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Background and Purpose Cerebral venous thrombosis (CVT) is associated with a high degree of morbidity and mortality. Our objective is to elucidate characteristics, treatments, and outcomes of patients with cancer and CVT (CA-CVT). Methods The 2016–2019 National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of CVT. Patients with a currently active diagnosis of malignancy (CA-CVT) were then identified. Demographics and comorbidities were compared between CA-CVT and CVT patients. Subgroup analyses explored patients with hematopoietic cancer and non-hematopoietic cancers. Stroke severity and treatment were explored. Inpatient outcomes studied were discharge disposition, length of stay, and mortality. Results Between 2016 and 2019, 6,140 patients had a primary diagnosis code of CVT, and 370 (6.0%) patients had a coexisting malignancy. The most common malignancy was hematopoietic (n=195, 52.7%), followed by central nervous system (n=40, 10.8%), respiratory (n=40, 10.8%), and breast (n=40, 10.8%). These patients tended to be older than non-CA-CVT and were more likely to have coexisting comorbidities. CA-CVT patients had higher severity scores on the International Study of Cerebral Vein and Dural Sinus Thrombosis Risk Score (ISCVT-RS) and increased complications. In a propensity-score matched cohort, there were no differences in inpatient outcomes. Conclusion Malignancy occurs in 6% of patients presenting with CVT and should be considered a potential comorbidity in instances where clear causes of hypercoagulabilty have not been identified. Malignancy was linked to higher mortality rates. Nonetheless, after adjusting for the severity of CVT, the outcomes for inpatients with cancer-associated CVT were comparable to those without cancer, indicating that the increased mortality associated with malignancy is probably due to more severe CVT conditions.

Background This study proposes a modification to the traditional Hunt and Hess (tHH) grading scale for prognostication in aneurysmal subarachnoid hemorrhage (aSAH), which differentiates the most severe‐grade patients based on the presence or absence of brainstem dysfunction [determined by Glasgow Coma Scale (GCS) scores 3‐5]. Methods Weighted aSAH hospitalizations were retrospectively identified in the National Inpatient Sample from 2015 to 2019 and were stratified by tHH and modified HH (mHH) grades. mHH grade 5 was defined as tHH grade 5 with GCS score 3–5, while mHH grade 4 comprised tHH grade 5 with GCS score 6–8 and tHH grade 4. HH grades 1–3 do not differ between the traditional and modified scales. Measures of diagnostic performance were compared for the primary study end point [poor outcome as determined by the previously validated NIS‐SAH Outcome Measure (NIS‐SOM), shown to have high concordance with modified Rankin Scale scores > 2]. External validation of the mHH was performed using data from a prospectively maintained aSAH registry. Results Among 6130 aSAH hospitalizations, 2245 (36%) were tHH grade 5. Seven hundred and eighty‐five (35%) of these had a GCS 3–5 and were designated as mHH grade 5. Poor outcomes were identified in 78% and 77% of grade 4 tHH and mHH, respectively, and in 83% and 95% of grade 5 tHH and mHH, respectively. In comparison with the tHH, the mHH achieved superior discrimination [c‐statistic 0.793 (95% CI 0.768, 0.818) versus 0.780 (95% CI 0.750, 0.807); DeLong p < 0.001] for poor outcome, as well as improved specificity (0.929 versus 0.304) and positive predictive value (PPV) (0.949 versus 0.827). External registry validation of the mHH demonstrated excellent discrimination [c‐statistic 0.835 (95% CI 0.801, 0.870)], with a specificity of 0.950 and PPV of 0.905. Conclusion The mHH achieved a favorable diagnostic performance profile using retrospective data and may aid in the prognostication of high‐severity patients with aSAH.

In recent decades, significant advancements in pharmacological, catheter-based, and surgical reperfusion technologies have markedly improved outcomes for individuals undergoing acute myocardial infarction. Despite these remarkable progressions, a segment of patients, particularly those with extensive infarctions or delays in revascularization, remains vulnerable to the onset of mechanical complications associated with myocardial infarction. These complications, spanning mechanical, electrical, ischemic, inflammatory, and thromboembolic events, pose substantial risks of morbidity, mortality, and increased utilization of hospital resources. The management of patients experiencing these complications is intricate, necessitating collaborative efforts among various specialties. Timely identification, accurate diagnosis, hemodynamic stabilization, and decision-making support are crucial for guiding patients and their families in choosing between definitive treatments or palliative care. This review underscores the critical importance of promptly identifying and initiating therapy to reduce prolonged periods of cardiogenic shock and the potential for fatality. By presenting key clinical and diagnostic insights, this review aims to further improve early diagnosis and offer an updated perspective on current management strategies for the diverse range of complications associated with acute myocardial infarction.

