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OBJECTIVE: To validate a brief tool for screening migraine. BACKGROUND: Migraine is a common, but underdiagnosed condition. Effective utilization of nonphysician personnel to reliably screen patients for migraine may improve identification of migraineurs for clinical treatment and research. METHODS: An 8-question Migraine Assessment Tool (based on International Headache Society criteria) was designed for administration by a nurse with no specialized headache training as a pre-assessment for the diagnosis of migraine for use in either a research or clinical environment. A community sample of 80 adults (71 women, 9 men; mean age, 33.7 years; 80% white, 14% African American, 2.5% Asian American) with self-reported headache was recruited through advertisements. A headache specialist independently diagnosed subjects using clinical assessment, and a nurse who works in a balance disorder clinic used the Migraine Assessment Tool. Agreement between physician and nurse-administered Migraine Assessment Tool diagnoses was determined. Each subject returned in 2 to 4 weeks for a second assessment, administered by the same nurse. Agreement between the 2 diagnoses from the Migraine Assessment Tool was calculated. RESULTS: Comparison between diagnosis by the physician versus the Migraine Assessment Tool revealed a positive predictive value of 0.85; negative predictive value, 0.84; sensitivity, 0.89; specificity, 0.79; and observed agreement, 0.85. Cohen's kappa reliability measure was 0.69, indicating good test reliability. Interestingly, in 8 of the 12 cases of disagreement, the examiner diagnosing nonmigraine diagnosed analgesic overuse headache. Comparing diagnoses assigned by the 2 separate administrations of the Migraine Assessment Tool revealed a Cohen's kappa of 0.69. Notably, 9 of the 12 cases of nonagreement on the 2 assessments were due to subjects endorsing analgesic overuse in only 1 of the 2 testing sessions. CONCLUSIONS: This study showed good reliability and stability of a new, brief, nurse-administered migraine questionnaire. In addition, the study also showed that consistency in self-reporting analgesic overuse within individuals with headache is poor. This suggests the need for repeat questioning about analgesic overuse on subsequent appointments to ensure absence of analgesic overuse headache. [ABSTRACT FROM AUTHOR]

A practical strategy for obtaining novel 5-seleno-substituted spirocyclopenta[b]pyridines-2,5-dien-4-ones and benzo[h]quinolines via radical cyclization is reported. The synthetic protocol explores the reaction between arylethynylpyridines and diorganyl diselenides in acetonitrile as solvent and Oxone® as oxidant at 82 °C. This easy-to-handle, eco-friendly metal-free approach was carried out under an open atmosphere, affording functionalized organoselenium compounds in good to excellent yields. Control experiments and scale-up test were performed to demonstrate the efficiency of this methodology., (© 2024 Wiley-VCH GmbH.)

A general methodology to access valuable 4-(phenylchalcogenyl)tetrazolo[1,5- a ]quinolines was developed by the reaction of 2-azidobenzaldehyde with phenylchalcogenylacetonitriles (sulfur and selenium) in the presence of potassium carbonate (20 mol%) as a catalyst. The reactions were conducted using a mixture of dimethylsulfoxide and water (7:3) as solvent at 80 °C for 4 h. This new methodology presents a good functional group tolerance to electron-deficient and electron-rich substituents, affording a total of twelve different 4-(phenylchalcogenyl)tetrazolo[1,5- a ]quinolines selectively in moderate to excellent yields. The structure of the synthesized 4-(phenylselanyl)tetrazolo[1,5- a ]quinoline was confirmed by X-ray analysis.

Two new Cu(II) complexes based on 4-(arylchalcogenyl)-1H-pyrazoles monodentate bis(ligand) containing selenium or sulfur groups (2a and 2b) have been synthesized and characterized by IR spectroscopy, high-resolution mass spectrometry (HRMS), and by X-ray crystallography. In the effort to propose new applications for the biomedical area, we evaluated the antioxidant activity and cytotoxicity of the newly synthesized complexes. The antioxidant activity of the Cu(II) complexes (2a - 2b) were assessed through their ability to inhibit the formation of reactive species (RS) induced by sodium azide and to scavenge the synthetic radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS + ). Both copper complexes containing selenium (2a) and sulfur (2b) presented in vitro antioxidant activity. The (1a - 1b and 2a - 2b) compounds did not show cytotoxicity in V79 cells at low concentrations. Furthermore, the antiproliferative activity of free ligands (1a - 1b) and their complexes (2a - 2b) were tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and HepG2 (hepatocarcinoma). Also, 2a was tested against U2OS (osteosarcoma). Our results demonstrated that 1a and 1b show little or no growth inhibition activities on human cell lines.The 2a compound exhibited good cytotoxic activity toward human tumor cell lines. However, 2a showed no selectivity, with a selectivity index of 1.12-1.40. Complex 2b was selective for the MCF-7 human tumor cell lines with IC 50 of 59 ± 2 μM. This study demonstrates that the Cu(II) complexes 2a and 2b represent promising antitumoral compounds, and further studies are necessary to understand the molecular mechanisms of these effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We report a strategy for the direct synthesis of 3-organylselanylthiochromones and 3-organylselanylchromones via the radical cyclization reaction between alkynyl aryl ketones containing an ortho -thiopropyl/methoxy group and diorganyl diselenides promoted by Oxone®. This method allows the construction and seleno -functionalization of thiochromones and chromones using Oxone® as a stable and non-hazardous oxidizing agent in the presence of CH 3 CN at 82 °C. These reactions tolerate a variety of substituents, and allowed the synthesis of twenty-one new 3-organylselanylthiochromones and selanylchromones in good to excellent yields (55-95%). Additionally, the developed method proved to be suitable for scale up (3.0 mmol, 80%), and the synthetic usefulness of the prepared compounds was demonstrated in the oxidation of 2-phenyl-3-(phenylselanyl)-4 H -thiochromen-4-one.

