Development of Parkinsonism following exposure to aripiprazole: two case reports

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction: Aripiprazole is a novel atypical neuroleptic used in the treatment of psychosis. A few recent studies have demonstrated an association between the use of aripiprazole and an exacerbation of Parkinsonism, although this relationship is poorly defined. To our knowledge, this is the first case series describing an onset of Parkinsonism in patients without prior history of Parkinson’s diseas

High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer. The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome (CFS) has not been studied previously.</p> <p>Methods</p> <p>We conducted a double blinded, randomised, clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate (HCL/PR) in comparison to simulated iso-calorific chocolate (cocoa liquor free/low polyphenols(CLF/LP)) on fatigue and residual function in subjects with chronic fatigue syndrome. Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate.</p> <p>Results</p> <p>Ten subjects were enrolled in the study. The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range) Exact Sig. (2-tailed)] [33 (25 - 38) vs. 21.5 (6 - 35) 0.01], but that deteriorated significantly when subjects were given simulated iso-calorific chocolate (CLF/CP) [ 28.5 (17 - 20) vs. 34.5 (13-26) 0.03]. The residual function, as assessed by the London Handicap scale, also improved significantly after the HCL/PR arm [0.49 (0.33 - 0.62) vs. 0.64 (0.44 - 0.83) 0.01] and deteriorated after iso-calorific chocolate [00.44 (0.43 - 0.68) vs. 0.36 (0.33 - 0.62)0.03]. Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm, but deteriorated after CLF/CP. Mean weight remained unchanged throughout the trial.</p> <p>Conclusion</p> <p>This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome.</p

Information seeking, mental health and loneliness: Longitudinal analyses of adults in the UK COVID-19 mental health and wellbeing study

Information seeking has generally been seen as an adaptive response to the COVID-19 pandemic. However, it may also result in negative outcomes on mental health. The present study tests whether reporting COVID-related information seeking throughout the pandemic is associated with subsequently poorer mental health outcomes. A quota-based, non-probability-sampling methodology was used to recruit a nationally representative sample. COVID-related information seeking was assessed at six waves along with symptoms of depression, anxiety, mental wellbeing and loneliness (N = 1945). Hierarchical linear modelling was used to assess the relationship between COVID-related information seeking and mental health outcomes. Information seeking was found to reduce over time. Overall, women, older and higher socioeconomic group individuals reported higher levels of information seeking. At waves 1-4 (March-June 2020) the majority of participants reported that they sought information on Covid 1-5 times per day, this decreased to less than once per day in waves 5 and 6 (July-November 2020). Higher levels of information seeking were associated with poorer mental health outcomes, particularly clinically significant levels of anxiety. Use of a non-probability sampling method may have been a study limitation, nevertheless, reducing or managing information seeking behaviour may be one method to reduce anxiety during pandemics and other public health crises

Measurement invariance of the 4-item entrapment scale short-form (E-SF): a transnational examination across race/ethnicity, sexual orientation, and suicide attempt history among minoritized adults

Feelings of entrapment—posited to arise when attempts to escape from defeating or humiliating circumstances are blocked—may confer increased risk for psychopathology and suicidal thoughts and behaviors (STB), particularly among minoritized individuals who often have more frequent exposure to such experiences. Including entrapment in empirical models may aid research efforts in further exploring its role in minority mental health. The Entrapment Scale Short-Form (E-SF), a brief version of the 16-item Entrapment Scale, is one tool that may be utilized towards this end; however, to do so meaningfully, its psychometric properties and measurement invariance must be evaluated in diverse samples. The current study aimed to examine the factor structure, measurement invariance, and convergent validity of the E-SF across race/ethnicity and sexual orientation in a combined transnational sample of minoritized adults (total N = 1194). Results supported a one-factor model of the E-SF that was invariant across samples, race/ethnicity, sexual orientation, and history of suicide attempt. Further, significant positive correlations observed between theoretically relevant constructs of anxiety, depression, and posttraumatic stress disorder symptoms supported its convergent validity. Implications include disproportionate levels of entrapment experienced by minoritized individuals— particularly by sexual minorities—which likely reflect the discrimination frequently endured by these individuals

