Magnetic resonance-guided focused ultrasound thalamotomy for tremor.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has emerged as an effective treatment for tremor, particularly in those patients who are excluded from deep brain stimulation. The authors illustrate an example of MRgFUS thalamotomy, targeting the ventralis intermedius nucleus, in a 78-year-old patient with tremor who had features of essential tremor and tremor-predominant Parkinson's disease. Significant tremor improvement was seen during the procedure. The authors review step-by-step the preoperative considerations, Vim targeting, treatment, and outcomes for this evolving treatment modality. The video can be found here: https://stream.cadmore.media/r10.3171/2024.7.FOCVID249.

Endocapillary proliferative glomerulonephritis associated with Q fever endocarditis: A case report.

Acute Coxiella burnetti (Q fever) infection is known to activate the autoimmune inflammatory response. We report a rare case of glomerulonephritis associated with the Coxiella infection. An elderly male first presented with recurrent fevers of unknown origin and was subsequently diagnosed with Q fever infection and treated with doxycycline. He represented 2 months later with an acute kidney injury and active urinary sediment. Renal biopsy demonstrated a mesangiopathic pattern with staining for both C1q and IgM, raising possibilities of infection-related glomerulonephritis, C1q nephropathy and lupus nephritis. This case demonstrates glomerulonephritis as a complication of Q fever infection and the differential diagnosis and workup up that needs to be considered in cases of chronic Q fever.

Accuracy of machine learning in predicting outcomes post-percutaneous coronary intervention: a systematic review.

Background: Recent studies have shown potential in introducing machine learning (ML) algorithms to predict outcomes post-percutaneous coronary intervention (PCI). Aims: We aimed to critically appraise current ML models' effectiveness as clinical tools to predict outcomes post-PCI. Methods: Searches of four databases were conducted for articles published from the database inception date to 29 May 2021. Studies using ML to predict outcomes post-PCI were included. For individual post-PCI outcomes, measures of diagnostic accuracy were extracted. An adapted checklist comprising existing frameworks for new risk markers, diagnostic accuracy, prognostic tools and ML was used to critically appraise the included studies along the stages of the translational pathway: development, validation, and impact. Quality of training data and methods of dealing with missing data were evaluated. Results: Twelve cohorts from 11 studies were included with a total of 4,943,425 patients. ML models performed with high diagnostic accuracy. However, there are concerns over the development of the ML models. Methods of dealing with missing data were problematic. Four studies did not discuss how missing data were handled. One study removed patients if any of the predictor variable data points were missing. Moreover, at the validation stage, only three studies externally validated the models presented. There could be concerns over the applicability of these models. None of the studies discussed the cost-effectiveness of implementing the models. Conclusions: ML models show promise as a useful clinical adjunct to traditional risk stratification scores in predicting outcomes post-PCI. However, significant challenges need to be addressed before ML can be integrated into clinical practice.

Supercharged Phosphotriesterase for improved Paraoxon activity.

Phosphotriesterases (PTEs) represent a class of enzymes capable of efficient neutralization of organophosphates (OPs), a dangerous class of neurotoxic chemicals. PTEs suffer from low catalytic activity, particularly at higher temperatures, due to low thermostability and low solubility. Supercharging, a protein engineering approach via selective mutation of surface residues to charged residues, has been successfully employed to generate proteins with increased solubility and thermostability by promoting charge-charge repulsion between proteins. We set out to overcome the challenges in improving PTE activity against OPs by employing a computational protein supercharging algorithm in Rosetta. Here, we discover two supercharged PTE variants, one negatively supercharged (with -14 net charge) and one positively supercharged (with +12 net charge) and characterize them for their thermodynamic stability and catalytic activity. We find that positively supercharged PTE possesses slight but significant losses in thermostability, which correlates to losses in catalytic efficiency at all temperatures, whereas negatively supercharged PTE possesses increased catalytic activity across 25°C-55°C while offering similar thermostability characteristic to the parent PTE. The impact of supercharging on catalytic efficiency will inform the design of shelf-stable PTE and criteria for enzyme engineering.

Radiologic anatomic study of the humeral medullary canal.

