Transcranial direct current stimulation (tDCS) has been investigated for the treatment of major depressive disorders in recent years. Here, we review the implications of current research for the ...clinical use of tDCS in the treatment of major depressive disorder. Meta-analyses, randomized, placebo-controlled clinical trials, open-label trials, case reports and review articles were identified through a systematic search of the literature database of the National Institutes of Health (USA). Available articles were evaluated with regard to their clinical relevance. Results of tDCS efficacy are inconsistent due to the small sample sizes, the heterogeneous patient samples and the partially high treatment resistance in some studies. Overall, tDCS has very low side effects. Meta-analyses suggest some efficacy of tDCS in the treatment of acute depressive disorder with moderate effect size, and low efficacy in treatment-resistant depression. A general statement about the efficacy of tDCS as a therapeutic tool in major depression seems to be premature. tDCS is considered as a safe therapeutic option and is associated with only minor side effects. The effectiveness of tDCS decreases with resistance to treatment. Psychotropic drugs may attenuate or amplify its effects. The use of 2 mA current strength over 20 min per day over a short time span can be considered as safe.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The chemical background of olfactory perception has been subject of intensive research, but no available model can fully explain the sense of smell. There are also inconsistent results on the role of ...the isotopology of molecules. In experiments with human subjects it was found that the isotope effect is weak with acetone and D6‐acetone. In contrast, clear differences were observed in the perception of octanoic acid and D15‐octanoic acid. Furthermore, a trained sniffer dog was initially able to distinguish between these isotopologues of octanoic acid. In chromatographic measurements, the respective deuterated molecule showed weaker interaction with a non‐polar liquid phase. Quantum chemical calculations give evidence that deuterated octanoic acid binds more strongly to a model receptor than non‐deuterated. In contrast, the binding of the non‐deuterated molecule is stronger with acetone. The isotope effect is calculated in the framework of statistical mechanics. It results from a complicated interplay between various thermostatistical contributions to the non‐covalent free binding energies and it turns out to be very molecule‐specific. The vibrational terms including non‐classical zero‐point energies play about the same role as rotational/translational contributions and are larger than bond length effects for the differential isotope perception of odor for which general rules cannot be derived.
The scent of deuterium: For a mechanistic understanding of the olfactory perception of molecules, it is an interesting aspect whether or not isotopological substances are perceived differently. To investigate this question, humans and a trained sniffer dog were exposed to deuterated and non‐deuterated substances. The experimental results, supplemented by quantum mechanical calculations, provide insights into the interaction of molecules with receptors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•rTMS can produce significant clinical improvement in various neurological and psychiatric disorders.•Updated guidelines on the therapeutic use of rTMS are presented, including 2014–2018 ...publications.•Higher evidence of efficacy is present in the areas of depression, pain, and postacute motor stroke.
A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 Lefaucheur et al., Clin Neurophysiol 2014;125:2150–206. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson’s disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Pharmaceutical residues in the aquatic environment are an emerging issue of global concern because of their effects on ecosystems including; antibacterial resistance development and endocrine ...disruption. Lake Victoria is the largest freshwater lake in Africa, and the second largest lake in the world. It is also the main source of the White Nile River, arguably the longest river in the world, flowing through South Sudan, Sudan, Ethiopia and Egypt, discharging into the Mediterranean Sea. However, its ecology is threatened by rapid industrialisation, urbanization, and increased agricultural activities, which have led to increased pollution via polluted runoffs. In this study, the occurrence of twenty-five pharmaceutical compounds (14 antibiotics, four anti-epileptic and antidepressant drugs, three analgesic and anti-inflammatory drugs, three beta-blockers, and one lipid regulator) was studied in 55 sediment samples obtained from the Ugandan sector of Lake Victoria, and their ecotoxic risk assessed. All the target compounds were quantifiable with levofloxacin (2–120 ng g−1 dm; dry mass), ciprofloxacin (3–130 ng g−1 dm) enoxacin (9–75 ng g−1 dm), ibuprofen (6–50 ng g−1 dm), metoprolol (1–92 ng g−1 dm) and propranolol (1–52 ng g−1 dm) being predominant. Murchison Bay, being the chief recipient of sewage effluents, municipal and industrial waste from Kampala city and its suburbs, had the highest levels. Ecotoxic risk assessment revealed that ciprofloxacin, levofloxacin, sulfamethoxazole, sulfamethazine, oxytetracycline, tetracycline, erythromycin, norfloxacin, ibuprofen, diclofenac, carbamazepine, atenolol, and metoprolol posed high toxic risks to sediment-dwelling organisms (risk quotients, RQ >1). This is the first study reporting concentrations and ecotoxic risks of pharmaceuticals in sediments of Lake Victoria, Uganda, and the whole of East Africa. Detection, identification and quantification of pharmaceuticals in Lake Victoria sediments is essential for gaining knowledge on their occurrence and fate which can ultimately be used to assist in constructing relevant policy and management recommendations.
