Not Be Sensitive Indicators of Taurine Deficiency When Dietary Sulfur Amino Acid Content Is Reduced.

Background: Taurine status is impacted by dietary supply of methionine and cysteine (SAA) and possibly intestinal microbial activity, where plasma and whole blood taurine concentrations are currently used to evaluate taurine status. Objective: We determined effects of dietary SAA restriction on rate and extent of taurine depletion of blood and skeletal muscle in dogs of two body sizes, and whether oral antibiotic administration affected the taurine depletion and fecal bile acid excretion of the dogs. Methods: Adult, male, Beagles (n = 6; 10.1-13.1 kg) and larger mixed-breed dogs (n = 6; 28.5-41.1 kg) were given four dry-expanded diets, whereby each successive diet contained lower protein and/or SAA concentration. After receiving the final diet for 44 weeks, all dogs were orally administered a mixture of ampicillin, neomycin sulfate, and metronidazole for 12 weeks. Taurine concentrations were determined every 2-4 weeks in venous blood and voided urine and every 4 to 16 weeks in biopsied semimembranosus muscle. Fecal bile acid excretion before and after antibiotics administration were quantified. Results: When given for 36 weeks the lowest SAA diet, 3.4% methionine and 2.9% cystine, taurine concentrations in whole blood were not different between groups, while taurine in plasma declined (P < 0.05) in large but not in small dogs, and taurine in biopsied muscle decreased (P < 0.05) by 50% in large and by 37% in small dogs. Concentrations of taurine in muscle were lower (P < 0.01) and fecal bile acids greater (P = 0.001) in large than small dogs. Antibiotic administration restored plasma and muscle taurine to initial concentrations and halved fecal bile acid excretion by dogs of both groups. Conclusions: Blood taurine concentration may not be a sensitive indictor of taurine depletion caused by low intake of bioavailable SAA in dogs, especially in large dogs. Taurine status and dietary SAA requirements of dogs may substantively depend on taurine loss mediated by intestinal microbiota.

Addressing COVID-19 Testing Inequities Among Underserved Populations in Massachusetts: A Rapid Qualitative Exploration of Health Center Staff, Partner, and Resident Perceptions.

Introduction: Access to COVID-19 testing has been inequitable and misaligned with community need. However, community health centers have played a critical role in addressing the COVID-19 testing needs of historically disadvantaged communities. The aim of this paper is to explore the perceptions of COVID-19 testing barriers in six Massachusetts communities that are predominantly low income and describe how these findings were used to build tailored clinical-community strategies to addressing testing inequities. Methods: Between November 2020 and February 2021, we conducted 84 semi-structured qualitative interviews with 107 community health center staff, community partners, and residents. Resident interviews were conducted in English, Spanish, Vietnamese, and Arabic. We used a 2-phase framework analysis to analyze the data, including deductive coding to facilitate rapid analysis for action and an in-depth thematic analysis applying the Social Ecological Model. Results: Through the rapid needs assessment, we developed cross-site suggestions to improve testing implementation and communications, as well as community-specific recommendations (e.g., locations for mobile testing sites and local communication channels). Upstream barriers identified in the thematic analysis included accessibility of state-run testing sites, weak social safety nets, and lack of testing supplies and staffing that contributed to long wait times. These factors hindered residents' abilities to get tested, which was further exacerbated by individual fears surrounding the testing process and limited knowledge on testing availability. Discussion: Our rapid, qualitative approach created the foundation for implementing strategies that reached underserved populations at the peak of the COVID-19 pandemic in winter 2021. We explored perceptions of testing barriers and created actionable summaries within 1-2 months of data collection. Partnering community health centers in Massachusetts were able to use these data to respond to the local needs of each community. This study underscores the substantial impact of upstream, structural disparities on the individual experience of COVID-19 and demonstrates the utility of shifting from a typical years' long research translation process to a rapid approach of using data for action.

Effects of co-incubation of LPS-stimulated RAW 264.7 macrophages on leptin production by 3T3-L1 adipocytes: a method for co-incubating distinct adipose tissue cell lines.

