Optical Monitoring of In Situ Iron Loading into Single, Native Ferritin Proteins.

Ferritin is a protein that stores and releases iron to prevent diseases associated with iron dysregulation in plants, animals, and bacteria. The conversion between iron-loaded holo-ferritin and empty apo-ferritin is an important process for iron regulation. To date, studies of ferritin have used either ensemble measurements to quantify the characteristics of a large number of proteins or single-molecule approaches to interrogate labeled or modified proteins. Here we demonstrate the first real-time study of the dynamics of iron ion loading and biomineralization within a single, unlabeled ferritin protein. Using optical nanotweezers, we trapped single apo- and holo-ferritins indefinitely, distinguished one from the other, and monitored their structural dynamics in real time. The study presented here deepens the understanding of the iron uptake mechanism of ferritin proteins, which may lead to new therapeutics for iron-related diseases.

Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

Clinical performance of single implant prostheses restored using titanium base abutments: A systematic review and meta-analysis.

PURPOSE: The aim of this review was to evaluate the survival rates of restorations utilizing titanium base abutments (TBA) for restoring single-unit implant prostheses. MATERIALS AND METHODS: This review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The focus question was: In patients who require the restoration of a single dental implant utilizing a titanium base abutment, what are the determining factors and outcomes relating to implant prosthesis prognosis and survival? A comprehensive search of databases (PubMed, EMBASE, and Cochrane Library) was conducted on 16 April 2023 and updated on 5 May 2023. Randomized clinical trials (RCT), retrospective studies and prospective studies, reporting on the use of TBA for single implant prostheses, were reviewed. A Cochrane collaboration risk of bias assessment analysis was performed for randomized clinical studies, and the Newcastle-Ottawa Scale tool was applied for non-randomized studies. A meta-analysis was performed on clinical trials reporting on survival rates of both TBA and other abutments. Other clinical studies, reporting on TBA only, were included for descriptive statistics. RESULTS: The search provided 1159 titles after duplicates were removed. Six RCTs were included to perform a meta-analysis and compare the survival of the TBA to other abutments [OR 0.74; 95% CI: 0.21-2.63, heterogeneity; I2 0%; p = .99]. Twenty-three prospective and retrospective studies fulfilled the criteria and were included in the meta-analysis after 12 months of function. A total of 857 single implant-supported prostheses fabricated with a TBA were included. TBA abutments have an estimate 98.6% survival rate after 1 year in function (95% CI: 97.9%-99.4%). The mean follow-up period was 31.2 ± 16.9 months. CONCLUSIONS: Single implant prosthesis restored with titanium base abutments showed favourable short-term survival rates.

Attachment-focused iMAgery therapy for PSychosis (A-iMAPS): A case series targeting psychosis-related trauma.

OBJECTIVES: The experience of psychosis and its sequelae (including treatment experiences) can be traumatic and affect feelings of safety and security. Until relatively recently, trauma therapy has been avoided with psychosis populations due to concerns about additional harm. Intervention-based research is growing, but focus on psychosis-related trauma is limited. Engendering psychological safety may support engagement with trauma-focused therapy, for which attachment theory provides a strong foundation. Imagery can enhance felt security and is an effective modality for working with trauma. Therefore, this study aimed to examine feasibility and preliminary outcomes of a novel attachment-focused imagery therapy (A-iMAPS) addressing psychosis-related trauma. METHODS: A multiple baseline case series: Participants received between two and five baseline assessments then engaged in the six-session A-iMAPS intervention. Participants completed weekly measures of trauma symptoms and felt security. Further measures were completed pre- and post-intervention. RESULTS: Twelve clinical participants were recruited from NHS services in Northwest England and eight retained through baseline and intervention to the end-of-therapy assessment (attending all sessions). A significant improvement was seen for felt security between baseline and intervention phases. Other measures of trauma symptoms, core schemas, paranoia and attachment varied in change from baseline to end of therapy, but some promising preliminary results were seen. CONCLUSIONS: This study shows that a brief attachment-focused imagery therapy is a promising intervention for targeting psychosis-related trauma, for which there are currently no other specific intervention studies. Utilizing an attachment-informed framework when working with trauma in psychosis should be considered in future intervention studies.

