Vanillic Acid Nanocomposite: Synthesis, Characterization Analysis, Antimicrobial, and Anticancer Potentials.

Recently, nanoparticles have received considerable attention owing to their efficiency in overcoming the limitations of traditional chemotherapeutic drugs. In our study, we synthesized a vanillic acid nanocomposite using both chitosan and silver nanoparticles, tested its efficacy against lung cancer cells, and analyzed its antimicrobial effects. We used several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to determine the stability, morphological characteristics, and properties of the biosynthesized vanillic acid nanocomposites. Furthermore, the vanillic acid nanocomposites were tested for their antimicrobial effects against Escherichia coli and Staphylococcus aureus, and Candida albicans. The data showed that the nanocomposite effectively inhibited microbes, but its efficacy was less than that of the individual silver and chitosan nanoparticles. Moreover, the vanillic acid nanocomposite exhibited anticancer effects by increasing the expression of pro-apoptotic proteins (BAX, Casp3, Casp7, cyt C, and p53) and decreasing the gene expression of Bcl-2. Overall, vanillic acid nanocomposites possess promising potential against microbes, exhibit anticancer effects, and can be effectively used for treating diseases such as cancers and infectious diseases.

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

Glutathione S-Transferases in Cancer.

In humans, the glutathione S-transferases (GST) protein family is composed of seven members that present remarkable structural similarity and some degree of overlapping functionalities. GST proteins are crucial antioxidant enzymes that regulate stress-induced signaling pathways. Interestingly, overactive GST proteins are a frequent feature of many human cancers. Recent evidence has revealed that the biology of most GST proteins is complex and multifaceted and that these proteins actively participate in tumorigenic processes such as cell survival, cell proliferation, and drug resistance. Structural and pharmacological studies have identified various GST inhibitors, and these molecules have progressed to clinical trials for the treatment of cancer and other diseases. In this review, we discuss recent findings in GST protein biology and their roles in cancer development, their contribution in chemoresistance, and the development of GST inhibitors for cancer treatment.

Prognosis after Mild Traumatic Brain Injury: Influence of Psychiatric Disorders.

BACKGROUND: We evaluated the prevalence of psychiatric disorders in mild traumatic brain injury (MTBI) patients and investigated psychiatric comorbidity in relation to subjective symptoms and return to work (RTW). METHODS: We recruited 103 MTBI patients (mean age 40.8 years, SD 3.1) prospectively from University Hospital. The patients were followed up for one year. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) and Extended Glasgow Outcome Scale (GOSE) were administered one month after MTBI. Three months after MTBI, any psychiatric disorders were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders. RESULTS: Psychiatric disorders were diagnosed in 26 patients (25.2%). The most common disorders were previous/current depression. At three months, there was no difference between patients with psychiatric disorders versus those without them in RTW (95.7% vs. 87.3%, p = 0.260) or at least in part-time work (100% vs. 94.4%, p = 0.245). In Kaplan-Meier analysis, the median time to RTW was 10 days for both groups. The median RPQ score was 13.0 (Interquartile range (IQR) 6.5-19.0) in patients with a psychiatric disorder compared to 8.5 (IQR 2.3-14.0) in those without one (p = 0.021); respectively, the median GOSE was 7.0 (IQR 7.0-8.0) compared to 8.0 (IQR 7.0-8.0, p = 0.003). CONCLUSIONS: Approximately every fourth patient with MTBI had a psychiatric disorder. These patients reported more symptoms, and their functional outcome measured with GOSE at one month after MTBI was worse. However, presence of any psychiatric disorder did not affect RTW. Early contact and adequate follow-up are important when supporting the patient's return to work.

Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors.

Purpose: The PARP inhibitor (PARPi) talazoparib may potentiate activity of chemotherapy and toxicity in cells vulnerable to DNA damage.Experimental Design: This phase I study evaluated the safety, tolerability, pharmacokinetics, and efficacy of talazoparib and carboplatin. Pharmacokinetic modeling explored associations between DNA vulnerability and hematologic toxicity.Results: Twenty-four patients (eight males; 16 females) with solid tumors were enrolled in four cohorts at 0.75 and 1 mg daily talazoparib and weekly carboplatin (AUC 1 and 1.5, every 2 weeks or every 3 weeks), including 14 patients (58%) with prior platinum treatment. Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia; the MTD was not reached. Grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). After cycle 2's dose, delays/reductions were required in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. Four patients showed stable disease beyond 4 months, three of which had known mutations in DNA repair pathways. Pharmacokinetic toxicity modeling suggests that after three cycles of carboplatin AUC 1.5 every 3 weeks and talazoparib 1 mg daily, neutrophil counts decreased 78% [confidence interval (CI), 87-68] from baseline in gBRCA carriers and 63% (CI, 72-55) in noncarriers (P < 0.001). Pharmacokinetic toxicity modeling suggests an intermittent, pulse dosing schedule of PARP inhibition, differentiated by gBRCA mutation status, may improve the benefit/risk ratio of combination therapy.Conclusions: Carboplatin and talazoparib showed efficacy in DNA damage mutation carriers, but hematologic toxicity was more pronounced in gBRCA carriers. Carboplatin is best combined with intermittent talazoparib dosing differentiated by germline and somatic DNA damage mutation carriers. Clin Cancer Res; 23(21); 6400-10. ©2017 AACR.

A Real-Time Programmable Pulsatile Flow Pump for In Vitro Cardiovascular Experimentation.

Benchtop in vitro experiments are valuable tools for investigating the cardiovascular system and testing medical devices. Accurate reproduction of the physiologic flow waveforms at various anatomic locations is an important component of these experimental methods. This study discusses the design, construction, and testing of a low-cost and fully programmable pulsatile flow pump capable of continuously producing unlimited cycles of physiologic waveforms. It consists of a gear pump actuated by an AC servomotor and a feedback algorithm to achieve highly accurate reproduction of flow waveforms for flow rates up to 300 ml/s across a range of loading conditions. The iterative feedback algorithm uses the flow error values in one iteration to modify the motor control waveform for the next iteration to better match the desired flow. Within four to seven iterations of feedback, the pump replicated desired physiologic flow waveforms to within 2% normalized RMS error (for flow rates above 20 mL/s) under varying downstream impedances. This pump device is significantly more affordable (∼10% of the cost) than current commercial options. More importantly, the pump can be controlled via common scientific software and thus easily implemented into large automation frameworks.

Perimesencephalic subarachnoid hemorrhage with a positive angiographic finding: case report and review of the literature.

The vast majority of perimesencephalic subarachnoid hemorrhage cases are reported as negative-finding etiologies. Recently, high-resolution images allowed us to overcome the previous difficulty of finding the source of bleeding, which underlies the concept of a "negative finding". We discovered a venous etiology, hidden behind the tip of the basilar artery; namely, the lateral pontine vein. Here, we review the literature on perimesencephalic subarachnoid hemorrhage and on venous aneurysm. We highlight this type of aneurysm as a candidate source of perimesencephalic hemorrhage. This case may change our way of dealing with what we have termed a negative finding of subarachnoid hemorrhage.