Hypothesis/Background: Patient-specific implants have become an increasingly researched area to improve surgical outcomes. Patient-specific implants have been suggested to provide advantages for better implant alignment and thus improve surgical outcomes. One such area for application is in the use of intramedullary nails for humeral fracture stabilization. However, the anatomy of the canal is not well defined, especially in a larger scale demographic study. Methods: In this observational cross-sectional study, axial computed tomography scans of 150 humeri were used to measure the cortical thickness and canal width in both coronal and sagittal orientations. Measurements were made at 7 evenly spaced levels along the humerus from the surgical neck to the point immediately superior to the supracondylar ridge. X-rays were used to measure the valgus, recurvatum, and procurvatum angles, along with their associated locations. Demographic data recorded included age, gender, body mass index (BMI), race, and ethnicity. Results: The mean coronal canal widths decreased inferiorly from the surgical neck to midshaft before increasing to the supracondylar fossa. Mean sagittal widths decreased along the complete course of the canal. The ratio of coronal to sagittal canal widths decreased from 1.09 at level 1 to 0.83 at level 5 before increasing to 1.30 at level 7. Females had significantly smaller canal widths and cortex thicknesses in both the sagittal and coronal planes throughout the course of the canal. There were no significant differences in canal widths among ethnicities. Age was positively correlated with the canal width in the coronal and sagittal orientations but was negatively correlated with cortical thickness in all 7 levels. BMI was not significantly correlated with canal width. Conclusion/Discussion: The data included in this study may be used to determine standard widths and measurements of the humerus. However, there are notable patterns or differences in the shape of the medullary canal of the humerus between subgroups. This study is the first to conduct a larger scale demographic investigation comparing the humeral canal characteristics among sex, ethnicity, age, and BMI. These data may serve as a platform to further investigate the course of the medullary canal.

A strong priority effect in the assembly of a specialized insect-microbe symbiosis.

Specialized host-microbe symbioses are ecological communities, whose composition is shaped by various processes. Microbial community assembly in these symbioses is determined in part by interactions between taxa that colonize ecological niches available within habitat patches. The outcomes of these interactions, and by extension the trajectory of community assembly, can display priority effects-dependency on the order in which taxa first occupy these niches. The underlying mechanisms of these phenomena vary from system to system and are often not well resolved. Here, we characterize priority effects in colonization of the squash bug (Anasa tristis) by bacterial symbionts from the genus Caballeronia, using pairs of strains that are known to strongly compete during host colonization, as well as strains that are isogenic and thus functionally identical. By introducing symbiont strains into individual bugs in a sequential manner, we show that within-host populations established by the first colonist are extremely resistant to invasion, regardless of strain identity and competitive interactions. By knocking down the population of an initial colonist with antibiotics, we further show that colonization success by the second symbiont is still diminished even when space in the symbiotic organ is available and ostensibly accessible for colonization. We speculate that resident symbionts exclude subsequent infections by manipulating the host environment, partially but not exclusively by eliciting tissue remodeling of the symbiont organ. IMPORTANCE: Host-associated microbial communities underpin critical ecosystem processes and human health, and their ability to do so is determined in turn by the various processes that shape their composition. While selection deterministically acts on competing genotypes and species during community assembly, the manner by which selection determines the trajectory of community assembly can differ depending on the sequence by which taxa are established within that community. We document this phenomenon, known as a priority effect, during experimental colonization of a North American insect pest, the squash bug Anasa tristis, by its betaproteobacterial symbionts in the genus Caballeronia. Our study demonstrates how stark, strain-level variation can emerge in specialized host-microbe symbioses simply through differences in the order by which strains colonize the host. Understanding the mechanistic drivers of community structure in host-associated microbiomes can highlight both pitfalls and opportunities for the engineering of these communities and their constituent taxa for societal benefit.

Clinical review of substitutions or alternatives for critical chemotherapy drug shortages in hematologic malignancies.

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: Over the past decade, drug shortages have become increasingly more problematic for clinicians, with over 300 drug shortages reported in the first quarter of 2023. Shortages of chemotherapy drugs can have a negative impact on patient care, as omission or delay of treatment can lead to worse outcomes. Although many articles have been published on this topic, currently no review articles discuss strategies for using alternative regimens or substitutions in the event of severe chemotherapy drug shortages. SUMMARY: In this article, we review the literature on antineoplastic agents used to treat hematologic malignancies that experienced a drug shortage from 2010 through 2023, providing recommendations for substitutions and alternative regimens in the event of a critical shortage. In particular, we discuss how shortages of fludarabine, cytarabine, daunorubicin, methotrexate, and platinum agents may be addressed, including supporting clinical evidence. CONCLUSION: Further publications assessing possible alternatives and substitutions for chemotherapy agents and examining the efficacy of previous strategies are needed to mitigate potentially devastating interruptions to care for patients with cancer during severe drug shortages.