Essential oils (EO) are plant extracts widely used for various pharmacological applications and their antioxidant and anti-inflammatory effects have received a lot of attention because they hold the potential to reduce oxidative stress, and neuroinflammation, alterations involved in the pathophysiology of major depressive disorder. This study examined the benefits of administration of flower EO of the Tagetes minuta (10 and 50 mg/kg, intragastric route) in attenuating behavioral, neurochemical, and neuroendocrine changes in animal models of depressive-like behavior induced by acute restraint stress and lipopolysaccharide (0.83 mg/kg, intraperitoneally). We demonstrated that the treatment of mice with flower EO of the T. minuta reversed the depressive-like behavior induced by stress or inflammatory challenge in mice. This effect is most likely due to the reversal of oxidative stress in the hippocampus of mice, the decrease in plasma corticosterone levels, and restoration of the mRNA levels of brain-derived neurotrophic factor, phosphatidylinositol-3-kinase, protein kinase B, and extracellular signal-regulated kinase 2. As an outcome, flower EO of the T. minuta has promising antidepressant properties and could be considered for new therapeutic strategies for major depressive disorder., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.

Oxone is a commercially available oxidant, composed of a mixture of three inorganic species, being the potassium peroxymonosulfate (KHSO 5 ) the reactive one. Over the past few decades, this cheap and environmentally friendly oxidant has become a powerful tool in organic synthesis, being extensively employed to mediate the construction of a plethora of important compounds. This review summarizes the recent advances in the Oxone-mediated synthesis of N-, O- and chalcogen-containing heterocyclic compounds, through a wide diversity of reactions, starting from several kinds of substrate, highlighting the main synthetic differences, advantages, the scope and limitations.

The derivatization of chitosan (CS) is widely exploited to endow this polysaccharide with enhanced physicochemical and biological properties. Beyond the synthetic route, the nature of the compounds used to functionalize the CS-derivatives exerts a pivotal role in their final properties. Making use of a simple "click" reaction, we synthesized for the first time an organoselenium-CS derivative through a 1,2,3-triazole formation. The product (CS-TSe) was characterized in detail by FTIR, NMR ( 1 H, 13 C, and 77 Se) and UV-Vis techniques, and SEM microscopy. The antioxidant activity of CS-TSe was examined by ABTS + and DPPH (free radical-scavenging) assays. Experimentally, it was demonstrated that CS-TSe has superior antioxidant activity compared with raw CS and "free" organoselenium compound, suggesting a benign and synergistic effect due to the derivatization. In short, the antioxidant property of CS-TSe combined with the other attractive properties of CS and selenium could be useful in the formulation of advanced materials for biomedical and packaging applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A new method was developed for the synthesis of 4-chalcogenyl-1 H -isochromen-1-ones through the 6- endo - dig electrophilic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides under ultrasound irradiation. The reactions were performed under mild conditions, using Oxone as a green oxidant to promote the cleavage of the chalcogen-chalcogen bond in diorganyl diselenides and ditellurides to generate electrophilic species in situ . A total of 25 compounds were selectively obtained after 30-70 min, in good to excellent yields (74-95%). This procedure was extended to prepare 5 H -selenopheno[3,2- c ]isochromen-5-ones. Additionally, for the first time, the 4-chalcogenyl-1 H -isochromen-1-ones were used as substrates in the thionation reaction, using Lawesson's reagent and microwave irradiation under solvent-free conditions, obtaining the thio derivatives in yields of up to 99% in only 15 min.

We describe herein an alternative and transition-metal-free procedure for the access of benzo[b]chalcogenophenes fused to selenophenes via intramolecular cyclization of 1,3-diynes. This efficient protocol involves a double cyclization of 1,3-diynyl chalcogen derivatives promoted by the electrophilic species of organoselenium generated in situ by the oxidative cleavage of the Se-Se bond of dibutyl diselenide using Oxone® in acetonitrile as solvent in an open-flask at 80 °C. In this study, 15 selenophenes with broad substrate scope were prepared in moderate to excellent yields (55-98%) with short reaction times (0.5-3.0 h).

The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bearing in mind that pain and major depressive disorder (MDD) often share biological pathways, this condition is classified as depression-pain syndrome. Mounting evidence suggests that oxidative stress is implicated in the pathophysiology of this syndrome. The development of effective pharmacological interventions for the depression-pain syndrome is of particular importance as clinical treatments for this comorbidity have shown limited efficacy. Therefore, the present study aimed to evaluate whether the 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) was able to reverse the depression-pain syndrome induced by intracerebroventricular (i.c.v) streptozotocin (STZ) in mice and the possible modulation of oxidative and nitrergic pathways in its effect. The treatment with SePy (1 and 10 mg/kg) administered intragastrically (i.g.) reversed the increased immobility time in the tail suspension test, decreased grooming time in the splash test, latency time to nociceptive response in the hot plate test, and the response frequency of Von Frey hair (VFH) stimulation induced by STZ (0.2 mg/4 μl/per mouse). Additionally, SePy (10 mg/kg, i.g.) reversed STZ-induced alterations in the levels of reactive oxygen species, nitric oxide, and lipid peroxidation and the superoxide dismutase and catalase activities in the prefrontal cortices (PFC) and hippocampi (HC) of mice. Treatment with SePy (10 mg/kg, i.g.) also reversed the STZ-induced increased expression of inducible nitric oxide synthase (iNOS) and glycogen synthase kinase 3 beta (GSK3β) in the PFC and HC. An additional molecular docking investigation found that SePy binds to the active site of iNOS and GSK3β. Altogether, these results indicate that the antidepressant-like effect of SePy is accompanied by decreased hyperalgesia and mechanical allodynia, which were associated with its antioxidant effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1 H -pyrazol ( 1a ), 3,5-dimethyl-4-(phenylselanyl)-1 H -pyrazole ( 2a ), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 3a ), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 4a ), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1 H -pyrazole ( 1b ), 3,5-dimethyl-4-(phenylthio)-1 H -pyrazole ( 2b ), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 3b ), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 4b ), and 3,5-dimethyl-1-phenyl-1 H -pyrazole ( 1c ). In vitro, 4-(arylcalcogenyl)-1 H -pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a , 1b , and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a , 1b , and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a , 1b , and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.

