Improvement of the Prediction Power of the CoMFA and CoMSIA Models on Histamine H3 Antagonists by Different Variable Selection Methods

The aim of this study is to enhance the predictivity power of CoMFA and CoMSIA models by means of different variable selection algorithms. The genetic algorithm (GA), successive projection algorithm (SPA), stepwise multiple linear regression (SW-MLR), and the enhanced replacement method (ERM) were used and tested as variable selection algorithms. Then, the selected variables were used to generate a simple and predictive model by the multilinear regression algorithm. A set of 74 histamine H₃ antagonists were split into 40 compounds as a training set, and 17 compounds as a test set, by the Kennard-Stone algorithm. Before splitting the data, 17 compounds were randomly selected from the pool of the whole data set as an evaluation set without any supervision, pretreatment, or visual inspection. Among applied variable selection algorithms, ERM had noticeable improvement on the statistical parameters. The r² values of training, test, and evaluation sets for the ERM-MLR model using CoMFA fields were 0.9560, 0.8630, and 0.8460 and using the CoMSIA fields were 0.9800, 0.8521, and 0.9080, respectively. In this study, the principles of organization for economic cooperation and development (OECD) for regulatory acceptability of QSARs are considered.     

Destructive Adsorption of Diazinon Pesticide by Activated Carbon Nanofibers Containing Al2O3 and MgO Nanoparticles

We report the destructive adsorption of Diazinon pesticide by porous webs of activated carbon nanofibers containing Al₂O₃ and MgO nanoparticles. The results show that, the presence of Al₂O₃ and MgO nanoparticles in the activated carbon nanofibers increases the amount of destructively adsorbed Diazinon pesticide by activated carbon nanofibers. Moreover, type, amount, and specific surface area of metal oxide nanoparticles affect the adsorption rate as well as the total destructively adsorbed Diazinon. Liquid chromatography proved the degradation of Diazinon by chemical reaction with Al₂O₃ and MgO nanoparticles. Liquid chromatography–mass spectrometry showed that the main product of reaction between Diazinon and the metal oxides is 2-isopropyl-6-methyl-4-pyrimidinol with less toxicity than Diazinon.     

Elder abuse and its sociocultural factors from the perspectives of Kurdish rural older people: Does gender matter?

Abstract

We aimed to explore the meaning of elder abuse and its sociocultural factors from the perspectives of Kurdish older people. We purposively selected the participants, 38 female and 17 male, from a rural area in Boukan country, Iran. Data were collected using semi-structured interviews and focus group discussions and were analyzed applying conventional content analysis. Researchers finally characterized viewpoints of the participants into two themes including structural changes in family interactions and changes in sociocultural values. Public education about moral norms and enactment of supportive laws for elderly people may help minimize elder abuse.     

Involvement of nitric oxide pathway in the acute anticonvulsant effect of melatonin in mice

Melatonin, the major hormone produced by the pineal gland, is shown to have anticonvulsant effects. Nitric oxide (NO) is a known mediator in seizure susceptibility modulation. In the present study, the involvement of NO pathway in the anticonvulsant effect of melatonin in pentylenetetrazole (PTZ)-induced clonic seizures was investigated in mice. Acute intraperitoneal administration of melatonin (40 and 80 mg/kg) significantly increased the clonic seizure threshold induced by intravenous administration of PTZ. This effect was observed as soon as 1 min after injection and lasted for 30 min with a peak effect at 3 min after melatonin administration. Combination of per se non-effective doses of melatonin (10 and 20 mg/kg) and nitric oxide synthase (NOS) substrate L-arginine (30, 60 mg/kg) showed a significant anticonvulsant activity. This effect was reversed by NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg), implying an NO-dependent mechanism for melatonin effect. Pretreatment with L-NAME (30 mg/kg) and N(G)-nitro-L-arginine (L-NNA, 10 mg/kg) inhibited the anticonvulsant property of melatonin (40 and 80 mg/kg) and melatonin 40 mg/kg, respectively. Specific inducible NOS (iNOS) inhibitor aminoguanidine (100 and 300 mg/kg) did not affect the anticonvulsant effect of melatonin, excluding the role of iNOS in this phenomenon, while pretreatment of with 7-NI (50 mg/kg), a preferential neuronal NOS inhibitor, reversed this effect. The present data show an anticonvulsant effect for melatonin in i.v. PTZ seizure paradigm, which may be mediated via NO/L-arginine pathway by constitutively expressed NOS.     

Total allograft transplantation of the elbow joint after wide resection of synovial cell sarcoma: a case series

Total elbow allograft transplantation is an option for patients who have extensive joint defects secondary to tumor surgery, trauma, or failed total elbow arthroplasty. This salvage procedure provides patients with a useful, painless range of motion of the elbow. We report our experience with two complete elbow allograft reconstructions after tumor resection surgery with 5 and 6 years of follow-up.     

Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies promotes long-term survival and function of neonatal porcine islet xenografts in spontaneously diabetic NOD mice

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic islet beta-cells, which are required for the production of insulin. Islet transplantation has been shown to be an effective treatment option for TIDM; however, the current shortage of human islet donors limits the application of this treatment to patients with brittle T1DM. Xenotransplantation of pig islets is a potential solution to the shortage of human donor islets provided xenograft rejection is prevented. We demonstrated that a short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) was highly effective in preventing rejection of neonatal porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune-prone nonobese diabetic (NOD) mice is not known. Given that the current application of islet transplantation is for the treatment of T1DM, we set out to determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote long-term survival of NPI xenografts in NOD mice. Short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in preventing rejection of NPI xenografts in B6 mice, failed to promote long-term survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted in xenograft function in 9/12 animals and long-term graft (>100 days) survival in 2/12 mice. Immunohistochemical analysis of islet grafts from these mice identified numerous insulin-producing beta-cells. Moreover, the anti-porcine antibody as well as autoreactive antibody responses in these mice was reduced similar to those observed in naive nontransplanted mice. These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice.     

Mitral valve‐in‐valve replacement supported by a transapically snared guidewire via septostomy

We describe a 72‐year‐old woman, a known case of rheumatic heart disease with a history of mitral and aortic valve replacement 8 years previously, who underwent mitral valve‐in‐valve replacement supported by a transapically snared guidewire through septostomy.     

Comparison of main molecular markers involved in autophagy and apoptosis pathways between spermatozoa of infertile men with varicocele and fertile individuals

Abnormal dilatation and tortuosity of the pampiniform plexus within the spermatic cord are termed varicocele which leads to impaired spermatogenesis due to heat‐related oxidative stress and cell death. Previously, it was shown that both apoptosis and autophagy pathways were activated by heat in germ cells of mouse in vivo and in vitro. But, status of these pathways is not clear in chronic state of heat stress such as varicocele. Therefore, we aimed to access sperm apoptotic markers (active caspases 3/7 and DNA fragmentation), and autophagic markers (Atg7 and LC3 proteins) as primary outcomes, and also sperm parameters and protamine deficiency as secondary outcomes between 23 infertile men with varicocele and 16 fertile individuals. Sperm parameters were assessed according to World Health Organization 2010 protocol. Apoptotic markers (active caspases 3/7 and DNA fragmentation), autophagic markers (Atg7 and LC3 proteins), and protamine deficiency were evaluated by flow cytometry, fluorescence microscope, and western blotting techniques. Mean of autophagy and apoptosis markers, and also protamine deficiency have significantly increased in infertile men with varicocele compared to fertile individuals, but autophagy and apoptosis markers did not significantly correlate with each other. In conclusion, it seems that both apoptosis and autophagy pathways are independently active in spermatozoa of infertile men with varicocele.