The Role of Corticosteroid Injections in the Treatment of Sacroiliitis: A Narrative Review.

OBJECTIVES: Axial spondyloarthritis (axSpA) is a chronic rheumatic, musculoskeletal, inflammatory disease with a propensity to present as sacroiliitis, which manifests as low back, buttock, or thigh pain. Effective primary management of axSpA requires a comprehensive approach specific to each patient and disease severity. Non-pharmacological measures form the cornerstone of treatment. With refractory disease, management also consists of local periarticular and intraarticular injections. The use of sacroiliac joint (SIJ) corticosteroid injections for the treatment of axSpA and localised inflammation, however, is a continuously burgeoning management option. This narrative review aims to present consolidated findings and summarise previously unreferenced or recently available evidence regarding corticosteroid injections to the SIJ for treating sacroiliitis and axSpA. METHODS: A comprehensive literary review with the following electronic databases was searched: MEDLINE via PubMed, Web of Science, Cochrane Library, and EMBASE. RESULTS: The initial search yielded a total of 126 references. After duplicates were removed and the remainder analysed for inclusion criteria, 7 studies were included. To stratify each study, injection methodology and characteristics were defined. DISCUSSION: The use of SIJ corticosteroid injections can be an appropriate and effective treatment option for refractory axSpA. The studies presented in this review reported a general trend towards a reduction in pain severity after SIJ corticosteroid injections. Because of the complexity and heterogeneity of the anatomy of the SIJ, image guidance is recommended when performing SIJ injections. Image-guided injections seem to produce better outcomes when compared to anatomic landmark-guided injections.

Adapting the Zero Suicide framework to the adult emergency department setting: Strategies for nurse leaders.

The ED has been increasingly recognized as a key setting for suicide prevention. Zero Suicide (ZS) is an aspirational goal to eliminate suicide for all patients within a health care system through utilization of best practices. However, there has been limited exploration of ZS implementation within the ED. As ED nurses play an important role in suicide prevention through their close contact with patients at risk for suicide, ZS implementation would benefit from tailored strategies for ED nurse leadership. We describe the ZS framework and provides strategies for nurse leaders to adapt each ZS component in the adult ED.

Robot-assisted deep brain stimulation of the centromedian nucleus of the thalamus for generalized epilepsy: targeting and operative video.

The centromedian (CM) nucleus of the thalamus is a promising target for a range of brain diseases including drug-resistant generalized and multifocal epilepsy. CM is highly connected to cortical and subcortical regions including frontoparietal/sensorimotor cortex, striatum, brainstem, and cerebellum, which are involved in some generalized epilepsy syndromes like Lennox-Gastaut syndrome (LGS). In this video, the authors describe their methodology for targeting CM for deep brain stimulation (DBS). Delineation of an optimal and consistent target will expand the efficacy of neuromodulation of CM in intractable epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID245.

Correction: Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor.

[This corrects the article DOI: 10.1371/journal.pone.0266608.].

Case Report: Low-grade glioma with NF1 loss of function mimicking diffuse intrinsic pontine glioma.

Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial. This study presents the case of a 19-year-old female with clinical and imaging hallmarks of DIPG, who underwent a biopsy of a tumor in the region of the right middle cerebellar peduncle. Her lesional cells were negative for H3K27M alterations and had low-grade histologic features. Next-generation sequencing revealed a frameshift mutation in the NF1 gene as the likely driver mutation. These features suggest a diagnosis of a low-grade glioma associated with NF1 loss of function, with far-reaching consequences regarding both treatment strategy and prognosis. This case provides support for the utility of diagnostic tissue biopsy in cases of suspected DIPG.

The Case for Neurosurgical Intervention in Cancer Neuroscience.