Emotional and non-emotional mental imagery and auditory verbal hallucinations (hearing voices): A systematic review of imagery assessment tools.

It is unknown to what extent mental imagery and auditory verbal hallucinations (AVHs) are related. Trials evaluating this issue used both emotional and non-emotional mental imagery tools, thereby complicating outcomes comparisons. Therefore, the present study aimed to systematically review the literature on mental imagery in individuals with AVHs to (1) inventory imagery assessment tools used in this population, (2) to collect information on the relation between emotional and non-emotional mental imagery in all sensory domains and AVHs and (3) to integrate the outcomes of this systematic review in a model of different mental imagery domains and related assessment tools. We conducted a systematic literature search in the PubMed Database. After full-text screening, 17 papers were included. Findings showed that a variety of assessment methods have been used to assess various aspects of mental imagery in people with AVHs, suggesting that there is a lack of agreed theoretical conceptualization of mental imagery and AVHs. In addition, the studies confirmed as was expected that non-emotional mental imagery seemed unrelated to AVHs whereas emotional mental imagery was related to AVHs. Lastly, we proposed a model of mental imagery domains and corresponding assessment methods distinguishing between emotional and non-emotional mental imagery.

Commentary: Bringing together lived experience, clinical and research expertise - a commentary on the May 2022 debate (should CAMH professionals be diagnosing personality disorder in adolescence?).

BACKGROUND: There is a wealth of evidence to suggest that the Borderline Personality Disorder (BPD, or similar Emotionally Unstable Personality Disorder, EUPD) construct is harmful. We provide a commentary on the ideas expressed in the May Debate issue, highlighting both concerns and alternatives. METHOD: We bring together lived experience, clinical and research expertise. This commentary was written collaboratively drawing on all these sources of evidence. RESULTS: We outline evidence that the BPD construct is invalid, harmful, not necessary for effective treatment and a potential block to the development and evaluation of alternatives. CONCLUSIONS: We ask readers to consider these concerns, perspectives and ideas.

Perspectives of Respiratory Physicians toward Need and Integration of Palliative Care in Advanced Respiratory Diseases.

Objectives: Patients with chronic life-limiting or advanced respiratory diseases often suffer from high symptom burden, requiring palliative care to alleviate symptoms, improve quality of life and restore dignity. The present study explored the perception of respiratory physicians and their current practice of integrating palliative care for adult patients with chronic advanced respiratory diseases. Materials and Methods: An exploratory survey method using Google survey forms and SurveyMonkey was emailed to respiratory physicians between December 2020 and May 2021. Results: One hundred and seventy-two respiratory physicians responded to the survey. The majority of respiratory physicians (n = 153; 88.9%) thought that early integration of palliative care early was beneficial. They did not feel referring to palliative care would result in loss of control on patient care (n = 107; 62.21%) and 66 (38.37%) strongly disagreed that the referral would result in a loss of hope in patients. Further exploration into the training needs of respiratory physicians revealed that 121 (70.35%) felt the need for training in end-of-life care. Conclusion: Respiratory physicians in our study had an inclination toward palliative care integration into their routine clinical practice. A majority of them expressed the need to enhance their skills in palliative care. Therefore, concerted efforts at integration and a mutual exchange of knowledge between respiratory physicians and palliative care physicians will ensure that patients with advanced respiratory diseases are provided high-quality palliative care.

Is routine pre-entry chest radiograph necessary in a high tuberculosis prevalence country?

