Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.

OBJECTIVE: The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics. METHODS: A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores. RESULTS: Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes. CONCLUSIONS: Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

Predicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning.

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care. METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70). RESULTS: The models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor. CONCLUSION: The current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor's location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.

Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP).

OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

Predicting survival in glioblastoma with multimodal neuroimaging and machine learning.

PURPOSE: Glioblastoma (GBM) is the most common and aggressive malignant glioma, with an overall median survival of less than two years. The ability to predict survival before treatment in GBM patients would lead to improved disease management, clinical trial enrollment, and patient care. METHODS: GBM patients (N = 133, mean age 60.8 years, median survival 14.1 months, 57.9% male) were retrospectively recruited from the neurosurgery brain tumor service at Washington University Medical Center. All patients completed structural neuroimaging and resting state functional MRI (RS-fMRI) before surgery. Demographics, measures of cortical thickness (CT), and resting state functional network connectivity (FC) were used to train a deep neural network to classify patients based on survival (< 1y, 1-2y, >2y). Permutation feature importance identified the strongest predictors of survival based on the trained models. RESULTS: The models achieved a combined cross-validation and hold out accuracy of 90.6% in classifying survival (< 1y, 1-2y, >2y). The strongest demographic predictors were age at diagnosis and sex. The strongest CT predictors of survival included the superior temporal sulcus, parahippocampal gyrus, pericalcarine, pars triangularis, and middle temporal regions. The strongest FC features primarily involved dorsal and inferior somatomotor, visual, and cingulo-opercular networks. CONCLUSION: We demonstrate that machine learning can accurately classify survival in GBM patients based on multimodal neuroimaging before any surgical or medical intervention. These results were achieved without information regarding presentation symptoms, treatments, postsurgical outcomes, or tumor genomic information. Our results suggest GBMs have a global effect on the brain's structural and functional organization, which is predictive of survival.

Second-Order Nonlinear Optics as an Orientation-Independent Probe of Molecular Environments at Interfaces.

Measurement techniques that probe the second-order susceptibility, such as second-harmonic and sum-frequency generation, are recognized for their ability to study environments with broken centrosymmetry. As a result, they serve as reporters of molecules at surfaces because the second-order susceptibility is often zero in the adjacent bulk media. Although the signals measured in such experiments carry unique information about the interfacial environment, the challenge is to disentangle properties related to the electronic structure as they are wrapped up in the orientation distribution. Over the past 30 years, this challenge has been turned into an opportunity, as many studies have sought to learn about the arrangement of molecules at surfaces. Here we demonstrate that the flipped case is possible, where fundamental properties of the interfacial environment can be extracted in a manner that is completely independent of, and therefore oblivious to, the orientation distribution. Using p-cyanophenol adsorbed at the air-water interface as an example, we illustrate that the cyano group polarizability varies less along the direction of the C-N bond when at the surface than when the same molecules are in the bulk aqueous phase.

Trends and Characteristics of Blood Pressure Prescription Fills Before and During the COVID-19 Pandemic in the United States.

BACKGROUND: The COVID-19 pandemic disrupted healthcare in the United States and raised concerns about certain antihypertensives, and may have impacted both prescribing practices and access to blood pressure (BP) medications. METHODS: We assessed trends in BP prescription fills before and during the first year of the COVID-19 pandemic, using cross-sectional data for BP fills and tablets in the IQVIA (IMS Health) National Prescription Audit® database. Drugs filled via retail (92% coverage), mail-order (78% coverage), and long-term care (72% coverage) channels from January 2018 through December 2020 were included. Data were projected nationally and by state. RESULTS: Between 2.9 and 3.4 billion BP tablets were dispensed monthly until February 2020, increasing sharply to 3.8 billion in March 2020 and declining to 3.5 billion in April, then increasing at 3-month intervals until December 2020. The number of tablets per fill increased slightly over time, with the largest increase (from 66.7 to 68.6) during February-March, 2020. Tablets were dispensed through retail channels (99.7 billion), mail-order (14.7 billion), and long-term care (5.3 billion). Rates of patients initiating new medications decreased during 2020 compared to prior years. Fills did not vary significantly by drug class. CONCLUSIONS: A sharp increase in BP fills occurred with COVID-19 emergence, suggesting patients may have secured medications in preparation for potential access limitations. A decrease in new fills, indicating decreased initiation and/or modification of treatment regimens, suggests need for efforts to re-engage patients in the healthcare system and provide alternative ways to obtain medication refills and adjustments.

Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain.

Cerebrospinal fluid (CSF) is essential for the development and function of the central nervous system (CNS). However, the brain and its interstitium have largely been thought of as a single entity through which CSF circulates, and it is not known whether specific cell populations within the CNS preferentially interact with the CSF. Here, we develop a technique for CSF tracking, gold nanoparticle-enhanced X-ray microtomography, to achieve micrometer-scale resolution visualization of CSF circulation patterns during development. Using this method and subsequent histological analysis in rodents, we identify previously uncharacterized CSF pathways from the subarachnoid space (particularly the basal cisterns) that mediate CSF-parenchymal interactions involving 24 functional-anatomic cell groupings in the brain and spinal cord. CSF distribution to these areas is largely restricted to early development and is altered in posthemorrhagic hydrocephalus. Our study also presents particle size-dependent CSF circulation patterns through the CNS including interaction between neurons and small CSF tracers, but not large CSF tracers. These findings have implications for understanding the biological basis of normal brain development and the pathogenesis of a broad range of disease states, including hydrocephalus.

Deploying digitalisation and artificial intelligence in sustainable development research.

Many industrialised countries have benefited from the advent of twenty-first century technologies, especially automation, that have fundamentally changed manufacturing and industrial production processes. The next step in the evolution of automation is the development of artificial intelligence (AI), i.e. intelligence which is demonstrated by machines and systems, which cannot only perform tasks but also work synergistically with humans and nature. Intelligent systems that can see, analyse situations and respond sensitively to real-time cues, from human gestures and facial expressions to pedestrians crossing a busy street, will reshape transportation, precision agriculture, biodiversity conservation, environmental modelling, public health, construction and manufacturing, as well as initiatives designed to promote prosperity on Earth. This paper explores the connections between AI systems and sustainable development (SD) research. By means of a literature review, world survey, and case studies, ways in which AI can support research on SD and, inter alia, contribute to a more sustainable and equitable world, are identified.

Deferoxamine Prevents Neonatal Posthemorrhagic Hydrocephalus Through Choroid Plexus-Mediated Iron Clearance.

Posthemorrhagic hydrocephalus occurs in up to 30% of infants with high-grade intraventricular hemorrhage and is associated with the worst neurocognitive outcomes in preterm infants. The mechanisms of posthemorrhagic hydrocephalus after intraventricular hemorrhage are unknown; however, CSF levels of iron metabolic pathway proteins including hemoglobin have been implicated in its pathogenesis. Here, we develop an animal model of intraventricular hemorrhage using intraventricular injection of hemoglobin at post-natal day 4 that results in acute and chronic hydrocephalus, pathologic choroid plexus iron accumulation, and subsequent choroid plexus injury at post-natal days 5, 7, and 15. This model also results in increased expression of aquaporin-1, Na+/K+/Cl- cotransporter 1, and Na+/K+/ATPase on the apical surface of the choroid plexus 24 h post-intraventricular hemorrhage. We use this model to evaluate a clinically relevant treatment strategy for the prevention of neurological sequelae after intraventricular hemorrhage using intraventricular administration of the iron chelator deferoxamine at the time of hemorrhage. Deferoxamine treatment prevented posthemorrhagic hydrocephalus for up to 11 days after intraventricular hemorrhage and prevented the development of sensorimotor gating deficits. In addition, deferoxamine treatment facilitated acute iron clearance through the choroid plexus and subsequently reduced choroid plexus iron levels at 24 h with reversal of hemoglobin-induced aquaporin-1 upregulation on the apical surface of the choroid plexus. Intraventricular administration of deferoxamine at the time of intraventricular hemorrhage may be a clinically relevant treatment strategy for preventing posthemorrhagic hydrocephalus and likely acts through promoting iron clearance through the choroid plexus to prevent hemoglobin-induced injury.

