Personality Pathology and Momentary Stress Processes.

The expression of personality pathology differs between people and within a person in day-to-day life. Personality pathology may reflect, in part, dysregulation in basic behavioral processes. Thus, a useful approach for studying maladaptive trait expression comes from literature on stress and daily hassles, which provide dynamic accounts for the relations between individual differences and maladaptive dysregulation. This study sought to integrate maladaptive traits and dynamic stress processes to further dynamic models of personality pathology. In a combined clinical/community sample (N=297) oversampled for interpersonal problems, we used ecological momentary assessment (observation N=19,968) to investigate how maladaptive traits moderated the processes of stress generation, stress reactivity, and affective spillover/inertia. Tests of our preregistered hypotheses provided a mix of supportive and null findings for stress processes identified in past research, and mixed support for the moderating role of personality. The results provide insights into the relations between everyday stressors and personality pathology.

Reconsideration of the alar base cinch suture technique involving the perinasal musculature: an in-depth review.

Orthognathic surgery affects both function and aesthetics. An important aesthetic complication is the nasal alteration that can result from Le Fort I osteotomy. A common method for countering this complication is the alar base cinch suture technique. Although the method for this suture has been standardized, the results vary and are inconsistent; further improvements are therefore required. The objective of this study was to review the literature data on the alar base cinch suture technique and associated results. In this review, the PubMed, Ovid, and Ichushi-Web electronic databases were searched using logical combinations of keywords related to the perinasal musculature and alar base cinch suture technique. Following screening of the results, 42 publications were included. The review findings prompted several conclusions. The anatomy of the myrtiformis muscle and depressor septi nasalis may differ between ethnicities, and it is essential to take certain factors related to ethnicity into account when implementing the alar base cinch suture technique. It is also important to consider factors such as the patient's aesthetic preferences.

Determinants of riverine migration success by Atlantic salmon (Salmo salar) smolts from rivers across the UK and Ireland.

There is some evidence that the river migration success of Atlantic salmon smolts, on their first migration to sea, varies both spatially and temporally. However, we have only a poor understanding of what may be driving this variation. In this study, we used acoustic telemetry to quantify the spatial and temporal variations in river migration success in Atlantic salmon smolts on their first migration to sea. In total 4120 Atlantic salmon smolts migrating through 22 rivers in Scotland, England, Ireland, and Northern Ireland over multiple years were included in the study. Individuals were defined as successful migrants if detected leaving the river to enter marine waters. The results show significant temporal (up to 4 years) and spatial (river) variations in migration success, with overall between-river migration success varying from 3.4% to 97.0% and between years from 3.4% and 61.0%. Temporal variation in migration success was river specific, with some rivers being more temporally stable (exhibiting little variation between years) than others. Across all rivers and years, individual migration success was predicted positively by body condition and negatively by tag burden. The rate of migration success for a population (migration success standardized to a common river distance [proportion km-1]) was predicted by a number of environmental factors. The proportion of river catchment that comprised wetland and woodland positively predicted migration success, whereas the proportion of grassland and peatland in a catchment negatively predicted the rate of migration success. Although the mechanisms through which these effects may be operating were not directly examined in this study, we discuss some potential routes through which they may occur.

Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management.