Several research papers available in notable publications have been dedicated to different stages of helical gearbox. However, most of the previous investigation was focused on single stage and double stage helical gearboxes, while only a few studies covered triple stage helical gearboxes even though it has numerous advantages. Recently, the significance of three stage helical gearboxes has received a lot of attention among various research professionals associated in this area. In this study, comprehensive assessment was conducted on the current three stage helical gearbox literatures for examining most currently used distinct research designs, methods, tools & techniques, enablers & barriers and also identifying diverse research inclinations, major findings, shortcomings and suggesting the potential directions in futuristic research. This exploration perilously investigated 275 research papers on various stages of helical gearbox and conducted a structured literature review of 28 articles on three stage helical gearboxes published in various journals over the last two decades using content analysis methodology with inductive research approach. The major findings shows that there are immense potential for dominating the research field and several opportunities still exists for three stage helical gearboxes development, which in turn open up new avenues for experts and industries.

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Introduction Due to the relative rarity of unruptured intracranial aneurysms (UIA) in the pediatric population, evidence regarding treatment modalities and clinical outcomes remains limited. This study aims to characterize the utilization and clinical outcomes of endovascular therapy (EVT) and microsurgical clipping (MSC) for pediatric UIAs over a two‐decade interval using a large national registry. Methods Pediatric (< 18 years of age) UIA hospitalizations were identified in the National Inpatient Sample from 2002 to 2019. Temporal utilization and clinical outcomes were compared for treatment with EVT and MSC. Results Among 734 UIAs identified during the study period, 64.9% (n = 476) were treated with EVT. Utilization of EVT significantly increased during the study period from 54.3% (2002‐2004) to 78.6% (2017‐2019) (p = 0.002 by Cochrane‐Armitage test). Treatment with EVT did not differ as a function of increasing age, but was mostly highly utilized in the youngest age grouping [70.4% (0‐2 years), 64.0% (3‐12 years), 64.3% (13‐17 years); p = 0.578]. In comparison with those treated with MSC, pediatric patients treated with EVT demonstrated higher rates of favorable outcomes (discharge to home without services) (96.0% vs. 91.1%, p = 0.006), shorter durations of hospital stay (4.6 vs. 10.0 days, p < 0.001), and lower rates of ischemic or hemorrhagic procedural‐related complications (1% vs. 4%, p = 0.010). Conclusion A retrospective evaluation of nearly twenty years of population‐level data from the United States demonstrates increasing utilization of EVT for the treatment of pediatric UIAs with high rates of favorable outcomes and shorter hospital stays in comparison to those treated with microsurgery. However, limitations of available registry data (such as absence of radiographic parameters and aneurysm morphological characteristics) temper any definitive claims regarding treatment efficacy.

Introduction Existing evidence remains conflicting regarding the association between oral hormonal contraceptive (OCP) use and the risk of acute ischemic stroke (AIS). Large‐scale analyses and observational data evaluating this clinical question in recent years are scarce, despite widespread use of hormonal contraception in adult females of child‐bearing age. Modern OCP formulations contain lower doses of estrogen, the putative causative agent for AIS in this population, and underscores the need to re‐evaluate the risk initially demonstrated in older formulations containing higher levels of estrogen. Methods Hospitalizations for female patients aged 15‐50 were identified in the National Inpatient Sample (NIS) registry from 2015‐2020, excluding admissions associated with pregnancy or the postpartum period. The study exposure was use of OCPs and the primary endpoint was AIS, identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) coding. Propensity score (PS) adjustment by inverse probability weighting (IPW) was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between OCP and non‐OCP users to reduce measured confounding. In addition to age and race/ethnicity, a battery of more than forty confounding covariates representing established risk factors for AIS in the general and young population were identified (cardiovascular disease, lifestyle risk factors, congenital abnormalities, vasculopathies, hypercoagulable states, migraine with aura, among others) and balanced between OCP and non‐OCP users. Sensitivity testing was performed by evaluating stroke incidence in a sub‐group of patients without any risk factors present and by assessing a negative control (head trauma), with which an association of OCP use would not be expected. The effect size of the association between OCPs and AIS was presented as an adjusted odds ratio (aOR) with 95% confidence interval (CI), with statistical significance evaluated at p < 0.001. Results PS adjustment by IPW to balance all available AIS risk factors between OCP users and non‐users yielded 23,253,209 hospitalizations, 11,654,398 (50.1%) of which were associated with OCP use. The incidence of AIS was significantly greater in OCP users compared to non‐OCP users (2.8% vs. 0.4%; aOR 7.50, 95% CI 7.43 to 7.58; p < 0.001). Sub‐group analysis of hospitalizations without any stroke risk factors also demonstrated a significant association of OCP use with the development of AIS (1.3% vs. 0.1%; aOR 14.84, 95% CI 13.16 to 16.72; p < 0.001) following adjustment for age and race/ethnicity. In negative control analysis, OCP use was not associated with admissions associated with head trauma (1.4% vs. 1.4%; OR 1.03, 95% CI 0.95 to 1.10; p = 0.485). Conclusion Retrospective observational data from the United States in recent years suggests an association between OCP use and AIS, independent of well‐established risk factors for stroke and despite widespread adoption of lower estrogen formulations.