Trends in Lipid-Lowering Prescriptions: Increasing Use of Guideline-Concordant Pharmacotherapies, U.S., 2017‒2022.

INTRODUCTION: Almost one third of U.S. adults have elevated low-density lipoprotein cholesterol, increasing their risk of atherosclerotic cardiovascular disease. The 2018 American College of Cardiology/American Heart Association Multisociety Cholesterol Management Guideline recommends maximally tolerated statin for those at increased atherosclerotic cardiovascular disease risk and add-on therapies (ezetimibe and PCSK9 inhibitors) in those at very high risk and low-density lipoprotein cholesterol ≥70 mg/dL. Prescription fill trends are unknown. METHODS: Using national outpatient retail prescription data from the first quarter of 2017 to the first quarter of 2022, authors determined counts of patients who filled low-, moderate-, or high-intensity statins alone and with add-on therapies. The overall percentage change and joinpoint regression were used to assess trends. Analyses were conducted in March 2022-May 2022. RESULTS: During the first quarter of 2017 to the first quarter of 2022, patients filling a statin increased by 25.0%, with the greatest increase in high-intensity statins (64.1%, range=6.6-10.9 million). Low-intensity statins decreased by 29.2% (range=3.3-2.4 million). Concurrent fills of high-intensity statin and ezetimibe rose by 210% to 579,012 patients by the first quarter of 2022, with an increase in slope by the first quarter of 2019 for all statin intensities (p<0.01). Concurrent fills of a statin and PCSK9 inhibitor increased to 2,629, 16,169, and 28,651 by the first quarter of 2022 for low-, moderate-, and high-intensity statins, respectively. For patients on all statin intensities and PCSK9 inhibitor, there were statistically significant increases in slope in the second quarter of 2019 and decreases in the first quarter of 2020. CONCLUSIONS: Patients filling moderate- and high-intensity statins and add-on ezetimibe and PCSK9 inhibitors have increased, indicating uptake of guideline-concordant lipid-lowering therapies. Improvements in the initiation and continuity of these therapies are important for atherosclerotic cardiovascular disease prevention.

Modeling Neonatal Intraventricular Hemorrhage through Intraventricular Injection of Hemoglobin.

Neonatal intraventricular hemorrhage (IVH) is a common consequence of premature birth and leads to brain injury, posthemorrhagic hydrocephalus (PHH), and lifelong neurological deficits. While PHH can be treated by temporary and permanent cerebrospinal fluid (CSF) diversion procedures (ventricular reservoir and ventriculoperitoneal shunt, respectively), there are no pharmacological strategies to prevent or treat IVH-induced brain injury and hydrocephalus. Animal models are needed to better understand the pathophysiology of IVH and test pharmacological treatments. While there are existing models of neonatal IVH, those that reliably result in hydrocephalus are often limited by the necessity for large-volume injections, which may complicate modeling of the pathology or introduce variability in the clinical phenotype observed. Recent clinical studies have implicated hemoglobin and ferritin in causing ventricular enlargement after IVH. Here, we develop a straightforward animal model that mimics the clinical phenotype of PHH utilizing small-volume intraventricular injections of the blood breakdown product hemoglobin. In addition to reliably inducing ventricular enlargement and hydrocephalus, this model results in white matter injury, inflammation, and immune cell infiltration in periventricular and white matter regions. This paper describes this clinically relevant, simple method for modeling IVH-PHH in neonatal rats using intraventricular injection and presents methods for quantifying ventricle size post injection.

Etiology- and region-specific characteristics of transependymal cerebrospinal fluid flow.

