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Functionalization of unactivated C(sp3)–H bonds represents one of the interesting transformations in organic synthesis. This review highlights the most recent developments in the cobalt-catalyzed functionalization of unactivated C(sp3)–H bonds.

Over the past decade, visible-light photoredox catalysis has blossomed as a powerful strategy and offers a discrete activation mode complementary to thermal controlled reactions. Visible-light-mediated photoredox catalysis also offers exciting opportunities to achieve challenging carbon-carbon and carbon-heteroatom bond formations with excellent chemo-, regio-, or stereoselectivity under mild and ecologically benign conditions. The greater part of photoredox reactions depends on heavy metals like ruthenium(II) or iridium(III) based complexes as photoredox catalysts owing to their strong absorption, long-lived excited-state lifetimes and high oxidation or redox potentials. However, these transition metal complexes are expensive and pose severe drawbacks with respect to large scale application and sustainability. Organic dyes are also commonly used as a low-cost alternative to Ru- or Ir-based complexes. However, they have inferior photostability. Thus, further development of alternative photocatalysts based on copper salts or copper complexes is widely investigated because of their economic and environmental benefits. In recent years, visible-light-mediated direct functionalization of olefins or alkynes to afford a diverse range of organic compounds has received extensive interest from synthetic chemists due to their easy availability and reactivity towards a large number of reactants. In this review, we have highlighted the most recent significant advances that have been made in the use of copper-based photocatalysts for the functionalization of olefins and alkynes with an emphasis on substrate scope, limitations, mechanistic understanding and applications of these reactions. This review covers the literature from 2015 to 2021.

Molecular mechanisms of malignant transformation in spinal cord gliomas are not well-understood. Our objective was to investigate genetic causes of malignant transformation in a primary spinal cord glioma. A 32-year-old female patient presented with bilateral lower extremity weakness and was diagnosed with a primary spinal cord glioma from T9 to T12, with a syrinx extending from the craniocervical junction to the conus. She underwent resection in 2006. Pathology showed an abundance of Rosenthal fibers, calcification and degenerative features consistent with a low-grade pilocytic astrocytoma. She presented in 2020 with tumor recurrence and underwent re-resection. Whole exome sequencing, DNA methylation profiling and immunohistochemistry were performed on her initial and recurrent tumor samples. Immunohistochemical profiling of her recurrent tumor showed pleomorphic cells with extensive necrosis consistent with a high-grade glioma. DNA methylation profiling showed that the initial tumor clustered with pilocytic astrocytomas, whereas the recurrent lesion clustered with anaplastic astrocytomas, confirming malignant transformation. Whole-exome sequencing showed interim acquisition of a rare fibroblast growth factor receptor-transforming acidic coiled-coil (FGFR1-TACC1) gene fusion. We report an FGFR1-TACC1 fusion associated with malignant transformation in a primary spinal cord glioma. Our study adds to growing reports of FGFR-TACC fusions, which are amenable to receptor tyrosine kinase inhibition.

Objective A review of endovascular cerebral mycotic aneurysm treatment with Onyx liquid embolic, N-butyl-2-cyanoacrylate (NBCA), or coil embolization has not been reported. The authors conduct a systematic review on endovascular treatment methods of mycotic aneurysms. Methods A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2020. All studies assessing outcomes related to endovascular Onyx embolization, NBCA embolization, or coiling were included. Results A total of 74 studies were ultimately selected, including 180 (67% male) patients comprising 243 aneurysms treated endovascularly. The mean age was 38.2 ± 17.6 years, and the most common symptom on presentation was headache (31%). Most aneurysms were located on the middle cerebral artery (52.5%), and over half presented with rupture (53.8%). Coiling was the most commonly employed technique (50.4%), and obliteration rates were comparable across coiling, NBCA, and Onyx (99.1%, 100%, 100%, respectively). Complication rates were also comparable (4.3% vs. 15.2% vs. 8.1%). Conclusion Embolization for infectious intracranial aneurysm appears to be an effective treatment option for mycotic aneurysms. Embolization rates were comparable between coiling, NBCA, and Onyx embolization. Noninferiority among these modalities cannot be demonstrated given the retrospective nature of this review, evolution of endovascular techniques over the years, and changes in treatment paradigms in the last 2 decades. Ideally, further prospective research will be needed to find which treatment method offers the lowest complication rates and the best outcomes for patients with mycotic aneurysms.