Primary open angle glaucoma is a leading cause of visual impairment and blindness which is commonly treated with drugs or laser but may require surgery. Tenon's ocular fibroblasts are involved in wound-healing after glaucoma filtration surgery and may compromise a favourable outcome of glaucoma surgery by contributing to fibrosis. To investigate changes in gene expression and key pathways contributing to the glaucomatous state we performed genome-wide RNA sequencing. Human Tenon's ocular fibroblasts were cultured from normal and glaucomatous human donors undergoing eye surgery (n = 12). mRNA was extracted and RNA-Seq performed on the Illumina platform. Differentially expressed genes were identified using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts and edgeR. Changes in biological functions and pathways were determined using Enrichr and clustered using Cytoscape. A total of 5817 genes were differentially expressed between Tenon's ocular fibroblasts from normal versus glaucomatous eyes. Enrichment analysis showed 787 significantly different biological functions and pathways which were clustered into 176 clusters. Tenon's ocular fibroblasts from glaucomatous eyes showed signs of fibrosis with fibroblast to myofibroblast transdifferentiation and associated changes in mitochondrial fission, remodeling of the extracellular matrix, proliferation, unfolded protein response, inflammation and apoptosis which may relate to the pathogenesis of glaucoma or the detrimental effects of topical glaucoma therapies. Altered gene expression in glaucomatous Tenon's ocular fibroblasts may contribute to an unfavourable outcome of glaucoma filtration surgery. This work presents a genome-wide transcriptome of glaucomatous versus normal Tenon's ocular fibroblasts which may identify genes or pathways of therapeutic value to improve surgical outcomes.

Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair.

The Fanconi anemia (FA) repair pathway governs repair of highly genotoxic DNA interstrand crosslinks (ICLs) and relies on translesion synthesis (TLS). TLS is facilitated by REV1 or site-specific monoubiquitination of proliferating cell nuclear antigen (PCNA) (PCNA-Ub) at lysine 164 (K164). A PcnaK164R/K164R but not Rev1-/- mutation renders mammals hypersensitive to ICLs. Besides the FA pathway, alternative pathways have been associated with ICL repair (1, 2), though the decision making between those remains elusive. To study the dependence and relevance of PCNA-Ub in FA repair, we intercrossed PcnaK164R/+; Fancg-/+ mice. A combined mutation (PcnaK164R/K164R; Fancg-/- ) was found embryonically lethal. RNA-seq of primary double-mutant (DM) mouse embryonic fibroblasts (MEFs) revealed elevated levels of replication stress-induced checkpoints. To exclude stress-induced confounders, we utilized a Trp53 knock-down to obtain a model to study ICL repair in depth. Regarding ICL-induced cell toxicity, cell cycle arrest, and replication fork progression, single-mutant and DM MEFs were found equally sensitive, establishing PCNA-Ub to be critical for FA-ICL repair. Immunoprecipitation and spectrometry-based analysis revealed an unknown role of PCNA-Ub in excluding mismatch recognition complex MSH2/MSH6 from being recruited to ICLs. In conclusion, our results uncovered a dual function of PCNA-Ub in ICL repair, i.e. exclude MSH2/MSH6 recruitment to channel the ICL toward canonical FA repair, in addition to its established role in coordinating TLS opposite the unhooked ICL.

Limiting extracellular matrix expansion in diet-induced obese mice reduces cardiac insulin resistance and prevents myocardial remodelling.

OBJECTIVE: Obesity increases deposition of extracellular matrix (ECM) components of cardiac tissue. Since obesity aggregates with insulin resistance and heart disease, it is imperative to determine whether the increased ECM deposition contributes to this disease cluster. The hypotheses tested in this study were that in cardiac tissue of obese mice i) increased deposition of ECM components (collagens and hyaluronan) contributes to cardiac insulin resistance and that a reduction in these components improves cardiac insulin action and ii) reducing excess collagens and hyaluronan mitigates obesity-associated cardiac dysfunction. METHODS: Genetic and pharmacological approaches that manipulated collagen and hyaluronan contents were employed in obese C57BL/6 mice fed a high fat (HF) diet. Cardiac insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and cardiac function was measured by pressure-volume loop analysis in vivo. RESULTS: We demonstrated a tight association between increased ECM deposition with cardiac insulin resistance. Increased collagen deposition by genetic deletion of matrix metalloproteinase 9 (MMP9) exacerbated cardiac insulin resistance and pirfenidone, a clinically available anti-fibrotic medication which inhibits collagen expression, improved cardiac insulin resistance in obese mice. Furthermore, decreased hyaluronan deposition by treatment with PEGylated human recombinant hyaluronidase PH20 (PEGPH20) improved cardiac insulin resistance in obese mice. These relationships corresponded to functional changes in the heart. Both PEGPH20 and pirfenidone treatment in obese mice ameliorated HF diet-induced abnormal myocardial remodelling. CONCLUSION: Our results provide important new insights into the role of ECM deposition in the pathogenesis of cardiac insulin resistance and associated dysfunction in obesity of distinct mouse models. These findings support the novel therapeutic potential of targeting early cardiac ECM abnormalities in the prevention and treatment of obesity-related cardiovascular complications.