We described here our results on the use of thiourea as a ligand in the copper catalysed azide-alkyne cycloaddition (CuAAC) of 2-azidobenzaldehyde with alkynes. Reactions were performed reacting 2-azidobenzaldehyde with a range of terminal alkynes using 10 mol % of copper iodide as a catalyst, 20 mol % of thiourea as a ligand, triethylamine as base, DMSO as solvent at 100 °C under nitrogen atmosphere. The corresponding 2-(1H-1,2,3-triazoyl)-benzaldehydes (2-TBH) were obtained in moderated to excellent yields and according our experiments, the use of thiourea decreases the formation of side products. The obtained compounds were screened for their binding affinity with multiple therapeutic targets of AD by molecular docking: β-secretase (BACE), glycogen synthase kinase (GSK-3β) and acetylcholinesterase (AChE). The three compounds with highest affinity, 5 a (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde), 5 b (2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzaldehyde), and 5 d (2-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzaldehyde) were selected and evaluated on its antioxidant effect, in view of select the most promising one to perform the in vivo validation. Due the antioxidant potential ally to the affinity with BACE, GSK-3β and AChE, compound 5 b was evaluated in a mouse model of AD induced by intracerebroventricular injection of streptozotocin (STZ). Our results indicate that 5 b (1 mg/kg) treatment during 20 days is able to reverse the cognitive and memory impairment induced by STZ trough the modulation of AChE activity, amyloid cascade and GSK-3β expression., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/objectives: 4-(Arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur (0.001-50 mg/kg) were investigated regarding the intragastric route effect (ig) administration on nociception in mice. In this study, nociception and inflammation were induced by chemical agents such as formalin (0.92%), sodium L-glutamate 1-hydrate (20 μmol), croton oil (2.5%), acetic acid (1.6%) and thermic model with a hot plate test., Results: Compounds 1a-c had the ability to reduce licking time in both phases (neurogenic and inflammatory) of the formalin test and glutamate. Only compounds 1a and 1b had the ability to reduce the number of abdominal writhes caused by acetic acid. The same was observed with the positive control celecoxib. To evaluate the possible anti-inflammatory activity of compounds 1a-c, the induction of paw edema by formalin and ear edema by croton oil was performed. For the inflammation induced by formalin, significant effects were observed from the dose of 0.1 mg/kg (1a-b) and 10 mg/kg (1c). In the ear edema test, it can be observed that only compound 1a had a significant effect. In the hotplate test, all the compounds had the ability to reduce the latency time., Conclusion: The results demonstrated that acute antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles 1a is better than compared with the compound 1b and 1c in mice. This resulted in these molecules attracting the interest of researchers to perform future studies to develop new drugs to treat pain and inflammatory clinical conditions.

A significant number of important acyl-transfer reactions, such as direct acylation, ortho acylation, heteroatom acylation, and a diversity of cyclization reactions using the title compound as a key starting material, have been described in recent years. Just like a sleeping beauty, α-oxocarboxylic acids were awakened from a 17-year sleep to become important reagents in classical and new acylation reactions. The greener characteristic of the coproduct formed in reactions using α-keto acid (only CO 2 ), together with its versatility as a building block in catalytic organic synthesis, accredit it as a candidate to green acylating agent, an alternative to acyl chloride, and other acyl-transfer reagents. This review presents the impressive breakthroughs achieved mainly in the past decade in the development of new catalytic reactions for the formation of C-C, C-N, and C-S bonds using α-keto acids.

Here, we report the general strategies by which NMR spectroscopy can be used to determine the enantiopurity and absolute configuration of chalcogen containing secondary alcohols, including the evaluation of the use of chiral solvating and chiral derivatizing agents. The BINOL/DMAP ternary complex demonstrated a simple and fast protocol for determining enantiopurity. The drug Naproxen afforded a stable, nonhygroscopic, and readily available chiral derivatizing agent (CDA) for NMR chiral discrimination of chalcogen containing secondary alcohols. The chiral recognition by CDA and chiral solvating agent (CSA) was assessed using 1 H, 77 Se-{1H}, and 125 Te-{1H} NMR spectroscopy. A simple model for the assignment of the absolute configuration from NMR data is presented., (© 2018 Wiley Periodicals, Inc.)

A one-pot iodine-catalyzed multicomponent reaction has been developed for the selective preparation of 5-amino-4-(arylselanyl)-1 H -pyrazoles from a diverse array of benzoylacetonitriles, arylhydrazines and diaryl diselenides. The reactions were conducted in MeCN as solvent at reflux temperature under air. The methodology presents a large functional group tolerance to electron-deficient, electron-rich, and bulky substituents and gave the expected products in good to excellent yields. The synthesized 1,3-diphenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis.

A green methodology to synthesize 2-organoselanyl-naphthalenes based on the reaction of alkynols with diaryl diselenides is described. The electrophilic species of selenium were generated in situ, by the oxidative cleavage of the Se-Se bond of diaryl diselenides by Oxone ® using water as the solvent. The reactions proceeded efficiently under ultrasonic irradiation as an alternative energy source, using a range of alkynols and diorganyl diselenides as starting materials. Through this methodology, the corresponding 2-organoselanyl-naphthalenes were obtained in moderate to good yields (56-94%) and in short reaction times (0.25-2.3 h)., Competing Interests: Eder J Lenardao is an Academic Editor for PeerJ.