Introduction Heparin‐induced thrombocytopenia (HIT) is a rare complication characterized by a decreased platelet count and hypercoagulability following heparin and light‐molecular weight heparin administration. Both anticoagulants can be used intraoperatively and postoperatively for DVT prophylaxis in patients undergoing subarachnoid hemorrhage (SAH) treatment. Patients with SAH are an understudied population in terms of assessing incidence and impact of HIT. This study aims to investigate the incidence, complications, and outcomes of SAH patients who develop HIT. Methods ICD‐9‐CM and ICD‐10‐CM codes were used to query the National Inpatient Sample for patients with SAH between 2010 and 2019. Subgroup analysis was stratified by HIT development. SAH severity was determined using the National Institute of Health Stroke Scale as a template. Patients from both groups were assessed for baseline clinical characteristics, comorbidities, interventions, complications, and outcomes. Cohorts containing ten or fewer patients must only be described qualitatively. Descriptive statistics, multivariate regressions, and propensity score‐matching were all performed using IBM SPSS 28. Results 76,387 patients were diagnosed with SAH between 2010 and 2019. 166 (.22%) had developed HIT in response to anticoagulant administration. The incidence of HIT was higher in patients who were younger (58.04 vs 61.39, p = 0.01), obese (0.4% vs 0.2%, p < 0.01), on long‐term anticoagulant use (10.84% vs 5.72%, p < 0.01), and had an implanted cerebrospinal fluid drainage device (p < 0.01). Patients with HIT were associated with higher SAH severity (1.42 vs 1.06, p < 0.01). Through both the complete cohort and propensity score‐matched cohort, patients with HIT were associated with higher rates of endovascular coiling, external ventricular drain placement (p < 0.01), and ventriculoperitoneal shunt placement (p < 0.01). HIT patients had significantly higher rates of deep vein thrombosis (p < 0.01), pulmonary embolism (p < 0.01), central venous sinus thrombosis (p = 0.01), pneumonia (p < 0.01), urinary tract infection (p < 0.01), acute kidney injury (p < 0.01), and cerebral vasospasm (p < 0.01). Patients who develop HIT had a longer length of stay (LOS) (24.04 vs 10.48, p < 0.01). HIT continued to be a significant predictor of having an above average LOS (OR: 6.799, CI: 3.985 ‐ 11.6, p < 0.01) when controlling for age, SAH severity, and significant comorbidities. Conclusion Our study revealed that younger SAH patients with various comorbidities are more prone to developing HIT, leading to higher rates of thrombotic events, acute kidney injury, and nosocomial infections, which can significantly prolong their hospital stay. Considering the extended postoperative recovery period for SAH, investigating the causes of HIT can facilitate earlier detection and prevention of thrombotic complications. This nationwide, multicenter, retrospective study provides valuable insights for clinicians on how to prevent and manage HIT in patients with subarachnoid hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) carries significant morbidity and mortality. Previous single-center retrospective analysis suggests that end-stage renal disease (ESRD) is a risk factor for severe ICH and worse outcomes. This investigation aims to examine the impact of ESRD on ICH severity, complications, and outcomes using a multicenter national database. METHODS: The International Classification of Disease, Ninth and Tenth Revision Clinical Modification codes were used to query the National Inpatient Sample for patients with ICH and ESRD between 2010 and 2019. Primary endpoints were the functional outcome, length of stay (LOS), and in-hospital mortality. Multivariate variable regression models and a propensity-score matched analysis were established to analyze patient outcomes associated with baseline patient characteristics. RESULTS: We identified 211,266 patients with ICH, and among them, 7,864 (3.77%) patients had a concurrent diagnosis of ESRD. Patients with ESRD were younger (60.85 vs. 67.64, P < 0.01) and demonstrated increased ICH severity (0.78 vs. 0.77, P < 0.01). ESRD patients experienced higher rates of sepsis (15.9% vs. 6.15%, P < 0.01), acute myocardial infarction (8.05% vs. 3.65%, P < 0.01), and cardiac arrest (5.94% vs. 2.4%, P < 0.01). In addition, ESRD predicted poor discharge disposition (odds ratio [OR]: 2.385, 95% confidence interval [CI]: 2.227–2.555, P < 0.01), longer hospital LOS (OR: 1.629, 95% CI: 1.553–1.709, P < 0.01), and in-hospital mortality (OR: 2.786, 95% CI: 2.647–2.932, P < 0.01). CONCLUSIONS: This study utilizes a multicenter database to analyze the effect of ESRD on ICH outcomes. ESRD is a significant predictor of poor functional outcomes, in-hospital mortality, and prolonged stay in the ICH population.

Ion mobility has become a ubiquitous tool in many aspects of Analytical Chemistry due to its ability to separate compounds in the gas phase prior to feeding them to a Mass Spectrometer. To understand how this complex separation occurs, it is necessary to thoroughly explain the ion-gas interaction. In particular, this manuscript aims to describe the physics behind the collisions at high fields using the two-temperature approximation. The two-temperature theory has been recently employed to describe the mobility of polyatomic ions quite successfully and thus a proper account is warranted. A concise description is provided along with rigorous mathematical arguments behind its success at predicting the ion's drift velocity. Moreover, a thorough procedure for obtaining the equations (including the matrix elements) for higher-order mobility approximations is also provided with high detail, making this work suitable for beginners and experts in ion mobility. In particular, a discussion is brought forth on the choice of the base temperature and its relation to both the effective temperature and the drift velocity of the ion. A comparison between a 12-6-4 potential and the Maxwell model is made, pointing at the possible errors of using the Maxwell model for low- and high-field calculations. Using our in-house algorithm IMoS, successive approximations up to the fourth are tested against previous ones and against experimental results, showing both, asymptotic convergence, as well as a good agreement for monoatomic gases and small ions.

