A case of monoclonal gammopathy of undetermined significance and minimal change disease complicated by bilateral pulmonary emboli.

Nephrotic syndrome and monoclonal gammopathy of undetermined significance are thought to be associated with venous thromboembolism. However, the association is thought to be weak and is often ignored by clinicians. We present a rare case of sudden-onset bilateral pulmonary emboli with lower extremity deep vein thrombosis in a patient diagnosed with both minimal change disease and immunoglobulin M (IgM) kappa monoclonal gammopathy of undetermined significance. No previous report has been published describing venous thromboembolism in a patient with plasma cell dyscrasia and minimal change disease. This case establishes the importance of considering a diagnostic workup for both disorders in patients with venous thromboembolism. Furthermore, venous thromboembolism risk in patients with both of these diseases is significant. Benefits of prophylactic anticoagulation in these patients are still controversial.

Theoretical Approach to Evaluate the Gas-Sensing Performance of Graphene Nanoribbon/Oligothiophene Composites.

Composite formation with graphene is an effective approach to increase the sensitivity of polythiophene (nPT) gas sensors. The interaction mechanism between gaseous analytes and graphene/nPT composite systems is still not clear, and density functional theory calculations are used to explore the interaction mechanism between graphene/nPT nanoribbon composites (with n = 3-9 thiophene units) and gaseous analytes CO, NH3, SO2, and NO2. For the studied analytes, the interaction energy ranges from -44.28 kcal/mol for (C54H30-3PT)-NO2 to -2.37 kcal/mol for (C54H30-3PT)-CO at the counterpoise-corrected ωB97M-V/def2-TZVPD level of theory. The sensing mechanism is further evaluated by geometric analysis, ultraviolet-visible spectroscopy, density of-states analysis, calculation of global reactivity indices, and both frontier and natural bond orbital analyses. The variation in the highest occupied molecular orbital/lowest unoccupied molecular orbital gap of the composite indicates the change in conductivity upon complexation with the analyte. Energy decomposition analysis reveals that dispersion and charge transfer make the largest contributions to the interaction energy. The graphene/oligothiophene composite is more sensitive toward these analytes than either component taken alone due to larger changes in the orbital gap. The computational framework established in the present work can be used to evaluate and design graphene/nPT nanoribbon composite materials for gas sensors.

Polyaniline emeraldine salt as selective electrochemical sensor for HBr over HCl: a systematic density functional theory study through oligomer approach.

Density functional theory (DFT) calculations are performed to rationalize the experimentally observed sensitivity and selectivity of polyaniline emeraldine for hydrogen bromide over hydrogen chloride. The interaction behaviour is studied at UB3LYP method of density functional theory through oligomer approach. The properties for polymers are obtained extrapolation through second-degree polynomial fit. Optimized of geometries, interaction energies, Mulliken and natural bond orbital charges are analysed to study the sensing behaviour. In the preferred orientation modes, emeraldine salt acts as a hydrogen donor, whereas HBr and HCl are hydrogen acceptors (nucleophile). Basis set superposition error corrected interaction energies are calculated for accurate determination of interaction strength between sensor and analyte. The basis set superposition error is significant for HBr complex compared to HCl. The decrease in energy gap between highest occupied and lowest unoccupied molecular of conducting polymer (sensor) on complex formation with both analytes has been studied. The results of computational study show that polyaniline emeraldine salt shows more selectivity towards HBr as compared to HCl and this outcome is in agreement with reported results based on experimental observations. Graphical abstract.

Remarkable enhancement in sensor ability of polyaniline upon composite formation with ZnO for industrial effluents.

Polyaniline emeraldine salt and Polyaniline Zinc Oxide composite are comprehensively studied to compare their sensing ability towards ammonia, acetone, methanol and ethanol. Sensing ability is evaluated through thermodynamic, geometric and electronic parameters. A number of orientations are evaluated in search for the lowest energy structure. The comparison of thermodynamic, geometric and electronic parameters of simple and composite sensors confirmed that composite sensor shows better sensing ability than simple PANI. Composite formation between polyaniline and zinc oxide is a thermodynamically feasible process with interaction energy of -42.8 kcal/mol. Both sensor shows highest interaction energy for ethanol among four analytes. Composite sensor shows almost twice the interaction with ethanol, methanol and acetone while 1.5 times the interaction energy for ammonia. The results of run simulations and subsequent calculations showed that in composite sensors, zinc oxide not only enhances the binding power of conducting polymer with analytes but also interacts directly with analytes. Strong hydrogen bonding as well as weak dispersion forces of attraction are responsible for the stability of composite and all complexes, as revealed by non-covalent interaction (NCI) studies. Acetone shows a different behaviour in composite sensor complex than other analytes.