Study Design: Systematic Review. Objectives: To review the literature surrounding the cost-effectiveness of implanting spinal cord stimulators for failed back surgery syndrome. Methods: A systematic review was conducted inclusive of all publications in the Medline database and Cochrane CENTRAL trials register within the last 10 years (English language only) assessing the cost-effectiveness of Spinal Cord Stimulator device implantation (SCSdi) in patients with previous lumbar fusion surgery. Results: The majority of reviewed publications that analyzed cost-effectiveness of SCSdi compared to conventional medical management (CMM) or re-operation in patients with failed back surgery syndrome (FBSS) showed an overall increase in direct medical costs; these increased costs were found in nearly all cases to be offset by significant improvements in patient quality of life. The cost required to achieve these increases in quality adjusted life years (QALY) falls well below $25 000/QALY, a conservative estimate of willingness to pay. Conclusions: The data suggest that SCSdi provides both superior outcomes and a lower incremental cost: effectiveness ratio (ICER) compared to CMM and/or re-operation in patients with FBSS. These findings are in spite of the fact that the majority of studies reviewed were agnostic to the type of device or innervation utilized in SCSdi. Newer devices utilizing burst or higher frequency stimulation have demonstrated their superiority over traditional SCSdi via randomized clinical trials and may provide lower ICERs.

Heterocyclic compounds are widely present in the core structures of several natural products, pharmaceuticals and agrochemicals, and thus great efforts have been devoted to their synthesis in a mild and simpler way. In the past decade, remarkable progress has been made in the field of heterocycle synthesis by employing C–H functionalization as an emerging synthetic strategy. As a complement to previous protocols, transition metal catalyzed C–H functionalization of arenes using various directing groups has recently emerged as a powerful tool to create different classes of heterocycles. This review is mainly focussed on the recent key progress made in the field of the synthesis of N,O-heterocycles from olefins and allenes by using nitrogen based and oxidizing directing groups.

OBJECTIVES To analyze the association between dosvolume relationships and adverse events in brainstem lesions treated with Gamma Knife radiosurgery (GKRS). METHODS Treatment plans were generated on BrainLab Elements and GammaPlan software. Dosimetric data were analyzed as continuous variables for patients who received GKRS to brain metastases or arteriovenous malformations (AVM) within or abutting the brainstem. Adverse events were classified as clinical and/or radiographic. Logistic and cox regression were used to assess the relationship between dosimetric variables and adverse events. RESULTS Sixty-one patients who underwent single fraction GKRS for brain metastases or AVM were retrospectively analyzed. Median age was 62 years (range: 12-92 years) and the median prescription dose was 18 Gy (range: 13-25 Gy). Median follow-up was 6months. Clinical and radiographic complications were seen in ten (16.4%) and 17 (27.9%) patients, respectively. On logistic regression, increasing D05% was found to be associated with an increased probability of developing a clinical complication post-GKRS (OR: 1.18; 95% CI: 1.01-1.39; p = 0.04). Furthermore, mean brainstem dose (HR: 1.43; 95% CI: 1.05-1.94; p

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Covid-19 caused by the novel SARS-CoV-2 has emerged as a global health crisis with various clinical complications. Covid-19 related respiratory manifestations have been reported as mild, moderate to severe including acute lung injury and acute respiratory distress syndrome necessitating non-invasive forms of oxygenation to mechanical ventilation (MV). MV patients frequently undergo prolonged hospitalizations with substantial morbidity and mortality. We sought to evaluate risk factors for MV in our cohort. METHODS: We conducted a retrospective cohort study of patients admitted in our institution from March 1st to June 21st2020, to assess risk factors for Covid-19 related respiratory failure requiring MV. The original cohort encompassed 166 MV and 503 non MV patients. Information from our hospital medical records was extracted, which included demographics, presenting symptoms, past medical history, vital signals, and laboratory data and need for MV. We propensity matched 166 MV with a concurrent cohort of non MV patients in our institution. Covariates applied in matching included age, gender, race, and body mass index (BMI). The admission clinical attributes and laboratory parameters were analyzed, along with outcomes. RESULTS: The mean age of our matched cohort was 63.8 years. Mechanically Ventilated patients had a higher incidence of tachycardia (heart rate > 125) (p 24 cycles per minute (p 97.8 F (Temperature > (p =.037), shortness of breath (p =.001), and headaches (p =.005). In addition, mechanically ventilated patients had a lower serum albumin (g/dl) ≤ 3 units (p 6.6 units (p =.004), serum lactic acid (mmol/L) > 1.7 units (p =.003), serum LDH U/L > 465 U/L (p .305 units (p 8.4 k/ul (p

