An unexpected diagnosis of disseminated sarcoidosis in a patient investigated for drug-resistant tuberculosis: a case report

Background Sarcoidosis can mimic both pulmonary and extrapulmonary tuberculosis (TB). Past TB infection or exposure can lead to diagnostic overshadowing. We present a case of a patient exposed to drug-resistant TB presenting with a multisystem inflammatory syndrome ultimately diagnosed as disseminated sarcoidosis. Case Report: A 55-year-old Congolese male with type 2 diabetes presented to clinic with a one-month history of cough. There were no fevers, night sweats or weight loss and a chest radiograph showed bilateral miliary changes. Five years previously his daughters had both been treated for isoniazid and ethambutol resistant TB and he had received preventive therapy with rifampicin and isoniazid. Computed tomography scanning showed diffuse bilateral tiny nodules in the lungs, enlarged mediastinal, hilar and abdominal lymph nodes and splenomegaly. He subsequently developed headache and complex partial seizures. Lumbar puncture and magnetic resonance imaging of the brain were normal. Early diagnostics on induced sputum were inconclusive. One sputum sample detected Mycobacterium tuberculosis DNA, but not to a reportable amplification level and this result was deemed invalid on further testing. Endobronchial ultrasound and mediastinal lymph node biopsy showed histology typical of sarcoidosis with poorly defined, non-caseating granulomas and foci of dystrophic calcification. Tissue staining for mycobacteria and fungi were negative. A serum ACE level was markedly elevated at 264 U/L. The patient was diagnosed with a flare of disseminated sarcoidosis and the illness remitted without immunosuppression. Conclusion In patients with a suspected diagnosis of pulmonary or extrapulmonary TB without microbiological confirmation, consider sarcoidosis in the differential diagnosis and consider tissue sampling to support histological differentiation. Molecular tests are increasingly used to diagnose TB and establish TB resistance profiles, but expert knowledge and specialist input regarding the technological pitfalls of molecular tests is essential to guide correct interpretation

Recreational Fishing Impacts in an Offshore and Deep-Water Marine Park: Examining Patterns in Fished Species Using Hybrid Frequentist Model Selection and Bayesian Inference

No-take marine reserves are often located in remote locations far away from human activity, limiting perceived impact on extractive users but also reducing their use for investigating impacts of fishing. This study aimed to establish a benchmark in the distribution of fished species across the Ningaloo Marine Park – Commonwealth (NMP-Commonwealth), and adjacent comparable habitats within the Ningaloo Marine Park - State (NMP-State), in Western Australia to test if there was evidence of an effect of recreational fishing, as no commercial fishing is allowed within either marine park. We also examined whether the remote location of the newly established (2018) No-take Zone (NTZ), in NMP-Commonwealth, limits its use for studying the effects of fishing. Throughout the NMP-Commonwealth and NMP-State, where recreational fishing is permitted, we expected the abundance of recreationally fished fish species to increase with increasing distance to the nearest boat ramp, as a proxy of recreational fishing effort. Conversely, we did not expect the abundance of non-fished species and overall species richness to vary in response to the proxy for human activity. Distance to the nearest boat ramp was found to be a strong predictor of fished species abundance, indicating that the effect of recreational fishing can be detected across the NMP-Commonwealth. The effect of the NTZ on fished species abundance was weakly positive, but this difference across the NTZ is expected to increase over time. Habitat composition predictors were only found to influence species richness and non-fished species abundance. This study suggests a clear footprint of recreational fishing across the NMP-Commonwealth and as a result the new NTZ, despite its remote location, can act as a control in future studies of recreational fishing effects.publishedVersio

Designer Receptors Enhance Memory in a Mouse Model of Down Syndrome

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer\u27s disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. Previous studies have shown that LC-enhancing drugs can slow the progression of AD pathology, including amyloid aggregation, oxidative stress, and inflammation. We have shown that LC degeneration in Ts65Dn mice leads to exaggerated memory loss and neuronal degeneration. We used a DREADD, hM3Dq, administered via adeno-associated virus into the LC under a synthetic promoter, PRSx8, to selectively stimulate LC neurons by exogenous administration of the inert DREADD ligand clozapine-N-oxide. DREADD stimulation of LC-NE enhanced performance in a novel object recognition task and reduced hyperactivity in Ts65Dn mice, without significant behavioral effects in controls. To confirm that the noradrenergic transmitter system was responsible for the enhanced memory function, the NE prodrug l-threo-dihydroxyphenylserine was administered in Ts65Dn and normosomic littermate control mice, and produced similar behavioral results. Thus, NE stimulation may prevent memory loss in Ts65Dn mice, and may hold promise for treatment in individuals with DS and dementia

