Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Analysis of Hip Preservation Questions on the Orthopaedic In-Training Examination Over the Past 20 Years.

Background: The orthopaedic in-training examination (OITE) is a 275-question test for orthopaedic residents administered annually. As the field of orthopaedics changes, the OITE evolves its content. The incidence of hip preservation-related procedures has increased substantially over the past decade; nonetheless, an analysis of the trends of hip preservation questions on the OITE has not yet been performed. Purpose/Hypothesis: The purpose of the study was to evaluate the number and type of questions on the OITE related to hip preservation to determine whether trends over time paralleled the increases in hip-related care in clinical practice. It was hypothesized that the frequency of hip preservation questions on the OITE would increase with time. Study Design: Cross-sectional study. Methods: Each OITE between 2002 and 2021 was reviewed for questions related to hip preservation. The types of questions included under "hip preservation" were those related to femoroacetabular impingement (FAI), athletic soft tissue injuries of the hip, acetabular labral tears, hip arthroscopy, and surgical management of adult hip dysplasia-excluding arthroplasty. Questions were quantified and categorized by topic, taxonomy level, associated imaging, and cited sources. Results: There were 30 hip preservation-related questions between 2002 and 2021. Of these, 77% occurred within the past 10 years. Also, 14 questions (47%) had associated images in the question stem-the most common being radiographs (n = 8 questions). The most commonly tested subcategories were FAI (n = 11 questions [37%]), athletic injuries (n = 7 questions [23%]), and anatomy (n = 7 questions [23%]). Over the last 10 years, 97.9% of citations were from journal articles-the most common being the Journal of the American Academy of Orthopaedic Surgeons, Clinical Orthopedics and Related Research, and the American Journal of Sports Medicine. Conclusion: The frequency of hip preservation-related questions on the OITE has increased with time, reflecting trends in clinical practice.

Preoperative motor weakness and the impact on patient reported outcomes in lateral lumbar interbody fusion.

This study measures the impact of preoperative motor weakness (MW) on Patient-Reported Outcome Measures (PROMs) in lateral lumbar interbody fusion (LLIF) patients. Retrospectively-sourced data from a prospectively-maintained, single-surgeon database created two cohorts of LLIF patients: patients with/without documented MW. Demographics/perioperative characteristics/PROMs were collected preoperatively and at six-weeks/final follow-up (FF). Studied outcomes were Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), 12-Item Short Form (SF-12) Physical/Mental Component Score (PCS/MCS), Patient Health Questionnaire (PHQ-9), Visual Analog Scale Back/Leg Pain (VAS-BP/LP), and Oswestry Disability Index (ODI). Multivariable linear/logistic regression calculated/compared intercohort minimum clinically important difference (MCID). Mean postoperative follow-up time was 11.5 ± 7.52 months. In total, 214 LLIF patients from December 2010 to May 2023 were included, with 149 having documented MW. In Table 1, self-reported gender was significant between cohorts (p < 0.025). Other significant demographic characteristics were smoker status (p < 0.002), diabetes (p < 0.016), and CCI score (p < 0.011). Table 2 shows notably significant perioperative characteristics: spinal pathology (degenerative spondylolisthesis/foraminal stenosis/herniated nucleus pulposus) (p < 0.005, all), estimated blood loss/length of stay/postoperative day (POD)-zero narcotic consumption (p < 0.001, all). Table 3 outcomes/MCID achievement percentages demonstrated insignificant intercohort differences besides a weakly significant FF ODI score (p < 0.036). MW, a frequently reported symptom in spine surgery, is poorly studied in LLIF patients. Thus, this study evaluates MW impact on PROMs and notes no significant differences. However, one exception regarding FF disability scores was recorded. MW did not affect MCID achievement for our patient population. Therefore, the preliminary findings suggest preoperative MW imparts minimal influence on PROMs/MCID in LLIF patients.

Prognostic value in preoperative Veterans RAND-12 mental Component score on clinical outcomes for patients undergoing minimally invasive transforaminal lumbar interbody fusion.

