Vortex fluidic mediated synthesis of polysulfone

Polysulfone (PSF) was prepared under high shear in a vortex fluidic device (VFD) operating in confined mode, and its properties compared with that prepared using batch processing. This involved reacting the pre-prepared disodium salt of bisphenol A (BPA) with a 4,4′-dihalodiphenylsulfone under anhydrous conditions. Scanning electron microscopy (SEM) established that in the thin film microfluidic platform, the PSF particles are sheet-like, for short reaction times, and fibrous for long reaction times, in contrast to spherical like particles for the polymer prepared using the conventional batch synthesis. The operating parameters of the VFD (rotational speed of the glass tube, its tilt angle and temperature) were systematically varied for establishing their effect on the molecular weight (M_w), glass transition temperature (T_g) and decomposition temperature, featuring gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) respectively. The optimal VFD prepared PSF was obtained at 6000 rpm rotational speed, 45° tilt angle and 160 °C, for 1 h of processing with M_w ∼10 000 g mol⁻¹, T_g ∼158 °C and decomposition temperature ∼530 °C, which is comparable to the conventionally prepared PSF.

Polysulfone (PSF) was prepared under high shear in a vortex fluidic device (VFD) operating in confined mode. This involved reacting the pre-prepared disodium salt of bisphenol A (BPA) with a 4,4′-dihalodiphenylsulfone under anhydrous conditions.     

In silico and in vitro metabolism of ribociclib: a mass spectrometric approach to bioactivation pathway elucidation and metabolite profiling

Ribociclib (RBC, Kisqali®) is a highly selective CDK4/6 inhibitor that has been approved for breast cancer therapy. Initially, prediction of susceptible sites of metabolism and reactivity pathways were performed by the StarDrop WhichP450™ module and the Xenosite web predictor tool, respectively. Later, in vitro metabolites and adducts of RBC were characterized from rat liver microsomes using LC-MS/MS. Subsequently, in silico data was used as a guide for the in vitro work. Finally, in silico toxicity assessment of RBC metabolites was carried out using DEREK software and structural modification was proposed to reduce their side effects and to validate the bioactivation pathway theory using the StarDrop DEREK module. In vitro phase I metabolic profiling of RBC was performed utilizing rat liver microsomes (RLMs). Generation of reactive metabolites was investigated using potassium cyanide (KCN) as a trapping nucleophile for the transient and reactive iminium intermediates to form a stable cyano adduct that can be identified and characterized using mass spectrometry. Nine phase I metabolites and one cyano adduct of RBC were characterized. The proposed metabolic pathways involved in generation of these metabolites are hydroxylation, oxidation and reduction. The reactive intermediate generation mechanism of RBC may provide an explanation of its adverse reactions. Aryl piperazine is considered a structural alert for toxicity as proposed by the DEREK report. We propose that the generation of only one reactive metabolite of RBC in a very small concentration is due to the decreased reactivity of the piperazine ring compared to previous reports of similar drugs. Docking analysis was performed for RBC and its proposed derivatives at the active site of the human CDK6 enzyme. Methyl-RBC exhibited the best ADMET and docking analysis and fewer side effects compared to RBC and fluoro-RBC. Further drug discovery studies can be conducted taking into account this concept allowing the development of new drugs with enhanced safety profiles that were confirmed by using StarDrop software. To the best of our knowledge, this is the first literature report of RBCin vitro metabolic profiling and structural characterization and toxicological properties of the generated metabolites.

Nine phase I metabolites and one product of KCN trapping of RBC were characterized. Aryl piperazine is considered a structural alert for toxicity as proposed by the DEREK report. Methyl-RBC exhibited less toxicity and more binding affinity to CDK6.     

Bi-doping improves the magnetic properties of zinc oxide nanowires

Room-temperature ferromagnetism in the large and direct bandgap diluted magnetic semiconductor zinc oxide (ZnO) is attributed to the intrinsic defects and p-orbital–p-orbital (p–p) coupling interaction. However, due to oxidation, the ferromagnetism induced by defects is unstable. In the present work, the solution process synthesis route was utilized to grow pristine and bismuth-doped, highly crystalline ZnO nanowire (ZnO NW)-based samples. The FE-SEM images showed that the grown ZnO NWs have a preferred orientation along the c-axis in the (001) direction due to the anisotropic crystal nature of ZnO. X-ray photoelectron spectroscopy (XPS) confirmed the presence of Bi, and at a higher doping content, the bismuth oxide phase appeared. The XRD patterns showed the wurtzite crystal structure, and the large intensity of the (002) peak suggests that most of the reflection was from the top hexagonal face of the NWs, and thus, the wires are predominantly aligned along the c-axis. The TEM analysis further confirmed the crystal growth direction along the (001) direction. The UV-Visible absorption and PL measurements also showed a decrease in the bandgap with an increase in doping concentration, which may be associated with the sp–d exchange interaction between the localized d-electrons and band electrons of the Bi ions. Bi-doping tended to increase the PL intensity in the visible region. The magnetic properties measured by SQUID at 4 and 300 K showed ferromagnetic behaviour for both the pristine and Bi-doped samples. However, the saturation magnetization for the Bi-doped samples was higher compared to that of the pristine ZnO samples until the threshold doping value. The obtained results demonstrated that Bi-doping can be used to tune both the optical and magnetic properties of ZnO NWs, hence paving the way for future spintronics and spin-polarized optoelectronics applications.