Electronic structure of polythiophene gas sensors for chlorinated analytes.

Density functional theory studies are performed to investigate the response of polythiophene as a sensor for chlorinated gaseous analytes. Interaction of polythiophene with these analytes is studied from both H-side (dipole-dipole) and Cl-side (halogen bonding) of analyte to get the most stable interaction site. Inferences from interaction energy, natural bond orbital, and Mulliken charge analyses are in line with those from geometric analysis. Interaction energies reveal that polythiophene has specificity and selectivity towards chlorine. Interestingly, the halogen bond in PT-Cl2 complexes is stronger than ion-dipole bond in the complexes of polythiophene with other analytes. The sensing of polythiophene towards these analytes is also measured by perturbing the electronic properties including ionization potential, electron affinity, λmax, and H→L gap. The spectroscopic properties (UV absorption spectra) reveal the interaction behavior of polythiophene with these chlorinated analytes. All these parameters including orbital analysis and H→L energies indicate high sensitivity of polythiophene for chlorine. Graphical abstractInteraction of chlorinated gaseous analytes with polythiophene surface.

Severe Case of Plasmodium falciparum Malaria in a Pregnant Woman from Nigeria.

Human malaria has arguably affected more of human history than any other pathogen. Pregnant women have a higher risk of developing severe malaria as well as the risk of severe complications. We present a case of severe malaria in a pregnant patient from sub-Saharan Africa who was treated successfully with artesunate. A 28-year-old Nigerian woman with a 20-week intrauterine pregnancy presented with a five-day history of fever and diffuse joint pains. Evaluation of peripheral thin blood smear demonstrated a parasitemia of 9.8%. The patient was admitted to the intensive care unit, and oral clindamycin/quinine was initiated until intravenous artesunate was obtained. The patient completed four doses of IV artesunate, and after the 4th dose of artesunate, no blood parasites were seen on peripheral smear. The patient was discharged home and, upon clinic follow-up, did not have any further complications associated with either her disease or therapy. A review on the treatment of severe malaria in all trimesters of pregnancy supports the WHO recommendation for intravenous artesunate as the drug of choice. This case illustrates the importance of recognizing malaria in pregnant women from endemic countries and shows that artesunate compounds can be used safely in pregnancy, particularly with high parasitemia.

Lenvatinib - A multikinase inhibitor for radioiodine-refractory differentiated thyroid cancer.

Lenvatinib, an oral multikinase inhibitor, was approved by the US Food and Drug Administration in February 2015. In a pivotal phase III study of 392 patients with progressive radioiodine-refractory thyroid cancer, the overall response rate of patients receiving lenvatinib was 64.8%, with complete response in four patients. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in patients receiving placebo. Median overall survival was not reached in either arm. Lenvatinib is a promising new treatment for patients with radioiodine (iodine-131)-refractory differentiated thyroid cancer.

Pulmonary Embolism Following Outpatient Vasectomy.

Venous thromboembolic events have several known major risk factors such as prolonged immobilization or major surgery. Pulmonary embolism has rarely been reported after an outpatient vasectomy was completed. We present the rare case of a healthy 32-year-old Caucasian male with no known risk factors who presented with pleuritic chest pain 26 days after his outpatient vasectomy was performed. Subsequently, he was found to have a pulmonary embolism as per radiological imaging. We explore the association between outpatient vasectomies and venous thromboembolic events. A review of the literature is also included.

Superior mesenteric artery syndrome: a unique complication following carboplatin-based chemotherapy.

Superior mesenteric artery syndrome (SMAS) is an uncommon condition, attributable to vascular compression of the third part of the duodenum between the superior mesenteric artery and the abdominal aorta. It can present in patients due to mechanical compression or severe weight loss. We present a unique case of SMAS in a patient undergoing carboplatin-based chemotherapy for mesothelioma. An 81-year-old male with mesothelioma was treated with carboplatin-based chemotherapy. He subsequently suffered a progressive, unintentional 18 kg weight loss and presented acutely with intense epigastric pain, severe nausea, and vomiting. Diagnosis was confirmed by abdominal computed tomography and esophagogram with upper gastrointestinal series, which revealed gastric and duodenal distention and a narrow angle between the superior mesenteric artery and aorta, causing compression of the duodenum. Prompt recognition of this syndrome allowed us to treat our patient successfully and avoid the risks of operative interventions. To our knowledge, this is the first reported case of SMAS in patients receiving carboplatin. Furthermore, this case of SMAS was unique in that it was due to weight loss as compared with mechanical obstruction. Our experience illustrates the importance of considering SMAS in chemotherapy patients, especially those with substantial weight loss. A high index of suspicion for this potential complication coupled with appropriate radiographic studies are necessary for early diagnosis and can prevent severe consequences.