No study has examined the prognostic value of the Veterans RAND-12 (VR-12) Mental Component Score (MCS) on postoperative outcomes in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) patients. This study examines the effect of preoperative VR-12 MCS on postoperative patient-reported outcome measures (PROMs) in MIS-TLIF patients. Patients were separated into 2 cohorts: VR-12 MCS < 50 and VR-12 MCS ≥ 50. PROMs of VR-12 MCS/Physical Component Score (PCS), Short Form-12 (SF-12) MCS/PCS, Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Patient Health Questionnaire-9 (PHQ-9), Visual Analog Scale (VAS) Back/Leg Pain (VAS-BP/LP), and Oswestry Disability Index (ODI) were collected.Of 329 patients, 151 were in the VR-12 MCS < 50 cohort. The VR-12 MCS < 50 cohort reported significantly inferior scores in all PROMs preoperatively, significantly inferior VR-12 MCS, SF-12 MCS, PROMIS-PF, PHQ-9, and ODI scores at 6-weeks postoperatively, and significantly inferior scores in all PROMs, except for VAS-BP at final follow-up. Magnitude of 6-week postoperative improvement was significantly greater in the VR-12 MCS < 50 cohort for VR-12 MCS, SF-12 MCS, and PHQ-9. Magnitude of final postoperative improvement was significantly greater in the VR-12 MCS < 50 cohort for VR-12 MCS, SF-12 MCS/PCS, and PHQ-9. MCID achievement rates were significantly greater in the VR-12 MCS < 50 cohort for VR-12 MCS, SF-12 MCS, and PHQ-9. MIS-TLIF patients with lesser preoperative VR-12 MCS reported inferior postoperative outcomes in mental health, physical function, pain, and disability. However, patients with inferior preoperative mental health reported greater rates of clinically meaningful improvement in mental health. Inferior preoperative mental health does not limit postoperative improvement in patients undergoing MIS-TLIF.

Defining the "ideal state": A primer on critical care pharmacy practice models.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Critical care pharmacists (CCPs) have been clearly established as value-added members of the interprofessional team, and their contributions positively impact patient outcomes in the intensive care unit (ICU). Despite this, not every critically ill patient in the US receives care from a CCP and the model through which CCPs practice is variable, which has important implications. The purpose of this primer is to review current CCP models and discuss elements of the optimal CCP practice model. SUMMARY: Current CCP practice models are defined, including the drug processing and dispensing model, clinical pharmacy specialist model, integrated pharmacy generalist model, and hybrid model, as well as unit-based vs service-based models. The optimal CCP practice model considers the Triple Domain of CCP workload, which includes direct patient care, indirect patient care, and professional service. Elements of the ideal CCP practice model including 24/7/365 CCP services, unit- vs service-based models, prescriptive authority, operational support, and CCP-to-patient ratio are discussed. Other vital elements include protected offline time, use of appropriate workload metrics, development of career ladders, opportunities for professional development, and providing wellness resources. The ideal CCP practice model must also be considered through the lens of the patient and medical team, the CCP, the institution, and professional organizations. Strategies for optimizing current CCP practice models are provided, and application of optimal CCP practice model elements is explored through 5 case studies. CONCLUSION: The optimal CCP practice model includes multiple elements and incorporates the viewpoints of patients, providers, CCPs, institutions, and professional organizations; this model will increase access of all ICU patients to CCPs, enhance the scope of CCP cognitive services, and ensure the economic sustainability of CCP practice while establishing CCP involvement in activities outside of patient care and in professional service.

A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons.

Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs and play key roles in chronic drug usage 1-3 . As the synaptic and transcriptional changes that follow an acute cocaine exposure are mostly resolved within a few days 4,5 , the molecular changes that encode the long-term cellular memory of the exposure within DNs remain unknown. To investigate whether a single cocaine exposure induces long-term changes in the 3D genome structure of DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic analyses in the mouse midbrain. We found extensive rewiring of 3D genome architecture at 24 hours past exposure which remains or worsens by 14 days, outlasting transcriptional responses. The cocaine-induced chromatin rewiring occurs at all genomic scales and affects genes with major roles in cocaine-induced synaptic changes. A single cocaine exposure triggers extensive long-lasting changes in chromatin condensation in post-synaptic and post-transcriptional regulatory genes, for example the unfolding of Rbfox1 which becomes most prominent 14 days post exposure. Finally, structurally remodeled genes are most expressed in a specific DN sub-type characterized by low expression of the dopamine auto-receptor Drd2 , a key feature of highly cocaine-sensitive cells. These results reveal an important role for long-lasting 3D genome remodelling in the cellular memory of a single cocaine exposure, providing new hypotheses for understanding the inception of drug addiction and 3D genome plasticity.