The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.

Abstract Delayed cerebral ischemia (DCI) secondary to vasospasm is a determinate of outcomes following non-traumatic subarachnoid hemorrhage (SAH). SAH patients are monitored using transcranial doppler (TCD) to measure cerebral blood flow velocities (CBFv). However, the accuracy and precision of manually acquired TCD can be operator dependent. The NovaGuide robotic TCD system attempts to standardize acquisition. This investigation evaluated the safety and efficacy of the NovaGuide system in SAH patients in a Neuro ICU. We retrospectively identified 48 NovaGuide scans conducted on SAH patients. Mean and maximum middle cerebral artery (MCA) CBFv were obtained from the NovaGuide and the level of agreement between CBFv and computed tomography angiography (CTA) for vasospasm was determined. Safety of NovaGuide acquisition of CBFv was evaluated based on number of complications with central venous lines (CVL) and external ventricular drains (EVD). There was significant agreement between the NovaGuide and CTA (Cohen’s Kappa = 0.74) when maximum MCA CBFv ≥ 120 cm/s was the threshold for vasospasm. 27/48 scans were carried out with CVLs and EVDs present without negative outcomes. The lack of adverse events associated with EVDs/CVLs and the strong congruence between maximal MCA CBFv and CTA illustrates the diagnostic utility of the NovaGuide.

BACKGROUND: There is emerging evidence that COVID-19 can trigger thrombosis because of a hypercoagulable state, including large-vessel occlusion ischemic strokes. Bihemispheric ischemic stroke is uncommon and is thought to indicate an embolic source. Here, we examine the findings and outcomes of patients with bihemispheric stroke in the setting of COVID-19. METHODS: We performed a retrospective cohort study at a quaternary academic medical center between March 1, 2020, and April 30, 2020. We identified all patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who presented with simultaneous bihemispheric ischemic strokes. RESULTS: Of 637 COVID-19 admissions during the 2-month period, 13 had a diagnosis of acute ischemic stroke, including 5 who developed bihemispheric cerebral infarction. Three of those 5 (60%) were female, median age was 54 (range 41–67), and all five were being managed for severe COVID-19-related pneumonia complicated by acute kidney injury and liver failure before the diagnosis of cerebral infarction was established. Five presented with elevated ferritin, lactate dehydrogenase, and interleukin-6 (IL-6) levels, and four had lymphopenia and elevated D-dimer levels. All patients underwent neuroimaging with computed tomography for persistent depressed mentation, with or without a focal neurologic deficit, demonstrating multifocal ischemic strokes with bihemispheric involvement. Outcome was poor in all patients: two were discharged to a rehabilitation facility with moderate-to-severe disability and three (60%) patients died. CONCLUSIONS: Stroke is implicated in SARS-CoV-2 infection. Although causality cannot be established, we present the imaging and clinical findings of patients with COVID-19 and simultaneous bihemispheric ischemic strokes. Multifocal ischemic strokes with bihemispheric involvement should be considered in COVID-19 patients with severe infection and poor neurologic status and may be associated with poor outcomes.

Background The findings of the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformation) trial, which determined that medical management was superior to prophylactic interventional therapy for the treatment of unruptured cerebral arteriovenous malformations (cAVMs), remain polarizing and controversial. Methods Adult cAVM patient admissions were identified in the National Inpatient Sample from 2009 to 2019. The incidence of cAVM rupture and in‐hospital mortality were compared between the pre‐ (2009–2013) and post‐ARUBA trial eras (2014–2019) using complex samples‐weighted estimates and multivariable logistic regression analyses. A control cohort composed of an alternate pathology (ruptured and unruptured cerebral aneurysms) was also assessed during the study period to evaluate potential bias. Results Among 121 415 hospitalizations for cAVM during the study period, 31 389 (25.9%) were admissions for ruptured malformations. The incidence of ruptured cAVM increased in the post‐ARUBA trial era (13.3% versus 34.4%; P

PURPOSE: Aneurysmal recurrence represents a significant drawback of endovascular coiling, particularly in aneurysms that have previously ruptured. Given the high recurrence rate of coiled aneurysms and particularly the risk of posttreatment rupture in previously ruptured aneurysms that have been treated by coiling, the question of how best to treat ruptured aneurysms that recur postcoiling remains. MATERIALS AND METHODS: We conducted a retrospective analysis of twenty patients who underwent pipeline embolization of previously ruptured, coiled cerebral aneurysms. RESULTS: Pipeline embolization device (PED) treatment resulted in complete aneurysmal occlusion in 10 patients (62.5%) at first angiographic follow-up, and 11 patients (68.75%) at last follow-up. No PED-related complications were encountered and there were no peri-procedural or postprocedural hemorrhages, or symptomatic ischemic events following flow diversion. CONCLUSIONS: PED as a second-line treatment is a safe and effective modality for achieving aneurysmal occlusion in recurrent, previously ruptured, primarily coiled aneurysms. Additionally, a staged coil-to-PED approach may be considered for the management of acutely ruptured aneurysms to achieve aneurysmal obliteration in an effort to mitigate recurrence, and reduce the amount of postprocedural studies.