The emerging field of cancer neuroscience reshapes our understanding of the intricate relationship between the nervous system and cancer biology; this new paradigm is likely to fundamentally change and advance neuro-oncological care. The profound interplay between cancers and the nervous system is reciprocal: Cancer growth can be induced and regulated by the nervous system; conversely, tumors can themselves alter the nervous system. Such crosstalk between cancer cells and the nervous system is evident in both the peripheral and central nervous systems. Recent advances have uncovered numerous direct neuron-cancer interactions at glioma-neuronal synapses, paracrine mechanisms within the tumor microenvironment, and indirect neuroimmune interactions. Neurosurgeons have historically played a central role in neuro-oncological care, and as the field of cancer neuroscience is becoming increasingly established, the role of neurosurgical intervention is becoming clearer. Examples include peripheral denervation procedures, delineation of neuron-glioma networks, development of neuroprostheses, neuromodulatory procedures, and advanced local delivery systems. The present review seeks to highlight key cancer neuroscience mechanisms with neurosurgical implications and outline the future role of neurosurgical intervention in cancer neuroscience.

Systematic Review-Role of MRI in Cervical Cancer Staging.

A systematic review of the diagnostic accuracy of MRI in the staging of cervical cancer was conducted based on the literature from the last 5 years. A literature search was performed in the Cochrane Library, EMBASE, MEDLINE and PubMed databases using the MeSH terms "cervical cancer", "MRI" and "neoplasm staging". A total of 110 studies were identified, of which 8 fit the inclusion criteria. MRI showed adequate accuracy (74-95%) and high sensitivity (92-100%) in assessing stromal invasion. The data for MRI in terms of assessing vaginal and pelvic side wall involvement were wide ranging and inconclusive. In assessing lymph node metastasis, MRI showed an adequate accuracy (73-90%), specificity (75-91%) and NPV (71-96%) but poor sensitivity (52-75%) and PPV (52-75%). MRI showed high accuracy (95%), sensitivity (78-96%), specificity (87-94%), and NPV (98-100%) but poor PPV (27-42%) in detecting bladder involvement. There was a paucity of data on the use of MRI in assessing rectal involvement in cervical cancer. Overall, the literature was heterogenous in the definitions and language used, which reduced the comparability between articles. More research is required into the diagnostic accuracy of MRI in the staging of cervical cancer and there must be increased consistency in the definitions and language used in the literature.

County Characteristics and Veteran Suicide in the United States, 2011-2018.

INTRODUCTION: Few studies have examined county-level hotspots of veteran suicide and associated place-based contributors, limiting development of targeted community-level prevention strategies. The objectives of this national spatial analysis of all veteran suicides were to identify areas of the United States with higher-than-expected veteran suicide rates and determine county-level social and economic characteristics associated with areas of higher risk. METHODS: Using Bayesian hierarchical modeling, county-level standardized mortality ratios for veteran suicide deaths were estimated for time periods 2011-2018, 2011-2014, and 2015-2018. Adjusted relative risk, accounting for community characteristics, for each county was then estimated and associations between community characteristics and veteran suicide risk were examined. Analyses were conducted in 2023-2024. RESULTS: Risk of veteran suicide is predominantly concentrated in the Mountain West and West. Significant predictors of risk across all time periods were per capita number of firearm retailers (2011-2018 relative risk [RR]=1.065 [95% credible interval [CI] 1.030-1.102]), the proportion of residents who moved in the past year (2011-2018 RR=1.060 [95% CI 1.039-1.081]), the proportion of residents who live alone (2011-2018 RR=1.067 [95% CI 1.046-1.089]), the proportion of residents in rental housing (2011-2018 RR=1.041 [95% CI 1.018-1.065]), and the proportion of married residents (2011-2018 RR=0.915 [95% CI 0.890-0.941]). CONCLUSIONS: This study contributes to a comprehensive public health approach to veteran suicide prevention by identifying where resources are needed most, and which place-based intervention targets have the largest potential for impact. Findings suggest that public health efforts to address suicide among veterans should address community-level firearm access and identify ways to alleviate deleterious effects of social fragmentation.

Septic arthritis of the cervical facet joint: Clinical report and review of the literature.