The proposed work presents an Holistic approach for Face-sketch matching using a Siamese scenario. Proposed scheme is simple yet effective in overcoming the computational complexity of the feature based scheme and also provides a F1 score of 0.73 and accuracy of nearly 74%. The results are in demanding circumstances of using ageing effects in sketches. Optimum model from Siamese linkages is acquired with augmented sketches on CUHK dataset. The sketches are trained under augmented versions of zooming, distortion and cropped versions of them. The validation curve with merely L1 regularization peaks at 73% while it finds one at 77% with a combined L1 and L2 regularization for an average batch size of eight. The efficacy of the regularization in conjunction with augmentation prevents overfitting and provides effective results in ageing sketches.

Objective A review of endovascular cerebral mycotic aneurysm treatment with Onyx liquid embolic, N-butyl-2-cyanoacrylate (NBCA), or coil embolization has not been reported. The authors conduct a systematic review on endovascular treatment methods of mycotic aneurysms. Methods A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2020. All studies assessing outcomes related to endovascular Onyx embolization, NBCA embolization, or coiling were included. Results A total of 73 studies were ultimately selected including 180 (67% male) patients comprising 243 aneurysms treated endovascularly. The mean age was 38.2 ± 17.6 years, and the most common symptom on presentation was headache (31%). Most aneurysms were located on the middle cerebral artery (52.5%), and over half presented with rupture (53.8%). Coiling was the most commonly employed technique (50.4%), and obliteration rates were comparable across coiling, NBCA, and Onyx (99.1%, 100%, 100%, respectively). Complication rates were also comparable (4.3% vs. 15.2% vs. 8.1%). Conclusions Embolization for infectious intracranial aneurysm appears to be an effective treatment option for mycotic aneurysms. Embolization rates were comparable among coiling, NBCA, and Onyx embolization. Noninferiority among these modalities cannot be demonstrated given the retrospective nature of this review, evolution of endovascular techniques over the years, and changes in treatment paradigms in the past 2 decades. Ideally, further prospective research will be necessary to find which treatment method offers the lowest complication rates and the best outcomes for patients with mycotic aneurysms.

Introduction: Medial Gonarthrosis of Knee in middle-aged (40-60yrs) physically active individuals has become a considerable cause for pain, immobility and disability. Varus malalignment at knee joint compromises biomechanics and sets up a vicious cycle which leads to progressive deterioration of medial compartment. Medial open-wedge osteotomy using dynamic external fixator is a recent procedure introduced for axis correction and restoring joint biomechanics with good clinical results. Material and Methods: We retrospectively reviewed 75 patients (78 knees) who were operated for medial compartment arthritis by High Tibial Osteotomy using Hemicallostasis between 2001-2007. Preoperative full length Hip knee axis standing radiographs were taken and femoro-tibial angle determined. Medial open wedge osteotomy using dynamic external fixator was done and axis correction by gradual distraction was achieved to desired angle. Post-operative full length radiographs were compared and evaluated. Oxford Knee Score was used as a clinical tool for assessment. Results: In a mean follow-up period of 83 months, 54% patients showed excellent outcome with improved Oxford knee score. Most significant improvement was observed in females aged 51-60 years. Amongst 75 patients, 11 patients encountered pin-track infection, 4 patients had delayed union, 1 patient had lateral cortical fracture, and 7 patients had knee stiffness. No patients had loss of reduction or non-union of osteotomy site. No patients had conversion to total knee arthroplasty till last follow-up. Conclusion: High Tibial Osteotomy using dynamic external fixator provides cheap alternative in young active patients with initial stages of Medial Compartment Arthritis with good survivorship, no internal implant, less difficulty in subsequent total knee arthroplasty, minimal scar, minimal tissue disturbance, re-usability of fixator frame and good long-term results.