INTRODUCTION: Anterior cerebral artery (ACA) aneurysms are commonly encountered in clinical practice but can be challenging to treat. Flow diversion is a viable treatment in this population. METHODS: We retrospectively evaluated patients treated at our center from May 2017 to December 2020 who underwent flow diversion for an ACA aneurysm at or distal to the anterior communicating artery (ACOM). We defined ACA aneurysms as any aneurysm involving the ACOM itself, at the junction of the ACA with the ACOM (A1/A2), or in distal A2/A3 branches; both ruptured and unruptured aneurysms were included. Baseline and follow-up clinical and angiographic data were collected; the primary measure was elimination of the aneurysm on follow-up angiogram. Patients underwent flow diversion with a Pipeline stent. A single flow diverting stent was placed in the dominant ACA spanning from the A2 segment extending into the A1 segment; two patients required H-pipe technique. Distal aneurysms were treated with a single Pipeline device deployed across the parent vessel, covering the aneurysm. RESULTS: Two-seven patients underwent a total of 28 flow diversion procedures; median age was 57 and 16 (59.3%) were male. Thirteen (48.2%) patients presented with subarachnoid hemorrhage; of these, four were treated within 6 weeks of the index hemorrhage. Most patients (22; 81.5%) had significant ACA asymmetry. There was one postoperative intracerebral hemorrhage and one groin complication. Follow-up data were available for 19 patients, 15 (78.9%) of which showed no residual aneurysm and 17 (89.5%) had protection of the dome. CONCLUSION: Flow diversion of ACA aneurysms can be a primary treatment modality in an unruptured aneurysm or a complement to initial coil protection of a ruptured aneurysm. Further studies are needed to confirm these results.

Introduction: Malnutrition refers to the situation where there is an unbalanced diet in which some nutrients are in excess, lacking or wrong proportion. Simply put, we can categorise it to be under-nutrition and over-nutrition. Despite India's 50% increase in GDP since 1991,3 more than one third of the world's malnourished children live in India. The present study was conducted to assess utility of CANSCORE and it compared with other commonly used measures for defining the nutritional status at birth. Methodology: The current study was conducted by the department of Paediatrics, S.M.S. Medical College, Jaipur. All neonates delivered at Mahila and Zenana Hospital, S.M.S. Medical College, Jaipur. All neonates delivered at the hospital and fulfilling inclusion criteria during one year period were included in the study. Different indices to measure nutritional status of newborns like Birth weight to Gestational Age, Ponderal Index, Mid Arm Circumference/ Head Circumference Ratio and CANSCORE were calculated. Clinical Assessment of Nutrition Score (CANSCORE)- is done within 48 hours on the basis of superficial readily detectable signs of malnutrition in the newborn as described by Metcoff. Results: According to Birth weight to Gestational Age criteria, 116 (23.2%) newborns were malnourished (Small for Gestational Age). According to Ponderal Index, 120 (24%) newborns were malnourished (PI < 2.2). According to Mid Arm Circumference/ Head Circumference Ratio criteria, 205 (41%) newborns were malnourished (MAC/HC < 0.27). According to CANSCORE, 177 (35.4%) newborns were malnourished (CANSCORE < 25). It was observed that out of total 116 newborns diagnosed with malnutrition by Birth weight to Gestational Age index, only 81 (69.8%) were also diagnosed with malnutrition by CANSCORE. Out of total 120 newborns diagnosed with malnutrition by Ponderal index, only 73 (60.8%) were also diagnosed with malnutrition by CANSCORE. Out of total 205 newborns diagnosed with malnutrition by Mid Arm Circumference/ Head Circumference Ratio index, only 127 (61.9%) were also diagnosed with malnutrition by CANSCORE.

Background The purpose of this study is to evaluate the impact multiple overlapping flow‐diverting stents have on aneurysm occlusion rates and iatrogenic complications relative to single flow‐diverting stents. Methods A retrospective review of a multicenter aneurysm database from 2012 to 2020 was performed to identify saccular aneurysms treated initially with single and multiple flow‐diverting stents with ≥12‐month angiographic and clinical follow‐up. Aneurysm occlusion rates as a function of stent number served as a primary outcome measure with iatrogenic complications serving as a secondary outcome measure. Results A total of 250 patients were initially treated with a single Pipeline embolization device (PED), and 48 patients were initially treated with multiple PEDs. There was no significant difference in aneurysm size, morphology, or dual‐antiplatelet therapy regimen used between groups. There was no significant difference in the aneurysm occlusion (single, 83.6%, versus multiple, 83.4%; P=0.65) or retreatment rates (single, 8.0%, versus multiple, 10.4%; P=0.58) between groups. There was no significant difference in the number of procedure‐related complications between groups (single, 8.0%, versus multiple, 4.2%; P=0.42), with 0.8% of patients treated with a single PED and 2.1% of patients treated with multiple PEDs experiencing a procedure‐related ischemic stroke. Conclusions There is no significant difference in overall aneurysm occlusion rates between aneurysms treated initially with single versus multiple overlapping PEDs nor are there significant differences in procedure‐related complications. Single PED flow diversion may be preferred whenever possible, with multiple PED constructs reserved for extenuating clinical circumstances as may be encountered with giant aneurysms.