Background: The main constituents of Cymbopogonnardus (L) Rendle and C. citratus (DC) Stapfessential oils are ( R )-citronellal and citral, respectively. Organochalcogen compounds can boost the biological activities of natural products. Methods: Several chalcogen-containing nitrones derived from ( R )-citronellal and citral were prepared and evaluated for their antimicrobial and antioxidant activities. The antimicrobial activity was evaluated by the disc diffusion test and the antioxidant properties were evaluated in vitro by DPPH (1,1-diphenyl-2-picryl-hydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and FRAP (ferric ion reducing antioxidant power) assays. Results: In the antimicrobial assay, ( E )- N ,3,7-trimethyl-3-(phenylthio)oct-6-en-1-imine oxide 5c exhibited halos between 21.5 mm ( Escherichia coli O157:H7) and 26.0 mm ( Listeria monocytogenes ), while ( E )- N ,3,7-trimethyloct-6-en-1-imine oxide 5d presented halos between 22.5 mm ( E. coli O157:H7) and 31.0 mm ( L. monocytogenes ). ( E )- N ,3,7-Trimethyl-2-(phenylthio)oct-6-en-1-imine oxide 5a showed the lowest minimal inhibitory concentration (MIC) value against Bacillus cereus (0.48 mM), and 5c was the most potent bactericide, with a minimal bactericidal concentration (MBC) of 0.52 mM for E. coli O157:H7. In the antioxidant assays, 5c , 5d , and 10 (( E )-3,7-dimethyl-2-(phenylselanyl)oct-6-enal oxime) were the most actives in the DPPH, ABTS, and FRAP assays, respectively. Conclusions: The presence of a phenylthio group in the nitrone increases its antimicrobial activity against Gram-positive and Gram-negative foodborne pathogens in the disk diffusion test and the antioxidant activity in vitro.

The use of sonochemistry is described in the organocatalytic enamine-azide [3 + 2] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These sonochemically promoted reactions were found to be amenable to a range of 1,3-diketones or aryl azidophenyl selenides, providing an efficient access to new ((arylselanyl)phenyl-1 H -1,2,3-triazol-4-yl)ketones in good to excellent yields and short reaction times. In addition, this protocol was extended to β-keto esters, β-keto amides and α-cyano ketones. Selanyltriazoyl carboxylates, carboxamides and carbonitriles were synthesized in high yields at short times of reaction under very mild reaction conditions.

A simple and efficient protocol to prepare divinyl selenides has been developed by the regio- and stereoselective addition of sodium selenide species to aryl alkynes. The nucleophilic species was generates in situ , from the reaction of elemental selenium with NaBH₄, utilizing PEG-400 as the solvent. Several divinyl selenides were obtained in moderate to excellent yields with selectivity for the ( Z , Z )-isomer by a one-step procedure that was carried out at 60 °C in short reaction times. The methodology was extended to tellurium, giving the desired divinyl tellurides in good yields. Furthermore, the Fe-catalyzed cross-coupling reaction of bis(3,5-dimethoxystyryl) selenide 3f with (4-methoxyphenyl)magnesium bromide 5 afforded resveratrol trimethyl ether 6 in 57% yield.

We described herein the use of sonochemistry in the organocatalytic enamine-azide [3+2] cycloadditions of β-oxo-amides with a range of substituted aryl azides. These sonochemical promoted reactions were found to be amenable to a range of β-oxo amides or aryl azides, providing an efficient access to new N-aryl-1,2,3-triazoyl carboxamides in good to excellent yields and short times of reaction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Even if water is the natural environment for bioorganic reactions, its use in organic chemistry is often severely limited by the high insolubility of the organic derivatives. In this review, we introduce some examples of the use of water to perform organoselenium chemistry. We mainly discuss the advantages of this medium when the recyclability is demonstrated and when the water can control the selectivity of a reaction or enhance the reaction rate.

Ultrasonic (US) irradiation was successfully used as an alternative energy source to prepare 3-selanylindoles through the direct selanylation of indoles with diorganyl diselenides using CuI (20 mol%) as catalyst and DMSO as the solvent. By using this US-promoted reaction, eleven 3-organylselanylindoles were prepared selectively and in good yields. A comparative study between the reactions under conventional heating, microwave and ultrasound irradiations was performed, and it was observed advantage in using US over the other heating systems., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The present study aimed to evaluate the in vitro antimicrobial action of Origanum vulgare, Origanum majorana, Mentha piperita and Rosmarinus officinalis on Pythium insidiosum oomycete zoospores. The antimicrobial activity evaluation was performed by the broth microdilution method according to CSLI M38-A2 documentation adapted to phytopharmaceuticals. Twenty-two P. insidiosum isolates were evaluated, and the minimum inhibitory concentration was determined at 100% growth inhibition. All P. insidiosum isolates evaluated showed a minimum inhibitory concentration ranging from 0.05 to 1.75 mg/mL when O. vulgare oil was used and from 0.11 to 3.5 mg/mL for O. majorana, M. piperita and R. officinalis oils. The results obtained indicate that the essential oils tested showed antimicrobial activity on P. insidiosum, with O. vulgare essential oil showing the best performance. These findings emphasize the potential use of plant essential oils as control agents in P. insidiosum infections; further research, however, is needed so as the in vivo activity of these oils can also be evaluated.