Racial disparities in breast cancer diagnosis in Central Georgia in the United States.

BACKGROUND: Mortality rates in breast cancer are worse for African Americans than for whites. OBJECTIVE: To investigate the presence of racial disparities in clinical staging in women diagnosed with breast cancer and understand whether such disparities exist in Central Georgia in the United States. METHODS: We retrospectively reviewed records from the Tumor Registry of the Medical Center Navicent Health in Macon, Georgia, of women who had been diagnosed with breast cancer during 2011-2013. The chi-square test was used to assess statistically significant differences between whites and African Americans. We also assessed the patients' health insurance status and age at diagnosis. RESULTS: A total of 578 participants were identified. Statistically significant differences existed in the clinical stage between the races (𝑃 = .0003). Whites were more often clinical stage I at diagnosis, whereas African Americans had a greater percentage of stages II, III, or IV. African Americans were more than twice as likely to be diagnosed at clinical stage IV than were their white counterparts. Statistical differences also existed with age at diagnosis (𝑃 = .0066) and insurance coverage (𝑃 = .0004). A greater percentage of white patients were aged 65 years or older at diagnosis, whereas a greater percentage of African American patients were aged 49 years or younger. A greater percentage of African Americans had Medicaid insurance, whereas a greater percentage of whites had private health insurance. LIMITATIONS: As a single-center study, it is difficult to generalize these results elsewhere. Furthermore, this study focused on association and not on causation. It is difficult to pinpoint why such disparities exist. CONCLUSIONS: The etiology of racial disparities between African American and white women with breast cancer seems to be multifaceted. Screening mammography remains an important tool for identifying breast cancer. Low socioeconomic and educational status as well as a lack of a primary care physician may play a role in these disparities. Other factors that may have a role include biological factors and possible mistrust of the health care system.

Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions.

The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.

MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin.

The p53 tumor suppressor plays a key role in maintaining genomic stability and protection against malignant transformation. MDM2 and MDMX are both p53-binding proteins that regulate p53 stability and activity. Recent development of the MDM2 inhibitor Nutlin 3 has greatly facilitated functional analysis of MDM2-p53 binding. We found that although MDMX is homologous to MDM2 and binds to the same region on p53 N terminus, Nutlin does not disrupt p53-MDMX interaction. The ability of Nutlin to activate p53 is compromised in tumor cells overexpressing MDMX. Combination of Nutlin with MDMX siRNA resulted in synergistic activation of p53 and growth arrest. These results suggest that MDMX is also a valid target for p53 activation in tumor cells. Development of novel compounds that are MDMX-specific or optimized for dual-inhibition of MDM2 and MDMX are necessary to achieve full activation of p53 in tumor cells.

Efficient synthesis of a beta-peptide combinatorial library with microwave irradiation.

The predictable relationship between beta-amino acid sequence and folding has inspired several biological applications of beta-peptides. For many such applications, it would be desirable to prepare and screen beta-peptide libraries. However, standard peptide synthesis protocols are not efficient enough to support a library approach for many types of beta-peptides. We recently optimized the solid-phase synthesis of beta-peptides using microwave irradiation, and we have now adapted this approach to synthesis on polystyrene macrobeads. We rapidly prepared a high-quality beta-peptide combinatorial library via a split-and-mix strategy. This library was screened in search of beta-peptide antagonists of the p53-MDM2 protein-protein interaction.

p53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53.

Overexpression or hyperactivation of MDM2 contributes to functional inactivation of wild-type p53 in nearly 50% of tumors. Inhibition of p53 by MDM2 depends on binding between an NH(2)-terminal (residues 16-28) p53 alpha-helical peptide and a hydrophobic pocket on MDM2, presenting an attractive target for development of inhibitors against tumors expressing wild-type p53. Here we report that novel p53 alpha-helical peptide mimics based on a terphenyl scaffold can inhibit MDM2-p53 binding in vitro and activate p53 in vivo. Several active compounds have been identified that inhibit MDM2-p53 binding in an ELISA assay with IC(50) of 10 to 20 micromol/L and induce p53 accumulation and activation in cell culture at 15 to 40 micromol/L. These results suggest that p53 alpha-helical mimetics based on the terphenyl scaffold may be developed into potent p53 activators.