CONTEXT: Chest radiographs have been used worldwide as a screening tool before employment and training, by various healthcare and other government and nongovernment institutions. Many studies done in the past have demonstrated a relatively low yield for tuberculosis detection and therefore, the authors have questioned this practice. AIMS: To compare the value of the preadmission/employment chest radiograph in two groups, namely, those who have been previously exposed to a healthcare setting (post-exposure group) and those who have not been exposed (pre-exposure group) and to determine if there is a significant difference in tuberculosis detection between these two groups. SETTINGS AND DESIGN: A retrospective review of the reports of the chest radiographs of all candidates appearing for admission to various undergraduate and postgraduate courses in our institute between 2014 and 2017 was performed. MATERIALS AND METHODS: The various abnormalities detected were recorded and the findings in the two groups were compared. STATISTICAL ANALYSIS USED: Chi-square test was used to compare between two group proportions. RESULTS: Thirty out of 4333 (0.69%) candidates in the pre-exposure group and 53 out of 3379 (1.57%) candidates in the post-exposure group showed abnormalities on chest radiographs involving the lung parenchyma, mediastinum, heart, or pleura. In the pre-exposure group, six (0.14%) were found to have underlying cardiac disease and one (0.02%) had tuberculosis. Among the six candidates in the post-exposure group who underwent further investigations in our institute, five (0.15%) were diagnosed to have tuberculosis. Although there was no statistically significant difference in tuberculosis detection between the groups (P = 0.051), there is a trend towards higher detection of tuberculosis in the post-exposure group. CONCLUSIONS: In a country where the prevalence of tuberculosis is high, the pre-employment chest radiograph may still have a role in detecting tuberculosis in the post-exposure group.

Characterizing core beliefs in psychosis: a qualitative study.

BACKGROUND: Cognitive behavioural treatments are recommended for people with psychosis. Core beliefs regarding the self and others are a key part of the models underpinning cognitive behavioural therapy but detailed understanding of these putative beliefs in people with psychosis are limited. A greater understanding of these mechanisms is necessary to improve and refine treatments. AIMS: This study utilized a qualitative approach to explore core schematic beliefs in psychosis (strongly held positive and negative beliefs about the self and others) and their relation to hallucinations and delusions. METHOD: Twenty individuals with psychosis participated in individual semi-structured interviews. Inductive thematic analysis was used to analyse the interviews. RESULTS: Four emergent themes were identified: (i) the solidity and permanency of core beliefs, (ii) the causes and development of core beliefs, (iii) a synergistic relationship between core beliefs and symptoms, and (iv) core beliefs associated with images and their influence on psychotic symptoms. CONCLUSIONS: This study provides new insights into the range and character of core beliefs in psychosis and provides important data to guide ongoing and future development of treatment approaches for psychosis.

iMAgery focused psychological therapy for persecutory delusions in PSychosis (iMAPS): a multiple baseline experimental case series.

BACKGROUND: Many people with psychosis experience persecutory delusions and report negative schematic beliefs and intrusive mental images which may be maintaining factors for psychotic symptoms. AIMS: This study examined the feasibility and acceptability of a new psychological therapy targeting schemas and images (iMAPS therapy). METHOD: The study used a randomised multiple baseline design. Participants with first episode psychosis were randomised using a multiple baseline design with 2-5 assessments. Six sessions of therapy, consisting of a combination of imagery techniques and imagery rescripting techniques, was used. In each session, participants completed a Mental Imagery in Psychosis Questionnaire (MIPQ) and imagery interview. Mood and delusional beliefs (PSYRATS) were also measured at each session. RESULTS: Five participants with first episode psychosis completed the baseline visits and attended all therapy sessions. One participant declined the final assessment. Results demonstrated significant reductions in negative schematic beliefs, delusions, imagery distress and other measures of schema (YSQ, SMI). Although multiple baseline randomisation strengthens the study, it lacked a control arm and blind assessments. CONCLUSIONS: iMAPS appears a feasible and acceptable treatment for psychosis, and further evaluation is indicated.

Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1.

OBJECTIVES: Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures. METHODS: Assessments included Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), CMTNSv2-Rasch modified, nerve conduction studies, quantitative sensory testing, intraepidermal nerve fibre density (thigh), computerised myometry (lower limbs), plasma 1-deoxysphingolipid levels, calf-level intramuscular fat accumulation by MRI and patient-based questionnaires (Neuropathic Pain Symptom Inventory and 36-Short Form Health Survey version 2 [SF-36v2]). RESULTS: 35 patients with HSN1 were recruited. There was marked heterogeneity in the phenotype mainly due to differences between the sexes: males generally more severely affected. The outcome measures that significantly changed over 1 year and correlated with CMTNSv2, SF-36v2-physical component and disease duration were MRI determined calf intramuscular fat accumulation (mean change in overall calf fat fraction 2.36%, 95% CI 1.16 to 3.55, p=0.0004), pressure pain threshold on the hand (mean change 40 kPa, 95% CI 0.7 to 80, p=0.046) and myometric measurements of ankle plantar flexion (median change -0.5 Nm, IQR -9.5 to 0, p=0.0007), ankle inversion (mean change -0.89 Nm, 95% CI -1.66 to -0.12, p=0.03) and eversion (mean change -1.61 Nm, 95% CI -2.72 to -0.51, p=0.006). Intramuscular calf fat fraction was the most responsive outcome measure. CONCLUSION: MRI determined calf muscle fat fraction shows validity and high responsiveness over 12 months and will be useful in HSN1 clinical trials.

