Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment.

Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases.

Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae): A review of the traditional uses, phytochemistry and pharmacology of African birch.

Anogeissus leiocarpus (DC.) Guill. & Perr. belongs to the family Combretaceae and is used both by African traditional medical practitioners and livestock rearers to treat diseases such as African trypanosomiasis, animal diarrhoea, asthma, cancer, cough, diabetes, dysentery, erectile dysfunction, fever, giardiasis, helminthiases, meningitis, menstrual disorders, monkeypox, oral infections, poliomyelitis, sickle cell anaemia, snake bites, toothache, urinary schistosomiasis, and yellow fever. Some of these activities have been associated with the presence of polyphenols in the plant which include ellagic acid derivatives, flavonoids, stilbenes, tannins, and triterpenes. Several bioactive molecules have been identified from A. leiocarpus. These include the main active constituents, ellagitannins, ellagic acid derivates, flavonoids and triterpenes. Pharmacological studies have confirmed its antibacterial, antifungal, antihyperglycemic, antihypertensive, antimalarial, antioxidative, antiparasitic, antitumour and anti-ulcer effects. The stem bark has been investigated mainly for biological activities and phytochemistry, and it is the most mentioned plant part highlighted by the traditional users in ethnomedicinal surveys. In vitro and in vivo models, which revealed a wide range of pharmacological actions against parasites causing helminthiasis, leishmaniasis, malaria and trypanosomiasis, have been used to study compounds from A. leiocarpus. Because of its uses in African traditional medicine and veterinary practices, A. leiocarpus has received considerable attention from researchers. The current review provides a comprehensive overview and critical appraisal of scientific reports on A. leiocarpus, covering its traditional uses, pharmacological activities and phytochemistry.

Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.

BACKGROUND: Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples. METHODS: The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics. RESULTS: From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings. LIMITATIONS: Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets. CONCLUSION: This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.

Ceibinin, a new positional isomer of mangiferin from the inflorescence of Ceiba pentandra (Bombacaceae), elicits similar antioxidant effect but no anti-inflammatory potential compared to mangiferin.

Ceiba pentandra (L.) Gaertn. (Bombacaceae) is popular for the quality of its wood. However, its leaf, stem bark and root bark have been popular in ethnomedicine and, apart from the inflorescence, have been subject of extensive phytochemical investigations. In this study, two compounds were isolated from the crude methanol extract of the inflorescence. Through data from UV, NMR, MS, electrochemical studies, differential scanning calorimetry, and thermogravimetric analysis, the structures were elucidated as 3-C-ß-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (1) and 2-C-ß-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (mangiferin, 2). They were assessed for antioxidant efficacy (DCFDA assay) and for anti-inflammatory efficacy using the lipopolysaccharide (LPS)-induced inflammation model in the RAW 264.7 macrophages (nitrite levels quantified, using Griess Assay, as surrogate for nitric oxide (NO)). Compound 1 (named ceibinin) was established as a novel positional isomer of mangiferin (2). While both 1 and 2 were antioxidant against basal and hydrogen peroxide (100 µM)-induced oxidative stress (6.25 µg/ml abrogated peroxide-induced oxidative stress), ceibinin (1) demonstrated no anti-inflammatory potential, unlike mangiferin (2) which, as previously reported, showed anti-inflammatory effect. Our work reports a positional isomer of mangiferin for the first time in C. pentandra and demonstrates how such isomerism could underlie differences in biological activities and thus the potential for development into therapeutics.

Evaluating a Remote Monitoring Program for Respiratory Diseases: Prospective Observational Study.