Mental health and wellbeing during the COVID-19 pandemic: longitudinal analyses of adults in the UK COVID-19 Mental Health & Wellbeing study

Background The effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting. Aims To investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK. Method A quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness. Results A total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18–29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors. Conclusions The mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning

Chronic fatigue syndrome: identifying zebras amongst the horses

There are currently no investigative tools or physical signs that can confirm or refute the presence of chronic fatigue syndrome (CFS). As a result, clinicians must decide how long to keep looking for alternative explanations for fatigue before settling on a diagnosis of CFS. Too little investigation risks serious or easily treatable causes of fatigue being overlooked, whilst too many increases the risk of iatrogenic harm and reduces the opportunity for early focused treatment. A paper by Jones et al published this month in BMC Medicine may help clinicians in deciding how to undertake such investigations. Their results suggest that if clinicians look for common psychiatric and medical conditions in those complaining of prolonged fatigue, the rate of detection will be higher than previously estimated. The most common co-morbid condition identified was depression, suggesting a simple mental state examination remains the most productive single investigation in any new person presenting with unexplained fatigue. Currently, most diagnostic criteria advice CFS should not be diagnosed when an active medical or psychiatric condition which may explain the fatigue is identified. We discuss a number of recent prospective studies that have provided valuable insights into the aetiology of chronic fatigue and describe a model for understanding chronic fatigue which may be equally relevant regardless of whether or not an apparent medical cause for fatigue can be identified

Antitumor Pentamethylcyclopentadienyl Rhodium Complexes of Maltol and Allomaltol: Synthesis, Solution Speciation and Bioactivity

The reaction of the dimer [RhIII(pentamethylcyclopentadienyl)(m-Cl)Cl]2 ([RhIII(Cp*)(m- Cl)Cl]2) with the hydroxypyrone ligands maltol and allomaltol affords complexes of the general formula [RhIII(Cp*)(L)Cl] under standard and microwave conditions. The organometallic compounds were characterized by standard analytical methods and in the case of the allomaltol derivative in the solid state by single-crystal X-ray diffraction analysis. The complexes showed similar cytotoxicity profiles and were proved to be moderately active against various human cancer cell lines. The stoichiometry and stability of these complexes were determined in aqueous solution by pH-potentiometry, 1H NMR spectroscopy and UVvisible spectrophotometry. Speciation was studied in the presence and in the absence of chloride ions. Hydrolysis of [RhIII(Cp*)(H2O)3]2+ gave dimeric mixed hydroxido species [(RhIII(Cp*))2(m-OH)3]+ and [(RhIII(Cp*))2(m-OH)2Z2] (Z = H2O/Cl‒). Formation of the mononuclear complexes [RhIII(Cp*)(L)Z] of maltol and allomaltol with similar and moderate stability was found. These species predominate at physiological pH and decompose only partially at micromolar concentrations. In addition, hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange resulted in the formation of the mixed-hydroxido species [RhIII(Cp*)(L)(OH)] in the basic pH range. Replacement of the chlorido by an aqua ligand in the complex [RhIII(Cp*)(L)Cl] was monitored and with the help of the equilibrium constants the extent of aquation at various chloride concentrations of the extra- and intracellular milieu can be predicted. Complexation of these RhIII complexes was compared to analogous [RuII(h6-p-cymene)] species and higher conditional stabilities were found in the case of the RhIII compounds at pH 7.4

Investigation into the Presence of and Serological Response to XMRV in CFS Patients

The novel human gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), originally described in prostate cancer, has also been implicated in chronic fatigue syndrome (CFS). When later reports failed to confirm the link to CFS, they were often criticised for not using the conditions described in the original study. Here, we revisit our patient cohort to investigate the XMRV status in those patients by means of the original PCR protocol which linked the virus to CFS. In addition, sera from our CFS patients were assayed for the presence of xenotropic virus envelope protein, as well as a serological response to it. The results further strengthen our contention that there is no evidence for an association of XMRV with CFS, at least in the UK

Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction

The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning