Dye functionalized cryogel columns for reversible lysozyme adsorption

In this study, poly (methyl methacrylate–glycidyl methacrylate) [poly(MMA-GMA)] cryogels were prepared by radical cryocopolymerization of MMA with GMA as a functional comonomer. Reactive Green 19 dye was then attached to the cryogel by nucleophilic substitution reaction, and this dye-attached cryogel column was used for lysozyme adsorption. Characterization of the cryogel was performed by Fourier transform infrared spectroscopy, environmental scanning electron microscopy, Brunauer–Emmett–Teller, and energy dispersive X-ray analysis. Pore size of the cryogels was 15–30?μm and pores were interconnected structure. Attached amount of Reactive Green 19 to cryogel support was calculated as 106.25?μmol/g cryogel. Lysozyme adsorption studies were carried out by using a continuous system. It was found that the maximum amount of lysozyme adsorption (32?mg/g cryogel) obtained from experimental results was found to be approximately same with the calculated Langmuir adsorption capacity (33?mg/g cryogel). Desorption of adsorbed lysozyme was carried out by using 1.5?M NaCl in pH 4.5 acetate buffer, and desorption yield was found to be 97.4%. Cryogels were very stable, and it was found that there was no remarkable reduction in the adsorption capacity at the end of ten adsorption–desorption cycles. As a result, Reactive Green 19-attached cryogels have great advantages such as easy preparation, rapid adsorption, and desorption, being economic and allowing the direct separation of proteins.     

Virtual Reality Simulation in Ear Microsurgery: A Pilot Study

Classically, teaching of otological micro procedures is achieved by cadaveric dissection of the temporal bones, achieved by attending expensive temporal bone dissection courses. The difficulty in acquiring cadaveric specimens and the cost of courses has led to the development of alternative techniques. The aim of this study is to evaluate the efficacy of using virtual reality temporal bone simulation in training otolaryngology residents for mastoidectomy procedures. Four senior residents were evaluated during six canal wall down mastoidectomy procedures. Three of these procedures were done conventionally. The other three procedures were preceded by virtual reality simulation 1 day before the operation. In simulated cases, the residents scored higher on the global rating scale and task-based checklist, and were faster and more confident. Further, fewer instructions were required during the actual operation. This outcome is encouraging for the utilization of virtual reality simulation in otolaryngology residency training. Further studies should be performed on a larger number of simulators and surgical procedures to validate our results.     

In vitro responses to known in vivo genotoxic agents in mouse germ cells

Genotoxic compounds have induced DNA damage in male germ cells and have been associated with adverse clinical outcomes including enhanced risks for maternal, paternal and offspring health. DNA strand breaks represent a great threat to the genomic integrity of germ cells. Such integrity is essential to maintain spermatogenesis and prevent reproduction failure. The Comet assay results revealed that the incubation of isolated germ cells with n‐ethyl‐n‐nitrosourea (ENU), 6‐mercaptopurine (6‐MP) and methyl methanesulphonate (MMS) led to increase in length of Olive tail moment and % tail DNA when compared with the untreated control cells and these effects were concentration‐dependent. All compounds were significantly genotoxic in cultured germ cells. Exposure of isolated germ cells to ENU produced the highest concentration‐related increase in both DNA damage and gene expression changes in spermatogonia. Spermatocytes were most sensitive to 6‐MP, with DNA damage and gene expression changes while spermatids were particularly susceptible to MMS. Real‐time PCR results showed that the mRNA level expression of p53 increased and bcl‐2 decreased significantly with the increasing ENU, 6‐MP and MMS concentrations in spermatogonia, spermatocytes and spermatids respectively for 24 hr. Both are gene targets for DNA damage response and apoptosis. These observations may help explain the cell alterations caused by ENU, 6‐MP and MMS in spermatogonia, spermatocytes and spermatids. Taken together, ENU, 6‐MP and MMS induced DNA damage and decreased apoptosis associated gene expression in the germ cells in vitro. Environ. Mol. Mutagen. 58:99–107, 2017. © 2017 Wiley Periodicals, Inc.     

