Self-Assembly Propensity Dictates Lifetimes in Transient Naphthalimide-Dipeptide Nanofibers.

Transient self-assembly of dipeptide nanofibers with lifetimes that are predictably variable through dipeptide sequence design are presented. This was achieved using 1,8-naphthalimide (NI) amino acid methyl-esters (Phe, Tyr, Leu) that are biocatalytically coupled to amino acid-amides (Phe, Tyr, Leu, Val, Ala, Ser) to form self-assembling NI-dipeptides. However, competing hydrolysis of the dipeptides results in disassembly. It was demonstrated that the kinetic parameters like lifetimes of these nanofibers can be predictably regulated by the thermodynamic parameter, namely the self-assembly propensity of the constituent dipeptide sequence. These lifetimes could vary from minutes, to hours, to permanent gels that do not degrade. Moreover, the in-built NI fluorophore was utilized to image the transient nanostructures in solution with stimulated emission depletion (STED) based super-resolution fluorescence microscopy.

Correlation between X-ray diffraction and Raman spectra of 16 commercial graphene-based materials and their resulting classification.

Structural properties of sixteen (16) commercial samples of graphene-based materials (GBM) labelled as graphene, graphene oxide or reduced graphene oxide are investigated at room temperature using X-ray diffraction (XRD) and Raman spectroscopy. Based on the observed correlation between the results obtained with these two techniques, these samples are classified into three groups: Group A of seven samples consisting of graphitic nanosheets with evaluated thickness ≃20 nm and exhibiting both the 2H and 3R phases in XRD; Group B of six samples exhibiting XRD spectra characteristic of either graphene oxides (GO) or carbons with some order; and Group C of three samples with XRD spectra characteristic of disordered carbons. The relative intensities and widths of D, G, D', 2D and (D + D') bands in the Raman spectra are equally distinguishable between the samples in groups A, B and C. The width of the D-band is the smallest for Group A samples, intermediate for group B and the largest for group C samples. The intensity ratio I(D)/I(G) of the D and G bands in the Raman spectra of the samples is used to quantify the Raman-active defects whose concentration increases in going from samples in Group A to those in Group C.

Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self-Assembling Peptide.

The reversible regulation of catalytic activity is a feature found in natural enzymes which is not commonly observed in artificial catalytic systems. Here, we fabricate an artificial hydrolase with pH-switchable activity, achieved by introducing a catalytic histidine residue at the terminus of a pH-responsive peptide. The peptide exhibits a conformational transition from random coil to ß-sheet by changing the pH from acidic to alkaline. The ß-sheet self-assembles to form long fibrils with the hydrophobic edge and histidine residues extending in an ordered array as the catalytic microenvironment, which shows significant esterase activity. Catalytic activity can be reversible switched by pH-induced assembly/disassembly of the fibrils into random coils. At higher concentrations, the peptide forms a hydrogel which is also catalytically active and maintains its reversible (de-)activation.

Coccidioidal Pulmonary Cavitation: A New Age.

Coccidioides species are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with symptomatic pneumonic diseases as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

Pulmonary Giant Cavitary Coccidioides With Fungal Ball and Hemoptysis.

Coccidioidomycosis (CM) is a fungal disease that results from inhalation of spores of Coccidioides immitis and C posadasii. If symptomatic, disease primarily manifests as community-acquired pneumonia; however, additional pulmonary manifestations such as pleural effusion, empyema, and cavitation may occur. Diabetic patients have an increased risk of severe and cavitary CM. Cavitary disease may erode vasculature and pulmonary parenchyma leading to further complications. Furthermore, chronic cavities can become colonized as well and develop superimposed infections. This is a case of cavitary CM in uncontrolled diabetic nonadherent to treatment presenting with hemoptysis and mycetoma.

Acute Pericarditis Leading to a Diagnosis of SLE: A Case Series of 3 Patients.

In systemic lupus erythematosus (SLE), cardiac manifestations are known to be present in up to 50% of patients. However, it is rare for acute pericarditis to be the leading symptom at the time of diagnosis of SLE occurring in up to 1% of patients. We present a case series in which 3 patients with no prior history of SLE presented with acute pericarditis. This was found to be the leading manifestation of their disease, which ultimately led to the diagnosis of SLE. These patients were initially treated with nonsteroidal anti-inflammatory drugs and colchicines; however, steroids and disease-modifying anti-rheumatologic agents were ultimately added to their medical therapy.

Coccidioidal Peritonitis: A Review of 17 Cases.