Room-temperature ferromagnetism in the large and direct bandgap diluted magnetic semiconductor zinc oxide (ZnO) is attributed to the intrinsic defects and p-orbital–p-orbital (p–p) coupling interaction.     

Comparison between the analgesic efficacy of transversus abdominis plane (TAP) block and placebo in open retropubic radical prostatectomy: a prospective,randomized, double-blinded study

Study ObjectiveTo compare the efficacy of ultrasound-guided tansversus abdominis plane (TAP) block with placebo for postoperative analgesia after retropubic radical prostatectomy (RRP).DesignProspective, randomized, double-blinded study.SettingTertiary-care Veterans Affairs (VA) hospital.PatientsASA physical status 1, 2, and 3 patients scheduled for RRP.InterventionsPatients were randomized to two groups: the TAP group and the control group. All patients underwent an ultrasound-guided TAP block procedure after induction of general anesthesia and received either local anesthetic (TAP group) or normal saline (control group).MeasurementsOpioid use and verbal analog pain scores at 1, 6, 12, and 24 hours after surgery were recorded, as was the frequency of side effects. Times to ambulation and first oral intake also were recorded.Main ResultsThe TAP block group had lower pain scores and required less total opioid in the first 24 hours after surgery. Time to first oral intake and time to ambulation were similar between the two groups.ConclusionThe TAP block has early benefits in postoperative analgesia after RRP.     

Anesthetic management of an infant with Joubert syndrome for cardiac surgery

The anesthetic implications of Joubert syndrome in an infant who required cardiac surgery using cardiopulmonary bypass (CPB) is presented. Children with Joubert syndrome present with central apnea due to malformations in the midbrain and cerebellum. These patients have a marked sensitivity to opioids. The use of dexmedetomidine along with remifentanil was effective in this case.     

Two-Stage Arthroplasty for Prosthetic Joint Infection : A Systematic Review of Acute Kidney Injury,Systemic Toxicity and Infection Control

Periprosthetic infections of hip and knee joints are now treated by two-stage revision arthroplasty with an infection control rate of 91%. The present systematic review studied the reported incidence of acute kidney injury (AKI) and infection recurrence from January 1989 to June 2012 to assess the risk–benefit ratio of antibiotic spacer use. Ten observational studies (n = 544 patients) with clinical outcomes showed an average incidence of AKI of 4.8%. The average reported persistence or recurrence rate of infection was 11% during a follow-up period that ranged from 13 to 108 months. The risk–benefit ratio presently favors treatment although there appears to be higher complication rates and incidence of AKI than previously reported. Marked heterogeneity in practice and lack of detail in reporting precluded more robust quantitative synthesis. Clinicians need to be aware of the potential risk of AKI, particularly in high-risk patients; practice patterns for the use of antibiotic spacers need to be standardized.     

Progressively increasing fracture risk with advancing age after initial incident fragility fracture: The Tromsø Study

The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population‐based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age‐adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2–1.5) in women, and 2.0 (95% CI, 1.6–2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50–59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk. © 2013 American Society for Bone and Mineral Research.     

Acute Renal Infarction: An Unusual Cause of Abdominal Pain

Acute renal infarction is an uncommon and under-diagnosed disease. Its clinical presentation is nonspecific and often mimics other more common disease entities. The diagnosis is usually missed or delayed, which frequently results in irreversible renal parenchyma damage. High index of suspicion is required for early diagnosis, as timely intervention may prevent loss of kidney function. We report a case of acute renal infarction following coronary angiography in a patient with paroxysmal atrial fibrillation who initially presented with acute abdominal pain mimicking appendicitis.     

Preoperative peritonsillar infiltration of dexamethasone and levobupivacaine reduces pediatric post-tonsillectomy pain: a double-blind prospective randomized clinical trial

Background

Preoperative corticosteroids reduce post-tonsillectomy morbidities. The present study was performed to compare the effect of peritonsillar dexamethasone infiltration to intravenous injection together with peritonsillar levobupivacaine infiltration before tonsillectomy on postoperative pain in children.

Methods

One hundred twenty children, ASA I–II, aged 6–12 years, scheduled for adenotonsillectomy were enrolled in the study. They were randomized equally into two equal groups; 60 children each. Group A received peritonsillar infiltration with dexamethasone and levobupivacaine, and group B received i.v. dexamethasone and peritonsillar levobupivacaine infiltration. Rest and swallowing pain in the first postoperative day using a visual analogue scale, time to first rescue analgesia, cumulative paracetamol dose, vomiting, and adverse effects related to both interventions during the first postoperative day were recorded. Children care givers were asked to score pain using a verbal rating scale and to disclose complications as halitosis, headache, fever and otalgia during the first postoperative week.

Results

Time to first rescue analgesia was significantly longer in group A. Rest and swallowing pain in the first postoperative day, cumulative paracetamol dose, pain in the second and third postoperative days, and otalgia were significantly lower in group A. None of children developed postoperative bleeding, or complications related to dexamethasone or levobupivacaine infiltration. There was no significant difference in postoperative emesis, fever and halitosis between the groups.

Conclusion

Addition of dexamethasone to levobupivacaine for preoperative peritonsillar infiltration has better postoperative analgesic effects than i.v. dexamethasone combined with peritonsillar levobupivacaine infiltration in children.