OBJECTIVE: Transependymal flow (TEF) of CSF, often delineated as T2-weighted hyperintensity adjacent to the lateral ventricles on MRI, is a known imaging finding, usually in the setting of CSF flow disturbances. Specific radiological features of TEF and their relationships with clinical markers of hydrocephalus and underlying disease pathology are not known. Here, the authors describe the radiological features and clinical associations of TEF with implications for CSF circulation in the setting of intracranial pathology. METHODS: After obtaining IRB review and approval, the authors reviewed the radiological records of all patients who underwent intracranial imaging with CT or MRI at St. Louis Children's Hospital, St. Louis, Missouri, between 2008 and 2019 to identify individuals with TEF. Then, under direct review of imaging, TEF pattern, degree, and location and underlying pathology and other radiological and clinical features pertaining to CSF circulation and CSF disturbances were noted. RESULTS: TEF of CSF was identified in 219 patients and was most prevalent in the setting of neoplasms (72%). In 69% of the overall cohort, TEF was seen adjacent to the anterior aspect of the frontal horns and the posterior aspect of the occipital horns of the lateral ventricles, and nearly half of these patients also had TEF dorsal to the third ventricle near the splenium of the corpus callosum. This pattern was independently associated with posterior fossa medulloblastoma when compared with pilocytic astrocytoma (OR 4.75, 95% CI 1.43-18.53, p = 0.0157). Patients with congenital or neonatal-onset hydrocephalus accounted for 13% of patients and were more likely to have TEF circumferentially around the ventricles without the fronto-occipital distribution. Patients who ultimately required permanent CSF diversion surgery were more likely to have the circumferential TEF pattern, a smaller degree of TEF, and a lack of papilledema at the time of CSF diversion surgery. CONCLUSIONS: CSF transmigration across the ependyma is usually restricted to specific periventricular regions and is etiology specific. Certain radiological TEF characteristics are associated with tumor pathology and may reflect impaired or preserved ependymal fluid handling and global CSF circulation. These findings have implications for TEF as a disease-specific marker and in understanding CSF handling within the brain.

Prescription Smoking-Cessation Medication Fills and Spending, 2009-2019.

INTRODUCTION: Smoking is the leading cause of preventable disease and death. However, effective medicines, including prescription medications often covered by health insurance, are available to aid cessation. METHODS: Trends of 7 U.S. Food and Drug Administration-approved prescription medications for smoking cessation during 2009-2019 (before and during Affordable Care Act implementation), including fill counts and spending (total and patient, adjusted to 2019 U.S. dollars), were assessed among U.S. adults aged ≥18 years. Symphony Health's Integrated Dataverse combines data on >90% of outpatient prescription fills with market purchasing data to create national estimates. Analyses were conducted in 2021. RESULTS: Annually, total fills (spending) decreased from 3.7 million ($577 million) in 2009 to 2.5 million ($465 million) in 2013 and increased to 4.5 million ($1.279 billion) in 2019; patient spending decreased from $174 million (30% of total annual spending) in 2009 to $54 million (4%) in 2019. Comparing 2009 with 2019, the total spending per fill increased by 80% (from $157 to $282), whereas patient spending per fill decreased by 75% (from $47 to $12). The total spending per fill for branded products increased by 175% (from $166 to $459) and decreased by 41% (from $75 to $44) for generic products. Branded product percentage decreased from 89% to 57%. CONCLUSIONS: Total fills and spending decreased from 2009 to 2013 and then increased through 2019, whereas patient spending decreased. Earlier studies suggest possible reasons for these trends, such as gradual implementation of federal requirements for insurance coverage of cessation medications and reduced cost sharing and financial barriers.

Single-center cost comparison analysis of stereoelectroencephalography with subdural grid and strip implantation.