Context: Psidium cattleianum Sabine (Myrtacea) is rich in vitamin C and phenolic compounds, including epicatechin and gallic acid as the main components., Objective: To evaluate the antifungal and antioxidant capacity in vitro of the essential oil of araçá (EOA). The acute toxicity of the EOA also was evaluated in mice., Materials and Methods: The leaves of the P. cattleianum were extracted by steam distillation. The antioxidant capacity was evaluated by in vitro tests [1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP), linoleic acid oxidation, thiobarbituric acid reactive species (TBARS)], and ex vivo analysis [TBARS, δ-aminulevunilate dehydratase (δ-Ala-D) and catalase activity, non-protein thiols (NPSH), and ascorbic acid levels]. The toxicity was studied in mice by a single oral administration of EOA; and the antifungal activity was performed with five strains of fungi., Results: The EOA exhibited antioxidant activity in the FRAP assay and reduced lipid peroxidation in the cortex (Imax = 32.90 ± 2.62%), hippocampus (IC50 = 48.00 ± 3.00 µg/ml and Imax = 32.90 ± 2.62%), and cerebellum (Imax = 45.40 ± 14.04%) of mice. Acute administration of the EOA by the oral route did not cause toxicological effects in mice (LD50 > 500 µg/ml). The EOA also showed antifungal activity through of the determination minimum inhibitory concentration (MIC) values ranging from 41.67 ± 18.04 to 166.70 ± 72.17 µg/ml for tested strains., Conclusion: The results of present study indicate that EOA possess antioxidant properties, antifungal and not cause toxicity at tested doses.

The present study aimed to evaluate the acaricidal action of the chemically modified essential oil of Cymbopogon spp. and Corymbia citriodora on Rhipicephalus (Boophilus) microplus. Citronellal was converted into N-butylcitronellylamine and in N-prop-2-inylcitronellylamine, analogs of juvenoids, by reductive amination using butylamine (N1 to N3) and propargylamine (N4 to N7). In vitro assays included the adult immersion, and larval packet tests. Engorged females were weighed in groups of 10 and tested in three replicates for six concentrations. They were immersed in the modified oils or control solution and incubated. In the larval packet test, the same substances and concentrations were evaluated in three replicates. In the in vivo test, six pastured heifers naturally infested with R. (B.) microplus were used per treatment: negative control, positive control (amitraz, Triatox(®)), original oil of C. citriodora at 1.5%, and modified oil containing 0.9% N-prop-2-inylcitronellylamine (N7). Ticks were counted in the right side of the body in 24 animals from day D-3 to D21. LC50 and LC90 were obtained by Probit analysis, while the in vivo results were log transformed and compared using the Tukey test. Among the nitrocellylamines tested in vitro, N6 was most effective on the engorged females (100% efficacy at 50mg/mL) and N7 on the larvae (100% efficacy at 6.25mg/mL). In the test with larvae, the original oil of C. citriodora was less effective than the counterpart modified oil (N7), proving that the chemical modification optimized its effect. In the in vivo test, no significant difference was observed between N7 and the negative control. The average numbers of ticks on the animals' right side were 32.8, 8.1, 37.9 and 35.4 for the negative control, positive control, original oil and N7, respectively. The chemical modification improved the efficacy in vitro, but it was not observed in vivo, perhaps due to the low stability of the amines under field conditions. The evaluation carried out here has not been previously studied, so this concept expands the horizon for research into chemically modified substances for parasite control and shed light on the challenges to find effective formulations and application methods., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The ionic liquid 1-butyl-3-methylimidazolium methylselenite, [bmim][SeO2(OCH3)], was successfully used as solvent in the catalyst-free preparation of 3-arylselenylindoles by the reaction of indole with ArSeCl at room temperature. The products were obtained selectively in good yields without the need of any additive and the solvent was easily reused for several cycles with good results.