Association Between Symptoms of Anxiety and Depression, Hip Pathology, and Patient-Reported Outcomes After Hip Arthroscopy for Femoroacetabular Impingement.

BACKGROUND: In patients with femoroacetabular impingement (FAI), mental health has been implicated in both symptom severity and postoperative outcomes. However, there are limited data regarding the independent influences of baseline mental health and hip pathology on patient-reported outcomes over time after hip arthroscopy. PURPOSE: To evaluate the association between mental health and structural hip pathology with pain, hip function, and quality of life (QOL). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patient records from a single surgeon's hip outcomes registry were retrospectively reviewed. Mental health was evaluated using the Patient-Reported Outcomes Measurement Information System Anxiety and Depression scores. Pain was evaluated with the Single Assessment Numeric Evaluation score for Activities of Daily Living (SANE-ADL), while hip-related QOL was evaluated with the 12-item International Hip Outcome Tool (iHOT-12). Hip function was assessed with the Hip Outcome Score (HOS) Sport-Specific (SS) and ADL subscales. Separate mixed models were used to predict pain, QOL, and hip function, including hip pathology measures (size of labral tear, grade of chondral damage, preoperative alpha angle), anxiety, depression, and time as fixed effects and individuals as a random effect. RESULTS: A total of 312 patients were included in this study. The preoperative alpha angle, degree of intraoperative cartilage damage, and size of the labral tear were not associated with pain or QOL (P > .05 for all). However, higher levels of anxiety and depression were significantly associated with lower SANE-ADL scores (estimate ± SE) (anxiety: -0.59 ± 0.07, P < .0001; depression: -0.64 ± 0.08, P < .0001), iHOT-12 scores (anxiety: -0.72 ± 0.07, P < .0001; depression: -0.72 ± 0.08, P < .0001), HOS-SS scores (anxiety: -0.68 ± 0.09, P < .0001; depression: -0.57 ± 0.10, P < .0001), and HOS-ADL scores (anxiety: -0.43 ± 0.05, P < .0001; depression: -0.43 ± 0.06, P < .0001). CONCLUSION: Patients had similar improvements in pain scores, QOL, and hip function after hip arthroscopy for FAI irrespective of their degree of hip pathology. Additionally, preoperative symptoms of anxiety and depression symptoms were associated with greater pain, decreased QOL, and worse hip function both pre- and postoperatively, independent of the degree of hip pathology. This suggests that efforts to directly address symptoms of anxiety and depression may improve outcomes after hip arthroscopy.

DengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus.

BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. CONCLUSIONS: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Synthesis and Characterization of Superparamagnetic Iron Oxide Nanoparticles: A Series of Laboratory Experiments.

The following laboratory procedure provides students with hands-on experience in nanomaterial chemistry and characterization. This three-day protocol is easy to follow for undergraduates with basic chemistry or materials science backgrounds and is suitable for inclusion in upper-division courses in inorganic chemistry or materials science. Students use air-free chemistry procedures to synthesize and separate iron oxide magnetic nanoparticles and subsequently modify the nanoparticle surface by using a chemical stripping agent. The morphology and chemical composition of the nanoparticles are characterized using electron microscopy and dynamic light scattering measurements. Additionally, magnetic characterization of the particles is performed using an inexpensive open-source (3D-printed) magnetophotometer. Possible modifications to the synthesis procedure, including the incorporation of dopants to modify the magnetic response and alternative characterization techniques, are discussed. The three-day synthesis, purification, and characterization laboratory will prepare students with crucial skills for advanced technology industries such as semiconductor manufacturing, nanomedicine, and green chemistry.