1.1 Introduction: The hand of a Man is his most prized possession, and any injury to it has the potential to produce significant and permanent impairment to hand functions and that in turn can cause mental and financial burden. Hand injuries are very common in present world mainly due to industrialization. Studies conducted show that hand injuries presenting in a tertiary care centre constitute approximately 10% of all the trauma cases and present from simple lacerations and contusions to crush injuries and amputations; requiring timely and skillful management to improve the prognosis. 1.2 Aim: The aim of this study is to evaluate the epidemiology of hand injuries and understand relation between mechanism of injury and prognosis and to study the Socio-economic impact. This study will provide us with better understanding of the various etiological factors for hand injuries and will help us to develop preventive and therapeutic measures for the same. 1.3 Methods: This study was conducted among 200 patients presenting with hand injuries, in the OPD and CASUALTY of our hospital over a period of two year from January 2015 to December 2016. 1.4 Results: Males (88%) are affected more as compared to females (12%). The commonest age group affected was 25-35 years (36%) followed by 15-25 years (28%). The commonest contributing factor was machine injury (52.5%) followed by road traffic accidents (25%) and assault (13.5%) respectively. The index (26%) and middle (24%) fingers were involved more commonly. 1.5 Conclusions: Hand injuries are more common in an adult male working in industries who required to operate complex machinery followed by Road Traffic Accidents.

Background New York City emerged as the Epicenter for Covid-19 due to novel Coronavirus SARS-CoV-2 soon after it was declared a Global Pandemic in early 2020 by the WHO. Covid-19 presents with a wide spectrum of illness from asymptomatic to severe respiratory failure, shock, multiorgan failure and death. Although the overall fatality rate is low, there is significant mortality among hospitalized patients. There is limited information exploring the impact of Covid-19 in community hospital settings in ethnically diverse populations. We aimed to identify risk factors for Covid-19 mortality in our institution. Methods We conducted a retrospective cohort study of hospitalized in our institution for Covid 19 from March 1st to June 21st 2020. It comprised of 425 discharged patients and 245 expired patients. Information was extracted from our EMR which included demographics, presenting symptoms, and laboratory data. We propensity matched 245 expired patients with a concurrent cohort of discharged patients. Statistically significant covariates were applied in matching, which included age, gender, race, body mass index (BMI), diabetes mellitus, and hypertension. The admission clinical attributes and laboratory parameters and outcomes were analyzed. Results The mean age of the matched cohort was 66.9 years. Expired patients had a higher incidence of dyspnea (P < 0.001) and headache (0.031). In addition, expired patients had elevated CRP- hs (mg/dl) ≥ 123 (< .0001), SGOT or AST (IU/L) ≥ 54 (p < 0.001), SGPT or ALT (IU/L) ≥ 41 (p < 0.001), and creatinine (mg/dl) ≥ 1.135 (0.001), lower WBC counts (k/ul) ≥ 8.42 (0.009). Furthermore, on multivariate logistic regression, dyspnea (OR = 2.56, P < 0.001), creatinine ≥ 1.135 (OR = 1.79, P = 0.007), LDH(U/L) > 465 (OR = 2.18, P = 0.001), systolic blood pressure < 90 mm Hg (OR = 4.28, p = .02), respiratory rate > 24 (OR = 2.88, p = .001), absolute lymphocyte percent (≤ 12%) (OR = 1.68, p = .001) and procalcitonin (ng/ml) ≥ 0.305 (OR = 1.71, P = .027) predicted in- hospital mortality in all matched patients. Conclusion Our case series provides admission clinical characteristics and laboratory parameters that predict in- hospital mortality in propensity Covid 19 matched patients with a large Hispanic population. These risk factors will require further validation. Disclosures All Authors: No reported disclosures