Extraordinary virtual multidisciplinary team meetings: a novel forum for coordinated care of patients with complex conditions within a secondary care setting

Multidisciplinary team (MDT) meetings are increasingly regarded as best practice for the successful management of chronic disease. However, for patients with undiagnosed illnesses, multiple interacting comorbidities or other complex needs that fall outside the remit of disease-specific MDTs or the scope of expertise of individual clinicians, there is often no suitable forum at which to discuss their care to develop a coordinated plan for management. We developed and piloted a new forum for interspecialty discussion and collaboration, an extraordinary virtual MDT, to enable clinicians to arrange an urgent meeting of all involved parties in response to challenging clinical scenarios. Here, we share our experience of implementing this innovation and suggest how this novel forum for coordinated care could be further developed to improve the integration, timeliness and quality of healthcare delivery for patients with complex needs

Duration of untreated psychosis/illness and brain volume changes in early psychosis

The time period during which patients manifest psychotic or unspecific symptoms prior to treatment (duration of untreated psychosis, DUP, and the duration of untreated illness, DUI) has been found to be moderately associated with poor clinical and social outcome. Equivocal evidence exists of an association between DUP/DUI and structural brain abnormalities, such as reduced hippocampus volume (HV), pituitary volume (PV) and grey matter volume (GMV). Thus, the goal of the present work was to examine if DUP and DUI are associated with abnormalities in HV, PV and GMV. Using a region of interest (ROI) based approach, we present data of 39 patients from the Basel FePsy (Früherkennung von Psychosen, early detection of psychosis) study for which information about DUP, DUI and HV, PV and GMV data could be obtained. Twenty-three of them were first episode psychosis (FEP) and 16 at-risk mental state (ARMS) patients who later made the transition to frank psychosis. In unadjusted analyses, we found a significant positive correlation between DUP and PV in FEP patients. However, when adjusted for covariates, we found no significant correlation between DUP or DUI and HV, PV or GMV anymore. There only was a trend for decreasing GMV with increasing DUI in FEP. Our results do not comprehensively support the hypothesis of a "toxic" effect of the pathogenic mechanism underlying untreated psychosis on brain structure. If there is any effect, it might rather occur very early in the disease process, during which patients experience only unspecific symptoms

Recreational Fishing Impacts in an Offshore and Deep-Water Marine Park: Examining Patterns in Fished Species Using Hybrid Frequentist Model Selection and Bayesian Inference

No-take marine reserves are often located in remote locations far away from human activity, limiting perceived impact on extractive users but also reducing their use for investigating impacts of fishing. This study aimed to establish a benchmark in the distribution of fished species across the Ningaloo Marine Park – Commonwealth (NMP-Commonwealth), and adjacent comparable habitats within the Ningaloo Marine Park - State (NMP-State), in Western Australia to test if there was evidence of an effect of recreational fishing, as no commercial fishing is allowed within either marine park. We also examined whether the remote location of the newly established (2018) No-take Zone (NTZ), in NMP-Commonwealth, limits its use for studying the effects of fishing. Throughout the NMP-Commonwealth and NMP-State, where recreational fishing is permitted, we expected the abundance of recreationally fished fish species to increase with increasing distance to the nearest boat ramp, as a proxy of recreational fishing effort. Conversely, we did not expect the abundance of non-fished species and overall species richness to vary in response to the proxy for human activity. Distance to the nearest boat ramp was found to be a strong predictor of fished species abundance, indicating that the effect of recreational fishing can be detected across the NMP-Commonwealth. The effect of the NTZ on fished species abundance was weakly positive, but this difference across the NTZ is expected to increase over time. Habitat composition predictors were only found to influence species richness and non-fished species abundance. This study suggests a clear footprint of recreational fishing across the NMP-Commonwealth and as a result the new NTZ, despite its remote location, can act as a control in future studies of recreational fishing effects