Clean Block Copolymer Microparticles from Supercritical CO2: Universal Templates for the Facile and Scalable Fabrication of Hierarchical Mesostructured Metal Oxides.

Metal oxide microparticles with well-defined internal mesostructures are promising materials for a variety of different applications, but practical routes to such materials that allow the constituent structural length scales to be precisely tuned have thus far been difficult to realize. Herein, we describe a novel platform methodology that utilizes self-assembled block copolymer (BCP) microparticles synthesized by dispersion polymerization in supercritical CO2 (scCO2) as universal structure directing agents for both hydrolytic and nonhydrolytic sol-gel routes to metal oxides. Spherically structured poly(methyl methacrylate- block-4-vinylpyridine) (PMMA- b-P4VP) BCP microparticles are translated into a series of the corresponding organic/inorganic composites and pure inorganic derivatives with a high degree of fidelity for the metal oxides TiO2 and LiFePO4. The final products are comprised of particles close to 1 µm in size with a highly ordered internal morphology of interconnected spheres between 20-40 nm in size. Furthermore, our approach is readily scalable, enabling grams of pure or carbon-coated TiO2 and LiFePO4, respectively, to be fabricated in a facile two step route involving ambient temperature mixing and drying stages. Given that both length scales within these BCP microparticles can be controlled independently by minor variations in the reagent quantities used, the present general strategy could represent a milestone in the design and synthesis of hierarchical metal oxides with completely tunable dimensions.

Addition of second-line steroid sparing immunosuppressants like mycophenolate mofetil improves outcome of Immunoglobulin G4-related disease (IgG4-RD): a series from a tertiary care teaching hospital in South India.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease. This disease may be associated with elevated serum and tissue IgG4 levels. Early treatment prevents fibrosis and organ damage. We retrospectively studied the clinicopathologic correlation and outcome of treatment in IgG4-RD. This single-center retrospective study was done using electronic records of patients subjected to assay of serum IgG4 levels in our laboratory by nephelometry. There were 473 patients with suspected IgG4-RD. Of them, 41 patients fulfilled comprehensive diagnostic criteria for IgG4-RD and 432 had diseases other than IgG4-RD. Clinical and histopathological data including tissue IgG4/IgG ratio, other relevant laboratory findings as well as management data of 41 patients with IgG4-RD were analyzed. There were 29 males and 12 females with mean age of 44.1 ± 2.19 years. Thirteen patients had definite, 19 had probable and 9 had possible IgG4-RD. Male predominance, multiple organ involvement and IgG4 responder Index were significantly higher in definite IgG4-RD as compared to probable and possible IgG4-RD. Serum IgG4 level was elevated in 37 patients (90.2%). Glucocorticoids were used in 35 patients (85.4%) and second-line immunosuppressive agent in 23 patients (65.7%). Of the 21 patients on follow-up, 19 (90.7%) had clinical improvement at the first follow-up visit. Nine (90%) out of the ten patients who were assessed by IgG4 responder index, also had shown improved score with treatment. Patients with IgG4-RD in our series showed favorable responses to treatment with glucocorticoids and addition of steroid sparing immunosuppressive agents (mainly mycophenolate mofetil) helped successful tapering of steroids, while maintaining the improvement.

Delivery of cognitive-behaviour therapy for psychosis: a service user preference trial.

