Sporadic Creutzfeldt-Jakob Disease Initially Presenting With Posterior Reversible Encephalopathy Syndrome: A Case Report.

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative condition caused by prion proteins. Cortical and subcortical diffusion-weighted imaging restriction on magnetic resonance imaging (MRI) is associated with sCJD. Posterior reversible encephalopathy syndrome (PRES) results from impaired vessel autoregulation due to an identifiable trigger, which is associated with subcortical fluid-attenuated inversion recovery changes on MRI. We report a case of sCJD initially presenting with PRES. CASE REPORT: A 70-year-old woman presented to an outside hospital with progressive confusion and difficulty in managing activities of daily living. Initial examination revealed stuporous mental state and stimulus-induced myoclonus. MRI revealed bilateral subcortical occipital lobe T2-fluid-attenuated inversion recovery hyperintensities without contrast enhancement suggestive of PRES. Electroencephalogram (EEG) revealed frequent generalized periodic discharges meeting criteria for nonconvulsive status epilepticus. Clinical examination and EEG did not improve despite escalating antiseizure medications. Initial lumbar puncture was unremarkable. She was transferred to our hospital with a presumptive diagnosis of PRES, although there was no clear trigger. Continuous EEG revealed ongoing generalized periodic discharges with myoclonic activity meeting criteria for myoclonic seizures that were refractory to multiple antiseizure medications. Repeat MRI showed resolution of PRES but revealed subtle diffuse cortical diffusion-weighted imaging restriction. Repeat lumbar puncture was performed and 14-3-3 and real-time quaking-induced conversion returned positive, confirming sCJD. CONCLUSIONS: This case reports highlights that sCJD can present with neuroimaging consistent with PRES. The diagnosis of sCJD should be considered in patients with PRES who continue to show neurological decline despite optimal management and radiographic improvement of PRES on MRI. Further research is needed to identify a pathophysiological relationship between these clinical phenotypes.

Vaporization, bioactive formulations and a marine natural product: different perspectives on antivirals.

This article examines three aspects of antivirals, such as hydroxychloroquine, chloroquine, and remdesvir, as they might relate to the treatment of a viral infection such as COVID-19: (i) the use of vaporization for the delivery of antivirals, with the bulk constituents having mild antiviral efficacy; (ii) the application of a marine natural product extract as opposed to a single molecule as an antiviral agent; and (iii) a counter intuitive approach to formulation that is, in part, based on delivering multiple species that fall into three categories: building blocks for the virus to accelerate replication; an energy source for the infected cell to boost its immune response; and the species that antagonize or provide toxicity to the virus.

A Copper10-Paclitaxel crystal; a medicinally active drug delivery platform.

Paclitaxel is a well-known cancer drug that functions as a mitotic inhibitor. This work focuses on a copper based crystal that encapsulates the pharmaceutical agent and serves as a drug delivery agent. A Copper10-Pacitaxil1 chloride (CU10PAC1) complex is synthesized and tested against the National Cancer Institute's sixty cell line panel. The 10:1 ratio results in a crystal that was examined by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spec (MALDI-TOF-MS), Scanning Electron Microscopy (SEM) and Proton (1H) and Carbon (13C) Nuclear Magnetic Resonance (NMR). The potential attributes of a copper based crystal as an in vivo drug carrier for Paclitaxel are discussed.

Pharmaceutical interventions for weight-loss maintenance: no effect from cabergoline.

BACKGROUND: Weight regain is a major limitation to successful weight maintenance following weight loss. Observational studies suggest that stimulation of dopamine receptors in the central nervous system is associated with weight loss and inhibition of weight gain. Our objective was to test the hypothesis that dopamine agonist treatment would prevent weight regain following acute weight loss in individuals with obesity. METHODS: We conducted a 2-year double blind randomised controlled trial comparing the effect of a dopamine agonist, cabergoline, with placebo on weight regain in obese individuals who had lost at least 5% of their body weight using an 800 kcal/day commercial meal replacement programme. The primary outcome measure was the difference in mean weight between the treatment and control groups over the 2-year period following randomisation. RESULTS: At 24 months, there was no difference in body weight between cabergoline and placebo treatment after adjustment for age, gender and baseline values (0.6 kg (95% CI: -1.5, 2.6), p = 0.58). The mean (±SD) baseline body weight of the randomised participants was 101.8 kg, the mean (±SD) weight loss with the 800 kcal/day diet was 7.1 ± 1.8 kg and the mean (±SD) weight regain at 24 months was 5.1 ± 7.5 kg. There were no significant differences in BMI, percent weight loss, waist circumference, resting energy expenditure, blood pressure or metabolic parameters at 24 months between the two groups. CONCLUSIONS: Treatment with the dopamine agonist cabergoline does not prevent weight regain in obese individuals following weight loss.