Essential oil (EO) of the leaves of Eugenia uniflora L. (Brazilian cherry tree) was evaluated for its antioxidant, antibacterial and antifungal properties. The acute toxicity of the EO administered by oral route was also evaluated in mice. The EO exhibited antioxidant activity in the DPPH, ABTS and FRAP assays and reduced lipid peroxidation in the kidney of mice. The EO also showed antimicrobial activity against two important pathogenic bacteria, Staphylococcus aureus and Listeria monocytogenes, and against two fungi of the Candida species, C. lipolytica and C. guilliermondii. Acute administration of the EO by the oral route did not cause lethality or toxicological effects in mice. These findings suggest that the EO of the leaves of E. uniflora may have the potential for use in the pharmaceutical industry., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this study, the antioxidant and antidepressant-like effects of α-(phenylselanyl) acetophenone (PSAP), an organoselenium compound, were investigated. To assess the in vitro antioxidant properties, PSAP was evaluated in four test systems (DPPH, ABTS, FRAP and inhibition of lipid peroxidation). PSAP (100-500 μM) showed potent antioxidant activity and protected against lipid peroxidation. Additionally, we investigated whether PSAP, when administered in mice (100, 200 and 400mg/kg, per oral, p.o.), could cause acute toxicity. Our results demonstrated that PSAP did not cause the death of any animal, significantly reduce body weight or cause any oxidative tissue stress following treatment. This study also evaluated the effect of PSAP (0.1-10 mg/kg, p.o) on mice in a forced swim test (FST) and tail suspension test (TST), assays that are predictive of depressant activity and motor activity in the open-field. PSAP (5-10 mg/kg) significantly reduced immobility time in the FST and TST without affecting motor activity. In addition, the antidepressant-like effect caused by PSAP (5m/kg, p.o) in mice during the TST was dependent on an interaction with the serotonergic system (5-HT(1A) receptors), but not with the noradrenergic, dopaminergic or adenosinergic system. Together, these results suggest that PSAP possesses antioxidant and antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Space and motion discomfort (SMD) refers to various symptoms that occur in environments with unreliable visual and kinesthetic information that do not permit adequate spatial orientation. Some studies have demonstrated that there is a stable and predictable relationship between vestibular dysfunction and anxiety disorders. Further, vestibular dysfunction can predispose or trigger the development of panic disorder with or without agoraphobia (PD/A) or reinforce phobic avoidance. It therefore seems clinically useful to develop and validate instruments for evaluating SMD in various populations. Measuring SMD could facilitate identification of individuals with PD/A who present comorbid vestibular dysfunction. Jacob et al. developed and validated such a questionnaire: the Situational characteristics questionnaire (SitQ). This questionnaire evaluates the presence of symptoms such as dizziness, vertigo, and instability under specific conditions. The SitQ comprises two subscales that measure SMD and one subscale (agoraphobia) that measures agoraphobic avoidance behaviours. The instrument has two sections. The first section is composed of the SMD-I and agoraphobia subscales, containing 19 and seven items, respectively. Each item consists of two contrasting descriptors of a specific situation or environment. The respondent is required to indicate to what extent the two described situations or environments cause discomfort. Each item includes a "criterion" descriptor for the situation (i.e., a descriptor that is presumed to engender SMD) and an alternative (non-criterion) descriptor. The second section comprises the SMD-II scale; this scale is composed of nine criterion situations, for which non-criterion situations are not supplied. The instrument takes approximately 20 minutes to complete., Objective: The present study focuses on the validation of the French-language version of the SitQ: the questionnaire des caractéristiques situationnelles (QCS)., Method: The sample was composed of French Canadians recruited across Quebec from an anxiety disorders treatment clinic, general psychiatric care clinics, a community organization for individuals with anxiety disorders, advertisements in local newspapers, and ads posted in various public locations. The sample included 141 participants who met the criteria for lifetime PD/A. Participants reported current PD/A (n=73) or PD/A in remission (n=68). The control sample was recruited from undergraduate courses in various disciplines. Two hundred and thirty-five (n=235) students completed the questionnaires. Data from 63 (26.8%) participants were excluded from the analyses due to failure to complete all of the research questionnaires., Results: Analysis of the global descriptive data and the descriptive data for each dependent variable revealed that the data were independent of sociodemographic variables and respected the assumptions of normal distribution (skewness and kurtosis). Parametric tests were subsequently conducted. Using the combined data from the control and clinical groups, the internal consistency of the scales was analyzed using Cronbach's alpha. The SMD-I and SMD-II scales demonstrated good homogeneity. The results were comparable or superior to those obtained with the English-language version of the questionnaire. The agoraphobia scale demonstrated weaker internal consistency and corresponding weaker homogeneity. This result was consistent with that of the original version of the agoraphobia scale; this scale was eliminated for the subsequent analyses. Construct validity was analyzed via t-tests comparing clinical and control groups. Effect sizes were estimated using percentage of variance explained. The SMD-I scale demonstrated weak construct validity and was also eliminated from subsequent analyses. The SMD-II scale demonstrated good construct validity and provided an adequate measure of the theoretical construct of SMD. This scale permitted discrimination of participants according to the presence or absence of PD/A. It is therefore possible to identify participants with PD/A by their level of SMD. This result is comparable to that of Jacob et al., Conclusion: The results of the present study are generally consistent with the results of the validation of the original version of the questionnaire. However, the SMD-I and agoraphobia scales in the French-language version of the measure did not achieve a level of significance sufficient to definitively establish validity., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

The comorbidity among balance disorders, anxiety disorders and migraine has been studied extensively from clinical and basic research perspectives. From a neurological perspective, the comorbid symptoms are viewed as the product of sensorimotor, interoceptive and cognitive adaptations that are produced by afferent interoceptive information processing, a vestibulo-parabrachial nucleus network, a cerebral cortical network (including the insula, orbitofrontal cortex, prefrontal cortex and anterior cingulate cortex), a raphe nuclear-vestibular network, a coeruleo-vestibular network and a raphe-locus coeruleus loop. As these pathways overlap extensively with pathways implicated in the generation, perception and regulation of emotions and affective states, the comorbid disorders and effective treatment modalities can be viewed within the contexts of neurological and psychopharmacological sites of action of current therapies.

Objective: Previous research suggested that panic disorder with agoraphobia is associated with abnormalities on vestibular and balance function tests. The purpose of this study was to further examine psychiatric correlates of vestibular/balance dysfunction in patients with anxiety disorders and the specific nature of the correlated vestibular abnormalities. The psychiatric variables considered included anxiety disorder versus normal control status, panic disorder versus non-panic anxiety disorder diagnosis, presence or absence of comorbid fear of heights, and degree of space and motion discomfort (SMD). The role of anxiety responses to vestibular testing was also re-examined., Methods: 104 subjects were recruited: 29 psychiatrically normal individuals and 75 psychiatric patients with anxiety disorders. Anxiety patients were assigned to four subgroups depending on whether or not they had panic disorder and comorbid fear of heights. SMD and anxiety responses were measured by questionnaires. Subjects were examined for abnormal unilateral vestibular hypofunction on caloric testing indicative of peripheral vestibular dysfunction, asymmetric responses on rotational testing as an indicator of an ongoing vestibular imbalance and balance function using Equitest dynamic posturography as an indicator of balance control. Logistic regression was used to establish the association between the psychiatric variables and vestibular or balance test abnormalities., Results: Rotational test results were not significantly related to any of the psychiatric variables. The presence of either panic attacks or fear of heights increased the probability of having caloric hypofunction in a non-additive fashion. SMD and anxiety responses were independently associated with abnormal balance. Among specific posturography conditions, the association with SMD was significant for a condition that involved the balance platform tilting codirectionally with body sway, suggesting an abnormal dependence on somatosensory cues in the control of balance., Conclusion: In patients with anxiety disorders, higher SMD is indicative of somatosensory dependence in the control of balance. The absence of both panic and fear of heights reduces the probability of having peripheral vestibular dysfunction. Future research should examine if vestibular rehabilitation can be of value for patients with anxiety disorders complicated by SMD.