The TGFß Induced MicroRNAome of the Trabecular Meshwork.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor ß (TGFß) in the anterior segment of the eye. Understanding how TGFß affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-ß1 and -ß2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFß-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Advances in Legume Systematics 14. Classification of Caesalpinioideae. Part 2: Higher-level classification.

Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica. Following the recent re-circumscription of 15 Caesalpinioideae genera as presented in Advances in Legume Systematics 14, Part 1, and using as a basis a phylogenomic analysis of 997 nuclear gene sequences for 420 species and all but five of the genera currently recognised in the subfamily, we present a new higher-level classification for the subfamily. The new classification of Caesalpinioideae comprises eleven tribes, all of which are either new, reinstated or re-circumscribed at this rank: Caesalpinieae Rchb. (27 genera / ca. 223 species), Campsiandreae LPWG (2 / 5-22), Cassieae Bronn (7 / 695), Ceratonieae Rchb. (4 / 6), Dimorphandreae Benth. (4 / 35), Erythrophleeae LPWG (2 /13), Gleditsieae Nakai (3 / 20), Mimoseae Bronn (100 / ca. 3510), Pterogyneae LPWG (1 / 1), Schizolobieae Nakai (8 / 42-43), Sclerolobieae Benth. & Hook. f. (5 / ca. 113). Although many of these lineages have been recognised and named in the past, either as tribes or informal generic groups, their circumscriptions have varied widely and changed over the past decades, such that all the tribes described here differ in generic membership from those previously recognised. Importantly, the approximately 3500 species and 100 genera of the former subfamily Mimosoideae are now placed in the reinstated, but newly circumscribed, tribe Mimoseae. Because of the large size and ecological importance of the tribe, we also provide a clade-based classification system for Mimoseae that includes 17 named lower-level clades. Fourteen of the 100 Mimoseae genera remain unplaced in these lower-level clades: eight are resolved in two grades and six are phylogenetically isolated monogeneric lineages. In addition to the new classification, we provide a key to genera, morphological descriptions and notes for all 163 genera, all tribes, and all named clades. The diversity of growth forms, foliage, flowers and fruits are illustrated for all genera, and for each genus we also provide a distribution map, based on quality-controlled herbarium specimen localities. A glossary for specialised terms used in legume morphology is provided. This new phylogenetically based classification of Caesalpinioideae provides a solid system for communication and a framework for downstream analyses of biogeography, trait evolution and diversification, as well as for taxonomic revision of still understudied genera.

Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells.

The Ca2+-activated Cl- channel regulator CLCA1 potentiates the activity of the Ca2+-activated Cl- channel (CaCC) TMEM16A by directly engaging the channel at the cell surface, inhibiting its reinternalization and increasing Ca2+-dependent Cl- current (ICaCC) density. We now present evidence of functional pairing between two other CLCA and TMEM16 protein family members, namely CLCA4 and the CaCC TMEM16B. Similar to CLCA1, (i) CLCA4 is a self-cleaving metalloprotease, and the N-terminal portion (N-CLCA4) is secreted; (ii) the von Willebrand factor type A (VWA) domain in N-CLCA4 is sufficient to potentiate ICaCC in HEK293T cells; and (iii) this is mediated by the metal ion-dependent adhesion site motif within VWA. The results indicate that, despite the conserved regulatory mechanism and homology between CLCA1 and CLCA4, CLCA4-dependent ICaCC are carried by TMEM16B, rather than TMEM16A. Our findings show specificity in CLCA/TMEM16 interactions and suggest broad physiological and pathophysiological links between these two protein families.