BACKGROUND: Facet joint septic arthritis (FJSA) is an uncommon cause of neck pain, most frequently occurring in the lumbosacral spine. Cervical facet joint septic arthritis is particularly rare. Symptoms typically include spinal or paraspinal pain and tenderness, with severe infections potentially causing neurological impairments. This condition can progress to discitis and osteomyelitis. High clinical suspicion is required for accurate diagnosis and timely treatment. OBJECTIVE: To present the first known case of cervical spine FJSA caused by Moraxella species and provide an updated narrative review of cervical spine FJSA. METHODS: A case study of a 66-year-old male with cervical spine FJSA caused by Moraxella osloensis is detailed. Additionally, a librarian-assisted literature search was conducted on MEDLINE Pubmed, filtering for adult human trials and including various study types, resulting in the inclusion of 9 relevant manuscripts. RESULTS: The patient's symptoms included neck, right upper thoracic, and periscapular pain, with episodes of numbness and tingling. MRI revealed septic arthritis at the C7-T1 facet joint and associated osteomyelitis. Cultures identified Moraxella osloensis as the causative agent. The patient was successfully treated with antibiotics and experienced significant symptom improvement. Literature review highlights that Staphylococcus aureus is the most common causative agent of cervical FJSA, with diagnosis typically involving MRI and culture tests. Treatment generally includes long-term antibiotics, with some cases requiring surgical intervention. CONCLUSIONS: This report underscores the need for high clinical suspicion in diagnosing FJSA and highlights the importance of early intervention. It documents the first known case of cervical spine FJSA caused by Moraxella osloensis, contributing valuable information to the limited literature on this rare condition.

Outcomes following allogeneic hematopoietic cell transplantation relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Improved first progression-free survival following allogeneic hematopoietic cell transplantation relapse with the use of immunotherapy.

Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope. Initially, 50 (27.0%) received imatinib, 118 (63.8%) received a second-generation TKI (2G-TKI), and 17 (9.2%) received ponatinib. A total of 77 patients (41.6%) required a dose reduction of their initial TKI due to toxicity. Sixty-six patients (35.7%) did not complete maintenance due to toxicity; 69 patients (37.3%) discontinued 1 TKI, and 11 (5.9%) discontinued 2 TKIs due to toxicity. Initial imatinib versus 2G-TKI versus ponatinib maintenance was discontinued in 19 (38.0%) versus 68 (57.6%) versus 3 (17.6%) patients due to toxicity (p = .003), respectively. Patients on ponatinib as their initial TKI had a longer duration of TKI maintenance versus 2G-TKI: 576.0 days (range, 72-921) versus 254.5 days (range, 3-2740; p = .02). The most common reasons for initial TKI discontinuation include gastrointestinal (GI) intolerance (15.1%), cytopenia (8.6%), and fluid retention (3.8%). The 5-year overall survival and progression-free survival for the total population were 78% and 71%, respectively. Our findings demonstrate the challenges of delivering post-HCT TKI maintenance in a large real-world cohort as toxicities leading to TKI interruptions, discontinuation, and dose reduction were common.

Structure-Dependent Water Responsiveness of Protein Block Copolymers.

Biological water-responsive (WR) materials are abundant in nature, and they are used as mechanical actuators for seed dispersal by many plants such as wheat awns and pinecones. WR biomaterials are of interest for applications as high-energy actuators, which can be useful in soft robotics or for capturing energy from natural water evaporation. Recent work on WR silk proteins has shown that ß-sheet nanocrystalline domains with high stiffness correlate with the high WR actuation energy density, but the fundamental mechanisms to drive water responsiveness in proteins remain poorly understood. Here, we design, synthesize, and study protein block copolymers consisting of two α-helical domains derived from cartilage oligomeric matrix protein coiled-coil (C) flanking an elastin-like peptide domain (E), namely, CEC. We use these protein materials to create WR actuators with energy densities that outperform mammalian muscle. To elucidate the effect of structure on WR actuation, CEC was compared to a variant, CECL44A, in which a point mutation disrupts the α-helical structure of the C domain. Surprisingly, CECL44A outperformed CEC, showing higher energy density and less susceptibility to degradation after repeated cycling. We show that CECL44A exhibits a higher degree of intermolecular interactions and is stiffer than CEC at high relative humidity (RH), allowing for less energy dissipation during water responsiveness. These results suggest that strong intermolecular interactions and the resulting, relatively steady protein structure are important for water responsiveness.