Despite the advances in pharmacotherapy for heart failure due to reduced left ventricular function, mortality still remains high and many patients are hospitalized over time due to worsening heart failure symptoms. There is some experimental evidence that vasoconstriction and nitric oxide (NO) deficiency in the vasculature play a role in aggravating the symptoms of heart failure, especially in patients of African-American origin. Treatment with high doses of isosorbide dinitrate (ISDN) has been shown to increase symptom-free walking time, but tolerance to the hemodynamic effects of ISDN develops rapidly. Experimental data suggests that hydralazine, given concomitantly, attenuates the development of hemodynamic tolerance to ISDN and may increase bioavailability of NO in the vasculature. In a racially mixed population, treatment with a combination of ISDN and hydralazine reduced mortality compared to placebo to a nearly statistically significant extent in the first Vasodilator Heart Failure Trial (V-HeFT I) but was inferior to treatment with angiotensin-converting enzyme (ACE) inhibitor enalapril in the V-HeFT II study. Subgroup retrospective analysis of published data, however, suggested that ISDN/hydralazine had a substantial effect in black patients and was apparently as effective as treatment with the ACE inhibitor, enalapril, in the same population, but had a much smaller, if any, effect in white patients. A recent placebocontrolled study showed that in self-identified black patients with heart failure, ISDN/hydralazine, given in addition to current state-of-the-art pharmacotherapy for heart failure, reduces mortality and first hospitalizations due to heart failure and improves quality of life. The usefulness of ISDN/hydralazine in ethnic groups other than self-identified blacks is unknown at present and is considered off-label use. This review focuses on ISDN/hydralazine for the management of patients with heart failure due to left ventricular dysfunction and the adverse effects which may be encountered with therapy., (Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.)

Postural sensitivity to moving visual environments in patients with anxiety disorders was studied. We hypothesized that patients with anxiety disorders would have greater sway in response to a moving visual environment compared to healthy adults, especially if they have space and motion discomfort (SMD). Twenty-one patients with generalized anxiety without panic (NPA) and 38 patients with panic and agoraphobia (PAG) were compared to 22 healthy controls. SMD was evaluated in all subjects via questionnaire. Subjects stood on a force platform that was either fixed or rotating with the subject (i.e., sway referenced) during exposure to a sinusoidally moving visual surround. Center of pressure (COP) data were computed from force transducers in the platform as a measure of sway. Results showed that patients swayed significantly more in response to the moving visual scene compared to control subjects, with no differences between the NPA and PAG groups. SMD was a predictor of sway response in the patients: patients with high SMD swayed significantly more than both Controls and anxiety patients with low SMD. These results indicate that patients with anxiety disorders, particularly those with SMD, are more visually dependent for balance. This subgroup of patients may be amenable to treatment used for patients with balance disorders (i.e., vestibular rehabilitation) that focuses on sensory re-integration processes that address visual sensitivity.

Previous studies of vestibulo-ocular function in patients with anxiety disorders have suggested a higher prevalence of peripheral vestibular dysfunction compared to control populations, especially in panic disorder with agoraphobia. Also, our recent companion studies have indicated abnormalities in postural control in patients with anxiety disorders who report a high degree of space and motion discomfort. The aim of the present study was to assess the VOR, including the semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular canal-otolith interaction, in a well-defined group of patients with anxiety disorders. The study included 72 patients with anxiety disorders (age 30.6 +/- 10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus; 11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic anxiety. Patients were further categorized based on the presence (45 of 72) or absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of 72) of excessive space and motion discomfort (SMD). Sinusoidal and constant velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used to assess both the otolith-ocular reflex and static semicircular canal-otolith interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal-otolith interaction. The eye movement response to rotation was measured using bitemporal electro-oculography. Results showed a significantly higher VOR gain and a significantly shorter VOR time constant in anxiety patients. The effect of anxiety on VOR gain was significantly greater in patients without SMD as compared to those with SMD. Anxiety patients without height phobia had a larger OVAR modulation. We postulate that in patients with anxiety, there is increased vestibular sensitivity and impaired velocity storage. Excessive SMD and height phobia seem to have a mitigating effect on abnormal vestibular sensitivity, possibly via a down-weighting of central vestibular pathways.

Background and Purpose: Acrophobia (fear of heights) may be related to a high degree of height vertigo caused by visual dependence in the maintenance of standing balance. The purpose of this case report is to describe the use of vestibular physical therapy intervention following behavioral therapy to reduce a patient's visual dependence and height vertigo., Case Description: Mr N was a 37-year-old man with agoraphobia (fear of open spaces) that included symptoms of height phobia. Exposure to heights triggered symptoms of dizziness. Intervention. Mr N underwent 8 sessions of behavioral therapy that involved exposure to heights using a head-mounted virtual reality device. Subsequently, he underwent 8 weeks of physical therapy for an individualized vestibular physical therapy exercise program., Outcomes: After behavioral therapy, the patient demonstrated improvements on the behavioral avoidance test and the Illness Intrusiveness Rating Scale, but dizziness and body sway responses to moving visual scenes did not decrease. After physical therapy, his dizziness and sway responses decreased and his balance confidence increased., Discussion: Symptoms of acrophobia and sway responses to full-field visual motion appeared to respond to vestibular physical therapy administered after completion of a course of behavioral therapy. Vestibular physical therapy may have a role in the management of height phobia related to excessive height vertigo.