Women have higher prevalence of asthma compared with men. In asthma, allergic airway inflammation is initiated by IL-33 signaling through ST2, leading to increased IL-4, IL-5, and IL-13 production and eosinophil infiltration. Foxp3+ Tregs suppress and ST2+ Tregs promote allergic airway inflammation. Clinical studies showed that the androgen dehydroepiandrosterone (DHEA) reduced asthma symptoms in patients, and mouse studies showed that androgen receptor (AR) signaling decreased allergic airway inflammation. Yet the impact of AR signaling on lung Tregs remains unclear. Using AR-deficient and Foxp3 fate-mapping mice, we determined that AR signaling increased Treg suppression during Alternaria extract (Alt Ext; allergen) challenge by stabilizing Foxp3+ Tregs and limiting the number of ST2+ ex-Tregs and IL-13+ Th2 cells and ex-Tregs. AR signaling also decreased Alt Ext–induced ST2+ Tregs in mice by limiting expression of Gata2, a transcription factor for ST2, and by decreasing Alt Ext–induced IL-33 production from murine airway epithelial cells. We confirmed our findings in human cells where 5α-dihydrotestosterone (DHT), an androgen, decreased IL-33–induced ST2 expression in lung Tregs and decreased Alt Ext–induced IL-33 secretion in human bronchial epithelial cells. Our findings showed that AR signaling stabilized Treg suppressive function, providing a mechanism for the sex difference in asthma.

Background After MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) demonstrated that endovascular therapy improved outcomes in patients with stroke, the number of endovascular procedures has risen sharply. We describe acute transient contrast‐induced neurological deficit (ATCIND), a group of neurological syndromes associated with arterial contrast administration during angiography. Our goal is to elucidate the incidence, risk factors, outcomes, pathogenesis, and diagnostic characteristics of ATCIND. Our primary objective is to elucidate the incidence of ATCIND in the setting of coronary or cerebral angiography. Secondary outcomes include potential risk factors, demographics, treatment modalities, and patient recovery. Methods The data that support the findings of this study are available from the corresponding author on reasonable request. The databases of the Cochrane Library, MEDLINE, Web of Science, and Embase were queried, yielding studies from 1974 to 2021. Inclusion criteria for articles were the following: (1) contrast‐induced encephalopathy, contrast‐induced neurotoxicity, or cortical blindness after contrast administration during angiography were the focus of the article; (2) incidence was reported; (3) studies included ≥3 cases; and (4) follow‐up tests were described to rule out other causes. Exclusion criteria included the following: (1) incidence was not reported; (2) unavailable in the English language; (3) abstracts and unpublished studies; and (4) did not exclude other possible causes, or findings suggested other possible causes, such as worsening ischemic injury. Of 627 articles, 7 were retained. This systematic review with meta‐analysis was performed in accordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) checklists. Independent extraction by multiple reviewers was performed. Data were pooled using a random‐effects model. Results The primary study outcome was incidence of ATCIND, which was formulated before data collection began. We hypothesized that the pooled incidence of ATCIND would be similar to that of individual studies. A total of 70 of 21007 patients had the diagnosis of contrast‐induced encephalopathy, contrast‐induced neurotoxicity or angiography‐associated cortical blindness, and ATCIND. The incidence rate of ATCIND is estimated to be 0.51% (CI, 0.3%–1.0%; P150 mL was a positive, significant predictor of visual disturbance (OR, 7.083; CI, 1.1742–42.793 [P=0.033]). Full recovery is estimated at 89.5% (95% CI, 76.9%–95.6%; P

Spinal cord injury (SCI) is a devastating condition that has physical and psychological consequences for patients. SCI is accompanied by scar formation and systemic inflammatory response leading to an intense degree of functional loss. The catechin, epigallocatechin gallate (EGCG), an active compound found in green tea, holds neuroprotective features and is known for its anti-inflammatory potential. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two functionally distinct complexes termed mTOR complex 1 and 2 (mTORC1; mTORC2). Inhibition of mTORC1 by rapamycin causes neuroprotection, leading to partial recovery from SCI. In this study the effects of EGCG, PP242 (an inhibitor of both complexes of mTOR), and a combination of EGCG and PP242 in SCI have been examined. It has been found that both EGCG and PP242 significantly improved sensory/motor functions following SCI. However, EGCG appeared to be more effective (BBB motor test, from 2 to 8 weeks after SCI, p = 0.019, p = 0.007, p = 0.006, p = 0.006, p = 0.05, p = 0.006, and p = 0.003, respectively). The only exception was the Von Frey test, where EGCG was ineffective, while mTOR inhibition by PP242, as well as PP242 in combination with EGCG, significantly reduced withdrawal latency starting from week three (combinatorial therapy (EGCG + PP242) vs. control at 3, 5, and 7 weeks, p = 0.011, p = 0.007, and p = 0.05, respectively). It has been found that EGCG was as effective as PP242 in suppressing mTOR signaling pathways, as evidenced by a reduction in phosphorylated S6 expression (PP242 (t-test, p < 0.0001) or EGCG (t-test, p = 0.0002)). These results demonstrate that EGCG and PP242 effectively suppress mTOR pathways, resulting in recovery from SCI in rats, and that EGCG acts via suppressing mTOR pathways.