OBJECTIVEAnterior cervical discectomy and fusion (ACDF) is a safe and effective intervention to treat cervical spine pathology. Although these were originally performed as single-level procedures, multilevel ACDF has been performed for patients with extensive degenerative disc disease. To date, there is a paucity of data regarding outcomes related to ACDFs of 3 or more levels. The purpose of this study was to compare surgical outcomes of 3- and 4-level ACDF procedures.METHODSThe authors performed a retrospective chart review of patients who underwent 3- and 4-level ACDF at the University of Virginia Health System between January 2010 and December 2017. In patients meeting the inclusion/exclusion criteria, demographics, fusion rates, time to fusion, and reoperation rates were evaluated. Fusion was determined by < 1 mm of change in interspinous distance between individual fused vertebrae on lateral flexion/extension radiographs and lack of radiolucency between the grafts and vertebral bodies. Any procedure requiring a surgical revision was considered a failure.RESULTSSixty-six patients (47 with 3-level and 19 with 4-level ACDFs) met the inclusion/exclusion criteria of having at least one lateral flexion/extension radiograph series ≥ 12 months after surgery. Seventy percent of 3-level patients and 68% of 4-level patients had ≥ 24 months of follow-up. Ninety-four percent of 3-level patients and 100% of 4-level patients achieved radiographic fusion for at least 1 surgical level. Eighty-eight percent and 82% of 3- and 4-level patients achieved fusion at C3–4; 85% and 89% of 3- and 4-level patients achieved fusion at C4–5; 68% and 89% of 3- and 4-level patients achieved fusion at C5–6; 44% and 42% of 3- and 4-level patients achieved fusion at C6–7; and no patients achieved fusion at C7–T1. Time to fusion was not significantly different between levels. Revision was required in 6.4% of patients with 3-level and in 16% of patients with 4-level ACDF. The mean time to revision was 46.2 and 45.4 months for 3- and 4-level ACDF, respectively. The most common reason for revision was worsening of initial symptoms.CONCLUSIONSThe authors’ experience with long-segment anterior cervical fusions shows their fusion rates exceeding most of the reported fusion rates for similar procedures in the literature, with rates similar to those reported for short-segment ACDFs. Three-level and 4-level ACDF procedures are viable options for cervical spine pathology, and the authors’ analysis demonstrates an equivalent rate of fusion and time to fusion between 3- and 4-level surgeries.

Pituitary adenomas are a rare but important central nervous system tumor in children. Because of differences in growth and development, the manifestations of pituitary adenomas in children may differ from those seen in adults. Unlike adult patients, the pediatric population more often presents with clinically secretory adenomas. Although medical management is first-line treatment of prolactinomas, transsphenoidal surgery is appropriate for most children with Cushing disease and gigantism. Although some pediatric patients present surgical challenges because of small anatomic dimensions or an incompletely developed sphenoid sinus, transsphenoidal surgery can be safely and effectively undertaken in most children, with low complication rates.

Cortical spreading depression (CSD) is a pathophysiologic phenomenon that describes an expanding wave of depolarization within the cortical gray matter. Originally described over 70 years ago, this spreading depression disrupts neuronal and glial ionic equilibrium, leading to increased energy demands that can cause a metabolic crisis. This results in secondary insult, further perpetuating brain injury and neuronal death. Initially not thought to be of clinical significance, the view of CSD was modified with the advent of intracranial electroencephalography, or electrocorticography. With these improved monitoring techniques, CSD has been identified as a major mechanism by which traumatic brain injury (TBI) imparts its negative sequalae. TBI is a heterogenous disease process that runs the gamut of clinical presentations. This includes concussion, epidural and subdural hematoma, diffuse axonal injury, and subarachnoid hemorrhage. Nonetheless, CSD appears to be frequently occurring among the various types of TBI, thus allowing for the potential development of targeted therapies in an otherwise ill-fated patient cohort. Although a complete understanding of the interplay between CSD and TBI has not yet been achieved, the authors recount the efforts that have been employed over the last several decades in an effort to bridge this gap. In addition, our current understanding of the role neuroimmune cells play in CSD is discussed in the context of TBI. Finally, current therapeutic strategies using CSD as a pharmacologic target are explored with respect to their clinical use in patients with TBI.