BACKGROUND: Clinical guidelines recommend cognitive behaviour therapy (CBT) for people with psychosis, however, implementation is poor and not everyone wishes to engage with therapy. Understanding service user (SU) preferences for receiving such treatments is a priority for services. AIMS: To explore SU preferences and outcomes of different methods of delivering CBT for psychosis. METHOD: SUs experiencing psychosis could choose between treatment as usual (TAU); TAU plus telephone-delivered CBT with self-help, CBT recovery manual (TS); high support CBT (HS - TAU plus TS plus group sessions) or randomisation. Participants received their option of choice and were followed-up on several outcomes over 9 and 15 months. RESULTS: Of 89 people recruited, three chose to be randomised and 86 expressed a treatment preference (32 chose TAU, 34 chose TS, 23 chose HS). There were few differences between those who chose therapy compared to those who chose TAU. Those who had more positive impacts from their symptoms were significantly more likely to choose TAU. CONCLUSIONS: Most people had strong preferences about treatment delivery and a substantial number did not wish to receive additional therapy. These findings have to be considered when planning and allocating resources for people with psychosis.

Tunable Pentapeptide Self-Assembled ß-Sheet Hydrogels.

Oligopeptide-based supramolecular hydrogels hold promise in a range of applications. The gelation of these systems is hard to control, with minor alterations in the peptide sequence significantly influencing the self-assembly process. We explored three pentapeptide sequences with different charge distributions and discovered that they formed robust, pH-responsive hydrogels. By altering the concentration and charge distribution of the peptide sequence, the stiffness of the hydrogels could be tuned across two orders of magnitude (2-200 kPa). Also, through reassembly of the ß-sheet interactions the hydrogels could self-heal and they demonstrated shear-thin behavior. Using spectroscopic and cryo-imaging techniques, we investigated the relationship between peptide sequence and molecular structure, and how these influence the mechanical properties of the hydrogel. These pentapeptide hydrogels with tunable morphology and mechanical properties have promise in tissue engineering, injectable delivery vectors, and 3D printing applications.

Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation.

The ability of materials to define the architecture and microenvironment experienced by cells provides new opportunities to direct the fate of human pluripotent stem cells (HPSCs) [Robinton DA, Daley GQ (2012) Nature 481(7381):295-305]. However, the conditions required for self-renewal vs. differentiation of HPSCs are different, and a single system that efficiently achieves both outcomes is not available [Giobbe GG, et al. (2012) Biotechnol Bioeng 109(12):3119-3132]. We have addressed this dual need by developing a hydrogel-based material that uses ionic de-cross-linking to remove a self-renewal permissive hydrogel (alginate) and switch to a differentiation-permissive microenvironment (collagen). Adjusting the timing of this switch can preferentially steer the HPSC differentiation to mimic lineage commitment during gastrulation to ectoderm (early switch) or mesoderm/endoderm (late switch). As an exemplar differentiated cell type, we showed that directing early lineage specification using this single system can promote cardiogenesis with increased gene expression in high-density cell populations. This work will facilitate regenerative medicine by allowing in situ HPSC expansion to be coupled with early lineage specification within defined tissue geometries.

Stability and sensitivity of water T2 obtained with IDEAL-CPMG in healthy and fat-infiltrated skeletal muscle.

Quantifying muscle water T2 (T2 -water) independently of intramuscular fat content is essential in establishing T2 -water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL-CPMG combines chemical shift fat-water separation with T2 relaxometry to obtain such a measure. Here we evaluate the reproducibility and B1 sensitivity of IDEAL-CPMG T2 -water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T2 -water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter-scan interval of 4 weeks using IDEAL-CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T2 -water and the fat signal amplitude muscle regions manually segmented. Overall mean calf-level muscle T2 -water in healthy subjects was 31.2 ± 2.0 ms, without significant inter-muscle differences (p = 0.37). Inter-subject and inter-scan coefficients of variation were 5.7% and 3.2% respectively for T2 -water and 41.1% and 15.4% for f.f. Bland-Altman mean bias and ±95% coefficients of repeatability were for T2 -water (0.15, -2.65, 2.95) ms and f.f. (-0.02, -1.99, 2.03)%. There was no relationship between T2 -water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B1 error or any correlation between T2 -water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T2 -water and f.f. (ρ = 0.59, p < 0.001). IDEAL-CPMG provides a feasible way to quantify T2 -water in muscle that is reproducible and sensitive to meaningful physiological changes without post hoc modeling of the fat contribution. In patients, IDEAL-CPMG measured elevations in T2 -water and f.f. while showing a weak relationship between these parameters, thus showing promise as a practical means of quantifying muscle water in patient populations.