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•25 pharmaceutical compounds analyzed in sediments from Lake Victoria•First findings of pharmaceuticals in sediments of Africa's largest freshwater lake•Ciprofloxacin, ibuprofen, levofloxacin, and propranolol were most dominant.•Risk assessment revealed high ecotoxic risk for many of the studied pharmaceuticals.•Pharmaceuticals detected at the source of the Nile may reach the Mediterranean Sea.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite many years of research, there is still an urgent need for new therapeutic options for the treatment of cognitive deficits in schizophrenia. Noninvasive brain stimulation (NIBS) has been ...proposed to be such a novel add-on treatment option. The main objective of this review was to systematically evaluate the cognitive effects of repetitive NIBS in schizophrenia. As most studies have not been specifically designed to investigate cognition as primary outcome, we have focused on both, primary and secondary outcomes. The PubMed/MEDLINE database (1985-2015) was systematically searched for interventional studies investigating the effects of repetitive NIBS on schizophrenia symptoms. All interventional clinical trials using repetitive transcranial stimulation, transcranial theta burst stimulation, and transcranial direct current stimulation for the treatment of schizophrenia were extracted and analyzed with regard to cognitive measures as primary or secondary outcomes. Seventy-six full-text articles were assessed for eligibility of which 33 studies were included in the qualitative synthesis. Of these 33 studies, only 4 studies included cognition as primary outcome, whereas 29 studies included cognitive measures as secondary outcomes. A beneficial effect of frontal NIBS could not be clearly established. No evidence for a cognitive disruptive effect of NIBS (temporal lobe) in schizophrenia could be detected. Finally, a large heterogeneity between studies in terms of inclusion criteria, stimulation parameters, applied cognitive measures, and follow-up intervals was observed. This review provides the first systematic overview regarding cognitive effects of repetitive NIBS in schizophrenia.
Highlights • A group of European experts reviewed current evidence for therapeutic efficacy of tDCS. • Level B evidence (probable efficacy) was found for fibromyalgia, depression and craving. • The ...therapeutic relevance of tDCS needs to be further explored in these and other indications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Methylxanthines are commonly recommended as anthropogenic markers, yet possible diffuse sources are largely unaccounted for. In this study, eight methylxanthines and xanthine were determined jointly ...in an entire river system for the first time. Overall, 49 samples were taken from the River Wietze (Lower Saxony, Germany) and its tributaries in four sampling campaigns. In addition, consecutive rainwater samples as well as influent and effluent samples from the largest adjacent municipal wastewater treatment plant (WWTP) were taken. All samples were enriched using SPE and analysed via LC-MS/MS. For xanthine, the standard addition method was applied. All investigated compounds were found in concentrations ranging from some dozen to some hundred ng L−1. For isocaffeine, 7-methylxanthine, and xanthine, measured concentrations in the River Wietze are the first available concentrations in surface water. Mass loads displayed a high seasonal variability and up to 144 g day−1 of methylxanthines were discharged into the receiving river. Municipal WWTPs were found to be an important and constant point source of all compounds. However, the high dependence of mass loads on discharges in the river as well as the detection of most methylxanthines at the blank site and in rainwater samples suggest additional diffuse introduction pathways. Solely the occurrence of isocaffeine in the River Wietze was found to be exclusively attributable to municipal wastewater discharge. Therefore, while caffeine and its degradation products are unsuitable for tracking the presence of treated or untreated wastewater in fluvial systems, isocaffeine can be recommended as a marker for the discharge of treated wastewater.
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•Methylxanthines were determined in an entire river system across the ng L−1 range.•Isocaffeine, 7-methylxanthine, and xanthine were first-time measured in a river.•Municipal wastewater is an important point source of all investigated compounds.•For caffeine and the di- and monomethylxanthines, diffuse sources exist as well.•Caffeine and demethylated xanthines are not suitable as anthropogenic markers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transcranial direct current stimulation (tDCS) has been proposed for experimental and therapeutic modulation of regional brain function. Specifically, anodal tDCS of the dorsolateral prefrontal ...cortex (DLPFC) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood, and have been suggested for the treatment of several neurological and psychiatric disorders. Although modeled mathematically, the distribution, direction, and extent of tDCS-mediated effects on brain physiology are not well understood. The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network (RSN) connectivity measured by functional magnetic resonance imaging (fMRI). Thirteen healthy subjects underwent real and sham tDCS in random order on separate days. tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region. Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI, and changes were analyzed for relevant networks related to the stimulation-electrode localizations. At baseline, four RSNs were detected, corresponding to the default mode network (DMN), the left and right frontal-parietal networks (FPNs) and the self-referential network. After real tDCS and compared with sham tDCS, significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions. These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain.
Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention for depression. It has mixed results, possibly caused by study heterogeneity.
To assess tDCS efficacy and to ...explore individual response predictors.
Systematic review and individual patient data meta-analysis.
Data were gathered from six randomised sham-controlled trials, enrolling 289 patients. Active tDCS was significantly superior to sham for response (34% v. 19% respectively, odds ratio (OR) = 2.44, 95% CI 1.38-4.32, number needed to treat (NNT) = 7), remission (23.1% v. 12.7% respectively, OR = 2.38, 95% CI 1.22-4.64, NNT = 9) and depression improvement (B coefficient 0.35, 95% CI 0.12-0.57). Mixed-effects models showed that, after adjustment for other predictors and confounders, treatment-resistant depression and higher tDCS 'doses' were, respectively, negatively and positively associated with tDCS efficacy.
The effect size of tDCS treatment was comparable with those reported for repetitive transcranial magnetic stimulation and antidepressant drug treatment in primary care. The most important parameters for optimisation in future trials are depression refractoriness and tDCS dose.
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