Objective As the ageing population continues to grow, the incidence of osteoporosis continues to rise. Patients with osteoporosis are often managed pharmacologically. It is unclear the impact of these medications on osteoporotic patients requiring lumbar interbody fusion, and whether differences exist with respect to patient outcomes among the different medication classes that are often employed. In this systematic review, the authors examine studies evaluating the impact of pharmacologic therapy on osteoporotic patients undergoing lumbar interbody fusion. Methods Using PubMed and MEDLINE databases, the authors conducted a systematic literature review for studies published between 1986 and 2020 following PRISMA guidelines. Results A total of 12 articles were ultimately selected. Studies assessing bisphosphonate usage, parathyroid hormone analogues, vitamin D, or combination therapies and their impact on lumbar interbody fusion were included. Conclusions The evidence regarding bisphosphonate therapy and improved fusion rates with reduced incidence of complications is inconsistent. While some studies suggest bisphosphonates to confer added benefit, other studies suggest no such improvements despite reduction in bone turnover biomarkers. Teriparatide, on the other hand, consistently demonstrated improved fusion rates and may reduce screw loosening events. In comparison studies against bisphosphonates, teriparatide demonstrates greater potential. A single study reported vitamin D3 to increase fusion rates, although more studies are needed to validate this finding. It is important to note that these benefits are only demonstrated in single-level fusion, with multi-level fusions not being significantly enhanced by teriparatide therapy. Combination therapy with denosumab further augment fusion rates. Further prospective randomized controlled trials are necessary before standardized recommendations regarding pharmacological intervention in patients undergoing LIF can be made.

Calcified disk herniation of the thoracic spine is by no means a rare clinical entity in neurosurgery. We present a 63-year-old woman with a long-standing giant calcified disk in the thoracic spine. Initial imaging studies indicated a differential diagnosis of calcified disk versus meningioma. Given her benign neurologic examination and the presumed morbidity of attempting to resect the lesion, we elected to follow her closely with serial imaging. Over 3 years of consistent follow-up, the lesion has not grown and she has remained free of neurologic changes.

Tranexamic acid (TXA) is an antifibrinolytic agent with demonstrated efficacy in reducing blood loss when administered systemically. However, in patients with contraindications to systemic or intravenous TXA, topical TXA (tTXA) has been shown to reduce perioperative blood loss, with some studies suggesting equivalence compared to systemic TXA. However, these studies have been conducted in healthy cohorts without contraindications to systemic TXA. In the surgical management of adult spinal deformity (ASD), comorbid disease is commonly encountered and may preclude use of systemic TXA. In this subset of patients with ASD who have contraindications for systemic TXA, use of tTXA has not been reported.The primary objective of this study was to conduct a systematic review on the use of tTXA in spine surgery and to present the authors’ initial experience with tTXA as a novel hemostatic technique for 2 patients with medically complex ASD. Both patients had contraindications to systemic TXA use and underwent high-risk, long-segment fusion operations for correction of ASD. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to obtain studies related to spine surgery and tTXA from the National Institutes of Health PubMed (www.pubmed.gov) database. Criteria for final selection included a demonstration of quantitative data regarding operative or postoperative blood loss with the use of tTXA, and selection criteria were met by 6 articles.Topical TXA may offer a potential therapeutic role in reducing intra- and postoperative blood loss following long-segment spinal fusion surgeries, particularly for medically complex patients with contraindications to systemic TXA. It is reasonable to consider the use of tTXA as a salvage technique in complex high-risk patients with contraindications to systemic TXA, although further research is needed to delineate safety, magnitude of benefit, and optimization of dosing.

Precision imaging is paramount to achieving success in surgical resection of many spinal tumors, whether the goal involves guiding a surgical cure for primary tumors or improving neurological decompression for metastatic lesions. Pre-operatively, image visualization is intimately involved with defining a clear target and surgical planning. Intra-operatively, image-guidance technology allows for surgeons to maximize the probability for gross total resection of spinal cord tumors and minimize damage to adjacent structures. Through this review, it is evident that spinal surgery has undergone significant advancements with the continued technological progression of different modalities of imaging guided technologies. Sophisticated imaging techniques compliment the surgeon’s knowledge by providing an intraoperative reference to spinal column anatomy. This review discusses research efforts focusing on immersive imaging guided interactions with subject specific medical images that could enhance a surgeon’s ability to plan and perform complex spinal oncology procedures with safety and efficiency.

Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic (long-term) volume monitoring system.

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.

Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic (long-term) volume monitoring system.

