Fatal Oedipism: A Case Report and Literature Review.

PURPOSE: To describe a unique case of a fatal self-enucleation and review previously published cases. METHODS: The authors describe a unique case of a complete unilateral self-enucleation while under the influence of drugs, which resulted in severe intracranial hemorrhages, right internal carotid artery opacification, and death. A literature review was performed by searching articles published before January 2023 in the Pubmed/MEDLINE database using the keywords "auto-enucleation or self-enucleation." Cases of self-inflicted damage to the globe without severing any connections were excluded. RESULTS: A literature review identified a total of 54 articles and 75 patients who had self-enucleated at least one globe completely (84.0%). Their average age was 37 years and 50.7% were male. At the time of auto-enucleation, 64.0% of these patients had known psychiatric disorders, and 28.0% were found to be under the influence of illicit drugs or alcohol. Auto-enucleation resulted in intracranial complications in 26.7% of cases. There has been 1 prior case, which, like the authors' case, resulted in death due to intracranial complications. However, this occurred in a patient who partially enucleated one eye after a self-inflicted injury to the fellow eye. The current case is unique as these complications resulted from a complete unilateral auto-enucleation. CONCLUSIONS: The severity of this case's presentation and outcome highlights the importance of prompt neuroimaging and a thorough assessment. Prompt psychiatric assessment and treatment are also required.

Facial Recognition Software Use on Surgically Altered Faces: A Systematic Review.

OBJECTIVE: Facial recognition software (FRS) is becoming pervasive in society for commercial use, security systems, and entertainment. Alteration of the facial appearance with surgery poses a challenge to these algorithms, but several methods are being studied to overcome this issue. This study systematically reviews methods used in facial recognition of surgically altered faces. MATERIALS AND METHODS: A systematic review was performed by searching PubMed and Institute of Electrical and Electronics Engineers (IEEE) databases to identify studies addressing FRS and surgery. On initial review, 178 manuscripts were identified relating to FRS and surgery and allowed division into multiple subgroups. The decision was made to focus on the recognition of surgically altered faces. RESULTS: Eligible studies included those reports in English on FRS of surgically altered faces, and 39 papers were included. Surgical procedures range from affecting skin surface, such as skin peeling, to altering facial features, such as rhinoplasty, mentoplasty, malar augmentation, brow lift, facelift, orthognathic surgery, facial reanimation, and facial feminization. Methods were classified into appearance-based, feature-based, and texture-based. Descriptive versus experimental protocols were characterized by different reporting outcomes and controls. Accuracy ranged from 19.1% to 85.35% using various analysis methods. CONCLUSIONS: Knowledge of available limitations and advantages can aid in counseling patients regarding personal technology use, security, and quell fears about surgery to evade authorities. Surgical knowledge can be utilized to improve FRS algorithms for postsurgical recognition.

Correction to: Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis.

The original article can be found online.

Myelin oligodendrocyte glycoprotein-specific antibodies from multiple sclerosis patients exacerbate disease in a humanized mouse model.

Myelin oligodendrocyte glycoprotein (MOG) is exposed on the outer surface of the myelin sheath, and as such, represents a possible target antigen for antibodies in multiple sclerosis (MS) and other demyelinating diseases. However, despite extensive analyses, whether MOG-specific antibodies contribute to pathogenesis in human MS remains an area of uncertainty. In the current study we demonstrate that antibodies derived from adult MS patients exacerbate experimental autoimmune encephalomyelitis (EAE) in 'humanized' mice that transgenically express human FcγRs (hFcγRs). Importantly, this exacerbation is dependent on MOG recognition by the human-derived antibodies. The use of mice that express hFcγRs has allowed us to also investigate the contribution of these receptors to disease in the absence of confounding effects of cross-species differences. Specifically, by engineering the Fc region of MOG-specific antibodies to modulate FcγR and complement (C1q) binding, we reveal that FcγRs but not complement activation contribute to EAE pathogenesis. Importantly, selective enhancement of the affinities of these antibodies for specific FcγRs reveals that FcγRIIA is more important than FcγRIIIA in mediating disease exacerbation. These studies not only provide definitive evidence for the contribution of MOG-specific antibodies to MS, but also reveal mechanistic insight that could lead to new therapeutic targets.

Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold.

Inspired by a rhodanine-based dual inhibitor of Bcl-xL and Mcl-1, a focused library of analogues was prepared wherein the rhodanine core was replaced with a less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b inhibited Mcl-1 with a Ki of 155 nM. Further investigation revealed comparable inhibition of Bcl-xL (Ki = 90 nM), indicating that the dual inhibitory profile of the initial rhodanine lead had been retained upon switching the heterocycle core.

Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissues in joints, leading to progressive destruction of cartilage and joints. The disease-modifying anti-rheumatic drugs currently in use have side-effects. Thus, there is an urgent need for safe anti-inflammatory therapies for RA. This study aimed to evaluate the therapeutic effect of the flavonoid quercetin on arthritis in mice immunized with type II collagen (CII). An arthritis model was established in C57/BL6 mice by intradermal administration of chicken CII mixed with Freund's complete adjuvant. Quercetin (30 mg/kg orally) and methotrexate (0.75 mg intraperitoneally twice a week) were administered to investigate their protective effects against collagen-induced arthritis (CIA). Levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, and the matrix metalloproteinases (MMP), 3, and 9 were detected to assess the anti-inflammatory effect of quercetin. The mRNA expression of MMP3, MMP9, CCL2, and TNF-α was also measured by quantitative real-time PCR. Quercetin significantly alleviated joint inflammation by reducing the levels of circulating cytokines and MMPs. There was a significant decrease in the expression of TNFα and MMP genes in the ankle joints of arthritic mice. A significant reduction in the levels of knee-joint inflammatory mediators were observed with combined quercetin and methotrexate treatment. Thus, quercetin has the potential to prevent joint inflammation and could be used as an adjunct therapy for RA patients who have an inadequate response to anti-rheumatic monotherapy.

The therapeutic potential of plant flavonoids on rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune condition that mainly affects peripheral joints. Although immunosuppressive drugs and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat this condition, these drugs have severe side effects. Flavonoids are the most abundant phenolic compounds which exhibit anti-oxidant, anti-inflammatory and immunomodulatory properties. Many bioactive flavonoids have powerful anti-inflammatory effects. However, a very few have reached clinical use. Dietary flavonoids have been reported to control joint inflammation and alleviate arthritis symptoms in both human RA and animal models of arthritis. There is little scientific evidence about their mechanism of actions in RA. We review the therapeutic effects of different groups of flavonoids belonging to the most common and abundant groups on RA. In particular, the probable mechanisms of major flavonoids on cells and chemical messengers involved in the inflammatory signaling components of RA are discussed in detail.

Ethical considerations in targeted paediatric neurosurgery missions.

Within the context of global health development approaches, surgical missions to provide care for underserved populations remain the least studied interventions with regard to their methodology. Because of the unique logistical needs of delivering operative care, surgical missions are often described solely in terms of cases performed, with a paucity of discourse on medical ethics. Within surgery, subspecialties that serve patients on a non-elective basis should, it could be argued, create mission strategies that involve a didactic approach and the propagation of sustainable surgical care. The ethical considerations have yet to be described for paediatric neurosurgical outreach missions. We present here the perspectives of neurosurgeons who have participated in surgical outreach missions in Central America, South America, Eastern Europe and sub-Saharan Africa from the vantage point of both the visiting mission team and the host team that accommodates the mission efforts.

Brain reinforcement system function is ghrelin dependent: studies in the rat using pharmacological fMRI and intracranial self-stimulation.

