Quantification of the environmental impact of radiotherapy and associated secondary human health effects: a multi-institutional retrospective analysis and simulation.

BACKGROUND: The health-care industry is a substantial contributor to global greenhouse gas emissions, yet the specific environmental impact of radiotherapy, a cornerstone of cancer treatment, remains under-explored. We aimed to quantify the emissions associated with the delivery of radiotherapy in the USA and propose a framework for reducing the environmental impact of oncology care. METHODS: In this multi-institutional retrospective analysis and simulation study, we conducted a lifecycle assessment of external beam radiotherapy (EBRT) for ten anatomical disease sites, adhering to the International Organization for Standardization's standards ISO 14040 and ISO 14044. We analysed retrospective data from Jan 1, 2017, to Oct 1, 2023, encompassing patient and staff travel, medical supplies, and equipment and building energy use associated with the use of EBRT at four academic institutions in the USA. The primary objective was to measure the environmental impacts across ten categories: greenhouse gases (expressed as kg of carbon dioxide equivalents [CO2e]), ozone depletion, smog formation, acidification, eutrophication, carcinogenic and non-carcinogenic potential, respiratory effects, fossil fuel depletion, and ecotoxicity. Human health effects secondary to these environmental impacts were also estimated as disability-adjusted life years. We also assessed the potential benefits of hypofractionated regimens for breast and genitourinary (ie, prostate and bladder) cancers on US greenhouse gas emissions using an analytic model based on the 2014 US National Cancer Database for fractionation patterns and patient commute distances. FINDINGS: We estimated that the mean greenhouse gas emissions associated with a standard 25-fraction EBRT course were 4310 kg CO2e (SD 2910), which corresponded to 0·0035 disability-adjusted life years per treatment course. Transit and building energy usage accounted for 25·73% (1110 kg CO2e) and 73·95% of (3190 kg CO2e) of total greenhouse gas emissions, respectively, whereas supplies contributed only 0·32% (14 kg CO2e). Across the other environmental impact categories, most of the environmental impact also stemmed from patient transit and energy use within facilities, with little environmental impact contributed by supplies used. Hypofractionated treatment simulations suggested a substantial reduction in greenhouse gas emissions-by up to 42% for breast and 77% for genitourinary cancer-and environmental impacts more broadly. INTERPRETATION: This comprehensive lifecycle assessment of EBRT delineates the environmental and secondary health impacts of radiotherapy, and underscores the urgent need for sustainable practices in oncology. The findings serve as a reference for future decarbonisation efforts in cancer care and show the potential environmental benefits of modifying treatment protocols (when clinical equipoise exists). They also highlight strategic opportunities to mitigate the ecological footprint in an era of escalating climate change and increasing cancer prevalence. FUNDING: Mount Zion Health Fund.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site.

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (Pinteraction=0.312) but did with functional independence (Pinteraction=0.010), with a similar trend on excellent outcome (Pinteraction=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (Pinteraction=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (Pinteraction=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.

Differential Diagnosis of Hematologic and Solid Tumors Using Targeted Transcriptome and Artificial Intelligence.

Diagnosis and classification of tumors is increasingly dependent on biomarkers. RNA expression profiling using next-generation sequencing provides reliable and reproducible information on the biology of cancer. This study investigated targeted transcriptome and artificial intelligence for differential diagnosis of hematologic and solid tumors. RNA samples from hematologic neoplasms (N = 2606), solid tumors (N = 2038), normal bone marrow (N = 782), and lymph node control (N = 24) were sequenced using next-generation sequencing using a targeted 1408-gene panel. Twenty subtypes of hematologic neoplasms and 24 subtypes of solid tumors were identified. Machine learning was used for diagnosis between two classes. Geometric mean naïve Bayesian classifier was used for differential diagnosis across 45 diagnostic entities with assigned rankings. Machine learning showed high accuracy in distinguishing between two diagnoses, with area under the curve varying between 1 and 0.841. Geometric mean naïve Bayesian algorithm was trained using 3045 samples and tested on 1415 samples, and showed correct first-choice diagnosis in 100%, 88%, 85%, 82%, 88%, 72%, and 72% of acute lymphoblastic leukemia, acute myeloid leukemia, diffuse large B-cell lymphoma, colorectal cancer, lung cancer, chronic lymphocytic leukemia, and follicular lymphoma cases, respectively. The data indicate that targeted transcriptome combined with artificial intelligence are highly useful for diagnosis and classification of various cancers. Mutation profiles and clinical information can improve these algorithms and minimize errors in diagnoses.