Coccidioidomycosis is the second most common endemic fungal infection in the United States. Prior descriptions of coccidioidal peritonitis include only single cases. We describe 17 new cases previously unreported from healthcare institutions in California. The majority of cases presented with nonspecific abdominal complaints. PubMed and Google Scholar were searched for additional case series and only single case reports and reviews of single cases were found. The diagnosis was confirmed by culture or histopathology and/or serology in each patient. All patients were treated with anti-fungal therapy. This case series demonstrates that coccidioidal peritonitis may be asymptomatic or present with only subtle abdominal symptoms. In a minority of our patients, the diagnosis was established incidentally during surgery. Based on this series, the overall outcome of coccidioidal peritonitis is favorable with long-term triazole treatment. The term cure is not usually used in disseminated coccidioidal disease because of the risk of late relapse.

Cannabis-Induced Pancreatitis in a Young Adult Male.

Drugs account for 2% of all the causes of acute pancreatitis. To date, there are approximately 26 reported cases of acute pancreatitis associated with the use of cannabis. We report the case of a 20-year-old male who presented with intractable nausea, vomiting, and epigastric pain and a lipase level of 1541 with reportedly no alcohol use, and no evidence of medication, biliary, or autoimmune etiology. However, the patient did endorse heavily smoking cannabis prior to symptom onset. He was instructed to abstain from cannabis use on discharge and has not presented to the hospital since this episode. The reporting of this case aims to increase awareness of cannabis as a differential diagnosis in cases of pancreatitis that is not due to typical etiologies such as gallstones, medications, and alcohol use. There has yet to be definitive evidence as to how cannabis can cause pancreatitis. Further studies must be conducted to better understand the association between cannabis use and acute pancreatitis and the mechanism by which cannabis affects the pancreas.

Echocardiographic Findings in Heart Failure Patients With Methamphetamine Use: A Case-Control Study.

Background Methamphetamine use is associated with cardiovascular disease and significant morbidity and mortality. There is only one previous study performed on echocardiographic parameters in patients with methamphetamine cardiomyopathy. Methods We performed a retrospective review of medical records in a county hospital in Southern California with a high population of methamphetamine users. We reviewed medical records and echocardiogram findings in patients seen in our institution from November 2019 to November 2020 who had cardiomyopathy with and without methamphetamine use. We excluded patients who either left the hospital or expired before appropriate assessment. We divided our patient population into a case group (methamphetamine users) and a control group (non-methamphetamine users) to study and compare their echocardiographic parameters. Results Case group included a total of 254 patients and control group included 268 patients. Majority of the patient population were males - 178 (70%) and 180 (67%) in the case and control group respectively. Age was found to be statistically significant with the younger population in the case group (p = 0.0000). Our analysis revealed statistically significant difference in methamphetamine users compared to non-users in regards to left ventricle ejection fraction (33.65% ± 18.02 vs. 41.55% ± 15.61, p=0.0000), left ventricle mass index (122.49 grams/m2 ± 40.66 vs. 108.62 grams/m2 ± 32.82, p=0.0000), left ventricle end diastolic volume index (85.91 mL/m2 ± 37.40 vs. 72.44 mL/m2 ± 25.44; p=0.0000) and marginally significant right ventricle systolic pressure (42.29mmHg ± 17.53 vs. 39.59mmHg ± 15.61; p=0.0540) Conclusion Our results indicated that methamphetamine users had echocardiogram findings with decreased ejection fraction and increased left ventricular mass index, end-diastolic volume index, and right ventricular systolic pressure consistent with worse dilated cardiomyopathy comparison to non-users.

Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity.

We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH2 (P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state with K D = 74 ± 3 µM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY through the KVYF terminus and this binding event disrupts the assembled structure. In absence of the target micellar aggregate, P7 was further found to dynamically alternate between multiple conformations, with a preferred hairpin-like conformation that was shown to contribute to supramolecular ligand binding. Three identified phages presented appreciable binding, and two showed to catalyze the hydrolysis of a model para-nitro phenol phosphate substrate, with P7 demonstrating conformation-dependent activity with a modest k cat/K M = 4 ± 0.3 × 10-4 M-1 s-1.

A Case of Testicular Granulomatous Inflammation Mistaken for Malignancy: Tuberculosis Identified Post Orchiectomy.

We describe the case of a 41-year-old Hispanic male, inconsistently adherent to visits and workup due to socioeconomic challenges, who presented with a right testicular mass. Because of the overriding concern that this was malignant, he underwent a right orchiectomy. Pathology revealed granulomatous disease with no evidence of malignancy. No specific diagnosis was made histologically or microbiologically on primary laboratory investigation. Six months later, he developed swelling of the left testicle and was subsequently seen in consultation at the Infectious Disease Clinic Kern Medical. An extensive evaluation for granulomatous inflammation was undertaken without a positive result. A clinical diagnosis of tuberculous epididymal orchitis was made and the patient was initiated on standard 4-drug antituberculous therapy. There was a gradual resolution of pain and swelling. After 6 months of therapy, there was no evidence of residual disease. The patient remains asymptomatic after 8 months of post-therapy follow-up.