Ludmila M Cosio-Lima, BhargavDesai, John W Stelzer, Petra B SchulerDepartment of Health, Leisure, and Exercise Science, University of West Florida, Pensacola, FL, USAPurpose: Intense or prolonged exercise and/or heat stress might affect the immune system creating a response similar to trauma or inflammation, resulting in an increase in the susceptibility to viral infections. For example, during prolonged exercise, inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and the stress hormone cortisol are produced and released. Although there have been several studies examining the effects of nutritional supplementation on cytokine release in elite athletes, few studies have investigated the effects of different energy drinks during exercise in adverse environmental conditions. Therefore, the purpose of this study was to compare plasma levels of inflammatory cytokines TNF-α and IL-6, and the stress hormone cortisol, during prolonged cycling under hot environmental conditions while ingesting fluid that contains a ratio of 4:1 carbohydrates and protein (4:1 CHO/PRO) versus a carbohydrate-only drink (CHO).Methods: Six male cyclists (aged 27 ± 8 years; weight 75.5 ± 3.4 kg; VO2max = 66 ± 2.7 mL/kg/min, mean ± standard error) rode on a stationary ergometer on two separate sessions for 2.5 hours at 75% VO2max in an environmental chamber set at 35°C and 60% relative humidity. During the first session the cyclists were given 4 mL/kg body weight of a 6% carbohydrate solution every 15 minutes. During the second session they were given 4 mL/kg body weight of a 4:1 carbohydrate/protein drink every 15 minutes. Subjects were not aware of which drink they were given in each trial. Blood samples were taken pre-, immediately post-, and 12 hours post-exercise. SPSS (IBM Corp, Armonk, NY) was utilized to analyze data through repeated measures analysis of variance.Results: No significant main effect was observed between treatments in either cortisol (P = 0.97), IL-6 (P = 0.64), or TNF-α (P = 0.37) responses. Total cortisol concentrations were significantly elevated (P < 0.05) immediately post-exercise, and from pre- to 12 hours post-exercise with both the 4:1 CHO/PRO and the CHO-alone solutions. TNF-α concentrations were only significantly (P = 0.045) elevated post-exercise with the CHO-alone solution. A significant (P < 0.05) elevation of IL-6 was seen immediately post-exercise and 12 hours post-exercise with both the CHO-alone and 4:1 CHO/PRO solutions.Conclusions: Consuming a 4:1 CHO/PRO solution during prolonged cycling under hot environmental conditions has comparable effects on inflammatory cytokines to drinking a CHO-alone solution.Keywords: carbohydrates, cytokines, heat, performance, protein

Ludmila M Cosio-Lima, Bhargav V Desai, Petra B Schuler, Lesley Keck, Logan ScheelerDepartment of Health, Leisure, and Exercise Science, University of West Florida, Pensacola, FL, USAPurpose: Components of immune function are affected by physical activity in an adverse environment. The purpose of this study was to compare plasma differences in inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), in addition to the stress hormone cortisol, during prolonged cycling under normal and hot environmental conditions in elite cyclists.Methods and design: Six trained elite male cyclists (27 ± 8 years; 75.5 ± 4 kg; maximum oxygen uptake [VO2max] = 66 ± 6 mL/kg/min, mean ± SD). The cyclists biked for 2.5 h at their prescribed 60% maximum exercise workload (Wmax) or 75% VO2max either in an environmental chamber set at 15°C and 40% relative humidity (NEUTRAL) or at 35°C and 40% relative humidity (HOT). The cyclists were given 4 mL of water/kg body weight every 15 min under both conditions.Results: Total cortisol concentrations were elevated (P < 0.05) immediately postexercise and 12 h postexercise in both the NEUTRAL and HOT conditions. TNF-α concentrations were only significantly (P = 0.045) elevated postexercise in HOT conditions. During the HOT conditions, a significant (P = 0.006 and 0.007, respectively) difference in IL-6 was seen immediately after and 12 h postexercise. During the NEUTRAL condition, IL-6 was only significantly elevated postexercise (P < 0.05).Conclusions: Heat exposure during a long bout of exercise is sufficient to elicit stress response in elite cyclists. However, the degree of release of anti-inflammatory and proinflammatory cytokines might be related to several factors that include the athlete’s fitness level, hydration status, exercise intensity, and length of exposure to hot environments.Keywords: cytokines, inflammation, heat, exercise, performance&nbsp