Decreased amygdala-sensorimotor connectivity mediates the association between prenatal stress and broad autism phenotype in young adults: Project Ice Storm.

Studies show that prenatal maternal stress (PNMS) is related to risk for child autism, and to atypical amygdala functional connectivity in the autistic child. Yet, it remains unclear whether amygdala functional connectivity mediates the association between PNMS and autistic traits, particularly in young adult offspring. We recruited women who were pregnant during, or within 3 months of, the 1998 Quebec ice storm crisis, and assessed three aspects of PNMS: objective hardship (events experienced during the ice storm), subjective distress (post-traumatic stress symptoms experienced as a result of the ice storm) and cognitive appraisal. At age 19, 32 young adults (21 females) self-reported their autistic-like traits (i.e., aloof personality, pragmatic language impairment and rigid personality), and underwent structural MRI and resting-state functional MRI scans. Seed-to-voxel analyses were conducted to map the amygdala functional connectivity network. Mediation analyses were implemented with bootstrapping of 20,000 resamplings. We found that greater maternal objective hardship was associated with weaker functional connectivity between the left amygdala and the right postcentral gyrus, which was then associated with more pragmatic language impairment. Greater maternal subjective distress was associated with weaker functional connectivity between the right amygdala and the left precentral gyrus, which was then associated with more aloof personality. Our results demonstrate that the long-lasting effect of PNMS on offspring autistic-like traits may be mediated by decreased amygdala-sensorimotor circuits. The differences between amygdala-sensory and amygdala-motor pathways mediating different aspects of PNMS on different autism phenotypes need to be studied further.

Mechanistic role of pyroptosis in tumor microenvironment and tumor immunotherapy.

In recent decades, extraordinary attention has been devoted to cell death pathways principally because of multifaceted regulatory roles in normal developmental and pathophysiological processes. The removal of functionally defective, infected or potentially malignant cells is regulated by programmed cell death (PCD) cascades.  Pyroptotic cell death is a highly complicated pro-inflammatory form of cell death. Pyroptosis is characterized by the formation of pores in the plasma membrane by oligomerization of the N-terminal fragment of gasdermins (gasdermin-NT) following the cleavage of gasdermin. Pyroptosis plays a pivotal role in the innate immune responses and mechanistically steered by inflammasome-mediated and inflammasome-independent cascades. In this review, we have comprehensively analyzed how different signaling pathways regulated pyroptosis in cancer inhibition and metastatic spread of cancer cells to the secondary sites. Comprehensive understanding of the interconnection between signaling pathways and pyroptosis will enable us to reap maximum benefits from the exciting mechanistic insights gained from pioneering studies related to pyroptosis.

Role of melatonin in carcinogenesis and metastasis: From mechanistic insights to intermeshed networks of noncoding RNAs.

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini-review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini-review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers.

Outcomes of biological therapy in patients with severe asthma with chronic rhinosinusitis in Saudi Arabia: patients with nasal polyps versus those without nasal polyps.