The anti-Shine-Dalgarno (ASD) sequence of 16S rRNA is highly conserved across Bacteria, and yet usage of Shine-Dalgarno (SD) sequences in mRNA varies dramatically, depending on the lineage. Here, we compared the effects of ASD mutagenesis in Escherichia coli, a Gammaproteobacteria which commonly employs SD sequences, and Flavobacterium johnsoniae, a Bacteroidia which rarely does. In E. coli, 30S subunits carrying any single substitution at positions 1,535–1,539 confer dominant negative phenotypes, whereas subunits with mutations at positions 1,540–1,542 are sufficient to support cell growth. These data suggest that CCUCC (1,535–1,539) represents the functional core of the element in E. coli. In F. johnsoniae, deletion of three ribosomal RNA (rrn) operons slowed growth substantially, a phenotype largely rescued by a plasmid-borne copy of the rrn operon. Using this complementation system, we found that subunits with single mutations at positions 1,535–1,537 are as active as control subunits, in sharp contrast to the E. coli results. Moreover, subunits with quadruple substitution or complete replacement of the ASD retain substantial, albeit reduced, activity. Sedimentation analysis revealed that these mutant subunits are overrepresented in the subunit fractions and underrepresented in polysome fractions, suggesting some defect in 30S biogenesis and/or translation initiation. Nonetheless, our collective data indicate that the ASD plays a much smaller role in F. johnsoniae than in E. coli, consistent with SD usage in the two organisms.

Introduction: Despite the success of mechanical thrombectomy in large vessel acute ischemic stroke, there remain cases where recanalization fails due to difficult anatomic access or peripheral arterial occlusive disease. In these cases, transbrachial or transcarotid access may be considered as alternatives to the transfemoral or increasingly popular transradial route. Of these approaches, the transcarotid route has not gained prominence due to safety concerns despite its prior routine use in angiography. In this study, we conducted a systematic review and meta‐analysis of the literature in order to better summate the data on transcarotid access. Methods: Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were used in order to perform a systematic review of articles published from 2010–2020 summarizing pre‐intervention characteristics of patients undergoing mechanical thrombectomy via transcarotid puncture. We performed a meta‐analysis focused on clinical outcomes, reperfusion times (in minutes), and overall complication rates of transcarotid access for mechanical thrombectomy. Pooled analyses were performed to examine predictors of complications and outcomes. Results: Six studies describing 72 patients, out of 80 attempts at carotid access (90% success rate), were included. Age ranged from the 5th to 9th decade (median 7.5). Initial National Institutes of Health Stroke Scale (NIHSS) score ranged from 4 to 28 (median 17). Direct carotid puncture was most often used as a rescue technique (86% of patients) secondary to failed femoral access. Successful recanalization was achieved in 85% of patients. Good 90‐day outcome (modified Rankin Scale ≤2) was achieved in 27% of patients. Median carotid puncture‐to‐reperfusion time was 32 minutes (CI = 24–40, p < 0.001). Cervical complications occurred at a rate of 23% (CI = 14– 35%, p < 0.001). Only one complication resulted in a fatal outcome and only one required an intervention (each 1.4%). Use of IV thrombolysis did not significantly predict better mTICI outcome. Complications were not predicted by use of IV thrombolysis or closure method. Carotid puncture as the primary access route was associated with significantly shorter procedure times and carotid puncture as a rescue route was associated with comparable procedure times to the classic femoral access route. Conclusions: Our results suggest that, despite current concerns about the use of transcarotid access, this technique can be considered a viable backup route in cases of failed transfemoral or transradial access. Though this method requires further research to better understand the variables that might play into clinical decision‐making for its use in acute stroke management, it is a promising area of study that could allow for thrombectomy in patients where it would otherwise be aborted.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Despite expanded antiretroviral therapy (ART) eligibility in South Africa, many people diagnosed with HIV do not initiate ART promptly, yet understanding of the reasons is limited. Using data from an 8-month prospective cohort interview study of women and men newly-diagnosed with HIV in three public-sector primary care clinics in the eThekwini (Durban) region, South Africa, 2010-2014, we examined if theoretically-relevant social-structural, social-cognitive, psychosocial, and health status indicators were associated with time to ART initiation. Of 459 diagnosed, 350 returned to the clinic for their CD4+ test results (linkage); 153 (33.3%) were ART-eligible according to treatment criteria at the time; 115 (75.2% of those eligible) initiated ART (median = 12.86 weeks [95% CI: 9.75, 15.97] after linkage). In adjusted Cox proportional hazard models, internalized stigma was associated with a 65% decrease in the rate of ART initiation (Adjusted hazard ratio [AHR] 0.35, 95% CI: 0.19-0.80) during the period less than four weeks after linkage to care, but not four or more weeks after linkage to care, suggesting that stigma-reduction interventions implemented shortly after diagnosis may accelerate ART uptake. As reported by others, older age was associated with more rapid ART initiation (AHR for 1-year age increase: 1.04, 95% CI: 1.01-1.07) and higher CD4+ cell count (≥300μL vs.