Review of Nutrition Guidelines and Evidence on Diet and Survival Outcomes for Cancer Survivors: Call for Integrating Nutrition into Oncology Care.

Several organizations have published nutrition guidelines for cancer survivors during and after treatment. This review compared nutrition guidelines for cancer survivors published in the United States for the topics that are covered in the guidelines and evaluated the evidence that these guidelines are based upon. A team of researchers, patient stakeholders, and healthcare providers collectively identified 5 nutrition guidelines for cancer survivors in the United States: the 2022 American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors, the 2018 American Institute for Cancer Research Cancer Nutrition Guide, the 2022 National Cancer Institute Physician Data Query and Eating Hints, the 2024 National Comprehensive Cancer Network Guidelines for Cancer Survivors, and the 2020 American Society for Clinical Oncology Guidelines. The 5 guidelines cover a comprehensive list of nutrition topics but overall promote to follow those recommendations for cancer prevention. This review also evaluated the current evidence from meta-analyses on dietary patterns and intakes of foods and nutrients in relation to survival outcomes among cancer survivors. Although the evidence on dietary patterns is strong, the evidence on most dietary factors is still limited and the current research was primarily conducted among breast and colorectal cancer survivors. Although nutrition recommendations are available for cancer survivors, practical strategies need to be implemented to integrate nutrition into oncology care and help cancer survivors follow these recommendations. Further research is warranted to provide additional evidence on the role of nutrition in the health outcomes of cancer survivors and guide the development of evidence-based nutrition recommendations. The protocol is registered in PROSPERO: CRD42023429240.

Glucagon-like Peptide 1 Receptor Agonist use and the effect on diabetic retinopathy: An uncertain relationship.

Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) are a group of relatively novel medications for the treatment of diabetes mellitus. These medications can mimic the naturally occurring incretins of the body, which promote the release of insulin in response to hyperglycaemia. The anti-glycaemic effects of these medications can be profound and carry other metabolic benefits such as promoting weight loss. Clinical trials have shown GLP-1 RAs are safe to use from a cardiovascular perspective. However, some trials have suggested a link between GLP-1 RA use and worsening diabetic retinopathy. The conclusions surrounding this link are poorly established as data is drawn primarily from cardiovascular outcome trials. If an association does exist, a possible explanation might be the observed phenomenon of early worsening diabetic retinopathy with rapid correction of hyperglycaemic states. Trials which look at diabetic retinopathy as a primary outcome in relation to use of GLP-1 RAs are sparse and warrant investigation given the growing use of this group of medications. Therefore currently, it is uncertain what effect, beneficial or adverse, GLP-1 RA use has on diabetic retinopathy. This article provides an overview of GLP-1 RA use as a treatment for diabetes mellitus and the current understanding of their relationship with diabetic retinopathy.

Characterizing Stress Processes by Linking Big Five Personality States, Traits, and Day-to-Day Stressors.

The accumulation of day-to-day stressors can impact mental and physical health. How people respond to stressful events is a key mechanism responsible for the effects of stress, and individual differences in stress responses can either perpetuate or prevent negative consequences. Most research on daily stress processes has focused on affective responses to stressors, but stress responses can involve more than just affect (e.g., behavior, cognitions). Additionally, most research has studied the role of neuroticism in shaping those responses, but many other individual differences are associated with stress. In this study, we more broadly characterized daily stress processes by expanding the nomological networks of stress responses to include Big Five personality states. We also linked those stress responses to all Big Five traits, as well as individual differences in stress variety, severity, and controllability. We studied a sample of participants (N = 1,090) who reported on stressful events, their appraisal of events in terms of severity and controllability, and their Big Five personality states daily for 8-10 days (N = 8,870 observations). Multi-level structural equation models were used to separate how characteristics of the perceived stressful situation and characteristics of the person play into daily stress processes. Results showed that (1) all Big Five personality states shift in response to perceived stress, (2) all Big Five personality traits relate to average levels of perceived stress variety, severity, and controllability, (3) individual differences in personality and average perceived stress variety and perceived severity relate to the strength of personality state responses to daily stress, albeit in a more limited fashion. Our results point to new pathways by which stressors affect people in everyday life and begin to clarify processes that may explain individual differences in risk or resilience to the harmful effects of stress.