Evaluation of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus: Frequency, course, and associated risk factors.

BACKGROUND: Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors. METHODS: Participants 8-18 years with cSLE completed baseline measures [demographic questionnaire, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Screen for Childhood Anxiety Related Disorders (SCARED), and psychiatric interview] and follow-up measures (CES-DC and SCARED) > 6 months later. Prevalence of clinically significant depressive (score >15 on CES-DC) or anxiety symptoms (score ≥25 on SCARED) was calculated at baseline and follow-up. Baseline psychiatric interview diagnoses were tabulated. Relationships between socio-demographics (neighborhood-level material deprivation, ethnic concentration, adverse childhood event history, psychiatric condition in a first-degree relative), disease-related factors (disease duration, major organ disease, disease activity, glucocorticoid use, comorbid medical condition) and baseline depressive and anxiety scores, were examined in linear regression models. Factors with univariate associations with p < 0.2 were included in multivariable adjusted models. RESULTS: At baseline, of 51 participants with a mean disease duration of 4.3 years (SD 2.7), 35% (n = 18) and 35% (n = 18) had clinically significant depressive and anxiety symptoms, respectively. Anxiety disorder was diagnosed by psychiatric interview in 14% (n = 7), depressive disorders in 6% (n = 3), and post-traumatic stress disorder in 4% (n = 2). Adverse childhood events and first-degree relative with psychiatric condition were present in 40% (n = 20) and 37% (n = 18), respectively. In multivariable regression analysis, baseline depressive symptoms were positively correlated with neighbourhood-level material deprivation (ß = 4.2, 95% CI [1.0, 7.3], p = 0.01) and psychiatric condition in a first-degree relative (ß = 7.3, 95% CI [2.2, 12.4], p = 0.006). No associations were found between baseline anxiety scores and patient factors. At a median follow-up of 13.5 months (IQR 10.5, 18) for CES-DC (n = 34) and SCARED (n = 44), depressive and anxiety symptoms were persistent (18%, n = 6; 16%, n = 7), and newly present (24%, n = 8; 16% n = 7) at follow-up. CONCLUSION: In this sample, depressive and anxiety symptoms were prevalent and persistent. Depressive symptoms correlated with neighborhood-level material deprivation, and family psychiatric history. These findings support routine psychosocial assessment in cSLE, and provision of appropriate resources.

Efficacy and safety of a transaortic approach to midventricular and apical septal myectomy.

OBJECTIVE: The study objective was to evaluate the safety and efficacy of a transaortic approach to midventricular and apical septal myectomy in patients with hypertrophic cardiomyopathy with left ventricular outflow tract or midventricular obstruction. METHODS: From January 2018 to August 2023, 940 patients underwent transaortic septal myectomy at the Cleveland Clinic, of whom 682 (73%) had midventricular or apical resection. Patients who underwent isolated basal myectomies were excluded. Templated operative reports designated septal regions resected as basal (opposition to mitral valve up to the leaflet tips), midventricular (leaflet tips to just beyond the papillary muscle heads), and apical (apical third of the ventricle). Myocardial resection specimen weights, intraventricular gradients, and clinical outcomes were assessed. RESULTS: Of the 682 patients, 582 (85%) had basal plus midventricular resection and 78 (11%) had basal, midventricular, and apical resection. Mean preoperative intraventricular gradient was 102 ± 41 mm Hg. Median resection weight was 10 g (15th, 85th percentiles: 7, 15), and mean postoperative intraventricular gradient was 16 ± 10 mm Hg, with 625 (96%) patients achieving gradients 36 mm Hg or less. There were no iatrogenic mitral or aortic valve injuries. Permanent pacemaker placement was required in 38 patients (5.6%), of whom 8 (1.2%) had normal preoperative conduction. Operative mortality occurred in 1 patient (0.1%) after an intraoperative ventricular septal defect. CONCLUSIONS: Most patients undergoing septal myectomy for relief of obstruction required resection beyond the basal septum. With specialized instrumentation, detailed imaging and knowledge of variable septal anatomy, resecting midventricular and apical septal muscle can be safely and effectively achieved through a transaortic approach.

