ASO Visual Abstract: Will It Play in Peoria? A Pilot Study of a Robotic Skills Curriculum for Surgical Oncology Fellows

Annals of Surgical Oncology -     

Desensitization of guanylyl cyclases in cultured human airway smooth-muscle cells

We previously showed that cultured human airway smooth-muscle cells (HASMC) contain soluble and particulate guanylyl cyclases (GCs). We studied the desensitization of soluble and particulate GCs in HASMC. Homologous desensitization of soluble GC occurred after incubation with S-nitroso-N-acetyl pencillamine (SNAP). SNAP-dependent desensitization was blocked by hemoglobin, a nitric oxide (NO) scavenger, suggesting that it was due to NO release. Cross-desensitization between SNAP and sodium nitroprusside (SNP) and the lack of thiol reduction after SNAP or SNP treatment suggested that thiol depletion was not involved. Assays for soluble GC activity and experiments using protein synthesis inhibitors suggested that SNAP-dependent desensitization was due to reduced soluble GC. Homologous desensitization of particulate GC occurred after pretreatment with atrial natriuretic peptide (ANP) accompanied by reduced particulate GC activity. Recovery required protein synthesis, suggesting that it was due to reduction in particulate GC. Homologous desensitization to either SNAP or ANP was not altered by phosphodiesterase (PDE) inhibitors, suggesting that increased PDE activity was not involved. Cross-desensitization experiments using SNAP and ANP and experiments using zaprinast to elevate cyclic guanosine monophosphate showed no evidence of heterologous desensitization. Our results suggest that pretreatment of HASMC with SNAP or ANP causes homologous, but not heterologous, desensitization of soluble and particulate GCs, respectively.     

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β₂-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.     

The case for extrathymic development of vaginal T lymphocytes

The vaginal tract mucosa is populated by a small, yet phenotypically diverse and functionally significant, subset of T cells that plays a major role in local cell-mediated immunity. Although phenotypic and functional characteristics of vaginal T cells have received some attention in recent years, little is known about the development of this cell population. In this mini review, the developmental origins of vaginal T cells are traced from published work related to vaginal T cells, the vaginal mucosa environment and vaginal tract infection animal models. A CD3(+)TCR(+)CD2(+)CD5(+)B220(-) (CD3(+)B220(-)) subpopulation, which is mostly CD4(+), makes up 30-40% of vaginal T lymphocytes. This population consists of a TCRalphabeta(+) subset and TCRgammadelta(+) subset. While CD3(+)B220(-)TCRalphabeta(+) vaginal T cells exhibit phenotypic and functional properties consistent with that of peripheral T cells, CD3(+)B220(-)TCRgammadelta(+) vaginal T cells exhibit unique phenotypic and functional features that set them apart from other TCRgammadelta(+) T cell subsets populating the periphery or other mucosal areas. The vaginal mucosa is populated also by CD3(+)TCRalphabeta(+)CD4(-)/8(-)B220(+)CD2(-)CD5(-) T cells (CD3(+)B220(+)) whose relative predominance increases significantly in systemic T cell deficiency. This subset is generally unresponsive to TCR-mediated stimuli and expresses high levels of CD25, perhaps indicative of a regulatory role. Current data suggest that, while CD3(+)B220(-) vaginal T cells are mostly thymic in origin, CD3(+)TCRalphabeta(+)B220(+) cells are exclusively extrathymic.     

Enhancement of Confinement in Scaled RC Columns using Steel Fibers Extracted from Scrap Tyres

Steel fibers are widely extracted from scrap tyres, causing environmental concerns. This paper presents the use of steel fibers in variable proportions extracted from scrap tyres. The enhancement of the confinement was envisaged through the addition of steel fibers obtained from scrap tyres. The study included an experimental program for the development of constitutive material models for ordinary Portland cement (OPC) concrete and concrete with added steel fibers. A mix design was carried out for OPC, targeting a compressive strength of 3000 psi. Steel fibers were added to OPC in ratios of 1.0% to 3.0%, with an increment of 0.5%. Concrete columns, with cross-sectional dimensions of 6 × 6 inches and a length of 30 inches, were cast with both OPC and fiber-reinforced concrete. The column confinement was evaluated with a different spacing of ties (3- and 4-inch center-to-center). Compression tests on the concrete columns indicate that the addition of steel fibers to a concrete matrix results in an appreciable increase in strength and ductility. Overall, increasing the percentage of steel fibers increased the compression strength and the ductility of concrete. The maximum strain in the concrete containing 2.5% steel fibers increased by 285% as compared to the concrete containing 1% of steel fibers. An optimum percentage of 2.5% steel fibers added to the concrete resulted in a 39% increase in compressive strength, accompanied by a significant improvement in ductility. The optimum content of steel fibers, when used in confined columns, showed that confined compression strength increased with the addition of steel fibers. However, it is recommended that additional columns on the basis of the optimum steel fiber content shall be tested to evaluate their effectiveness in reducing the stirrup spacing.     

