Profile of Sensory Integration Disorders in Migraine Patients-New Perspectives of Therapy.

Background: The involvement of sensory integration disorders in the pathophysiology of migraine has been suggested. This study aims to analyze the relationship between symptoms of sensory integration disorders and migraine in a broad scope, including all sensory domains, and examine its impact on migraine attacks. Methods: The study included 372 people diagnosed with migraine. The Daniel Travis Questionnaire was used to assess symptoms of sensory integration disorders and their severity across six domains. The relationships between the severity of these symptoms and headache features, as well as accompanying headache symptoms, were the subject of statistical analysis. Results: Current impairment in all sensory domains was significantly associated with headaches exacerbated by everyday life activities. A significant inverse relationship was found between the occurrence of throbbing headaches and symptoms of sensory integration disorders in terms of current sensory discrimination, current motor skills, and current emotional/social skills. Past under-responsiveness and past disturbances in emotional/social abilities were significantly associated with migraine aura. Conclusions: The severity of symptoms of sensory integration disorders affects the clinical picture of migraine. The significant association between migraine and emotional/social disorders, as well as under-responsiveness in the past, needs further research to assess whether this is a cause-and-effect relationship. There is a need for in-depth diagnostics of sensory integration disorders in migraine patients, which could be an additional target of their therapy.

Statins and 90-Day Functional Performance and Survival in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The neuroprotective effect of statins has become a focus of interest in spontaneous intracerebral hemorrhage (sICH). The purpose of this study was: (1) to evaluate the effect of statin use by the analyzed patients with sICH in the period preceding the onset of hemorrhage on their baseline neurological status and baseline neuroimaging of the head; (2) to evaluate the effect of statin use in the acute period of hemorrhage on the course and prognosis in the in-hospital period, taking into account whether the statin was taken before the hemorrhage or only after its onset; (3) to evaluate the effect of continuing statin treatment after in-hospital treatment on the functional performance and survival of patients up to 90 days after the onset of sICH symptoms, taking into account whether the statin was taken before the onset of sICH. MATERIAL AND METHODS: A total of 153 patients diagnosed with sICH were analyzed, where group I were not previously taking a statin and group II were taking a statin before sICH onset. After lipidogram assessment, group I was divided into patients without dyslipidemia and without statin treatment (Ia) and patients with dyslipidemia who received de novo statin treatment during hospitalization (Ib). Group II patients continued taking statin therapy. We evaluated the effect of prior statin use on the severity of hemorrhage; the effect of statin use during the acute period of sICH on its in-hospital course; and the effect of statin treatment on the severity of neurological deficit, functional capacity and survival of patients up to 90 days after the onset of sICH symptoms. RESULTS: There was no effect of prior statin use on the severity of hemorrhage as assessed clinically and by neuroimaging of the head. At in-hospital follow-up, subgroup Ia was the least favorable in terms of National Institutes of Health Stroke Scale (NIHSS) score. This subgroup had the highest percentage of deaths during hospitalization. In the post-hospital period, the greatest number of patients with improvement in the NIHSS, modified Rankin Scale (mRS) and Barthel scales were among those taking statins, especially group II patients. At 90-day follow-up, survival analysis fell significantly in favor of subgroup Ib and group II. CONCLUSIONS: 1. The use of statins in the pre-sICH period did not adversely affect the patients' baseline neurological status or the results of baseline neuroimaging studies. 2. Continued statin therapy prior to the onset of sICH or the inclusion of statins in acute treatment in patients with sICH and dyslipidemia does not worsen the course of the disease and the in-hospital prognosis. Statin therapy should not be discontinued during the acute phase of sICH. 3. To conclude the eventual beneficial effect on the functional performance and survival of patients after sICH onset, comparability of the analyzed groups in terms of clinical, radiological and other prognostic factors in spontaneous intracerebral hemorrhage would be needed. Future studies are needed to confirm these findings.

Application of Original Therapy for Stimulation of Oral Areas Innervated by the Trigeminal Nerve in a Child with Beckwith-Wiedemann Syndrome.