Cardiac magnetic resonance reveals biventricular impairment in Cushing's syndrome: a multicentre case-control study.

PURPOSE: Cushing's syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. METHODS: This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. RESULTS: Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. CONCLUSION: CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors.

U.S. Preparedness and Response to Increasing Clade I Mpox Cases in the Democratic Republic of the Congo - United States, 2024.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies.

Contemporary Approach to Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.

Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy. Treatment for metastatic disease is limited to cytotoxic chemotherapy and investigational clinical trials. In this article, we review the pathophysiology of this aggressive cancer and current approaches to surveillance and treatment.

Cervical Disk Replacement Versus Anterior Cervical Diskectomy and Fusion: Effect of Procedural Variant on Patients With a Prolonged Preoperative Duration of Symptoms From Disk Herniation.

INTRODUCTION: Patients with a prolonged preoperative symptom duration (PSD) in the setting of cervical disk herniation (DH) may suffer inferior outcomes after surgical intervention. Comparison between anterior cervical diskectomy and fusion (ACDF) versus cervical disk arthroplasty (CDA) in this at-risk population has not yet been conducted. METHODS: Patients undergoing ACDF or CDA for DH with a PSD > 180 days were selected. Six-week (6W) and final follow-up (FF) patient-reported outcome measures (PROMs) as well as magnitude of postoperative improvements (∆PROM) were compared between cohorts using multivariable linear regression. Intercohort achievement rates of minimal clinically important difference (MCID) in each PROM were compared. RESULTS: Seventy-seven of 190 patients were in the CDA cohort. 6W Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) was superior in the CDA cohort. The ACDF cohort demonstrated notable improvements in the 6W Neck Disability Index (NDI), visual analog scale-neck pain (VAS-N), visual analog scale-arm pain (VAS-A), and 9-item Patient Health Questionnaire (PHQ-9). The CDA cohort demonstrated notable improvements in 6W PROMIS-PF, NDI, VAS-N, and VAS-A. FF VAS-A was better in the CDA cohort. The ACDF cohort demonstrated notable improvements in FF PROMIS-PF, NDI, VAS-N, and VAS-A. The CDA cohort demonstrated notable improvements in all FF PROMs. ∆PROM-6W in PROMIS-PF was greater in the CDA cohort. CONCLUSION: Patients with prolonged PSD due to cervical DH demonstrated notable improvements in physical function, disability, pain, and mental health regardless of fusion versus arthroplasty techniques. Accounting for demographic variations, patients undergoing CDA demonstrated a greater magnitude of improvement and superior scores in physical function at the first postoperative follow-up. Rates of clinically tangible improvements in PROMs did not markedly vary by surgical procedure. Patients undergoing CDA may perceive greater early improvements to physical function compared with patients undergoing ACDF for prolonged PSD due to DH.

Understanding engagement in diet and dementia prevention research among British South Asians: a short report of findings from a patient and public involvement group.

BACKGROUND: Dementia is a global public health challenge. Evidence suggests that individuals from South Asian communities are an at-risk group for dementia, partly as a result of early and cumulative exposure to known dementia risk factors, such as obesity and type 2 diabetes. There needs to be more culturally appropriate community engagement to increase awareness of dementia and identify better strategies to encourage participation in dementia-related research. METHODS: We aimed to better understand the barriers and facilitators towards engaging with, and participating in, diet and dementia related research among British South Asians. This was achieved using a public and patient involvement (PPI) approach. A community-based, engagement event involving information sharing from experts and roundtable discussions with South Asian communities (n = 26 contributors) was held in June 2023 in Newcastle-upon-Tyne, UK. Collaboration from preidentified PPI representatives (n = 3) informed the content and structure of PPI activities, as well as recruitment. Data were synthesised using template analysis, a form of codebook thematic analysis. This involved deductively analysing data using relevant a priori themes, which were expanded upon, or modified, via inductive analysis. RESULTS: The findings highlighted the importance of trust, representation and appreciation of cultural barriers as facilitators to engagement in diet and dementia risk reduction research. Consideration of language barriers, time constraints, social influences and how to embed community outreach activities were reported as driving factors to maximise participation. CONCLUSIONS: This PPI work will inform the design and co-creation of a culturally adapted dietary intervention for brain health in accordance with the Medical Research Council and National Institute for Health and Care Research guidance for developing complex interventions.