Inshore and offshore marine migration pathways of Atlantic salmon post-smolts from multiple rivers in Scotland, England, Northern Ireland, and Ireland.

The migratory behavior of Atlantic salmon (Salmo salar) post-smolts in coastal waters is poorly understood. In this collaborative study, 1914 smolts, from 25 rivers, in four countries were tagged with acoustic transmitters during a single seasonal migration. In total, 1105 post-smolts entered the marine study areas and 438 (39.6%) were detected on a network of 414 marine acoustic receivers and an autonomous underwater vehicle. Migration pathways (defined as the shortest distance between two detections) of up to 575 km and over 100 days at sea were described for all 25 populations. Post-smolts from different rivers, as well as individuals from the same river, used different pathways in coastal waters. Although difficult to generalize to all rivers, at least during the year of this study, no tagged post-smolts from rivers draining into the Irish Sea were detected entering the areas of sea between the Hebrides and mainland Scotland, which is associated with a high density of finfish aquaculture. An important outcome of this study is that a high proportion of post-smolts crossed through multiple legislative jurisdictions and boundaries during their migration. This study provides the basis for spatially explicit assessment of the impact risk of coastal pressures on salmon during their first migration to sea.

The Suppression of the Epithelial to Mesenchymal Transition in Prostate Cancer through the Targeting of MYO6 Using MiR-145-5p.

Aberrant expression of miR-145-5p has been observed in prostate cancer where is has been suggested to play a tumor suppressor role. In other cancers, miR-145-5p acts as an inhibitor of epithelial-to-mesenchymal transition (EMT), a key molecular process for tumor progression. However, the interaction between miR-145-5p and EMT remains to be elucidated in prostate cancer. In this paper the link between miR-145-5p and EMT in prostate cancer was investigated using a combination of in silico and in vitro analyses. miR-145-5p expression was significantly lower in prostate cancer cell lines compared to normal prostate cells. Bioinformatic analysis of The Cancer Genome Atlas prostate adenocarcinoma (TCGA PRAD) data showed significant downregulation of miR-145-5p in prostate cancer, correlating with disease progression. Functional enrichment analysis significantly associated miR-145-5p and its target genes with EMT. MYO6, an EMT-associated gene, was identified and validated as a novel target of miR-145-5p in prostate cancer cells. In vitro manipulation of miR-145-5p levels significantly altered cell proliferation, clonogenicity, migration and expression of EMT-associated markers. Additional TCGA PRAD analysis suggested miR-145-5p tumor expression may be useful predictor of disease recurrence. In summary, this is the first study to report that miR-145-5p may inhibit EMT by targeting MYO6 in prostate cancer cells. The findings suggest miR-145-5p could be a useful diagnostic and prognostic biomarker for prostate cancer.

A biogeographical appraisal of the threatened South East Africa Montane Archipelago ecoregion.

Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the 'South East Africa Montane Archipelago' (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains' great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)-one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.

EXERT-BC: A pilot study of an exercise regimen designed to improve functional mobility, body composition, and strength after the treatment for breast cancer.