BACKGROUND: This study's purposes were to evaluate the impact of biological therapies on outcomes in patients with severe asthma (SA) and chronic rhinosinusitis (CRS) and to compare these effects among those with NP (CRSwNP) versus those without NP (CRSsNP) in the "real-world" setting in Saudi Arabian patients. METHODS: From March to September 2022, a retrospective observational cohort study was undertaken at the severe asthma clinics of the Armed Forces Hospital-Southern Region (AFHSR) and King Khalid University Hospital, Abha, Saudi Arabia, to delineate the effects of dupilumab therapy. Outcomes were assessed, including clinical outcomes, FEV1, and laboratory findings before and one year after dupilumab. Post-therapy effects were compared between CRSwNP and CRSsNP. RESULTS: Fifty subjects were enrolled, with a mean age of 46.56. There were 27 (54%) females and 23(46%) males. Significant improvements in clinical parameters (frequency of asthma exacerbations and hospitalizations, the use of OCs, anosmia, SNOTT-22, and the ACT), FEV1, and laboratory ones (serum IgE and eosinophilic count) were observed 6 and 12 months after using dupilumab (p < 0.001), respectively. However, after 12 months of dupilumab therapy, there were no significant differences between those with and without NP with regards to clinical (anosmia, ACT, and OCs use), laboratory (eosinophilic count, serum IgE level) parameters, and FEV1%. CONCLUSIONS: Patients with CRS experienced significant improvements in clinical, FEV1, and laboratory outcomes after dupilumab therapy. However, these improvements were not maintained when comparing CRSwNP with CRSsNP. There were no significant differences between those with and without NP regarding ACT and OCs use or laboratory (eosinophilic count, serum IgE level) parameters. Further prospective multicenter studies are warranted.

Ultrasound guidance to replicate transuterine BioGlue injection in the fetal hydrocephalus sheep model.

INTRODUCTION: Congenital hydrocephalus often results in irreversible and severe damage to the brain despite postnatal interventions. The potential for prenatal intervention to mitigate these deleterious effects underscores the importance of a suitable animal model. We aimed assess the results of an ultrasound guided transuterine approach to replicate the BioGlue injection fetal hydrocephalus model. METHODS: Pregnant ewes were anesthetized at 95 days of gestation and BioGlue was injected into the fetal cisterna magna under ultrasound guidance through the uterus. Ventriculomegaly was assessed by MRI and histology. RESULTS: Nine pregnant ewes were included in the study, and their fetuses were divided into the the BioGlue intervention group (n=9 fetuses) or the control group (n=7 fetuses) who were not injected. Although hydrocephalus was noted in 5 of 9 fetuses in the intervention group, the ability to induce hydrocephalus went from 0% to 100% in the last 3 fetuses following technical modifications. None of the controls developed hydrocephalus. Fetal brains with hydrocephalus demonstrated increased IBA1+ compared to control animals. CONCLUSIONS: While technical challenges were noted, the ultrasound guided transuterine approach to replicate the BioGlue fetal hydrocephalus model in sheep showed consistent and reproducible results. This model offers the advantage of directly visualizing the location of the needle tip and injection of the BioGlue. This technique offers an alternative for testing novel approaches for prenatal congenital hydrocephalus treatment.

Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma.

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers' expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

Factors affecting asthma control in pregnancy: A cross-sectional study.

Background and Objective: Asthma control in pregnant women remains of utmost importance; suboptimal control can have adverse repercussions on both fetal and maternal health. The objective was to identify the factors that affect asthma control in pregnant Pakistani women presenting to a tertiary care hospital. Methods: This descriptive, cross-sectional research was conducted at KRL General Hospital between 1st November 2022 to 30th April 2023. Non-probability technique was used to sample one hundred and forty-five pregnant women with confirmed bronchial asthma irrespective of their trimester presented. Data regarding demographics and factors affecting asthma control was collected. Results: The mean age was 30.39 ± 4.33 years, with two-thirds (65%) being multiparous. Approximately 48% of participants were non-compliant with treatment, and less than 40% achieved adequate asthma control. A chi-squared test applied showed that multiparity (p = 0.003), treatment compliance (p < 0.001), BMI (p < 0.001), and proper inhaler technique (p < 0.001) were statistically significant factors affecting asthma control in pregnant women while, the level of education and household income did not exhibit a significant association. Multiple regression analysis qualified higher BMI, multiparity, treatment compliance, and inhaler technique as significant predictors of asthma control amongst pregnant women. Conclusion: Ensuring asthma control during pregnancy is important. This study identified BMI, multiparity, inhaler technique, and treatment compliance as factors that affect asthma control in pregnant women. Addressing these factors through regular antenatal check-ups can significantly mitigate risks and promote the optimal health of both maternal and fetal lives.

