Genetic and Metabolite Variability in One-Carbon Metabolism Applied to an Insulin Resistance Model in Patients With Schizophrenia Receiving Atypical Antipsychotics.

Background: Patients with schizophrenia are at high risk of pre-mature mortality due to cardiovascular disease (CVD). Our group has completed studies in pharmacogenomics and metabolomics that have independently identified perturbations in one-carbon metabolism as associated with risk factors for CVD in this patient population. Therefore, this study aimed to use genetic and metabolomic data to determine the relationship between folate pharmacogenomics, one-carbon metabolites, and insulin resistance as measured using the homeostatic model assessment for insulin resistance (HOMA-IR) as a marker of CVD. Methods: Participants in this pilot analysis were on a stable atypical antipsychotic regimen for at least 6 months, with no diabetes diagnosis or use of antidiabetic medications. Participant samples were genotyped for MTHFR variants rs1801131 (MTHFR A1298C) and rs1801133 (MTHFR C677T). Serum metabolite concentrations were obtained with NMR. A least squares regression model was used to predict log(HOMA-IR) values based on the following independent variables: serum glutamate, glycine, betaine, serine, and threonine concentrations, and carrier status of the variant alleles for the selected genotypes. Results: A total of 67 participants were included, with a median age of 47 years old (IQR 42-52), 39% were female, and the median BMI was 30.3 (IQR 26.3-37.1). Overall, the model demonstrated an ability to predict log(HOMA-IR) values with an adjusted R 2 of 0.44 and a p-value of < 0.001. Glutamate, threonine, and carrier status of the MTHFR 1298 C or MTHFR 677 T allele were positively correlated with log(HOMA-IR), whereas glycine, serine, and betaine concentrations trended inversely with log(HOMA-IR). All factors included in this final model were considered as having a possible effect on predicting log(HOMA-IR) as measured with a p-value < 0.1. Conclusions: Presence of pharmacogenomic variants that decrease the functional capacity of the MTHFR enzyme are associated with increased risk for cardiovascular disease, as measured in this instance by log(HOMA-IR). Furthermore, serine, glycine, and betaine concentrations trended inversely with HOMA-IR, suggesting that increased presence of methyl-donating groups is associated with lower measures of insulin resistance. Ultimately, these results will need to be replicated in a significantly larger population.

Could Dietary Glutamate Play a Role in Psychiatric Distress?

Glutamate is an amino acid that functions as an excitatory neurotransmitter. It has also been associated with somatic and psychiatric distress and is implicated in the pathophysiology of psychiatric disorders such as schizophrenia. Ingestion of dietary glutamate, such as monosodium glutamate (MSG), has been mechanistically linked with greater distress among patients with chronic pain conditions, though findings have been equivocal. Preliminary research suggests that an MSG-restricted diet confers beneficial effects on somatic symptoms and well-being for some individuals with chronic pain conditions. In addition to associations with somatic distress, glutamate has been associated with the onset and progression of psychiatric symptoms. Thus, the role of dietary glutamate in psychiatric distress represents an underdeveloped and potentially important area for future research aimed at clarifying pathophysiological mechanisms and identifying targets for dietary intervention in psychiatric illnesses.

Retractorless interhemispheric transtentorial approach for large lesions in the posterior incisural space.

BACKGROUND: Surgical resection of lesions in the posterior incisural space presents a significant surgical challenge, which may result in postoperative visual complications and other neurological deficits. We, therefore, describe a retractorless interhemispheric transtentorial approach that avoids surrounding brain structures with positive outcomes and no complications or visual damage. CASE DESCRIPTION: We present four cases of lesions in the posterior incisural space that was treated with a retractorless interhemispheric transtentorial approach. Two patients were previously seen at another institution for a falcotentorial meningioma. We resected the meningiomas with a parietal-occipital interhemispheric transtentorial approach with no neurological deficits. A third patient presented with a large superior vermian hemangioblastoma with a steep angle of the tentorium. The fourth patient had a large upper vermian metastatic lesion with progressive enlargement, which was refractory to radiation treatments and chemotherapy, and we achieved partial resection. Postoperative visual function was completely preserved in all patients. CONCLUSION: A carefully executed retractorless interhemispheric approach in select cases is an effective option to reduce morbidity and prevent visual complications when removing lesions in the posterior tentorial incisure.