Ghrelin (GHR) is an orexigenic gut peptide that interacts with brain ghrelin receptors (GHR-Rs) to promote food intake. Recent research suggests that GHR acts as a modulator of motivated behavior, suggesting a direct influence of GHR on brain reinforcement circuits. In the present studies, we investigated the role of GHR and GHR-Rs in brain reinforcement function. Pharmacological magnetic resonance imaging was used to spatially resolve the functional activation produced by systemic administration of an orexigenic GHR dose. The imaging data revealed a focal activation of a network of subcortical structures that comprise brain reinforcement circuits-ventral tegmental area, lateral hypothalamus and nucleus accumbens. We next analyzed whether brain reinforcement circuits require functional GHR-Rs. To this purpose, wild-type (WT) or mutant rats sustaining N-ethyl-N-nitrosourea-induced knockout of GHR-Rs (GHR-R null rats) were implanted with stimulating electrodes aimed at the lateral hypothalamus, shaped to respond for intracranial self-stimulation (ICSS) and then tested using a rate-frequency procedure to examine ICSS response patterns. WT rats were readily shaped using stimulation intensities of 75 µA, whereas GHR-R null rats required 300 µA for ICSS shaping. No differences in rate-frequency curves were noted for WT rats at 75 µA and GHR-R null rats at 300 µA. When current intensity was lowered to 100 µA, GHR-R null rats did not respond for ICSS. Taken collectively, these data suggest that systemic GHR can activate mesolimbic dopaminergic areas, and highlight a facilitative role of GHR-Rs on the activity of brain reinforcement systems.

Attenuation of cocaine-induced locomotor sensitization in rats sustaining genetic or pharmacologic antagonism of ghrelin receptors.

Systemic infusions of the orexigenic peptide ghrelin (GHR) increase dopamine levels within the nucleus accumbens and augment cocaine-stimulated locomotion and conditioned place preference in rats; observations that suggest an important role for GHR and GHR receptors (GHR-Rs) in drug reinforcement. In the present studies, we examined the development of cocaine locomotor sensitization in rats, sustaining either pharmacologic antagonism or genetic ablation of GHR-Rs. In a pharmacologic study, adult male rats were injected (i.p.) with either 0, 3 or 6 mg/kg JMV 2959 (a GHR-R1 receptor antagonist), and 20 minutes later, with either vehicle or 10 mg/kg cocaine HCl on each of 7 consecutive days. Rats pretreated with JMV 2959 showed significantly attenuated cocaine-induced hyperlocomotion. In a second study, adult wild-type (WT) or mutant rats sustaining ENU-induced knockout of GHR-R [GHR-R ((-/-) )] received daily injections (i.p.) of vehicle (0.9% saline) or 10.0 mg/kg cocaine HCl for 14 successive days. GHR-R null rats treated repeatedly with cocaine showed diminished development of cocaine locomotor sensitization relative to WT rats treated with cocaine. To verify the lack of GHR-R function in the GHR-R ((-/-) ) rats, a separate feeding experiment was conducted in which WT rats, but not GHR-R ((-/-) ) rats, were noted to eat more after a systemic injection of 15 nmol GHR than after vehicle. These results suggest that GHR-R activity is required for the induction of locomotor sensitization to cocaine and complement an emerging literature implicating central GHR systems in drug reward. GHR is an orexigenic gut peptide that is transported across the blood-brain barrier and interacts with GHR-Rs located on ventral tegmental dopamine neurons.

Coverage for obesity prevention and treatment: analysis of state employee health plans and use of benefits.

OBJECTIVE: Using data from 2017, the authors have previously examined the coverage of obesity-related services in state employee health plans since 2009 and found improvements in coverage for obesity-related treatments. This study repeated the collection of similar data for 2021 and explored whether coverage had continued to increase or decline. METHODS: Data on obesity benefits for state employees were obtained from publicly available documents from relevant state websites. Source documents were reviewed for language that would indicate the availability of coverage for nutritional counseling, pharmacotherapy, and bariatric surgery. Use data were collected when available, but availability was limited. RESULTS: Coverage for some treatments of obesity continued to trend upward, as was the case between 2009 and 2017, but coverage for pharmacotherapy declined from 2017 to 2021. Use data were received from only eight states; analysis of these data indicated underuse of obesity benefits by plan enrollees compared with each state's rate of obesity. CONCLUSIONS: Despite promising new therapies, states in 2021 were less likely to provide coverage for antiobesity medications. Additionally, limited use data suggested that few eligible individuals may be receiving these services. In conclusion, state employee health plans are currently inadequate given the prevalence, severity, and costs of obesity.