Same People, Different Results: Categorizing Cancer Registry Cases Across the Rural-Urban Continuum.

BACKGROUND: Many rural-urban indexes are utilized in cancer research. This variation introduces inconsistencies between studies. Recommendations on index use have prioritized geographical unit over feasibility of inclusion in analysis. We evaluated rural-urban indexes and recommend one for use to increase comparability across studies. METHODS: We assessed 9 US rural-urban indexes regarding their respective rural and urban code ranges; geographical unit, land area, and population distributions; percent agreement; suitability for analysis; and integration feasibility for national, state, and local cancer research. We referenced 1569 Wisconsin Pancreatic Cancer Registry patients to demonstrate how index choice affects patient categorization. RESULTS: Six indexes categorized rural and urban areas. Indexes agreed on binary rural-urban designation for 88.8% of the US population. As ternary variables, they agreed for 83.4%. For cancer registry patients, this decreased to 73.4% and 60.4% agreement, respectively. Rural-Urban Continuum Codes (RUCC) performed the best in differentiating metropolitan, micropolitan, and rural counties; availability for retrospective and prospective studies; and continuous coding for analysis. CONCLUSIONS: Urban/rural patient categorization changed with index selection. We conclude that RUCC is an appropriate and feasible rural-urban index to include in cancer research, as it is standardly available in national cancer registries, can be matched to patient's county of residence for local research, and it had the least amount of fluctuation of the indices analyzed. Utilizing RUCC as a continuous variable across studies with a rural-urban component will increase reproducibility and comparability of results and eliminate rural-urban index choice as a potential source of discrepancy between studies.

Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. METHODS AND RESULTS: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells.

SARS-CoV-2 can re-structure chromatin organization and alter the epigenomic landscape of the host genome, but the mechanisms that produce such changes remain unclear. Here, we use polymer physics to investigate how the chromatin of the host genome is re-organized upon infection with SARS-CoV-2. We show that re-structuring of A/B compartments can be explained by a re-modulation of intra-compartment homo-typic affinities, which leads to the weakening of A-A interactions and the enhancement of A-B mixing. At the TAD level, re-arrangements are physically described by a reduction in the loop extrusion activity coupled with an alteration of chromatin phase-separation properties, resulting in more intermingling between different TADs and a spread in space of the TADs themselves. In addition, the architecture of loci relevant to the antiviral interferon response, such as DDX58 or IFIT, becomes more variable within the 3D single-molecule population of the infected model, suggesting that viral infection leads to a loss of chromatin structural specificity. Analysing the time trajectories of pairwise gene-enhancer and higher-order contacts reveals that this variability derives from increased fluctuations in the chromatin dynamics of infected cells. This suggests that SARS-CoV-2 alters gene regulation by impacting the stability of the contact network in time.

Insights into the activity of cefiderocol against PER-2 producing Enterobacterales.

The PER-2 ß-lactamase is a unique class A enzyme conferring broad spectrum cephalosporin resistance. In this study, we explored the stability of cefiderocol (FDC) against PER-2 ß-lactamase to gain insights into structure activity relationships (SAR) of this synthetic siderophore-conjugated antibiotic. Herein, we show that the MICs of FDC for PER-2 producing isolates and transformants ranged between 0.125 and 64 µg/mL; diazabicyclooctanes (DBOs) reduced the MIC values. In PER-2 mutants, MIC values decreased up to 10-12 dilutions in agreement with previous observations especially in the case of Arg220 substitutions. Catalytic efficiency for PER-2 was 0.072 µM-1 s-1, comparable with PER-1 (0.046 µM-1 s-1) and NDM-1 (0.067 µM-1 s-1). In silico models revealed that FDC within the active site of PER-2 demonstrates unique interactions as a result of the inverted Ω loop fold and extension of the ß3-ß4 connecting loop.