Microsurgical Technique for Basilar Apex Aneurysm Clipping: Two-Dimensional Video.

We present the case of a 57-year-old female with hypertension, current smoker status, and recent headaches. Imaging studies showed an unruptured 8-mm basilar apex wide neck aneurysm located 4 mm above posterior clinoid (Figure 1) with a 3-mm anterior communicant artery aneurysm. No contraindications were encountered for endovascular treatment, although after we evaluated endovascular and surgical options, surgical clipping was considered also a safe and favorable option based on anterior projection of aneurysm, height of the basilar artery bifurcation, small and elongated posterior communicant artery, and available space between posterior clinoid and basilar artery (4 mm). The presence of a second aneurysm increased the patient's interest in a more definitive treatment, as we mentioned the possibility of its treatment if considered safe intraoperatively. A cranio-orbito-zygomatic craniotomy, anterior clinoidectomy, and sylvian fissure dissection was performed with electrophysiology monitoring. The exposure was enhanced by sphenoparietal sinus ligation, and the anterior clinoidectomy allowed working spaces at optic-carotid and carotid-oculomotor spaces for Liliequist membrane dissection, without need for posterior clinoid removal (Figure 2). Brief temporary clipping at basilar trunk below superior cerebellar arteries at perforating free zone was performed. Two clips were applied, obliterating adequately the aneurysm respecting perforating vessels. After the basilar apex aneurysm clipping, we proceeded in a standard fashion to clip the additional anterior communicant artery aneurysm. Micro-Doppler and intraoperative angiogram confirmed aneurysm exclusion and patent parent vessels (Video 1). The patient developed minimal ptosis due to partial right oculomotor nerve palsy that recovered completely in 2 weeks; otherwise, her neurologic exam was normal. At 1-year follow up, computed tomography angiography showed complete aneurysm exclusion.

4 ways that clinical lab designs are changing.

New technology and work processes are transforming how clinical labs function. Well-designed spaces provide maximum flexibility so that they can be adapted as health care continues to evolve.

Constructing a modern cytology laboratory: A toolkit for planning and design.

INTRODUCTION: Constructing or renovating a laboratory can be both challenging and rewarding. UAB Cytology (UAB CY) recently undertook a project to relocate from a building constructed in 1928 to new space. UAB CY is part of an academic center that provides service to a large set of patients, support training of one cytotechnology program and one cytopathology fellowship training program and involve actively in research and scholarly activity. Our objectives were to provide a safe, aesthetically pleasing space and gain efficiencies through lean processes. METHODS: The phases of any laboratory design project are Planning, Schematic Design (SD), Design Development (DD), Construction Documents (CD) and Construction. Lab personnel are most critical in the Planning phase. During this time stakeholders, relationships, budget, square footage and equipment were identified. Equipment lists, including what would be relocated, purchased new and projected for future growth ensure that utilities were matched to expected need. A chemical inventory was prepared and adequate storage space was planned. Regulatory and safety requirements were discussed. Tours and high level process flow diagrams helped architects and engineers understand the laboratory daily work. Future needs were addressed through a questionnaire which identified potential areas of growth and technological change. Throughout the project, decisions were driven by data from the planning phase. During the SD phase, objective information from the first phase was used by architects and planners to create a general floor plan. This was the basis of a series of meetings to brainstorm and suggest modifications. DD brings more detail to the plans with engineering, casework, equipment specifics, finishes. Design changes should be completed at this phase. The next phase, CD took the project from the lab purview into purely technical mode. Construction documents were used by the contractor for the bidding process and ultimately the Construction phase. RESULTS: The project fitted out a total of 9,000 square feet; 4,000 laboratory and 5,000 office/support. Lab space includes areas for Prep, CT screening, sign out and Imaging. Adjacent space houses faculty offices and conferencing facilities. Transportation time was reduced (waste removal) by a Pneumatic Tube System, specimen drop window to Prep Lab and a pass thru window to the screening area. Open screening and prep areas allow visual management control. Efficiencies were gained by ergonomically placing CT Manual and Imaging microscopes and computers in close proximity, also facilitating a paperless workflow for additional savings. Logistically, closer proximity to Surgical Pathology maximized the natural synergies between the areas. CONCLUSIONS: Lab construction should be a systematic process based on sound principles for safety, high quality testing, and finance. Our detailed planning and design process can be a model for others undertaking similar projects.