About 90% of children diagnosed with classic BWS have macroglossia, and 40% of them are submitted to surgical tongue reduction. The purpose of our article is to present a case study of a 5-month-old child with BWS who was treated with an original therapy for stimulation of oral areas innervated by the trigeminal nerve. The therapy included stimulation of the upper and lower lip and muscles of the floor of the mouth. The treatment was provided by a therapist once a week. In addition, the child was stimulated every day at home by his mother. After 3 months, a significant improvement in oral alignment and function was achieved. Preliminary observations of therapy application for stimulation regions innervated by the trigeminal nerve in children with Beckwith-Wiedemann syndrome seem promising. The original therapy for stimulation of oral areas innervated by the trigeminal nerve is a good alternative to existing methods of surgical tongue reduction in children with BWS and macroglossia.

Antimicrobial activity of pharmaceutical cocktails in sewage treatment plant effluent - An experimental and predictive approach to mixture risk assessment.

Municipal wastewater contains multi-component mixtures of active pharmaceutical ingredients (APIs). This could shape microbial communities in sewage treatment plants (STPs) and the effluent-receiving ecosystems. In this paper we assess the risk of antimicrobial effects in STPs and the aquatic environment for a mixture of 18 APIs that was previously detected in the effluent of a European municipal STP. Effects on microbial consortia (collected from a separate STP) were determined using respirometry, enumeration of culturable microorganisms and community-level physiological profiling. The mixture toxicity against selected bacteria was assessed using assays with Pseudomonas putida and Vibrio fischeri. Additional data on the toxicity to environmental bacteria were compiled from literature in order to assess the individual and expected joint bacterial toxicity of the pharmaceuticals in the mixture. The reported effluent concentration of the mixture was 15.4 nmol/l and the lowest experimentally obtained effect concentrations (EC10) were 242 nmol/l for microbial consortia in STPs, 225 nmol/l for P. putida and 73 nmol/l for V. fischeri. The lowest published effect concentrations (EC50) of the individual antibiotics in the mixture range between 15 and 150 nmol/l, whereas 0.9-190 µmol/l was the range of bacterial EC50 values found for the non-antibiotic mixture components. Pharmaceutical cocktails could shape microbial communities at concentrations relevant to STPs and the effluent receiving aquatic environment. The risk of antimicrobial mixture effects was completely dominated by the presence of antibiotics, whereas other pharmaceutical classes contributed only negligibly to the mixture toxicity. The joint bacterial toxicity can be accurately predicted from the individual toxicity of the mixture components, provided that standardized data on representative bacterial strains becomes available for all relevant compounds. These findings argue for a more sophisticated bacterial toxicity assessment of environmentally relevant pharmaceuticals, especially for those with a mode of action that is known to specifically affect prokaryotic microorganisms.

Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity.

The presence of pharmaceuticals in the environment has triggered concern among the general population and received considerable attention from the scientific community in recent years. However, only a few publications have focused on anticancer drugs, a class of pharmaceuticals that can exhibit cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic effects. The present study investigated the photodegradation, biodegradation, bacterial toxicity, mutagenicity and genotoxicity of cyclophosphamide (CP) and 5-fluorouracil (5-FU). The photodegradation experiments were performed at a neutral to slight pH range (7-7.8) using two different lamps (medium-pressure mercury lamp and a xenon lamp). The primary elimination of the parent compounds was monitored by means of liquid chromatography tandem mass spectrometry (LC-IT-MS/MS). NPOC (non-purgeable organic carbon) analyses were carried out in order to assess mineralization rates. The Closed Bottle Test (CBT) was used to assess ready biodegradability. A new method using Vibrio fischeri was adopted to evaluate toxicity. CP was not degraded by any lamp, whereas 5-FU was completely eliminated by irradiation with the mercury lamp but only partially by the Xe lamp. No mineralization was observed for the experiments performed with the Xe lamp, and a NPOC removal of only 18% was registered for 5-FU after 256 min using the UV lamp. Not one of the parent compounds was readily biodegradable in the CBT. Photo transformation products (PTPs) resulting from photolysis were neither better biodegradable nor less toxic than the parent compound 5-FU. In contrast, the results of the tests carried out with the UV lamp indicated that more biodegradable and non-toxic PTPs of 5-FU were generated. Three PTPs were formed during the photodegradation experiments and were identified. The results of the in silico QSAR predictions showed positive mutagenic and genotoxic alerts for 5-FU, whereas only one of the formed PTPs presented positive alerts for the genotoxicity endpoint.