Effect of deltamethrin and fluoride co-exposure on the brain antioxidant status and cholinesterase activity in Wistar rats

The study evaluated the effect of commercial preparation of deltamethrin, Butox^®, and fluoride (F^?) co-exposure on the brain antioxidant status and cholinesterase activity in rats. Group A was untreated. Group B was gavaged Butox^®, providing deltamethrin at the dose rate of 1.28?mg per kg body weight per day. Group C was administered F^?, as NaF, in drinking water providing 20?ppm F^?. Group D received both deltamethrin and F^? at the same dosages as groups B and C, respectively. Although, glutathione S-transferase activity was induced only in Butox^® alone treated group, the activities of superoxide dismutase and catalase were inhibited in all treatment groups when compared to the control group. Elevated lipid peroxidation was observed in the groups exposed to F^?. The activity of erythrocyte acetylcholinesterase (AChE) was inhibited in Butox^® treated groups, whereas brain AChE activity was inhibited in all treatment groups. In conclusion, both deltamethrin (given as Butox^®) and F^? inhibit AChE activity and produce oxidative stress in brain with F^? producing more oxidative damage. However, compared to the individual exposures, the co-exposure of these chemicals does not produce any exacerbated alteration in these biochemical parameters.     

Subcutaneous Granuloma Annulare of the Penis Associated with a Urethral Anomaly: Case Report and Review of the Literature

Granuloma annulare (GA) is an uncommon benign inflammatory skin condition, most often found on the extremities of young females. The subcutaneous variant of GA involving the penis is very rare. We report a case of subcutaneous GA associated with a urethral anomaly in a 15‐year‐old boy that persisted for a year. Treatment options are discussed with a review of the current literature.     

Acquired erythroderma in adults: a clinical and prognostic study

Background Erythroderma is a severe syndrome and prognostic studies are rare in the literature. Objectives Through a retrospective study of erythroderma in adults, we have analysed epidemiological and clinical data and precised the relevant aetiologies and survival in our patients. Methods This study was performed at the Department of Dermatology of Charles Nicolle Hospital of Tunis (1995–2007) including 82 cases of acquired erythroderma (>16 years). We have recorded epidemio‐clinical, biological and histological data, treatment and outcome. Clinical–histological correlation was analysed [kappa coefficient (κ)]. Follow‐up time and disease‐free survival time were calculated as were Kaplan–Meier estimates of overall survival and relapse‐free survival for some aetiologies. Results Erythroderma represented 0.44‰ of all dermatoses with an age of 55.13 ± 18.16 and no sex predilection. Psoriasis was the predominant aetiology (32.9%) with a median duration of 6.75 years and previous one or more episodes of erythroderma. Psoriasis was significantly associated with pruritus (P = 0.0001), pachyonychia (P = 0.00001), palmoplantar keratoderma (P = 0.0001) and hypereosinophilia (P = 0.008). The latter is then not specific for drug induced erythroderma (P = 0.004). Carbamazepine (27.8%) and penicillin (22.2%) were the most implicated drugs. Positive Clinical–histological correlation was found in 77% of cases (κ = 0.753). Relapse was seen in all aetiologies, but drug reactions and had occurred in the first 3 years in 90% of them. Mortality rate was 11.3 per 1000 patients‐years. Conclusions Our study illustrates the severity of erythroderma. It alters heavily the quality of life of patients which is initially altered by the pre‐existent dermatosis. It may be life threatening as mortality rate is high.     

Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency

The objective of the study was to determine the degree of linear growth retardation of patients with vitamin D deficiency rickets at presentation and the magnitude of catch-up growth in relation to their calcium (Ca) homeostasis and hormones affecting it before and after treatment. This prospective study recorded the anthropometric data and measured the circulating 25-hydroxy vitamin D (25-OH-D), insulin-like growth factor I (IGF-I), parathyroid hormone, Ca, phosphate, and alkaline phosphatase concentrations in 46 infants and children with nutritional (vitamin D deficiency) rickets before and 6 months or more after treatment with one intramuscular injection of vitamin D3 megadose (300000 IU). Forty normal age- and sex-matched children were included as controls for the auxological data. At presentation, patients' mean age = 13.1 +/- 1.1 months, length standard deviation scores (LSDS) = -1.5 +/- 0.2, and body mass index = 16.3 +/- 0.85. They were significantly shorter and had markedly lower growth velocity standard deviation scores (GVSDS) compared with normal controls (LSDS = 0.25 +/- 0.18 and 0.31 +/- 0.22, respectively). Six months after treatment, the LSDS increased significantly in patients to -0.45 +/- 0.13, with a significantly increased GVSDS (2.76 +/- 0.45) and body mass index (16.9 +/- 0.65). They were still shorter but with significantly higher GVSDS compared with normal controls. Serum Ca and phosphate concentrations increased from 2.07 +/- 0.25 and 1.23 +/- 0.24 mmol/L, respectively, before treatment to 2.44 +/- 0.2 and 1.94 +/- 0.2 mmol/L, respectively, after treatment. Serum alkaline phosphatase and parathyroid hormone concentrations decreased from 1183 +/- 219 U/L and 294 +/- 87 pg/mL, respectively, before treatment to 334 +/- 75 U/L and 35.2 +/- 15.2 pg/mL, respectively, after treatment. The 25-OH-D level increased from 4.5 +/- 0.56 ng/mL before treatment to 44.5 +/- 3.7 ng/mL after treatment. Circulating concentrations of IGF-I increased significantly after treatment (52.2 +/- 18.9 ng/mL) vs before treatment (26.6 +/- 12.8 ng/mL). The 25-OH-D concentrations were correlated significantly with the IGF-I levels before and after treatment (r = 0.603 and r = 0.59, respectively; P < .001). The GVSDS after treatment was correlated with the increase of IGF-I and 25-OH-D levels (r = 0.325 and r= 0.314, respectively; P < .01). These data denote that the accelerated linear growth after treatment of nutritional vitamin D deficiency is mediated through activation of the growth hormone/IGF-I system and suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and growth hormone/IGF-I secretion. Three different sequential stages of vitamin D deficiency can be recognized according to the clinical/radiological, biochemical, and hormonal data of patients at presentation.     

Future of combination therapy with dabrafenib and trametinib in metastatic melanoma

Introduction: Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF^V600 mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy.

Areas covered: This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib, and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway.

Expert opinion: Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.     

Road towards promoting patient safety practices among hospital pharmacists: Hospital-based baseline patient safety culture assessment cross-sectional survey

Patient safety is a fundamental aspect of a healthcare system. The aim of this study was to assess the perception and determinants of the patient safety culture of pharmacists in hospitals, in Riyadh, Saudi Arabia.A survey was conducted with pharmacists in the pharmacies of governmental, /military and private hospitals in Riyadh, Saudi Arabia. The pharmacy survey on patient safety culture questionnaire developed by Agency for Healthcare Research and Qualtity, a hard copy was distriuted to the pharmacists. The positive response rate (RR) was calculated and compared across hospitals using a chi-square test. The predictors of patient safety grades were identified using the generalized estimating equation. The data was analyzed using SAS.A total of 538 questionnaires were distributed, of which 411 responded (RR 76.4%). Of the participants, 229 (56%) were females. The majority 255 (62%) were in the 18 to 34 years age range, and 361 (88%) had a bachelor''s degree. The majority of the sample 376 (92%) was a pharmacist. The Positive RR (PRR) ranged between (25.6%–74%). The highest PRR was observed in teamwork (74.4%), followed by ‘staff, training and skills’ (68%), and ‘organizational learning continuous improvement’ (66%). The lowest PRR was observed in ‘staffing, work pressure, and pace’ (25.5%). Comparing the PPR of the various healthcare sectors, the governmental hospitals scored the highest in all patient safety domains. Generalized Estimating Equation analysis showed that with increase in scores of all patient safety culture domains increased the likelihood of reporting a better patient safety grade, whereas respondents’ demographic characteristics had no effect except the working experience years 6 years and above had odds of poor reporting of the patient safety grade (odds ratio = 2.54, 95% confience interval (1.543, 4.194), (P = .0003).The grades achieved in the various domains of patient safety culture by pharmacists in Riyadh are below the expected standard. The highest scores were achieved in teamwork, with the lowest scores in staffing, work pressure and pace. Overall, pharmacists in government hospital settings have a better perception of patient safety than their peers in other settings. These results provide the baseline evidence for developing future interventional studies aiming at improving patient safety culture in hospital pharmacy settings.