OBJECTIVE: Use of invasive stereoelectroencephalography (SEEG) has gained traction recently. However, scant research has investigated the costs and resource utilization of SEEG compared with subdural grid (SDG)-based techniques in pediatric patients. Here, the authors have presented a retrospective analysis of charges associated with SEEG and SDG monitoring at a single institution. METHODS: The authors performed a retrospective case series analysis of pediatric patients with similar characteristics in terms of age, sex, seizure etiology, and epilepsy treatment strategy who underwent SEEG or SDG monitoring and subsequent craniotomy for resection of epileptogenic focus at St. Louis Children Hospital, St. Louis, Missouri, between 2013 and 2020. Financial data, including hospital charges, supplies, and professional fees (i.e., those related to anesthesia, neurology, neurosurgery, and critical care), were adjusted for inflation to 2020 US dollars. RESULTS: The authors identified 18 patients (9 underwent SEEG and 9 underwent SDG) with similar characteristics in terms of age (mean [range] 13.6 [1.9-21.8] years for SDG patients vs 11.9 [2.4-19.6] years for SEEG patients, p = 0.607), sex (4 females underwent SDG vs 6 females underwent SEEG, p = 0.637), and presence of lesion (5 patients with a lesion underwent SDG vs 8 underwent SEEG, p = 0.294). All patients underwent subsequent craniotomy for resection of epileptogenic focus. SEEG patients were more likely to have a history of status epilepticus (p = 0.029). Across 1 hospitalization for each SDG patient and 2 hospitalizations for each SEEG patient, SEEG patients had a significantly shorter mean operating room time (288 vs 356 minutes, p = 0.015), mean length of stay in the ICU (1.0 vs 2.1 days, p < 0.001), and tended to have a shorter overall length of stay in the hospital (8.4 vs 10.6 days, p = 0.086). Both groups underwent invasive monitoring for similar lengths of time (5.2 days for SEEG patients vs 6.4 days for SDG patients, p = 0.257). Time to treatment from the initial invasive monitoring evaluation was significantly longer in SEEG patients (64.6 vs 6.4 days, p < 0.001). Neither group underwent readmission within the first 30 days after hospital discharge. Seizure outcomes and complication rates were similar. After adjustment for inflation, the average total perioperative charges were $104,442 for SDG and $106,291 for SEEG (p = 0.800). CONCLUSIONS: Even though 2 hospitalizations were required for SEEG and 1 hospitalization was required for SDG monitoring, patients who underwent SEEG had a significantly shorter average length of stay in the ICU and operating room time. Surgical morbidity and outcomes were similar. Total perioperative charges for invasive monitoring and resection were approximately 2% higher for SEEG patients when corrected for inflation, but this difference was not statistically significant.

Multivariate analysis of associations between clinical sequencing and outcome in glioblastoma.

BACKGROUND: Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation, IDH1/2 mutation status, MGMT promoter methylation status, and extent of resection. High-throughput next-generation sequencing is a widely available diagnostic tool, but the independent impact of tumors harboring specific mutant genes on survival and the efficacy of extent of resection are not clear. METHODS: We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection. RESULTS: When controlling for factors with known prognostic significance including IDH1/2 mutation and after multiple comparisons analysis, CDKN2B and EGFR mutations were associated with reduced overall survival while PTEN mutation was associated with improved overall survival. Gross total resection, compared to other extent of resection, was associated with improved overall survival in patients with tumors harboring mutations in CDKN2A, CDKN2B, EGFR, PTEN, TERT promoter, and TP53. All patients possessed at least one of these 6 mutant genes. CONCLUSIONS: This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six commonly found mutant genes were associated with improved survival when gross total resection was achieved. Thus, even when accounting for known predictors of survival and multiple mutant gene comparisons, extent of resection continues to be strongly associated with survival.

Nonmedical Marijuana Use and Cardiovascular Events: A Systematic Review.