BACKGROUND: Patients with chronic respiratory diseases and those in the postdischarge period following hospitalization because of COVID-19 are particularly vulnerable, and little is known about the changes in their symptoms and physiological parameters. Continuous remote monitoring of physiological parameters and symptom changes offers the potential for timely intervention, improved patient outcomes, and reduced health care costs. OBJECTIVE: This study investigated whether a real-time multimodal program using commercially available wearable technology, home-based Bluetooth-enabled spirometers, finger pulse oximeters, and smartphone apps is feasible and acceptable for patients with chronic respiratory diseases, as well as the value of low-burden, long-term passive data collection. METHODS: In a 3-arm prospective observational cohort feasibility study, we recruited 60 patients from the Royal Free Hospital and University College Hospital. These patients had been diagnosed with interstitial lung disease, chronic obstructive pulmonary disease, or post-COVID-19 condition (n=20 per group) and were followed for 180 days. This study used a comprehensive remote monitoring system designed to provide real-time and relevant data for both patients and clinicians. Data were collected using REDCap (Research Electronic Data Capture; Vanderbilt University) periodic surveys, Remote Assessment of Disease and Relapses-base active app questionnaires, wearables, finger pulse oximeters, smartphone apps, and Bluetooth home-based spirometry. The feasibility of remote monitoring was measured through adherence to the protocol, engagement during the follow-up period, retention rate, acceptability, and data integrity. RESULTS: Lowest-burden passive data collection methods, via wearables, demonstrated superior adherence, engagement, and retention compared with active data collection methods, with an average wearable use of 18.66 (SD 4.69) hours daily (77.8% of the day), 123.91 (SD 33.73) hours weekly (72.6% of the week), and 463.82 (SD 156.70) hours monthly (64.4% of the month). Highest-burden spirometry tasks and high-burden active app tasks had the lowest adherence, engagement, and retention, followed by low-burden questionnaires. Spirometry and active questionnaires had the lowest retention at 0.5 survival probability, indicating that they were the most burdensome. Adherence to and quality of home spirometry were analyzed; of the 7200 sessions requested, 4248 (59%) were performed. Of these, 90.3% (3836/4248) were of acceptable quality according to American Thoracic Society grading. Inclusion of protocol holidays improved retention measures. The technologies used were generally well received. CONCLUSIONS: Our findings provide evidence supporting the feasibility and acceptability of remote monitoring for capturing both subjective and objective data from various sources for respiratory diseases. The high engagement level observed with passively collected data suggests the potential of wearables for long-term, user-friendly remote monitoring in respiratory disease management. The unique piloting of certain features such as protocol holidays, alert notifications for missing data, and flexible support from the study team provides a reference for future studies in this field. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/28873.

Shikonin and Juglone Inhibit Mycobacterium tuberculosis Low-Molecular-Weight Protein Tyrosine Phosphatase a (Mt-PTPa).

Low-molecular-weight protein tyrosine phosphatases (LMW-PTPs) are involved in promoting the intracellular survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis. These PTPs directly alter host signalling pathways to evade the hostile environment of macrophages and avoid host clearance. Among these, protein tyrosine phosphatase A (Mt-PTPa) is implicated in phagosome acidification failure, thereby inhibiting phagosome maturation to promote Mycobacterium tuberculosis (Mtb) survival. In this study, we explored Mt-PTPa as a potential drug target for treating Mtb. We started by screening a library of 502 pure natural compounds against the activities of Mt-PTPa in vitro, with a threshold of 50% inhibition of activity via a <500 µM concentration of the candidate drugs. The initial screen identified epigallocatechin, myricetin, rosmarinic acid, and shikonin as hits. Among these, the naphthoquinone, shikonin (5, 8-dihydroxy-2-[(1R)-1-hydroxy-4-methyl-3-pentenyl]-1,4-naphthoquinone), showed the strongest inhibition (IC50 33 µM). Further tests showed that juglone (5-hydroxy-1,4-naphthalenedione), another naphthoquinone, displayed similar potent inhibition of Mt-PTPa to shikonin. Kinetic analysis of the inhibition patterns suggests a non-competitive inhibition mechanism for both compounds, with inhibitor constants (Ki) of 8.5 µM and 12.5 µM for shikonin and juglone, respectively. Our findings are consistent with earlier studies suggesting that Mt-PTPa is susceptible to specific allosteric modulation via a non-competitive or mixed inhibition mechanism.

Cytotoxic triterpenoid saponins from the root of Olax subscorpioidea Oliv. (Olacaceae).