Assessing the environmental fate of S-metolachlor, its commercial product Mercantor Gold® and their photoproducts using a water-sediment test and in silico methods.

Pesticides enter surface and groundwater by several routes in which partition to sediment contributes to their fate by abiotic (e.g. photolysis, hydrolysis) and biotic processes. Yet, little is known about S-metolachlor (SM) transformation in water-sediment systems. Therefore, a newly developed screening water-sediment test (WST) was applied to compare biodegradation and sorption processes between pure SM and Mercantor Gold® (MG), a commercial formulation of SM. Photolysis in water was performed by Xe lamp irradiation. Subsequently, the biodegradability of SM and MG photolysis mixtures was examined in WST. The primary elimination of SM from water phase was monitored and structures of its TPs resulting from biotransformation (bio-TPs) were elucidated by LC-MS/MS. SM was extracted from sediment in order to estimate the role of sorption in WST for its elimination. A set of in silico prediction software tools was applied for toxicity assessment of SM and its bio-TPs. Obtained results suggest that the MG adjuvants do not significantly affect biodegradation, but do influence diffusion of SM into sediment. 50% of SM could not be re-extracted from sediment with 0.01 M CaCl2 aqueous solution recommended in OECD test guideline for adsorption. Neither the parent compound nor the photo-TPs were biodegraded. However, new bio-TPs have been generated from SM and MG photo-TPs due to bacterial activity in the water-sediment interphase. Moreover, according to in silico assessment of the bio-TPs the biotransformation might lead to an increased toxicity to the water organisms compared with the SM. This might raise concerns of bio-TPs presence in the environment.

Removal of the anti-cancer drug methotrexate from water by advanced oxidation processes: Aerobic biodegradation and toxicity studies after treatment.

Anti-cancer drugs are discussed as high risk substances in regard to human health and considered as problematic for the environment. They are of potential environmental relevance due to their poor biodegradability and toxicological properties. Methotrexate (MTX) is an antimetabolite that was introduced in the pharmaceutical market in the 40's and still today is one of the most consumed cytotoxic compounds around the world. In the present study MTX was only partially biodegraded in the closed bottle test (CBT). Therefore, it was submitted to three different advanced oxidation processes (AOPs): UV/H2O2, UV/Fe(2+)/H2O2 and UV/TiO2. The irradiation was carried out with a Hg medium-pressure lamp during 256min whereas the analytical monitoring was done through LC-UV-MS/MS and DOC analysis. MTX was easily removed in all the irradiation experiments, while the highest mineralization values and rates were achieved by the UV/Fe(2+)/H2O2 treatment. The lowest resulted from the UV/H2O2 reactions. The UV/H2O2 treatment resulted in little biodegradable transformation products (TPs). However, the same treatment resulted in a reduction of the toxicity of MTX by forming less toxic TPs. Analysis by LC-UV-MS/MS revealed the existence of nine TPs formed during the photo-catalytic treatments. The pH of the solutions decreased from 6.4 (t 0min) to 5.15 in the UV/H2O2 and from 6.4 (t 0min) to 5.9 in the UV/TiO2 at the end of the experiments. The initial pH of the UV/Fe(2+)/H2O2 experiments was adjusted to 5 and after the addition of H2O2 the pH decreased to around 3 and remained in this range until the end of the treatments.

Degradation of 5-FU by means of advanced (photo)oxidation processes: UV/H2O2, UV/Fe2+/H2O2 and UV/TiO2--Comparison of transformation products, ready biodegradability and toxicity.