Performance of minimally invasive sagittal synostectomy with supine patient positioning: technical note.

The authors report their initial experience with supine patient positioning for minimally invasive treatment of sagittal craniosynostosis. Supine positioning offers potential advantages that include reduced anesthetic risk and may be considered as an option by craniofacial surgeons performing minimally invasive synostectomy for sagittal craniosynostosis.

Demonstration of universal parametric entangling gates on a multi-qubit lattice.

We show that parametric coupling techniques can be used to generate selective entangling interactions for multi-qubit processors. By inducing coherent population exchange between adjacent qubits under frequency modulation, we implement a universal gate set for a linear array of four superconducting qubits. An average process fidelity of ℱ = 93% is estimated for three two-qubit gates via quantum process tomography. We establish the suitability of these techniques for computation by preparing a four-qubit maximally entangled state and comparing the estimated state fidelity with the expected performance of the individual entangling gates. In addition, we prepare an eight-qubit register in all possible bitstring permutations and monitor the fidelity of a two-qubit gate across one pair of these qubits. Across all these permutations, an average fidelity of ℱ = 91.6 ± 2.6% is observed. These results thus offer a path to a scalable architecture with high selectivity and low cross-talk.

Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih.

Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster.

Pharmacokinetic studies of a three-component complex that repurposes the front line antibiotic isoniazid against Mycobacterium tuberculosis.

The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a three component complex aimed at increasing the delivery efficiency and adding new avenues to its mechanism of action. This study focuses on pharmacokinetic studies of the isoniazid-sucrose-copper (II)-PEG-3350 complex. The assays include the Plasma Protein Binding Assay (85.8%), Caco-2 Permeability Assay (B→APapp, 0.13 × 10-6 cm/s), Cytochrome P450 Inhibition Assay (i.e. CYP2B6, IC50 = 7.26 µM), In vitro microsomal Stability Assay (t1/2 NADPH-Dependent > 240 min), and HepG2 Cytotoxicity (no toxicity). The National Cancer Institute's 60 cell line panel is used to measure activity against cancer cells. The percent growth values averaged over all 60 cell lines indicates the complex has no anti-cancer activity, which also suggests a lack of general toxicity. It also provides data for the complexes specificity against Mycobacterium tuberculosis.

Cell line studies and analytical measurements of three paclitaxel complex variations.

The copper(II) cation, sucrose, and hydroxychloroquine were complexed with the chemotherapy agent paclitaxel and studied for medicinal activity. Data (GI50, LD50) from single dose and five dose National Cancer Institute sixty cell line panels are presented. Analytical measurements of different complexes were made using Nuclear Magnetic Resonance (1H NMR), Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) and Fourier Transform-Ion Cyclotron Resonance (FT-ICR). Molecular modeling is utilized to better understand the impact that species could have on physical parameters associated with Lipinski's Rule of Five, such as logP and TPSA. On average, Cu(II) and hydroxychloroquine decreased GI50 values, while sucrose increased GI50 values of paclitaxel.

Isolation, analytical measurements, and cell line studies of the iron-bryostatin-1 complex.

Bryostatin-1 is a marine natural product that has demonstrated medicinal activity in pre-clinical and clinical trials for the treatment of cancer, Alzheimer's disease, effects of stroke, and HIV. In this study, iron-bryostatin-1 was obtained using a pharmaceutical aquaculture technique developed by our lab that cultivates marine bacteria for marine natural product extraction. Analytical measurements (1)H and (13)C NMR, mass spectrometry, and flame atomic absorption were utilized to confirm the presence of an iron-bryostatin-1 complex. The iron-bryostatin-1 complex produced was then tested against the National Cancer Institute's 60 cell line panel. Adding iron to bryostatin-1 lowered the anti-cancer efficacy of the compound.

Structural measurements and cell line studies of the copper­ PEG­Amikacin complex against Mycobacterium tuberculosis.

The bacterium responsible for causing tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis (XDR-TB) strains. In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, and LC­MS are used to study different aspects of the Copper­polyethylene glycol (PEG)­Amikacin complex. The Cu(II) cation and the aggregate formed by PEG serve as a carrier for the antibiotic. Several Cu­PEG­Amikacin complex variations were tested against NIH-NIAID cell lines containing both resistant and nonresistant strains of M. tuberculosis.

The role of cystectomy in elderly patients - a multicentre analysis.

INTRODUCTION: Life expectancy in developed countries is continuously increasing. Hence elderly patients are becoming more common in our clinical practice. Currently, one of the greatest challenges of medicine is balancing the life expectancy of elderly patients against aggressive treatments that carry significant risks. OBJECTIVE: To outline the complications and survival in surgical patients 80 years and over undergoing radical cystectomy for bladder cancer. PATIENTS AND METHODS: A review of a radical cystectomy in elderly recorded in four different institutional prospective databases during the period between 1991 and 2014. Clinical and pathologic features, complications and survival were evaluated. RESULTS: A total of 111 patients were available. Median (range) age 82.2 (80-89) years. Seventeen women and 94 men. Regarding the ASA score, 6 patients were ASA I, 47 patients were ASA II, 49 patients ASA III and 9 ASA IV. Prior to surgery, 48 patients had hydronephrosis. The median (range) creatinine series was 1.1 (0.71-11.1) ng/dL. In 88 cases an ileal conduit was performed, 17 a cutaneous ureterostomy diversion, 5 neobladders and 1 ureterosigmoidostomy case. The median (range) operative time was 230 (120-420) min and a total of 97 patients required blood transfusion. The median (range) hospital stay was 14 (7-126) days. The early and late complication rates were 50.4% and 32%, respectively. A total of 14 patients (12.6%) required surgical reintervention. Eight patients (7.2%) died in the immediate postoperative period. The readmission rate of the series was 27.2%. The mean follow-up of the series was 18 (0.27-134.73) months. During this period 66 patients died, 52 of them due to the tumor. Twelve month tumour progression free survival was 83.9% for ≤pT1, 70.2% for pT2 and 36% for ≥pT3, respectively. Twelve month cancer specific survival was 85.6% for ≤pT1, 75.1% for pT2 and 42.5% for ≥pT3, respectively. CONCLUSION: Radical cystectomy in elderly population is an aggressive surgical treatment with a significant complication rate, hospital readmission and perioperative mortality rate. Careful selection of patients is essential in order to minimize the complications of this surgery and balance benefits against risks in the elderly population. Tumour progression and cancer specific survival are poor for patients with ≥pT3 disease. Alternatives such as tri-modality therapy need to be considered within a multi-disciplinary approach. More data is required to determine which sub-groups of elderly patients would benefit from a complication, survival and quality of life perspective.

Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis.

The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis.

Systemic capillary leak syndrome: a case-report.

We report a case of a patient presenting with episodic hypotension, tachycardia and oedema, with an elevated serum IgG kappa paraprotein level. She was diagnosed as having systemic capillary leak syndrome and upon commencing oral theophylline has had no further presentations. The patient has since progressed to multiple myeloma.

Structural measurements and cell line studies of the copper-PEG-Rifampicin complex against Mycobacterium tuberculosis.

The bacterium responsible for tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used to study the copper-Rifampicin-Polyethylene glycol (PEG-3350) complex. The copper (II) cation is a carrier for the antibiotic Rifampicin as well as nutrients for the bacterium. The NIH-NIAID cell line containing several Tb strains (including antibiotic resistant strains) is tested against seven copper-PEG-RIF complex variations.

Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.

BACKGROUND: Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored. METHODS: Periostin expression levels and patterns were examined in human glioma cells and tissues by quantitative real-time PCR and immunohistochemistry and correlated with glioma grade, type, recurrence, and survival. Functional assays determined the impact of altering periostin expression and function on cell invasion, migration, adhesion, and glioma stem cell activity and tumorigenicity. The prognostic and functional relevance of periostin and its associated genes were analyzed using the TCGA and REMBRANDT databases and paired recurrent glioma samples. RESULTS: Periostin expression levels correlated directly with tumor grade and recurrence, and inversely with survival, in all grades of adult human glioma. Stromal deposition of periostin was detected only in grade IV gliomas. Secreted periostin promoted glioma cell invasion and adhesion, and periostin knockdown markedly impaired survival of xenografted glioma stem cells. Interactions with αvß3 and αvß5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the αvß3/ß5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. CONCLUSION: Periostin is a robust marker of glioma malignancy and potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after periostin inhibition provides support for exploring the therapeutic impact of targeting periostin.

The copper (II) ion as a carrier for the antibiotic capreomycin against Mycobacterium tuberculosis.

In recent years, the bacterium responsible for tuberculosis has been increasing its resistance to antibiotics resulting in new multidrug resistant Mycobacterium tuberculosis (MR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study we use several analytical techniques including NMR, FT-ICR, TOF-MS, LC-MS and UV/Vis to study the copper-capreomycin complex. The copper (II) cation is used as a carrier for the antibiotic capreomycin. Once this structure was studied using NMR, FT-ICR, and MALDI-TOF-MS, the NIH-NIAID tuberculosis cell line for several Tb strains (including antibiotic resistant strains) were tested against up to seven variations of the copper-capreomycin complex. Different variations of copper improved the efficacy of capreomycin against Tb up to 250 fold against drug resistant strains of Tb.