INTRODUCTION: Although marijuana use has increased since 2012, the perceived risk of adverse outcomes has decreased. This systematic review summarizes articles that examined the association between nonmedical marijuana use (ie, observed smoking, self-report, or urinalysis) and cardiovascular events in observational or experimental studies of adults aged ≥18. METHODS: We searched Medline, EMBASE, PsycInfo, CINAHL, Cochrane Library Database, and Global Health from January 1, 1970, through August 31, 2018. Of 3916 citations, 16 articles fit the following criteria: (1) included adults aged ≥18; (2) included marijuana/cannabis use that is self-reported smoked, present in diagnostic coding, or indicated through a positive diagnostic test; (3) compared nonuse of cannabis; (4) examined events related to myocardial infarction, angina, acute coronary syndrome, and/or stroke; (5) published in English; and (6) had observational or experimental designs. RESULTS: Of the 16 studies, 4 were cohort studies, 8 were case-control studies, 1 was a case-crossover study, 2 were randomized controlled trials, and 1 was a descriptive study. Studies ranged from 10 participants to 118 659 619 hospitalizations. Marijuana use was associated with an increased likelihood of myocardial infarction within 24 hours in 2 studies and stroke in 6 studies. Results of studies suggested an increased risk for angina and acute coronary syndrome, especially among people with a history of a cardiovascular event. CONCLUSION: This review suggests that people who use marijuana may be at increased risk for cardiovascular events. As states expand new laws permitting marijuana use, it will be important to monitor the effect of marijuana use on cardiovascular disease outcomes, perhaps through the inclusion of data on nonmedical marijuana use in diverse national and local surveillance systems.

An assessment of requirements in investments, new technologies, and infrastructures to achieve the SDGs.

Background: The implementation of the Sustainable Development Goals (SDGs) requires much planning and the provision of resources, especially regarding the necessary investments, technologies and infrastructures needed. Yet, it is presently unclear how available these elements are, what gaps exist, what changes have taken place in terms of their availability since the adoption of the SDGs and what their requirements will be in the future. The knowledge gap has become even more concerning because of the impact of the COVID-19 pandemic. Using a bibliometric analysis, an assessment of the global progress of SDG implementation and requirements, identifying challenges through the development of a matrix, and a set of 11 case studies to triangulate the holistic analysis, an assessment of the global progress of the SDGs implementation and the impact of the COVID-19 pandemic on this process was carried out. Results: The findings suggest that the scope and width of resources limitation are currently undermining the implementation of the SDGs. Apart from the fact that the pace of progress has been insufficient, the potential of the SDGs in pursuing sustainability and improving life quality is not fully realised. This trend suggests that a substantial acceleration of the efforts is needed, especially for the five SDGs whose progress since 2015 has not been optimal, namely SDG2, SDG11, SDG13, SDG15, and SDG16, while SDG3, SDG7, SDG9, SDG14, and SDG17 show signs of progress. The case studies showed that different industries have dissimilar effects on achieving the SDGs, with the food sector correlating with 15 SDGs, as opposed to the energy sector correlating with 6 SDGs. Accordingly, the priority level assessment in terms of achieving the SDGs, points to the need to further advance the above-mentioned five SDGs, i.e., 2, 11, 13, 15 and 16. Conclusions: This study fills in a knowledge gap in respect of the current need for and availability of investments, new technologies, and infrastructures to allow countries to pursue the SDGs. It is suggested that this availability is rather limited in specific contexts. In respect of the needs to be addressed, these include resource-related constraints, limited technologies and infrastructures, affecting SDG2, SDG11, SDG13, SDG15, and SDG16, whose progress needs to be enhanced. Since the global progress in the process of implementation of the SDGs depends directly and indirectly on addressing the resource gaps, it is suggested that this topic be further investigated, so that the present imbalances in the three dimensions of sustainable development: the economic, social and environmental, be adequately addressed. Supplementary Information: The online version contains supplementary material available at 10.1186/s12302-022-00629-9.

Empirical development and verification of career well-being scale for teachers in Taiwan: Implications for workplace counseling.

As it is one decade since the establishment of Kidd's model, an analysis of the career well-being (CWB) experienced by Eastern workers is both timely and necessary. To this end, we conducted a series of logical investigations of CWB in Taiwanese school teachers. Study 1 was conducted to conceptualize the main features of CWB (n = 135), and Study 2 was conducted using exploratory factor analysis to determine the validity of a four-factor measurement structure (n = 191). In Study 3, tests were completed to confirm the factor structure of the CWB (n = 533). Accordingly, we established a theory-based CWB measurement approach, and statistical analysis verified the convergent, divergent, and criterion validity of our CWB measurement model. Exploratory structural equation modeling rather than confirmatory factor analysis is recommended in discussions of CWB theory and practice in educational contexts. However, because our sample solely comprised Taiwanese teachers, our results are not generalizable to other occupations or cultures, even Eastern or Chinese-derived cultures. Implications for both theory and workplace counseling practice are presented.