Regulation of bat echolocation pulse acoustics by striatal dopamine.

The ability to control the bandwidth, amplitude and duration of echolocation pulses is a crucial aspect of echolocation performance but few details are known about the neural mechanisms underlying the control of these voice parameters in any mammal. The basal ganglia (BG) are a suite of forebrain nuclei centrally involved in sensory-motor control and are characterized by their dependence on dopamine. We hypothesized that pharmacological manipulation of brain dopamine levels could reveal how BG circuits might influence the acoustic structure of bat echolocation pulses. A single intraperitoneal injection of a low dose (5 mg kg(-1)) of the neurotoxin 1-methyl-4-phenylpyridine (MPTP), which selectively targets dopamine-producing cells of the substantia nigra, produced a rapid degradation in pulse acoustic structure and eliminated the bat's ability to make compensatory changes in pulse amplitude in response to background noise, i.e. the Lombard response. However, high-performance liquid chromatography (HPLC) measurements of striatal dopamine concentrations revealed that the main effect of MPTP was a fourfold increase rather than the predicted decrease in striatal dopamine levels. After first using autoradiographic methods to confirm the presence and location of D(1)- and D(2)-type dopamine receptors in the bat striatum, systemic injections of receptor subtype-specific agonists showed that MPTP's effects on pulse acoustics were mimicked by a D(2)-type dopamine receptor agonist (Quinpirole) but not by a D(1)-type dopamine receptor agonist (SKF82958). The results suggest that BG circuits have the capacity to influence echolocation pulse acoustics, particularly via D(2)-type dopamine receptor-mediated pathways, and may therefore represent an important mechanism for vocal control in bats.

Maria Auxiliadora Hospital in Lima, Peru as a model for neurosurgical outreach to international charity hospitals.

INTRODUCTION: A myriad of geopolitical and financial obstacles have kept modern neurosurgery from effectively reaching the citizens of the developing world. Targeted neurosurgical outreach by academic neurosurgeons to equip neurosurgical operating theaters and train local neurosurgeons is one method to efficiently and cost effectively improve sustainable care provided by international charity hospitals. The International Neurosurgical Children's Association (INCA) effectively improved the available neurosurgical care in the Maria Auxiliadora Hospital of Lima, Peru through the advancement of local specialist education and training. METHODS: Neurosurgical equipment and training were provided for the local neurosurgeons by a mission team from the University of California at San Diego. RESULTS: At the end of 3 years, with one intensive week trip per year, the host neurosurgeons were proficiently and independently applying microsurgical techniques to previously performed operations, and performing newly learned operations such as neuroendoscopy and minimally invasive neurosurgery. CONCLUSION: Our experiences may serve as a successful template for the execution of other small scale, sustainable neurosurgery missions worldwide.

Diagnostic Criteria of Recurrent Acute Rhinosinusitis: A Systematic Review.