PURPOSE: Resistance training may offer several unique advantages within breast cancer (BC) survivorship care; however, safety concerns have limited the application of high-intensity compound movements necessary to elicit optimal changes in body composition, strength, and quality of life in this population. The EXERT-BC trial assesses the safety and feasibility of an evidence-based, dose-escalated resistance training regimen among BC survivors, with the goal of improving physical and metabolic function, mobility, muscle mass, and body composition. METHODS: Participants included women with breast cancer underwent a 3-month thrice weekly exercise regimen involving dose escalation of high-intensity compound exercises. Coprimary outcomes included safety and adherence. Pre- and post-regimen assessment included body composition testing, functional mobility and balance, total load (weight × repetitions × sets) across compound exercises, and patient reported quality of life. Pairwise comparison was performed via the paired t test. RESULTS: Fourty participants completed a 3-month exercise regimen, with a median age of 57 years (range, 27-74 years) and 73% having stage 0-2 BC. BC therapies concurrent with exercise included anti-estrogen therapy (80%), radiotherapy (30%), and non-hormonal systemic therapy (15%). No adverse events were observed aside from a single case of self-limited knee pain. Session attendance exceeded a prespecified threshold of 75%, and 98% patients reported ongoing compliance to an exercise regimen following regimen completion. Significant reductions in percent body fat (p < 0.001) and increases in percent muscle mass (p = 0.011) were observed. Significant increases in resting metabolic rate (p = 0.023), bilateral grip strength (p < 0.001), functional movement screen (p < 0.001), bilateral Y-Balance testing (p < 0.001), and Godin questionnaire scores (p < 0.001) were observed. CONCLUSION: A 3-month dose-escalated resistance training regimen comprising high-intensity compound movements appears safe with a high degree of adherence among breast cancer survivors, resulting in demonstrable improvements in body composition, metabolic parameters, strength increases, and patient-reported quality of life.

Treatments for Morton's neuroma.