Cannabis use and brain structural alterations of the cingulate cortex in early psychosis

As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors

Duration of untreated psychosis and cognitive functioning

BACKGROUND: Studies examining the influence of duration of untreated psychosis (DUP) or duration of untreated illness (DUI) on cognition vary with regard to results and methods. This study is the first in this field to include an at risk mental state with later transition to psychosis (ARMS-T) sample and to analyse how the DUI relates to their cognitive functioning. Because methodological operationalization of cognitive functioning in previous studies is highly heterogeneous, we aimed to compare different approaches. METHOD: 60 first episode psychosis (FEP) patients and 24 ARMS-T patients were examined. Associations between DUP, DUI and neurocognitive performance were tested by three different operationalizations of cognition: as the raw outcome measure of different neuropsychological tests, as outcome scores which were normed on a sample of 75 healthy participants, and as the deterioration index (DI). RESULTS: There were no significant correlations between DUP or DUI and outcome of neuropsychological tests in both normed and raw scores. When adjusted for covariates, DUP and DUI also did not significantly predict any cognitive performance. There was no significant relationship between DUP or DUI and the DI index. However, longer DUP and DUI were significantly associated with stronger negative symptoms. CONCLUSIONS: This study could not confirm an association between duration of untreated psychosis or duration of untreated illness and neurocognitive performance in the ARMS-T and FEP samples. This could be because schizophrenic psychoses are neurodevelopmental disorders in which most cognitive deficits exist long before the onset of psychiatric symptoms

Bestial boredom: a biological perspective on animal boredom and suggestions for its scientific investigation

Boredom is likely to have adaptive value in motivating exploration and learning, and many animals may possess the basic neurological mechanisms to support it. Chronic inescapable boredom can be extremely aversive, and understimulation can harm neural, cognitive and behavioural flexibility. Wild and domesticated animals are at particular risk in captivity, which is often spatially and temporally monotonous. Yet biological research into boredom has barely begun, despite having important implications for animal welfare, the evolution of motivation and cognition, and for human dysfunction at individual and societal levels. Here I aim to facilitate hypotheses about how monotony affects behaviour and physiology, so that boredom can be objectively studied by ethologists and other scientists. I cover valence (pleasantness) and arousal (wakefulness) qualities of boredom, because both can be measured, and I suggest boredom includes suboptimal arousal and aversion to monotony. Because the suboptimal arousal during boredom is aversive, individuals will resist low arousal. Thus, behavioural indicators of boredom will, seemingly paradoxically, include signs of increasing drowsiness, alongside bouts of restlessness, avoidance and sensation-seeking behaviour. Valence and arousal are not, however, sufficient to fully describe boredom. For example, human boredom is further characterized by a perception that time ‘drags’, and this effect of monotony on time perception can too be behaviourally assayed in animals. Sleep disruption and some abnormal behaviour may also be caused by boredom. Ethological research into this emotional phenomenon will deepen understanding of its causes, development, function and evolution, and will enable evidence-based interventions to mitigate human and animal boredom

Orbit size and estimated eye size in dinosaurs and other archosaurs and their implications for the evolution of visual capabilities

Vision is one of the most important senses for animals, allowing them to interact with their environment and with further implications for evolutionary histories. However, relevant soft tissues, such as the eye and associated structures, are not preserved in fossil vertebrates, limiting our knowledge of their visual capabilities. Here, we quantified absolute and relative orbit size for 400 species of dinosaurs and other extinct archosaurs using linear measurements of the preserved skeletal elements as a proxy for visual capabilities. Our results demonstrate that the orbit makes up on average 20% of skull size with a strong and consistent correlation across all sampled groups. This trend is largely independent of temporal distribution, species richness, and phylogeny. In fact, relative orbit size is narrowly constrained and did not surpass 45% of skull size, suggesting physiological and functional controls. Estimated eye size was found to be absolutely larger in herbivores, whereas carnivores tended to have smaller eyes absolutely and compared with skull size. Relatively large eyes only occurred in small-bodied species and vice versa. However, eye size alone was not sufficient to discriminate between different activity patterns or to characterize visual capabilities in detail.</p