BACKGROUND: RARS is a challenging clinical phenomenon that affects many patients, and diagnostic criteria for this condition are not fully characterized in the literature. OBJECTIVE: To examine diagnostic criteria for recurrent acute rhinosinusitis (RARS). STUDY DESIGN: Systematic review. METHODS: Cochrane, PubMed (MEDLINE), clinicaltrials.gov, EMBASE, Google Scholar, and Web of Science databases were queried for articles related to RARS dating from 1990 to present, according to PRISMA statement guidelines. Full text articles pertinent to the diagnostic criteria of RARS were included in this review. Inclusion criteria included articles specifically addressing RARS; studies with 3 or more patients; and articles in English. RESULTS: A total of 1022 titles/abstracts potentially related to RARS were identified. Of these, sixty-nine full texts were selected for review, and 22 of these ultimately met inclusion criteria. The level of evidence was generally low. Studies and guidelines have used many different definitions for RARS diagnosis over the years based on symptomatology, physical examination, nasal endoscopy, imaging, and laboratory domains. Clinically important RARS has been defined most commonly as 4 or more discrete episodes of ARS per year, but this frequency is typically based on expert opinion. Additionally, radiologic anatomic associations such as concha bullosa, accessory maxillary os, and narrowed infundibular distance may be associated with RARS. Endoscopic visualization and imaging are sometimes used to confirm the presence of sinus disease during exacerbations of RARS, but there is variability in this practice. CONCLUSION: The diagnostic definition for RARS has developed over time and is currently based on low level 4 and 5 evidence. Because of the migratory definition of RARS, comparing inter-study results of RARS management remains difficult, and future studies should aim to follow current expert guidelines on diagnostic criteria of RARS.

Management of Recurrent Acute Rhinosinusitis: A Systematic Review.

BACKGROUND OBJECTIVE STUDY DESIGN: RARS is a challenging clinical problem that impacts many patients. This article seeks to systematically review the literature on RARS management. METHODS: Cochrane, PubMed, EMBASE, and other databases were queried for articles related to RARS dating from 1990 to present, according to PRISMA guidelines. Inclusion criteria included articles specifically addressing RARS management; studies with 3 or more patients; and articles in English. RESULTS: A total of 1022 titles/abstracts potentially related to RARS were identified. Of these, sixty-nine full texts were selected for review, and 10 met inclusion criteria (five with level 4 evidence, four with level 3 evidence, one with level 2 evidence). The studies included a total of 890 patients (Age range 5.8 to 53.5 years), with follow up ranging from 1 to 19 months. Endpoints were primarily based on symptomatic improvement, although some articles also reported post-treatment endoscopic and radiographic findings. Management options included medical therapy (intranasal steroids, antibiotics, nasal saline irrigations, N-acetylcysteine, allergy treatment, and decongestants), balloon sinus dilation (BSD), and endoscopic sinus surgery (ESS). Surgical patients (BSD and ESS) had a trend towards greater symptom control than medically-treated patients, but meta-analysis was not possible. CONCLUSION: Despite increasing interest in the treatment of RARS, there remains a lack of consensus regarding optimal management. The literature thus far, largely based on expert opinion, suggests that surgical management, either through balloon sinus dilation or endoscopic sinus surgery, may be helpful in improving symptoms and quality of life in those who do not respond to initial trials of medical management.

Biological horizons for targeting brain malignancy.

Though currently available clinical treatments and therapies have clearly extended the survival of patients with brain tumors, many of these advances are short lived, particularly with respect to high grade gliomas such as glioblastoma multiforme. The missing link to an efficacious treatment of high grade gliomas is a more complete understanding of the basic molecular and cellular origin of brain tumors. However, new discoveries of stem cell and developmental neurobiology have now borne the cancer stem cell hypothesis, drawing off of intriguing similarities between benign and malignant cells within the central nervous system. Investigation of cancer stem cell hypothesis and brain tumor propagation is the current frontier of stem cell and cancer biology. Neurosurgery is also watching closely this promising new area of focus. "Molecular neurosurgery", glioma treatments involving biologics using neural stem cells to target the cancer at the level of individual migratory cell, is a rapidly evolving field. This coming progression of applied cancer stem cell research, coupled with current modalities, promises more comprehensive brain cancer interventions.

Rationally Designed Polypharmacology: α-Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl-1 and HDM2.

Protein-protein interactions (PPIs), many of which are dominated by α-helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl-2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl-2 pro-life proteins, such as Mcl-1, and pro-death proteins, such as Bim, regulate the intrinsic pathway of apoptosis. p53, a tumor-suppressor protein, also has a pivotal role in apoptosis and is negatively regulated by its E3 ubiquitin ligase HDM2. Both Mcl-1 and HDM2 are upregulated in numerous cancers, and, interestingly, there is crosstalk between both protein pathways. Recently, synergy has been observed between Mcl-1 and HDM2 inhibitors. Towards the development of new anticancer drugs, we herein describe a polypharmacology approach for the dual inhibition of Mcl-1 and HDM2 by employing three densely functionalized isoxazoles, pyrazoles, and thiazoles as mimetics of key α-helical domains of their partner proteins.

Optical coherence tomography features in brothers with aspartylglucosaminuria.

Aspartylglucosaminuria is a lysosomal storage disorder enriched in Finland. We report on a pair of non-Finnish siblings with aspartylglucosaminuria with autofluorescent inclusion bodies on optical coherence tomography, a finding not previously reported in this disorder. We performed a record review, neurological and neuropsychological evaluation, brain MRI, and optical coherence tomography for each patient. They are compound heterozygous for a 34-kb deletion and a c.365C>A novel variant of the AGA gene. Autofluorescent inclusion bodies were found on optical coherence tomography in the older, more severely affected brother. We hypothesize the finding represents a noninvasive biomarker of disease severity for aspartylglucosaminuria.

Prolonged Jackson-Pratt drainage in the management of lumbar cerebrospinal fluid leaks.

BACKGROUND: Cerebrospinal fluid (CSF) leak is a complication of spinal surgery. Intraoperative or postoperative identification of a CSF leak often results in wound healing complications, lumbar drain placement, and/or reoperation. These complications usually extend a patient's hospital stay, can be painful, and have their own associated risks. The authors describe a technique that may improve on traditional interventions by managing postoperative CSF leaks after lumbar instrumentation without an additional procedure or extended hospitalization. METHODS: A retrospective review of lumbar instrumentation cases performed by 5 attending surgeons from the Division of Neurosurgery, University of California at San Diego, was performed. In all, 184 charts were reviewed, spanning a 3-year period. There were 16 cases in which a dural tear and repair were carried out and subsequently treated with subfascial Jackson-Pratt (JP) drainage. Of those 16 cases, 8 patients were managed with prolonged JP drainage using the intraoperatively placed subfascial drain. Patients were discharged home on oral antibiotics according to the customary criteria with the JP drain in place and were instructed regarding proper drain maintenance. Jackson-Pratt drains were removed in clinic in a delayed fashion, approximately 10 to 17 days postoperatively. Patients were subsequently reevaluated at regular intervals for any persistent CSF leak. RESULTS: In the 8 cases reviewed, all patients were discharged in a time frame comparable to that of patients undergoing similar instrumentation in which no CSF leak was identified, or in whom a CSF leak was identified and repaired intraoperatively. No patients suffered complications arising from prolonged drain presence. No patients suffered from persistent CSF leak after drains were removed. CONCLUSION: Our study suggests that routine intraoperative subfascial JP drain placement aids in the early diagnosis of postoperative lumbar CSF leak. Primary closure of dural tear remains the standard of care. Furthermore, in select cases, prolonged JP drainage in the setting of postoperative CSF leak may be a useful technique for the treatment of these leaks.

Minimally disruptive decompression and transforaminal lumbar interbody fusion.

BACKGROUND: Posterior spinal procedures through tubular exposures have been described. However, tubes restrain visibility and require co-axial instrument manipulation, increasing difficulty and potentially compromising surgical results. An independent-blade retractor system overcomes the obstacles of working through a tube and has been used to perform minimally-disruptive decompression and instrumented tranforaminal lumbar interbody fusion (TLIF). PURPOSE: To evaluate the advantages to patient recovery and surgical efficacy of this technique. METHODS/RESULTS: Retrospective review of technique employing a minimally-disruptive approach to decompression and transforaminal lumber interbody fusion (TLIF). CONCLUSIONS: Minimally-disruptive decompression and instrumented TLIF can be performed in a safe and effective manner using an independent-blade retractor system. Relative to traditional-open techniques, surgical goals can be accomplished, but with the benefits of minimally-disruptive surgery.