BACKGROUND: Morton's neuroma (MN) is a painful neuropathy resulting from a benign enlargement of the common plantar digital nerve that occurs commonly in the third webspace and, less often, in the second webspace of the foot. Symptoms include burning or shooting pain in the webspace that extends to the toes, or the sensation of walking on a pebble. These impact on weight-bearing activities and quality of life. OBJECTIVES: To assess the benefits and harms of interventions for MN. SEARCH METHODS: On 11 July 2022, we searched CENTRAL, CINAHL Plus EBSCOhost, ClinicalTrials.gov, Cochrane Neuromuscular Specialised Register, Embase Ovid, MEDLINE Ovid, and WHO ICTRP. We checked the bibliographies of identified randomised trials and systematic reviews and contacted trial authors as needed. SELECTION CRITERIA: We included all randomised, parallel-group trials (RCTs) of any intervention compared with placebo, control, or another intervention for MN. We included trials where allocation occurred at the level of the individual or the foot (clustered data). We included trials that confirmed MN through symptoms, a clinical test, and an ultrasound scan (USS) or magnetic resonance imaging (MRI). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We assessed bias using Cochrane's risk of bias 2 tool (RoB 2) and assessed the certainty of the evidence using the GRADE framework. MAIN RESULTS: We included six RCTs involving 373 participants with MN. We judged risk of bias as having 'some concerns' across most outcomes. No studies had a low risk of bias across all domains. Post-intervention time points reported were: three months to less than 12 months from baseline (nonsurgical outcomes), and 12 months or longer from baseline (surgical outcomes). The primary outcome was pain, and secondary outcomes were function, satisfaction or health-related quality of life (HRQoL), and adverse events (AE). Nonsurgical treatments Corticosteroid and local anaesthetic injection (CS+LA) versus local anaesthetic injection (LA) Two RCTs compared CS+LA versus LA. At three to six months: • CS+LA may result in little to no difference in pain (mean difference (MD) -6.31 mm, 95% confidence interval (CI) -14.23 to 1.61; P = 0.12, I2 = 0%; 2 studies, 157 participants; low-certainty evidence). (Assessed via a pain visual analogue scale (VAS; 0 to 100 mm); a lower score indicated less pain.) • CS+LA may result in little to no difference in function when compared with LA (standardised mean difference (SMD) -0.30, 95% CI -0.61 to 0.02; P = 0.06, I2 = 0%; 2 studies, 157 participants; low-certainty evidence). (Function was measured using: the American Orthopaedic Foot and Ankle Society Lesser Toe Metatarsophalangeal-lnterphalangeal Scale (AOFAS; 0 to 100 points) - we transformed the scale so that a lower score indicated improved function - and the Manchester Foot Pain and Disability Schedule (MFPDS; 0 to 100 points), where a lower score indicated improved function.) • CS+LA probably results in little to no difference in HRQoL when compared to LA (MD 0.07, 95% CI -0.03 to 0.17; P = 0.19; 1 study, 122 participants; moderate-certainty evidence), and CS+LA may not increase satisfaction (risk ratio (RR) 1.08, 95% CI 0.63 to 1.85; P = 0.78; 1 study, 35 participants; low-certainty evidence). (Assessed using the EuroQol five dimension instrument (EQ-5D; 0-1 point); a higher score indicated improved HRQoL.) • The evidence is very uncertain about the effects of CS+LA on AE when compared with LA (RR 9.84, 95% CI 1.28 to 75.56; P = 0.03, I2 = 0%; 2 studies, 157 participants; very low-certainty evidence). Adverse events for CS+LA included mild skin atrophy (3.9%), hypopigmentation of the skin (3.9%) and plantar fat pad atrophy (2.6%); no adverse events were observed with LA. Ultrasound-guided (UG) CS+LA versus non-ultrasound-guided (NUG) CS+LA Two RCTs compared UG CS+LA versus NUG CS+LA. At six months: • UG CS+LA probably reduces pain when compared with NUG CS+LA (MD -15.01 mm, 95% CI -27.88 to -2.14; P = 0.02, I2 = 0%; 2 studies, 116 feet; moderate-certainty evidence). (Assessed with a pain VAS.) • UG CS+LA probably increases function when compared with NUG CS+LA (SMD -0.47, 95% CI -0.84 to -0.10; P = 0.01, I2 = 0%; 2 studies, 116 feet; moderate-certainty evidence). We do not know of any established minimum clinical important difference (MCID) for the scales that assessed function, specifically, the MFPDS and the Manchester-Oxford Foot Questionnaire (MOXFQ; 0 to 100 points; a lower score indicated improved function.) • UG CS+LA may increase satisfaction compared with NUG CS+LA (risk ratio (RR) 1.71, 95% CI 1.19 to 2.44; P = 0.003, I2 = 15%; 2 studies, 114 feet; low-certainty evidence). • HRQoL was not measured. • UG CS+LA may result in little to no difference in AE when compared with NUG CS+LA (RR 0.42, 95% CI 0.12 to 1.39; P = 0.15, I2 = 0%; 2 studies, 116 feet; low-certainty evidence). AE included depigmentation or fat atrophy for UG CS+LA (4.9%) and NUG CS+LA (12.7%). Surgical treatments Plantar incision neurectomy (PN) versus dorsal incision neurectomy (DN) One study compared PN versus DN. At 34 months (mean; range 28 to 42 months), PN may result in little to no difference for satisfaction (RR 1.06, 95% CI 0.87 to 1.28; P = 0.58; 1 study, 73 participants; low-certainty evidence), or for AE (RR 0.95, 95% CI 0.32 to 2.85; P = 0.93; 1 study, 75 participants; low-certainty evidence) compared with DN. AE for PN included hypertrophic scaring (11.4%), foreign body reaction (2.9%); AE for DN included missed nerve (2.5%), artery resected (2.5%), wound infection (2.5%), postoperative dehiscence (2.5%), deep vein thrombosis (2.5%) and reoperation with plantar incision due to intolerable pain (5%). The data reported for pain and function were not suitable for analysis. HRQoL was not measured. AUTHORS' CONCLUSIONS: Although there are many interventions for MN, few have been assessed in RCTs. There is low-certainty evidence that CS+LA may result in little to no difference in pain or function, and moderate-certainty evidence that UG CS+LA probably reduces pain and increases function for people with MN. Future trials should improve methodology to increase certainty of the evidence, and use optimal sample sizes to decrease imprecision.

