Long-Term Resveratrol Supplementation as a Secondary Prophylaxis for Stroke

Stroke is a leading cause of mortality worldwide, as well as a source of long-term disabilities and huge socioeconomic costs. This study investigates the effects of resveratrol, an antioxidant supplement, on blood pressure, weight status, glucose, and lipid profile in patients who had a stroke in the last 12 months. Two hundred and twenty-eight patients were divided into three groups: group I received only allopathic treatment (control group), while groups II and III received allopathic treatment with a daily supplementation of oral resveratrol (100 and 200 mg, resp.) for 12 months. In all groups, the changes of the studied parameters were monitored at 6 and 12 months from the initial evaluation. In groups II and III, resveratrol induced significant changes (p<0.05) in the blood pressure, body mass index, as well as all parameters of the lipid profile, and glucose (in nondiabetic patients), compared to the control group. The supplementation of the allopathic treatment with resveratrol had a beneficial effect on all monitored parameters, which serve as major risk factors for stroke

Salvage stereotactic body radiotherapy for isolated lymph node recurrent prostate cancer : single institution series of 94 consecutive patients and 124 lymph nodes

A

A Point Mutation in the Pore Region Alters Gating, Ca2+Blockage, and Permeation of Olfactory Cyclic Nucleotide–Gated Channels

Upon stimulation by odorants, Ca2+ and Na+ enter the cilia of olfactory sensory neurons through channels directly gated by cAMP. Cyclic nucleotide–gated channels have been found in a variety of cells and extensively investigated in the past few years. Glutamate residues at position 363 of the α subunit of the bovine retinal rod channel have previously been shown to constitute a cation-binding site important for blockage by external divalent cations and to control single-channel properties. It has therefore been assumed, but not proven, that glutamate residues at the corresponding position of the other cyclic nucleotide–gated channels play a similar role. We studied the corresponding glutamate (E340) of the α subunit of the bovine olfactory channel to determine its role in channel gating and in permeation and blockage by Ca2+ and Mg2+. E340 was mutated into either an aspartate, glycine, glutamine, or asparagine residue and properties of mutant channels expressed in Xenopus laevis oocytes were measured in excised patches. By single-channel recordings, we demonstrated that the open probabilities in the presence of cGMP or cAMP were decreased by the mutations, with a larger decrease observed on gating by cAMP. Moreover, we observed that the mutant E340N presented two conductance levels. We found that both external Ca2+ and Mg2+ powerfully blocked the current in wild-type and E340D mutants, whereas their blockage efficacy was drastically reduced when the glutamate charge was neutralized. The inward current carried by external Ca2+ relative to Na+ was larger in the E340G mutant compared with wild-type channels. In conclusion, we have confirmed that the residue at position E340 of the bovine olfactory CNG channel is in the pore region, controls permeation and blockage by external Ca2+ and Mg2+, and affects channel gating by cAMP more than by cGMP

Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

BACKGROUND: To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. METHODS: TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. RESULTS: 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%). CONCLUSIONS: Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherap

Aspects Regarding the Pharmaceutical Waste Management in Romania

The issue of drug disposal, as well as the development and implementation of efficient collection strategies, represents an important concern at the highest European level. This research looks into the factors that could have an impact on the efficiency of pharmacies in collecting and disposing the medicinal waste of the population. There were 521 pharmacists from all over the country who filled in a questionnaire on their opinion/attitude related to the system of collecting and disposing the pharmaceutical waste of the population. Of the surveyed pharmacists, 16% work in pharmacies that do not collect unused/expired drugs from the population, and nearly 33% of those investigated have refused, at least once, to take the unused medicines from the people. Pharmacists&rsquo; most important reasons for refusing to collect the pharmaceutical waste were the lack of procedure, incomplete legislation, exceeding the amount contracted with the operators, and high costs. Results show that pharmacies in Romania face several deficiencies in the pharmaceutical waste collection services. The lack of implemented programs has contributed considerably to lower standards of pharmaceutical waste management in Romania. This study is the first research on this topic in Romania, a country where the management of drug-based waste generated by the population is at the beginning. The results shown in this survey can provide a reference point for competent authorities in developing and implementing a take-back program for waste medicine whose efficiency is superior to the existing ones

Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

Abstract Background To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. Methods TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. Results 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%). Conclusions Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherapy.</p

Multi atlas based segmentation: Should we prefer the best atlas group over the group of best atlases?

Multi atlas based segmentation (MABS) uses a database of atlas images, and an atlas selection process is used to choose an atlas subset for registration and voting. In the current state of the art, atlases are chosen according to a similarity criterion between the target subject and each atlas in the database. In this paper, we propose a new concept for atlas selection that relies on selecting the best performing group of atlases rather than the group of highest scoring individual atlases. Experiments were performed using CT images of 50 patients, with contours of brainstem and parotid glands. The dataset was randomly split into two groups: 20 volumes were used as an atlas database and 30 served as target subjects for testing. Classic oracle selection, where atlases are chosen by the highest dice similarity coefficient (DSC) with the target, was performed. This was compared to oracle group selection, where all the combinations of atlas subgroups were considered and scored by computing DSC with the target subject. Subsequently, convolutional neural networks were designed to predict the best group of atlases. The results were also compared with the selection strategy based on normalized mutual information (NMI). Oracle group was proven to be significantly better than classic oracle selection (p < 10−5). Atlas group selection led to a median ± interquartile DSC of 0.740 ± 0.084, 0.718 ± 0.086 and 0.670 ± 0.097 for brainstem and left/right parotid glands respectively, outperforming NMI selection 0.676 ± 0.113, 0.632 ± 0.104 and 0.606 ± 0.118 (p < 0.001) as well as classic oracle selection. The implemented methodology is a proof of principle that selecting the atlases by considering the performance of the entire group of atlases instead of each single atlas leads to higher segmentation accuracy, being even better then current oracle strategy. This finding opens a new discussion about the most appropriate atlas selection criterion for MABS