Background: Migraine and vestibular symptoms are co-morbid. Migraine is increasingly recognized as a cause of benign, recurrent vertigo. Although the International Headache Society does not currently include the diagnosis of migrainous vertigo, specific criteria have been proposed and utilized in clinical trials., Material/methods: Seventeen adult migraineurs were separately screened for the diagnosis of migrainous vertigo using a standardized structured interview for migrainous vertigo (SIM-V) and a clinical evaluation by an experienced neurotologist. The SIM-V was administered by a nurse who read and recorded subject responses, obtaining no additional information for the diagnosis of migrainous vertigo. Comparison of diagnoses between clinician and SIM-V was made using Cohen's kappa reliability testing. Subjects were asked to return for a second interview by the same nurse using the SIM-V, at least 2 weeks after the initial assessment. Testing stability was evaluated by comparing diagnoses obtained with each SIM-V administration., Results: Cohen's kappa demonstrated excellent test validity (kappa=0.75). Fourteen subjects returned for repeat testing, with excellent retest stability (kappa=0.85). The additional three subjects could not be relocated or were not interested in attending a retest appointment., Conclusions: The SIM-V is an easy-to-administer screening tool for the diagnosis of migrainous vertigo. Diagnostic comparison to a standard clinical assessment shows good test validity. Retest stability was also demonstrated. The SIM-V may be a useful screening tool for migraineurs with an additional complaint of dizziness.

Background: Individuals who fail to show a decline in blood pressure (BP) when asleep or at night (labeled nocturnal nondippers) are at elevated risk for hypertension and associated target-organ damage., Purpose: We tested whether the well-established changes in BP exhibited in response to daily activities are also blunted in nocturnal nondippers., Methods: Cross-sectional study of 41 women and 56 men, aged 27 to 71 years, residing in Benin, Nigeria, enrolled in a health survey of civil servants. Ambulatory 24-hr BP monitoring was performed with concurrent diary recordings of physical activity level, posture, location, state of mental activity, interpersonal interaction, and mood obtained during the waking hours., Results: Nocturnal nondippers exhibited smaller cardiovascular responses to changes in posture (from lying to sitting or to standing, ps <.02), location (from home to work or to driving/riding in a car, ps <.02), mental activity (from relaxed to active, p =.02), and mood (from feeling mellow to feeling elated-happy, p =.05) than did dippers. Statistical controls for posture substantially reduced the effects of nondipping status on responses to other daily activities and mood. Lack of systolic BP responsiveness to postural changes during the day is a strong predictor of nondipping status., Conclusions: Nondipping at night appears to extend to decreased cardiovascular responses to changes in activities during daytime hours.

This study investigated the relation between parental anxiety and family functioning. Parental anxiety and depression, child attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) symptoms were all included as predictors of 3 measures of family functioning to examine the independent contributions of each. Using a self-report battery completed by 45 mother-father pairs, 3 family functioning factors were derived: Parental Warmth and Positive Involvement, Intrusiveness and Negative Discipline, and Social Distress. Multilevel modeling simultaneously estimated the unique contributions of parental and child symptoms on family functioning. Results indicated that parental anxiety was negatively associated with Parental Warmth and Positive Involvement, Intrusiveness and Negative Discipline, and Social Distress; parental depression was only negatively associated with Social Distress. Child ODD symptoms had independent associations with all outcomes; no relations were found with ADHD. Sex moderated the effects of parental anxiety on Parental Warmth and Positive Involvement such that only for mothers did greater anxiety lead to less Parental Warmth and Positive Involvement.

Clinical trials that compare pharmacological and behavioural treatments require extra attention to design on the part of the investigators. Many of the standard control mechanisms for comparison of active drug to placebo and behavioural therapy to control therapy create problems when the two types of interventions are combined. The most important of these problems is the introduction of non-specific effects introduced by behavioural therapists and physicians that can bias the study. Solutions to these problems require procedures that are common to both types of studies and the introduction of more complex statistical designs to adequately control the proposed comparisons. It may also be necessary to have a robust statistical method to address informative censoring since patients assigned to behavioural therapy may drop out of the study for different reasons than patients who drop out of a pharmacological trial. In this paper we use the design of the Raynaud's Treatment Study to demonstrate methods that can be used to control for non-specific effects and differential drop-out from the study., (Copyright 2002 John Wiley & Sons, Ltd.)

The Raynaud's Treatment Study (RTS) compared temperature biofeedback training and a behavioral control procedure (frontalis EMG biofeedback) with nifedipine-XL and a medication placebo for treatment of primary Raynaud's phenomenon (RP) in a large (N = 313) multicenter trial. The present study describes the RTS biofeedback protocols and presents data on the acquisition of digital skin temperature and frontalis EMG responses in the RTS. The findings point to substantial problems with acquisition of physiological self-regulation skills in the RTS. Only 34.6% of the Temperature Biofeedback group (N = 81) and 55.4% of the EMG Biofeedback group (N = 74) successfully learned the desired physiological response. In contrast, 67.4% of a Normal Temperature Biofeedback group (N = 46) learned hand warming. Multivariate analysis found that coping strategies, anxiety, gender, and clinic site predicted acquisition of hand-warming skills whereas variables related to RP disease severity did not. Physiological data showed vasoconstriction in response to the onset of biofeedback and also found that performance in the initial sessions was critical for successful acquisition. These findings indicate that attention to the emotional and cognitive aspects of biofeedback training, and a degree of success in the initial biofeedback sessions, are important for acquisition.

Anxiety and dizziness are co-morbid symptoms in a larger percentage of patients than would be expected from chance alone. Such patients have an increased handicap and poorer prognosis. In this review, we discuss the interface between vestibular disorders and anxiety disorders. The two conditions are functionally related via both somatopsychic and psychosomatic mechanisms, and are linked via overlapping neural circuits that include monoaminergic pathways and the parabrachial nucleus network. An alternative conceptualization to the common notion of 'psychogenic' dizziness is presented. Implications for patient management are discussed.