EXERT-BC: Prospective Study of an Exercise Regimen After Treatment for Breast Cancer.

Purpose EXERT-BC is a dose-escalated resistance training regimen created to improve body composition, strength, and balance in women treated for breast cancer (BC). Herein, we report the interim analysis. Women treated for BC underwent this 3-month exercise regimen in an exercise oncology facility with continual monitoring of load and strength. Twenty women completed the IRB-approved protocol, with a mean age of 57 years (range 41-74). Concurrent therapies included anti-estrogen therapy (73%), chemotherapy (14%), and radiotherapy (23%). 27% of women endorsed prior exercise. Subjects missed an average of 1.75 classes (range 0-7), with all meeting adherence over 75%. No injuries or adverse events were reported aside from muscle soreness and 2 days of knee pain. Significant differences in body composition at completion included reduced body fat (38.2% vs. 36.7%, p=0.003), and increased muscle mass (33.1% vs. 37.1%, p<0.001), functional mobility screening (9.82 vs. 11.73, p=0.018), and Y-balance (left: 72.4 vs. 85.3, p=0.001; right: 70.3 vs. 85.2. p<0.001). Significant increases in load were demonstrated: split squat (p<0.001), trap bar deadlift (p=0.035), inclined dumbbell press (p<0.001), and bird dog rows (p<0.001). Dose-escalated resistance training in women with BC is safe and feasible, endorsing significant improvements across body composition, balance, and strength.

In vivo laser speckle contrast imaging of microvascular blood perfusion using a chip-on-tip camera.

Laser speckle contrast imaging (LSCI) is an important non-invasive capability for real-time imaging for tissue-perfusion assessment. Yet, the size and weight of current clinical standard LSCI instrumentation restricts usage to mainly peripheral skin perfusion. Miniaturization of LSCI could enable hand-held instrumentation to image internal organ/tissue to produce accurate speckle-perfusion maps. We characterized a 1mm2 chip-on-tip camera for LSCI of blood perfusion in vivo and with a flow model. A dedicated optical setup was built to compare chip-on-tip camera to a high specification reference camera (GS3) for LSCI. We compared LSCI performance using a calibration standard and a flow phantom. Subsequently the camera assessed placenta perfusion in a small animal model. Lastly, a human study was conducted on the perfusion in fingertips of 13-volunteers. We demonstrate that the chip-on-tip camera can perform wide-field, in vivo, LSCI of tissue perfusion with the ability to measure physiological blood flow changes comparable with a standard reference camera.

Resource instability undermines predictable plasticity-mediated morphological responses to diet in a postglacial fish.

Phenotypic plasticity has been presented as a potential rapid-response mechanism with which organisms may confront swift environmental change and increasing instability. Among the many difficulties potentially facing freshwater fishes in recently glaciated ecosystems is that of invertebrate prey communities becoming significantly altered in species composition and relative abundance. To test how the rapidity of diet resource change may affect phenotypic responses during development, we subjected juvenile brown trout to pelagic-type or littoral-type diets that alternated either daily, sub-seasonally, or not at all over a single growth season. The proportional intake of each diet was traced with stable isotopes of carbon and nitrogen and modelled with morphometric data on head and jaw shape. While those trout exposed to a single diet type developed predictable morphologies associated with pelagic or littoral foragers, those raised on alternating diets expressed more unpredictable morphologies. With extreme (daily) or even sub-seasonal (monthly) resource instability, the association of diet type with the phenotype was overwhelmed, calling into question the efficacy of plasticity as a means of adaptation to environments with rapidly fluctuating prey resources.