Muscle magnetic resonance imaging in congenital myasthenic syndromes.

INTRODUCTION: In this study we investigated muscle magnetic resonance imaging in congenital myasthenic syndromes (CMS). METHODS: Twenty-six patients with 9 CMS subtypes and 10 controls were imaged. T1-weighted (T1w) and short-tau inversion recovery (STIR) 3-Tesla MRI images obtained at thigh and calf levels were scored for severity. RESULTS: Overall mean the T1w score was increased in GFPT1 and DPAGT1 CMS. T1w scans of the AChR-deficiency, COLQ, and CHAT subjects were indistinguishable from controls. STIR images from CMS patients did not differ significantly from those of controls. Mean T1w score correlated with age in the CMS cohort. CONCLUSIONS: MRI appearances ranged from normal to marked abnormality. T1w images seem to be especially abnormal in some CMS caused by mutations of proteins involved in the glycosylation pathway. A non-selective pattern of fat infiltration or a normal-appearing scan in the setting of significant clinical weakness should suggest CMS as a potential diagnosis. Muscle MRI could play a role in differentiating CMS subtypes. Muscle Nerve 54: 211-219, 2016.

Extra-ocular muscle MRI in genetically-defined mitochondrial disease.

OBJECTIVES: Conventional and quantitative MRI was performed in patients with chronic progressive external ophthalmoplegia (CPEO), a common manifestation of mitochondrial disease, to characterise MRI findings in the extra-ocular muscles (EOMs) and investigate whether quantitative MRI provides clinically relevant measures of disease. METHODS: Patients with CPEO due to single mitochondrial DNA deletions were compared with controls. Range of eye movement (ROEM) measurements, peri-orbital 3 T MRI T1-weighted (T1w) and short-tau-inversion-recovery (STIR) images, and T2 relaxation time maps were obtained. Blinded observers graded muscle atrophy and T1w/STIR hyperintensity. Cross-sectional areas and EOM mean T2s were recorded and correlated with clinical parameters. RESULTS: Nine patients and nine healthy controls were examined. Patients had reduced ROEM (patients 13.3°, controls 49.3°, p < 0.001), greater mean atrophy score and increased T1w hyperintensities. EOM mean cross-sectional area was 43 % of controls and mean T2s were prolonged (patients 75.6 ± 7.0 ms, controls 55.2 ± 4.1 ms, p < 0.001). ROEM correlated negatively with EOM T2 (rho = -0.89, p < 0.01), whilst cross-sectional area failed to correlate with any clinical measures. CONCLUSIONS: MRI demonstrates EOM atrophy, characteristic signal changes and prolonged T2 in CPEO. Correlation between elevated EOM T2 and ROEM impairment represents a potential measure of disease severity that warrants further evaluation. KEY POINTS: Chronic progressive external ophthalmoplegia is a common clinical manifestation of mitochondrial disease. • Existing extra-ocular muscle MRI data in CPEO reports variable radiological findings. MRI confirmed EOM atrophy and characteristic signal changes in CPEO. EOM T2 was significantly elevated in CPEO and correlated negatively with ocular movements. EOM T2 represents a potential quantitative measure of disease severity in CPEO.

A comprehensive comparison of dye-sensitized NiO photocathodes for solar energy conversion.

We investigated a range of different mesoporous NiO electrodes prepared by different research groups and private firms in Europe to determine the parameters which influence good quality photoelectrochemical devices. This benchmarking study aims to solve some of the discrepancies in the literature regarding the performance of p-DSCs due to differences in the quality of the device fabrication. The information obtained will lay the foundation for future photocatalytic systems based on sensitized NiO so that new dyes and catalysts can be tested with a standardized material. The textural and electrochemical properties of the semiconducting material are key to the performance of photocathodes. We found that both commercial and non-commercial NiO gave promising solar cell and water-splitting devices. The NiO samples which had the two highest solar cell efficiency (0.145% and 0.089%) also gave the best overall theoretical H2 conversion.