A Rare Case of Cryptococcus gattii Meningitis in Advanced HIV Disease, Sagittal Thrombosis, and Immune Reconstitution Syndrome, Resolved With Isavuconazonium.

Cryptococcus gattii is a species that has received more recognition in the recent past as distinct from Cryptococcus neoformans. C gattii is known to cause meningeal disease in both immunocompetent and immunosuppressed hosts. Patients may be clinically asymptomatic until immunosuppressive conditions occur such as corticosteroid treatment or an HIV infection. HIV-associated cryptococcal infections are most often due to C neoformans. C gattii is found in a minority. Speciation and subtyping of Cryptococcus are not always accomplished. In many parts of the world, there is no availability for speciation of Cryptococcus. Travel history may provide a clue to the most probable species. This case demonstrates a case of C gattii meningitis with a multiplicity of complications. These include advanced HIV disease secondary to nonadherence, immune reconstitution inflammatory syndrome, and superior sagittal sinus thrombosis. The patient represented diagnostic and therapeutic dilemmas over time. Headache was the primary symptom in cryptococcal meningitis, immune reconstitution inflammatory syndrome, and superior sagittal sinus thrombosis. All are discussed in detail as potential etiologies for the primary disease. Isavuconazonium is a relatively new broad-spectrum antifungal azole that was used as salvage therapy.

A Progressive Case of Eosinophilic Myocarditis Due to Eosinophilic Granulomatosis With Polyangiitis in a Caucasian Male.

Vasculitis is an inflammatory process involving blood vessels of various sizes, including the small vessels in the kidneys to the large vessels, such as the aorta. This inflammatory condition is usually autoimmune in nature and is associated with involvement of many locations, such as the sinuses, lungs, kidneys, and even the heart. Specifically, eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that may initially hide as asthma, allergic rhinitis, and/or sinusitis. However, it is known to become a lethal disease once progressed to include cardiovascular manifestations. It is important to remember EGPA as a differential for any patient with a history of asthma, allergic rhinitis, and/or sinusitis who also presents with cardiovascular complaints and eosinophilia. Treatment recommendations focus on immunosuppression in such cases. In this article, we discuss the case of a 62-year-old male, with a known history of asthma, who presented to the emergency department with concern for his chest pain and right-sided weakness. He was later diagnosed with EGPA with eosinophilic myocarditis. Diagnosis and treatment are described.

Spatial defects nanoengineering for bipolar conductivity in MoS2.

Understanding the atomistic origin of defects in two-dimensional transition metal dichalcogenides, their impact on the electronic properties, and how to control them is critical for future electronics and optoelectronics. Here, we demonstrate the integration of thermochemical scanning probe lithography (tc-SPL) with a flow-through reactive gas cell to achieve nanoscale control of defects in monolayer MoS2. The tc-SPL produced defects can present either p- or n-type doping on demand, depending on the used gasses, allowing the realization of field effect transistors, and p-n junctions with precise sub-µm spatial control, and a rectification ratio of over 104. Doping and defects formation are elucidated by means of X-Ray photoelectron spectroscopy, scanning transmission electron microscopy, and density functional theory. We find that p-type doping in HCl/H2O atmosphere is related to the rearrangement of sulfur atoms, and the formation of protruding covalent S-S bonds on the surface. Alternatively, local heating MoS2 in N2 produces n-character.

Native Bypass of the Left Coronary Artery in a Male Patient Aged 63 Years.

This case report describes a 63-year-old male patient with a native bypass of the left coronary artery found incidentally while undergoing computed tomography angiography of the coronary arteries for clinical research purposes.

Amino-acid-encoded biocatalytic self-assembly enables the formation of transient conducting nanostructures.

Aqueous compatible supramolecular materials hold promise for applications in environmental remediation, energy harvesting and biomedicine. One remaining challenge is to actively select a target structure from a multitude of possible options, in response to chemical signals, while maintaining constant, physiological conditions. Here, we demonstrate the use of amino acids to actively decorate a self-assembling core molecule in situ, thereby controlling its amphiphilicity and consequent mode of assembly. The core molecule is the organic semiconductor naphthalene diimide, functionalized with D- and L- tyrosine methyl esters as competing reactive sites. In the presence of α-chymotrypsin and a selected encoding amino acid, kinetic competition between ester hydrolysis and amidation results in covalent or non-covalent amino acid incorporation, and variable supramolecular self-assembly pathways. Taking advantage of the semiconducting nature of the naphthalene diimide core, electronic wires could be formed and subsequently degraded, giving rise to temporally regulated electro-conductivity.

Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: enhancement of growth-inhibitory activity of Doxorubicin.

BACKGROUND: We previously showed that the anti-inflammatory drug, sulfasalazine (salicylazosulfapyridine, SASP), can arrest proliferation of MCF-7 and MDA-MB-231 mammary cancer cells by inhibiting uptake of cystine via the x(c-) cystine/glutamate antiporter. Here we examined SASP with regard to reduction of cellular glutathione (GSH) levels and drug efficacy-enhancing ability. METHODS: GSH levels were measured spectrophotometrically. Cellular drug retention was determined with 3H-labeled methotrexate, and drug efficacy with a colony formation assay. RESULTS: Incubation of the mammary cancer cells with SASP (0.3-0.5 mM) led to reduction of their GSH content in a time- and concentration-dependent manner. Similar to MK-571, a multidrug resistance-associated protein inhibitor, SASP increased intracellular accumulation of methotrexate. Preincubation of cells with SASP (0.3 mM) significantly enhanced the potency of the anticancer agent doxorubicin (2.5 nM). CONCLUSIONS: SASP-induced reduction of cellular GSH levels can lead to growth arrest of mammary cancer cells and enhancement of anticancer drug efficacy.

Simultaneous measurement of in vivo P-glycoprotein and cytochrome P450 3A activities.

Digoxin and midazolam are routinely used as probe drugs to measure in vivo activity of P-glycoprotein (P-gp) and cytochrome P450 3A4/5 (CYP3A), respectively. We investigated whether digoxin and midazolam could be coadministered to simultaneously determine P-gp and CYP3A activity without a significant pharmacokinetic interaction. In a randomized crossover design, digoxin (0.5 mg oral) or midazolam (2.0 mg oral) was administered individually or in combination (digoxin 1 hour after midazolam) to 14 healthy volunteers. Blood and urine samples were collected for up to 48 hours. Pharmacokinetic parameters of digoxin, midazolam and 1'-OH midazolam were evaluated to determine the presence of an interaction. The geometric mean ratios of all measured pharmacokinetic parameters of digoxin and midazolam were not significantly affected by coadministration. Coadministration of digoxin and midazolam can be used to simultaneously phenotype P-gp and CYP3A activity without a significant pharmacokinetic interaction.

Dynamic peptide libraries for the discovery of supramolecular nanomaterials.

Sequence-specific polymers, such as oligonucleotides and peptides, can be used as building blocks for functional supramolecular nanomaterials. The design and selection of suitable self-assembling sequences is, however, challenging because of the vast combinatorial space available. Here we report a methodology that allows the peptide sequence space to be searched for self-assembling structures. In this approach, unprotected homo- and heterodipeptides (including aromatic, aliphatic, polar and charged amino acids) are subjected to continuous enzymatic condensation, hydrolysis and sequence exchange to create a dynamic combinatorial peptide library. The free-energy change associated with the assembly process itself gives rise to selective amplification of self-assembling candidates. By changing the environmental conditions during the selection process, different sequences and consequent nanoscale morphologies are selected.

A combined-formulation tablet of lamivudine/nevirapine/stavudine: bioequivalence compared with concurrent administration of lamivudine, nevirapine, and stavudine in healthy Indian subjects.

Generic fixed-dose combinations of antiretrovirals are frequently prescribed for the treatment of human immunodeficiency virus infection. A randomized, 2-way study was conducted in 24 fasting, healthy, Indian male subjects to assess bioequivalence between a single combination tablet containing lamivudine, stavudine, and nevirapine (treatment A) with respect to separate marketed tablets administered simultaneously (treatment B). Each subject received treatments A and B separated by 19 days of a drug-free washout period. Plasma concentrations of antiretrovirals, determined by a validated liquid chromatography/tandem mass spectrometry assay, were used to assess pharmacokinetic parameters such as maximum observed plasma concentration and area under the plasma concentration curve. Pharmacokinetic parameters were comparable for either treatment. As geometric mean ratios (% treatment A/treatment B) of log-transformed parameters of area under the plasma concentration curve and plasma concentration, as well as their resultant 90% confidence intervals, were within 80% to 125% and 75% to 133%, respectively, 2 treatments were considered bioequivalent in the extent and rate of absorption. Both treatments exhibited similar tolerability under fasting conditions.