Activity restrictions after gynecologic surgery: is there evidence?

Many surgeons recommend rest and restricting activities to their patients after surgery. The aim of this review is to summarize the literature regarding types of activities gynecologic surgeons restrict and intra-abdominal pressure during specific activities and to provide an overview of negative effects of sedentary behavior (rest). We searched PubMed and Scopus for years 1970 until present and excluded studies that described recovery of activities of daily living after surgery as well as those that assessed intra-abdominal pressure for other reasons such as abdominal compartment syndrome and hypertension. For our review of intra-abdominal pressure, we excluded studies that did not include a generally healthy population, or did not report maximal intra-abdominal pressures. We identified no randomized trial or prospective cohort study that studied the association between postoperative activity and surgical success after pelvic floor repair. The ranges of intra-abdominal pressures during specific activities are large and such pressures during activities commonly restricted and not restricted after surgery overlap considerably. There is little concordance in mean peak intra-abdominal pressures across studies. Intra-abdominal pressure depends on many factors, but not least the manner in which it is measured and reported. Given trends towards shorter hospital stays and off work intervals, which both predispose women to higher levels of physical activity, we urge research efforts towards understanding the role of physical activity on recurrence of pelvic organ prolapse and urinary incontinence after surgery.     

Approaching a decade of cryo catheter ablation for type 1 atrial flutter—a meta-analysis and systematic review

Purpose  

Despite increasingly widespread use of cryo catheter ablation (CCA) in clinical practice, current ACC/AHA/ESC guidelines for management of supraventricular arrhythmias cite only radiofrequency catheter ablation (RFCA) as first-line treatment for type 1 atrial flutter (AFL). We performed a meta-analysis of efficacy and procedure outcomes from randomized controlled clinical trials comparing CCA with RFCA for type 1 AFL. A systematic review of non-randomized, single-arm clinical studies of CCA for type 1 AFL was also done.     

Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease

AIMS: To report the natural history of autochthonous hepatitis E and hepatitis E virus (HEV) IgG seroprevalence in Southwest England. METHODS: Patients with unexplained hepatitis were tested for hepatitis E and cases followed until recovery or death. Five hundred blood donors, 336 individuals over the age of 60 years and 126 patients with chronic liver disease were tested for HEV IgG. RESULTS: Forty cases of autochthonous hepatitis E (genotype 3) were identified. Hepatitis E was anicteric in 25% of cases and usually caused a self-limiting hepatitis predominantly in elderly Caucasian males. Six of 40 had a significant complication and three patients died, two of who had previously undiagnosed cirrhosis. Hepatitis E shows a seasonal variation with peaks in the spring and summer and no cases in November and December. HEV IgG prevalence increases with age, is more common in men and is 16% in blood donors, 13% in patients with chronic liver disease and 25% in individuals over 60 years. CONCLUSION: Autochthonous hepatitis E is more common than previously recognized, and should be considered in the differential diagnosis in patients with hepatitis, whatever their age or travel history. It carries a significant morbidity and when seen in the context of chronic liver disease carries an adverse prognosis.     

Facile complexation reactions for the selective spectrofluorimetric determination of albendazole in oral dosage forms and spiked human plasma

Two simple, sensitive, and rapid spectrofluorimetric methods were developed and validated for the determination of albendazole. The first method (method I) was based on the quenching effect of albendazole on the native fluorescence of erythrosine B. The fluorescence intensity was measured at 554 nm after extraction at 527 nm. In the second method (method II) the drug was reacted with lanthanum(iii) ions to form a metal complex, which was measured at 340 nm after excitation at 295 nm. The suitable pH was 3.4 (Teorell–Stenhagen buffer) and pH 5.5 (phosphate buffer solution), for method I and II, respectively. The influence of experimental factors on the fluorescence intensity of the reaction products was investigated and optimized. The linear concentration ranges were 0.2–3.5 and 0.06–0.90 μg mL⁻¹, with detection limits of 0.049 and 0.019 μg mL⁻¹ for method I and II, respectively. ICH guidelines were followed for validation of the developed procedures, and the results were acceptable. The Gibb''s free energy change of the reactions was −24.6 and −27.5 kJ mol⁻¹ for method I and II, respectively. These negative values indicated the high feasibility of these reactions at ambient temperature. The proposed procedures were applied successfully for the determination of albendazole in commercial dosage forms and spiked human plasma. The results showed high precision, accuracy and recovery of the reported methods without any significant interference from pharmaceutical excipients or plasma components.

Complexation of albendazole with erythrosine B quench the native fluorescence of the dye while complexation of the drug with lanthanum (iii) ions enhance the fluorescence of the drug.