Women have increased prevalence of Th17-mediated autoimmune diseases, including lupus and multiple sclerosis, and severe asthma. While estradiol and progesterone increased IL-17A production in Th17 cells by inhibiting Let7f miRNA expression and increasing IL-23 receptor (IL-23R) expression, it remained unclear how estrogen signaling through the canonical nuclear receptors, estrogen receptor α (ERα) and/or ERβ, regulated this pathway. We hypothesized that estrogen signaling through ERα increased IL-23R expression and IL-17A production from Th17 cells. To test this hypothesis, naïve T cells from WT female, WT male, Esr1−/− and Esr2−/− female mice were differentiated into Th17 cells. IL-17A production and IL-23R expression were significantly increased in Th17 cells from WT female mice compared to Th17 cells from WT male mice. Deletion of ERα (Esr1−/−), but not ERβ (Esr2−/−), significantly decreased IL-17A production and IL-23R expression in Th17 cells by limiting IL-23R expression in a Let-7f dependent manner. ERα deficiency also decreased Th17 cell proliferation as well as decreased T cell metabolism as measured by ATP-linked oxygen consumption rate and proton leakage. Further, we found that Cox20 expression, a protein involved in mitochondrial respiration through assembly of cytochrome c oxidase in the electron transport chain, was increased in Th17 cells from WT female mice compared to Th17 cells from WT male and Esr1−/− female mice. Inhibition of Cox20 decreased IL-17 production in Th17 cells from WT female mice. Combined these studies showed that ERα signaling increased IL-17A production in Th17 cells by upregulating IL-23R expression and promoting mitochondrial respiration and proliferation.

There is intense interest and effort toward regenerating the brain after severe injury. Stem cell transplantation after insult to the central nervous system has been regarded as the most promising approach for repair; however, engrafting cells alone might not be sufficient for effective regeneration. In this study, we have compared neural progenitors (NPs) from the fetal ventricular zone (VZ), the postnatal subventricular zone, and an immortalized radial glia (RG) cell line engineered to conditionally secrete the trophic factor insulin-like growth factor 1 (IGF-1). Upon differentiation in vitro , the VZ cells were able to generate a greater number of neurons than subventricular zone cells. Furthermore, differentiated VZ cells generated pyramidal neurons . In vitro , doxycycline-driven secretion of IGF-1 strongly promoted neuronal differentiation of cells with hippocampal, interneuron and cortical specificity. Accordingly, VZ and engineered RG-IGF-1-hemagglutinin (HA) cells were selected for subsequent in vivo experiments. To increase cell survival, we delivered the NPs attached to a multifunctional chitosan-based scaffold. The microspheres containing adherent NPs were injected subacutely into the lesion cavity of adult rat brains that had sustained controlled cortical impact injury. At 2 weeks posttransplantation, the exogenously introduced cells showed a reduction in stem cell or progenitor markers and acquired mature neuronal and glial markers. In beam walking tests assessing sensorimotor recovery, transplanted RG cells secreting IGF-1 contributed significantly to functional improvement while native VZ or RG cells did not promote significant recovery. Altogether, these results support the therapeutic potential of chitosan-based multifunctional microsphere scaffolds seeded with genetically modified NPs expressing IGF-1 to promote repair and functional recovery after traumatic brain injuries.

Traumatic spinal cord injury (SCI) is untreatable and remains the leading cause of disability. Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. However, mechanisms regulated by the mTOR pathway are not only controlled by mTORC1, but also by a second mTOR complex (mTORC2). Second-generation inhibitor, pp242, inhibits both mTORC1 and mtORC2, which led us to explore its therapeutic potential after SCI and compare it to RAPA treatment. In a rat balloon-compression model of SCI, the effect of daily RAPA (5 mg/kg; IP) and pp242 (5 mg/kg; IP) treatment on inflammatory responses and autophagy was observed. We demonstrated inhibition of the mTOR pathway after SCI through analysis of p-S6, p-Akt, and p-4E-BP1 levels. Several proinflammatory cytokines were elevated in pp242-treated rats, while RAPA treatment led to a decrease in proinflammatory cytokines. Both RAPA and pp242 treatments caused an upregulation of LC3B and led to improved functional and structural recovery in acute SCI compared to the controls, however, a greater axonal sprouting was seen following RAPA treatment. These results suggest that dual mTOR inhibition by pp242 after SCI induces distinct mechanisms and leads to recovery somewhat inferior to that following RAPA treatment.