Bioactivity-guided phytochemical fractionation of the methanol extract of Olax subscorpioidea root has led to the isolation of six triterpenes. Three of these compounds are previously undescribed triterpenoid saponins: oleanolic acid 3-O-[α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranosyl-(1 â†’ 2)-6-O-methyl-ß-D-glucuronopyranoside]-28-O-ß-D-glucopyranosyl ester (2), oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucopyranosyl-(1 â†’ 3)-ß-D-glucopyranoside] (3), and oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-6-O-methyl-ß-D-glucuronopyranoside] ester (5). Other reported known compounds include two triterpene glycosides: oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-6-O-methyl-ß-D-glucuronopyranoside]-28-O-ß-D-glucopyranosyl ester (1) and oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucuronopyranoside] (4); and a triterpene acid, oleanolic acid (6). The structures of these compounds were elucidated by spectroscopic means. The isolated compounds were tested against human cervical cancer (HeLa), colorectal cancer (Caco-2) and breast cancer (MCF-7) cell lines using the in vitro 3-[4,5-dimethylthiazole-2-yl] 3,5-diphenyltetrazolium bromide (MTT) assay, with vincristine as positive control. The cytotoxicity assay showed that compounds 3 and 5 exhibited significant inhibitory effects on the HeLa cell line, with IC50 values of 7.42 ± 0.34 µM and 10.27 ± 1.26 µM; and moderate effects on MCF-7 (IC50 values, 36.67 ± 1.23 µM and 43.83 ± 0.65 µM) and Caco-2 (IC50 values, 35.83 ± 0.55 µM and 39.03 ± 4.38 µM, respectively) cell lines. They were also more selectively cytotoxic than vincristine against the cancer cell lines, when compared with cytotoxicity against the normal lung cell line MRC5.

Multilingual markers of depression in remotely collected speech samples: A preliminary analysis.

BACKGROUND: Speech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data. METHODS: We collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features. RESULTS: Increased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses. LIMITATIONS: Our findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features. CONCLUSIONS: Participants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD.

A new method for the calculation of functional and path integrals.

This paper addresses a disconnect between the pivotal role of functional (path) integrals in modern theories, such as quantum mechanics and statistical thermodynamics, and the currently limited ability to perform the actual calculation. We present a new method for calculating functional integrals, based on a finite-element formulation, which solves all limitations of existing methods. This approach is far more robust, versatile, and powerful than the prevailing methods, thus allowing for more sophisticated computations and the study of problems that could not previously be tackled. Importantly, existing procedures, element libraries and shape functions, which have been developed throughout the years in the context of engineering analysis and partial differential equations, may be directly employed for this purpose.

Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.

BACKGROUND: Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features. OBJECTIVE: We aimed to address these 3 challenges to inform future work in stratified analyses. METHODS: Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model. RESULTS: We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression. CONCLUSIONS: This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.

Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.

OBJECTIVE: We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system. METHOD: We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40). RESULTS: The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes. CONCLUSION: Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.

Autonomic response to walk tests is useful for assessing outcome measures in people with multiple sclerosis.