The present study investigates the degradation of the antimetabolite 5-fluorouracil (5-FU) by three different advanced photo oxidation processes: UV/H2O2, UV/Fe(2+)/H2O2 and UV/TiO2. Prescreening experiments varying the H2O2 and TiO2 concentrations were performed in order to set the best catalyst concentrations in the UV/H2O2 and UV/TiO2 experiments, whereas the UV/Fe(2+)/H2O2 process was optimized varying the pH, Fe(2+) and H2O2 concentrations by means of the Box-Behnken design (BBD). 5-FU was quickly removed in all the irradiation experiments. The UV/Fe(2+)/H2O2 and UV/TiO2 processes achieved the highest degree of mineralization, whereas the lowest one resulted from the UV/H2O2 treatment. Six transformation products were formed during the advanced (photo)oxidation processes and identified using low and high resolution mass spectrometry. Most of them were formed and further eliminated during the reactions. The parent compound of 5-FU was not biodegraded, whereas the photolytic mixture formed in the UV/H2O2 treatment after 256 min showed a noticeable improvement of the biodegradability in the closed bottle test (CBT) and was nontoxic towards Vibrio fischeri. In silico predictions showed positive alerts for mutagenic and genotoxic effects of 5-FU. In contrast, several of the transformation products (TPs) generated along the processes did not provide indications for mutagenic or genotoxic activity. One exception was TP with m/z 146 with positive alerts in several models of bacterial mutagenicity which could demand further experimental testing. Results demonstrate that advanced treatment can eliminate parent compounds and its toxicity. However, transformation products formed can still be toxic. Therefore toxicity screening after advanced treatment is recommendable.

Transformation products of antibiotic and cytostatic drugs in the aquatic cycle that result from effluent treatment and abiotic/biotic reactions in the environment: an increasing challenge calling for higher emphasis on measures at the beginning of the pipe.

Pharmaceuticals may undergo transformation into new products during almost all possible processes along their life-cycle. This could either take place in the natural water environment and/or during water treatment processes. Numerous studies that address the issue of such transformation products (TPs) have been published, describing selected aspects of TPs in the environment and their formation within effluent and water treatment processes. In order to exemplify the number and quality of information published on TPs, we selected 21 active pharmaceutical ingredients from the groups of antibiotics and antineoplastics, and assessed the knowledge about their TPs that has been published until the end of May 2012. The goal of this work was to demonstrate, that the quality of data on pharmaceutical TPs greatly differs in terms of the availability of chemical structures for each TP, rather than to provide an exhaustive database of available TPs. The aim was to point out the challenge going along with so many TPs formed under different treatment and environmental conditions. An extensive review in the form of a table showing the existing data on 158 TPs for 15 compounds, out of 21 investigated, was presented. Numerous TPs are the result of different treatments and environmental processes. However, also numerous different TPs may be formed within only one type of treatment, applied under sometimes even very similar treatment conditions and treatments times. In general, the growing number of elucidated TPs is rationalized by ineffective removal treatments. Our results demonstrate a severe risk of drowning in much unrelated and non-assessable data, both from a scientific and from a technical treatment-related point of view. Therefore, limiting the input of pharmaceuticals into effluents as well as improving their (bio) degradability and elimination behavior, instead of only relying on advanced effluent treatments, is urgently needed. Solutions that focus on this "beginning of the pipe" approach should minimize the adverse effects of parent compounds by reducing and formation of TPs and their entrance into the natural environment.

Biodegradation screening of chemicals in an artificial matrix simulating the water-sediment interface.

Biodegradation is the most important attenuation process for most of organic chemicals in the environment. This process decides whether the organic substance itself or its degradation products rests in the environment and should be considered for a further risk assessment. This work presents the development of a water sediment screening test, based on OECD guideline 308, with a high significance to environmental conditions and with a good reproducibility and consistency of results. The increased reproducibility was achieved by creating an artificial and standardized medium, based on the existing OECD guidelines OECD 302C, 301D and 218. Each test consisted of five different series: blank, quality control, test, toxicity control and abiotic control. Biodegradation was assessed by measurement of pressure difference in closed vessels using the OxiTop(®) system. Aniline, diethylene glycol and sodium acetate were used to optimize and validate test conditions. Additionally, two pharmaceuticals: Acetaminophen and ciprofloxacin (CIP) were tested as an example of possible test application. Acetaminophen was mainly removed from the system by biodegradation whereas CIP was removed from water phase by sorption onto sediment. Water sediment test proved to be a promising tool for the biodegradation investigation of chemicals in the water-sediment interface.