Resting-State Functional Magnetic Resonance Imaging Networks as a Quantitative Metric for Impact of Neurosurgical Interventions.

Objective: Resting-state functional MRI (rs-fMRI) has been used to evaluate brain network connectivity as a result of intracranial surgery but has not been used to compare different neurosurgical procedures. Laser interstitial thermal therapy (LITT) is an alternative to conventional craniotomy for the treatment of brain lesions such as tumors and epileptogenic foci. While LITT is thought of as minimally invasive, its effect on the functional organization of the brain is still under active investigation and its impact on network changes compared to conventional craniotomy has not yet been explored. We describe a novel computational method for quantifying and comparing the impact of two neurosurgical procedures on brain functional connectivity. Methods: We used a previously described seed-based correlation analysis to generate resting-state network (RSN) correlation matrices, and compared changes in correlation patterns within and across RSNs between LITT and conventional craniotomy for treatment of 24 patients with singular intracranial tumors at our institution between 2014 and 2017. Specifically, we analyzed the differences in patient-specific changes in the within-hemisphere correlation patterns of the contralesional hemisphere. Results: In a post-operative follow-up period up to 2 years within-hemisphere connectivity of the contralesional hemisphere after surgery was more highly correlated to the pre-operative state in LITT patients when compared to craniotomy patients (P = 0.0287). Moreover, 4 out of 11 individual RSNs demonstrated significantly higher degrees of correlation between pre-operative and post-operative network connectivity in patients who underwent LITT (all P < 0.05). Conclusion: Rs-fMRI may be used as a quantitative metric to determine the impact of different neurosurgical procedures on brain functional connectivity. Global and individual network connectivity in the contralesional hemisphere may be more highly preserved after LITT when compared to craniotomy for the treatment of brain tumors.

Neonatal hydrocephalus: an atypical presentation of malignant infantile osteopetrosis.

PURPOSE: Autosomal recessive osteopetrosis has a variable presentation, most commonly including failure to thrive, hypocalcemia, seizures, hepatosplenomegaly, hydrocephalus, vision or hearing loss, and cytopenias. Multiple symptoms are usually seen at presentation. The variability of presentation often delays diagnosis and subsequent treatment. Here, we present a case of an infant with this condition who initially presented with triventricular hydrocephalus with Chiari I malformation. This alone is not a common presentation of this disease, and we present this case to highlight autosomal recessive osteopetrosis as a potential diagnosis in infants presenting with hydrocephalus and discuss the other associated symptoms, management, and prognosis of this condition. CASE REPORT: The patient was a full-term infant with a routine newborn period. At 6 months, the infant had macrocephaly and frontal bossing with a bulging fontanelle. She was found to have hydrocephalus with moderate ventriculomegaly involving the third and lateral ventricles with an associated Chiari 1 malformation. The infant was asymptomatic at the time. The infant was promptly referred to neurosurgery and underwent an uncomplicated ventriculoperitoneal shunt placement. Post-operative X-rays showed increased density of the skull with other bone changes suggestive of autosomal recessive osteopetrosis. Subsequent lab work and imaging studies were consistent with this condition. The diagnosis was confirmed by genetic testing, and the patient has undergone treatment with hematopoietic stem cell transplant. CONCLUSION: Hydrocephalus is a common feature of this condition, typically seen in conjunction with other systemic symptoms and laboratory findings. Our patient had a limited initial presentation of triventricular hydrocephalus with Chiari I malformation and was otherwise clinically asymptomatic. There is limited literature of such a presentation, and we highlight this case to increase awareness, as timely diagnosis of these patients is critical for treatment and future outcomes.