Objective: The aim of this study was to evaluate the association between changes in the autonomic control of cardiorespiratory system induced by walk tests and outcome measures in people with Multiple Sclerosis (pwMS). Methods: Electrocardiogram (ECG) recordings of 148 people with Relapsing-Remitting MS (RRMS) and 58 with Secondary Progressive MS (SPMS) were acquired using a wearable device before, during, and after walk test performance from a total of 386 periodical clinical visits. A subset of 90 participants repeated a walk test at home. Various MS-related symptoms, including fatigue, disability, and walking capacity were evaluated at each clinical visit, while heart rate variability (HRV) and ECG-derived respiration (EDR) were analyzed to assess autonomic nervous system (ANS) function. Statistical tests were conducted to assess differences in ANS control between pwMS grouped based on the phenotype or the severity of MS-related symptoms. Furthermore, correlation coefficients (r) were calculated to assess the association between the most significant ANS parameters and MS-outcome measures. Results: People with SPMS, compared to RRMS, reached higher mean heart rate (HRM) values during walk test, and larger sympathovagal balance after test performance. Furthermore, pwMS who were able to adjust their HRM and ventilatory values, such as respiratory rate and standard deviation of the ECG-derived respiration, were associated with better clinical outcomes. Correlation analyses showed weak associations between ANS parameters and clinical outcomes when the Multiple Sclerosis phenotype is not taken into account. Blunted autonomic response, in particular HRM reactivity, was related with worse walking capacity, yielding r = 0.36 r = 0.29 (RRMS) and r > 0.5 (SPMS). A positive strong correlation r > 0.7 r > 0.65 between cardiorespiratory parameters derived at hospital and at home was also found. Conclusion: Autonomic function, as measured by HRV, differs according to MS phenotype. Autonomic response to walk tests may be useful for assessing clinical outcomes, mainly in the progressive stage of MS. Participants with larger changes in HRM are able to walk longer distance, while reduced ventilatory function during and after walk test performance is associated with higher fatigue and disability severity scores. Monitoring of disorder severity could also be feasible using ECG-derived cardiac and respiratory parameters recorded with a wearable device at home.

Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.

Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.

Using Multiplex Amplicon PCR Technology to Efficiently and Timely Generate Rift Valley Fever Virus Sequence Data for Genomic Surveillance.

Rift Valley fever (RVF) is a febrile vector-borne disease endemic in Africa and continues to spread in new territories. It is a climate-sensitive disease mostly triggered by abnormal rainfall patterns. The disease is associated with high mortality and morbidity in both humans and livestock. RVF is caused by the Rift Valley fever virus (RVFV) of the genus Phlebovirus in the family Phenuiviridae. It is a tripartite RNA virus with three genomic segments: small (S), medium (M) and large (L). Pathogen genomic sequencing is becoming a routine procedure and a powerful tool for understanding the evolutionary dynamics of infectious organisms, including viruses. Inspired by the utility of amplicon-based sequencing demonstrated in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Ebola, Zika and West Nile viruses, we report an RVFV sample preparation based on amplicon multiplex polymerase chain reaction (amPCR) for template enrichment and reduction of background host contamination. The technology can be implemented rapidly to characterize and genotype RVFV during outbreaks in a near-real-time manner. To achieve this, we designed 74 multiplex primer sets covering the entire RVFV genome to specifically amplify the nucleic acid of RVFV in clinical samples from an animal tissue. Using this approach, we demonstrate achieving complete RVFV genome coverage even from samples containing a relatively low viral load. We report the first primer scheme approach of generating multiplex primer sets for a tripartite virus which can be replicated for other segmented viruses.

The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.

BACKGROUND: Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment. OBJECTIVE: A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement. METHODS: A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device. RESULTS: The overall retention rate was 60%. Higher-intensity treatment (χ21=4.6; P=.03) and higher baseline anxiety (t56.28=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t50.4=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list. CONCLUSIONS: Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.

The Use of Micro-Ribbons and Micro-Fibres in the Formulation of 3D Printed Fast Dissolving Oral Films.

Three-dimensional printing (3DP) allows production of novel fast dissolving oral films (FDFs). However, mechanical properties of the films may not be desirable when certain excipients are used. This work investigated whether adding chitosan micro-ribbons or cellulose microfibres will achieve desired FDFs by fused deposition modelling 3DP. Filaments containing polyvinyl alcohol (PVA) and paracetamol as model drug were manufactured at 170 °C. At 130 °C, filaments containing polyvinylpyrrolidone (PVP) and paracetamol were also created. FDFs were printed with plain or mesh patterns at temperatures of 200 °C (PVA) or 180 °C (PVP). Both chitosan micro-ribbons and cellulose micro-fibres improved filament mechanical properties at 1% w/w concentration in terms of flexibility and stiffness. The filaments were not suitable for printing at higher concentrations of chitosan micro-ribbons and cellulose micro-fibres. Furthermore, mesh FDFs containing only 1% chitosan micro-ribbons disintegrated in distilled water within 40.33 ± 4.64 s, while mesh FDFs containing only 7% croscarmellose disintegrated in 55.33 ± 2.86 s, and croscarmellose containing films showed signs of excipient scorching for PVA polymer. Cellulose micro-fibres delayed disintegration of PVA mesh films to 108.66 ± 3.68 s at 1% w/w. In conclusion, only chitosan micro-ribbons created a network of hydrophilic channels within the films, which allowed faster disintegration time at considerably lower concentrations.

EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.

EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.

Cola rostrata K. Schum. constituents induce cytotoxicity through reactive oxygen species generation and mitochondrial membrane depolarisation.

Aim: While the traditional use of Cola rostrata in treating illnesses and diseases has not been reported, the presence of cytotoxic principles has been reported in phylogenetically and biogeographically related species within the Cola genus. This study, therefore, evaluated the cytotoxic potential of extracts of the plant, and the associated cellular and molecular mechanisms. Methods: Activity-based fractionation of the extracts was carried out and cytotoxicity was assessed in the human cervical cancer cell line, HeLa, and the transformed human lung cell line, MRC5-SV2, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay complemented with brightfield imaging. The 2',7'-dichlorofluorescein diacetate (DCFDA) assay was used to assess induction of cellular reactive oxygen species (ROS), while flow cytometry of 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1)-stained cells assessed the loss of mitochondrial membrane potential (∆ΨM). Gas chromatography-mass spectrometry (GC-MS) analysis was carried out on an active fraction. Results: Extracts of the fruit epicarp and leaf were cytotoxic against the cell lines. Half-maximal inhibitory concentration (IC50) values for the 48 h cytotoxicity of the ethanol extract of the epicarp against HeLa and MRC5-SV2 cells were 48.0 µg/mL ± 12.1 µg/mL and 40.4 µg/mL ± 7.2 µg/mL, respectively, while fractions from second-level partitioning of the hexane fraction of the leaf extract elicited cytotoxicity with IC50 values ranging from 12.8 µg/mL ± 1.0 µg/mL to 39.6 µg/mL ± 7.2 µg/mL in both cell lines, following 48 h treatment. GC-MS revealed the presence of seventeen compounds in a hexane fraction of the leaf extract, including even- and odd-chain fatty acids, the most abundant of which were n-hexadecanoic acid, decanoic acid 10-(2-hexylcyclopropyl); and octadecanoic acid. The mechanisms of cytotoxicity of most active fractions involved generation of ROS and mitochondrial membrane depolarisation. Conclusions: The findings show that C. rostrata is rich in cytotoxic phytochemicals which could be isolated for developing new anti-cancer agents.

The utility of wearable devices in assessing ambulatory impairments of people with multiple sclerosis in free-living conditions.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a progressive inflammatory and neurodegenerative disease of the central nervous system affecting over 2.5 million people globally. In-clinic six-minute walk test (6MWT) is a widely used objective measure to evaluate the progression of MS. Yet, it has limitations such as the need for a clinical visit and a proper walkway. The widespread use of wearable devices capable of depicting patients' activity profiles has the potential to assess the level of MS-induced disability in free-living conditions. METHODS: In this work, we extracted 96 features in different temporal granularities (from minute-level to day-level) from wearable data and explored their utility in estimating 6MWT scores in a European (Italy, Spain, and Denmark) MS cohort of 337 participants over an average of 10 months' duration. We combined these features with participants' demographics using three regression models including elastic net, gradient boosted trees and random forest. In addition, we quantified the individual feature's contribution using feature importance in these regression models, linear mixed-effects models, generalized estimating equations, and correlation-based feature selection (CFS). RESULTS: The results showed promising estimation performance with R2 of 0.30, which was derived using random forest after CFS. This model was able to distinguish the participants with low disability from those with high disability. Furthermore, we observed that the minute-level (≤ 8 minutes) step count, particularly those capturing the upper end of the step count distribution, had a stronger association with 6MWT. The use of a walking aid was indicative of ambulatory function measured through 6MWT. CONCLUSIONS: This study demonstrates the utility of wearables devices in assessing ambulatory impairments in people with MS in free-living conditions and provides a basis for future investigation into the clinical relevance.