Clinical severity and high-resolution CT severity score in COVID-19: Is there an association.

Objectives: To identify a correlation between the clinical parameters and CT chest severity score in COVID-19. Methods: A total of 205 RT-PCR positive patients were included in this descriptive cross-sectional study with convenience sampling from November 2020 to June 2021 in KRL Hospital. The study population was stratified in disease severity as per the WHO's guidelines. Clinical and radiological characteristics were compared in survivors and non survivors to draw conclusion. Results: The mean age was 57 years and the majority of the patients 57% were male. Overall mortality was 22% and the mean CT severity score was 18. Non survivors were more tachypneic, hypoxic, had a higher CT chest severity score, higher clinical severity, more comorbid condition and higher TLC, D-Dimers, LDH, CRP, NLR. Raised CT severity score showed a conclusive correlation with greater disease severity. One way ANOVA showed a significant difference between mean CT severity score amongst different disease categories. Conclusion: Higher CT severity score corresponds to a higher clinical severity and higher chances of mortality.

Endovascular Versus Medical Management of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study.

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Atypical brain structure and function in young adults exposed to disaster-related prenatal maternal stress: Project Ice Storm.

Studies have shown that prenatal maternal stress (PNMS) affects brain structure and function in childhood. However, less research has examined whether PNMS effects on brain structure and function extend to young adulthood. We recruited women who were pregnant during or within 3 months following the 1998 Quebec ice storm, assessed their PNMS, and prospectively followed-up their children. T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI were obtained from 19-year-old young adults with (n = 39) and without (n = 65) prenatal exposure to the ice storm. We examined between-group differences in gray matter volume (GMV), surface area (SA), and cortical thickness (CT). We used the brain regions showing between-group GMV differences as seeds to compare between-group functional connectivity. Within the Ice Storm group, we examined (1) associations between PNMS and the atypical GMV, SA, CT, and functional connectivity, and (2) moderation by timing of exposure. Primarily, we found that, compared to Controls, the Ice Storm youth had larger GMV and higher functional connectivity of the anterior cingulate cortex, the precuneus, the left occipital pole, and the right hippocampus; they also had larger CT, but not SA, of the left occipital pole. Within the Ice Storm group, maternal subjective distress during preconception and mid-to-late pregnancy was associated with atypical left occipital pole CT. These results suggest the long-lasting impact of disaster-related PNMS on child brain structure and functional connectivity. Our study also indicates timing-specific effects of the subjective aspect of PNMS on occipital thickness.

Change in stage after neoadjuvant chemoradiation is associated with survival in patients with esophageal cancer.

BACKGROUND: The aim of this study was to determine if change in stage after neoadjuvant chemoradiation (CRT) was associated with improved survival in esophageal cancer using a national database. METHODS: Using the National Cancer Database, patients with non-metastatic, resectable esophageal cancer who received neoadjuvant CRT and surgery were identified. Comparing clinical to the pathologic stage, change in stage was classified as pathologic complete response (pCR), downstaged, same-staged, or upstaged. Univariable and multivariable Cox regression models were used to identify factors associated with survival. RESULTS: A total of 7745 patients were identified. The median overall survival (OS) was 34.9 months. Median OS was 60.3 months if pCR, 39.1 months if downstaged, 28.3 months if same-staged, and 23.4 months if upstaged (p < 0.0001). On multivariable analysis, pCR was associated with improved OS compared to the other groups (downstaged: hazard ratio [HR]: 1.32 [95% confidence interval [CI]: 1.18-1.46]; same-staged: HR: 1.89 [95% CI: 1.68-2.13]; upstaged: HR: 2.54 [95% CI: 2.25-2.86]; all p < 0.0001). CONCLUSIONS: In this large database study, change in stage after neoadjuvant CRT was strongly associated with survival for patients with non-metastatic, resectable esophageal cancer. There was a significant stepwise decline in survival, in descending order of pCR, downstaged tumor, same-staged tumor, and upstaged tumor.