Background: Adipose tissue is a major endocrine organ capable of releasing inflammatory adipokines that are linked to changes occurring in the overfed state, where tissue remodeling results in hypertrophic adipocytes that recruit monocytes to infiltrate the tissue and take on an inflammatory phenotype. Increases in macrophage-specific inflammatory mediator levels contribute to the inflamed state and worsen the inflammatory loop between the macrophages and adipocytes. Although most inflammatory adipokines are released by macrophages, adipocytes can also release immunomodulatory adipokines, such as leptin. The objective of this research was to determine if co-incubation of activated macrophages with mature adipocytes, using transwell inserts, affected adipocyte leptin release. We also examined if there were differences in levels of cell-secreted products quantified in cell-conditioned media collected from macrophage-containing (transwell insert) and adipocyte-containing (well) compartments. Methods: Mature adipocytes were co-incubated with control and lipopolysaccharide-stimulated (0.01 mg/ml) murine macrophages, and nitric oxide, interleukin-6, and leptin levels were quantified in the cell-conditioned media from both compartments. Results: Activation status of the macrophages did not affect leptin release by the adipocytes. We observed higher amounts of leptin in wells compared to transwells. Nitric oxide and interleukin-6 levels were similar between transwells and wells, suggesting that these adipokines travel through the transwell inserts and are reaching equilibrium between the two compartments. Conclusion: Our results suggest that co-incubating activated macrophages and adipocytes using transwell inserts can result in distinct microenvironments in the different cellular compartments and that separate sampling of these compartments is required to detect the subtle signaling dynamics that exist between these cells. Supplementary Information: The online version contains supplementary material available at 10.1186/s42269-022-00747-7.

Deep brain stimulation for extreme behaviors associated with autism spectrum disorder converges on a common pathway: a systematic review and connectomic analysis.

OBJECTIVE: Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD. METHODS: A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients' perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets. RESULTS: Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS. CONCLUSIONS: This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

¿Supone el abordaje de Stoppa una mejora en los resultados clínicos y radiográficos de las fracturas de acetábulo frente al ilioinguinal? Estudio comparativo de 44 casos / Does Stoppa approach improve clinical and radiographic results of acetabular fractures in regard to ilioinguinal approach? Comparative study of 44 cases

Objetivo del trabajo: Comparar el abordaje ilioinguinal y el abordaje de Stoppa para fracturas de acetábulo a través de las variables tiempo quirúrgico, calidad de reducción, resultados funcionales y complicaciones. Material y métodos: Se analizaron de manera retrospectiva los resultados de 44 fracturas de acetábulo comparando 20 pacientes intervenidos mediante abordaje ilioinguinal y 24 pacientes intervenidos mediante abordaje de Stoppa. Además, cada grupo se dividió en dos subgrupos en función de si se había realizado o no un abordaje a la columna posterior del acetábulo. Estos dos subgrupos fueron también comparados. Resultados: Los resultados globales entre las dos vías de abordaje no mostraron diferencias estadísticamente significativas en el tiempo quirúrgico, calidad de reducción, resultados funcionales y complicaciones. Al realizar la comparación entre los subgrupos sin abordaje a la columna posterior se obtuvo un resultado estadísticamente significativo en la calidad de la reducción quirúrgica (P=0.027) a favor del abordaje de Stoppa. Conclusiones: Ambas vías de abordaje dan buenos resultados en fracturas de acetábulo. En nuestra experiencia, con el abordaje de Stoppa se obtiene mejores resultados respecto al abordaje ilioinguinal en cuanto a calidad de reducción quirúrgica cuando no hay afectación de la columna posterior. (AU)

Objetive: To compare ilioinguinal and Stoppa approach- es in acetabular fractures considering some vari- ables like surgical time, quality of surgical reduc- tion, functional results and complications. Methods: 44 cases of acetabular fractures have been surgically treated in our Department. Of those, 20 cases were operated through an ilioinguinal approach. The other 24 patients were operated following Stoppa technique. Global results were analyzed in the two groups. Additionally, each group was divided into two subgroups consider- ing whether or not a posterior approach was also performed. The patients were followed up for two years. Results: Global results between the two groups were similar and there were no statistically significant differences in surgical time, surgical reduction quality, functional results and complications. When compared the two subgroups without pos- terior approach performed, the surgical reduc- tion quality was statistically significantly better, (p=0.027) in the Stoppa approach.Conclusions: Good results in acetabular fractures can be obtained in both groups. In our experience, with the Stoppa approach, better results are obtained with respect to the ilioinguinal approach consid- ering the surgical reduction quality when there is no need to perform a second posterior approach to obtain a satisfactory reduction. (AU)

Regulatory oversight on the use of experimental therapies during a pandemic: The case of early access to convalescent plasma therapy in three LMICs.

Clinicians, especially in low- and middle-income countries (LMICs), contend with limited economic and healthcare resources in deciding appropriate and feasible care for their patients. Some of the LMICs affected by COVID-19 implemented convalescent plasma therapy without sufficient regulatory guidance. Based on this experience, there are several requirements going forward, including: the need for an immediately accessible data gathering and processing system; the necessity of establishing regulatory pathways for early access to experimental treatment during emergency situations; and the accompanying reporting and monitoring requirements must be set. The different stakeholders must also be properly incorporated in the system that such a pathway will create, without neglecting to properly inform the public of the patient rights especially during an emergency situation.

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: a nationwide study in Spain.

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.