Regulatory role of circular RNAs in oral squamous cell carcinoma.

OSCC is a genomically complicated disease and advancements in the modern era of molecular oncology have enabled researchers to portray near-to-complete resolution of signaling landscape. Over the last two decades, overwhelming proof-of-concept has established mechanistic regulatory role of non-coding RNAs in carcinogenesis, including OSCC. Circular RNAs demonstrate a burgeoning facet of oncology research and molecular biologists are only beginning to appreciate and recognize the significance of circRNAs in the pathogenesis of OSCC. Regulatory roles of non-coding RNAs in the re-shaping of signaling pathways offer plausible strategies for prevention/inhibition of OSCC. Circular RNAs have mechanistic roles in OSCC and "sponge effects" mediated by a wider variety of circRNAs need to be rationally targeted for effective cancer prevention. Phenomenal and cutting-edge research works in different types of animal models will further refine our knowledge for selection of most promising circRNAs as pharmacologically valuable targets.

Tauroursodeoxycholic Acid (TUDCA) Regulates Inflammation and Hypoxia in Autonomic Tissues of Rats with Seizures.

Inflammation and hypoxia have an effect on the molecular mechanism of cardiovascular and respiratory pathologies accompanying seizures. Against this, Tauroursodeoxycholic Acid (TUDCA) can regulate oxidative stress, inflammation and cellular survival by suppressing endoplasmic reticulum (ER) stress. We evaluated the expression changes of NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins associated with seizures in brain stem, heart and lung tissues representing the autonomous network. Additionally, we examined the protective effects of TUDCA administration against damage caused by seizures in terms of immunohistochemistry and pathology. 4 groups of Wistar Albino male rats (250-300 g, n=32) were formed as control, pentylenetetrazole (PTZ), TUDCA and PTZ+TUDCA. The epilepsy kindling model was created by intraperitoneal (i.p.) injection of PTZ chemical (35 mg/kg, every 2 days) for one month. TUDCA (500 mg/kg; every 2 days) treatment was given intraperitoneally 30 minutes before seizures for 1 month. Brain stem, heart (atria, ventricle) and lung tissues of rats were isolated. NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins in the obtained tissues were evaluated by immunohistochemical staining. The immunoreactivity of the investigated proteins in the brainstem heart and lung tissues of rats with chronic PTZ administration was significantly increased. Recurrent seizures led to accumulation of inflammatory cells in tissues, hemorrhage, vasodilation, and apoptosis. Following TUDCA administration, expression of NF-κB p65, TNF-α and Kir6.2 was significantly reduced in all tissues (except the atrium of the heart) compared to control rats. HIF-1α levels were significantly suppressed in ventricular and lung tissues of epileptic rats given TUDCA. However, TUDCA pretreatment improved histopathological changes due to chronic seizures and partially reduced apoptosis. We showed that epileptic seizures may cause tissue damage with the development of inflammatory and hypoxic conditions in the brainstem and organs that represent the autonomic network. TUDCA therapy could be an effective agent in the treatment of cardiac and respiratory problems associated with seizures.

Sulfur X-ray Absorption and Emission Spectroscopy of Organic Sulfones.

The sulfones are a widespread group of organo-sulfur compounds, which contain the sulfonyl SO2 group attached to two carbons and have a formal sulfur oxidation state of +2. We have examined the sulfur K near-edge X-ray absorption spectroscopy (XAS) of a range of different sulfones and find substantial spectroscopic variability depending upon the nature of the coordination to the sulfonyl group. We have also examined the sulfur Kß X-ray emission spectroscopy (XES) of selected representative sulfones. Density functional theory simulations show satisfactory reproduction of both absorption and emission spectra while enabling assignment of the various transitions comprising the spectra. The correspondence between observed and simulated spectra shows promise for ab initio prediction of sulfur X-ray absorption and emission spectra of sulfones of any substituent. The absorption spectra and, to a lesser extent, the emission spectra are sensitive to the nature of the organic groups bound to the sulfonyl (SO2) moiety, clearly showing the potential of X-ray spectroscopy as an in situ probe of sulfone chemistry.