Chemical and transcriptomic analyses of leaf trichomes from Cistus creticus subsp. creticus reveal the biosynthetic pathways of certain labdane-type diterpenoids and their acetylated forms.

Labdane-related diterpenoids (LRDs), a subgroup of terpenoids, exhibit structural diversity and significant commercial and pharmacological potential. LRDs share the characteristic decalin-labdanic core structure that derives from the cycloisomerization of geranylgeranyl diphosphate (GGPP). Labdanes derive their name from the oleoresin known as 'Labdanum', 'Ladano', or 'Aladano', used since ancient Greek times. Acetylated labdanes, rarely identified in plants, are associated with enhanced biological activities. Chemical analysis of Cistus creticus subsp. creticus revealed labda-7,13(E)-dien-15-yl acetate and labda-7,13(E)-dien-15-ol as major constituents. In addition, novel labdanes such as cis-abienol, neoabienol, ent-copalol, and one as yet unidentified labdane-type diterpenoid were detected for the first time. These compounds exhibit developmental regulation, with higher accumulation observed in young leaves. Using RNA-sequencing (RNA-seq) analysis of young leaf trichomes, it was possible to identify, clone, and eventually functionally characterize labdane-type diterpenoid synthase (diTPS) genes, encoding proteins responsible for the production of labda-7,13(E)-dien-15-yl diphosphate (endo-7,13-CPP), labda-7,13(E)-dien-15-yl acetate, and labda-13(E)-ene-8α-ol-15-yl acetate. Moreover, the reconstitution of labda-7,13(E)-dien-15-yl acetate and labda-13(E)-ene-8α-ol-15-yl acetate production in yeast is presented. Finally, the accumulation of LRDs in different plant tissues showed a correlation with the expression profiles of the corresponding genes.

Dynamic Nanoindentation and Short-Range Order in Equiatomic NiCoCr Medium-Entropy Alloy Lead to Novel Density Wave Ordering.

Chemical short-range order is believed to be a key contributor to the exceptional properties of multicomponent alloys. However, its direct validation and confirmation has been highly elusive in most compounds. Recent studies for equiatomic NiCoCr alloys have shown that thermal treatments (i.e., annealing and aging) may facilitate and manipulate such ordering. In this work, by using molecular simulations, we show that nanomechanical probes, such as nanoindentation, may be utilized toward further manipulation of chemical short-range order, providing explicit validation pathways. By using well established interatomic potentials, we perform hybrid molecular-dynamics-Monte Carlo at room temperature to demonstrate that particular dwell nanoindentation protocols can lead, through thermal Monte Carlo equilibration, to local reorganization under the indenter tip, toward a density-wave stripe pattern. We characterize the novel density-wave structures, which are highly anisotropic and dependent on local, nanoindentation-induced stress concentrations, and we show how they deeply originate from intrinsic features of interelemental interactions. Furthermore, we show that these novel patterns consistently scale with the incipient plastic zone, under the indenter tip, justifying their observation at experimentally feasible nanoindentation depths.

Dominant dystrophic epidermolysis bullosa is associated with glycolytically active GATA3+ T helper 2 cells which may contribute to pruritus in lesional skin.

BACKGROUND: Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. OBJECTIVES: To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. METHODS: Using bulk RNA sequencing, we evaluated affected and unaffected skin biopsy samples from six patients with DDEB (all with the very itchy pruriginosa subtype) and four healthy individuals. Single-cell transcriptomes of affected (n = 2) and unaffected (n = 1) DDEB skin and healthy skin (n = 2) were obtained. Dupilumab treatment was provided for three patients. RESULTS: The skin bulk transcriptome showed significant enrichment of T helper (Th)1/2 and Th17 pathways in affected DDEB skin compared with nonlesional DDEB skin and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced visual analogue scale (VAS) itch scores after 12 weeks (mean VAS 3.83) compared with pretreatment (mean VAS 7.83). Bulk RNAseq and quantitative polymerase chain reaction showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin have similar transcriptomic profiles and reduced Th1/Th2 and Th17 pathway enrichment. CONCLUSIONS: Single-cell RNAseq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus.

Dominant dystrophic epidermolysis bullosa (DDEB) is a rare inherited skin disease that causes fragile skin that blisters easily, often triggered by minor injuries. These blisters are accompanied by intense itching, which can be distressing. The underlying cause of DDEB lies in genetic mutations in a gene called COL7A1. This gene encodes 'type VII collagen', a protein crucial for attaching the outer skin layer (epidermis) to the layer beneath (dermis). Although the genetic basis of DDEB is understood, the causes of itch are not known. As well as this, effective treatments for DDEB are lacking, which has driven scientists to explore innovative approaches like repurposing existing drugs. Drug repurposing involves using medications that have already been approved for other health conditions. One such drug is dupilumab, which is used for severe atopic dermatitis (eczema). Dupilumab targets immune cells called Th2 cells, which play a role in inflammation and allergies. While dupilumab has shown promise in relieving DDEB itching, the way it works in this condition is unclear. This study, carried out by a group of researchers in Taiwan, looked at gene expression in DDEB-affected and unaffected skin, and compared it to gene expression in healthy skin samples. We found heightened activity in Th2 immune cells and abnormal gene signals related to itching, similar to atopic dermatitis. These findings support using dupilumab and other anti-inflammatory drugs to alleviate itching in DDEB. Clinical trials will be crucial to evaluate the effectiveness of these drugs for managing DDEB symptoms. This research opens doors for enhanced treatment options and improving the quality of life of people living with DDEB.

TEMPI syndrome: difficult to diagnose, "easy" to treat?

TEMPI syndrome is a rare, acquired disorder with multisystemic manifestations. It is classified as a plasma cell disorder and is characterized by telangiectasias, erythrocytosis, monoclonal gammopathy, perinephric fluid collections and intrapulmonary shunt. Even though TEMPI's pathophysiology remains elusive, it responds to anti-myeloma therapy indicating that the monoclonal protein or clone plays a key role. We present a challenging case of a 73-year-old man with erythrocytosis and deteriorating renal function with nephrotic-range proteinuria in whom after extensive work up, the diagnosis of TEMPI syndrome was made. He was received treatment with daratumumab-bortezomib-cyclophosphamide and dexamethasone (Dara-VCD) and achieved a hematological and clinical response. We also report preliminary data on a multiplex assay for cytokines and growth factors for two patients with TEMPI syndrome and note lower levels for non-specific innate immunity related cytokines. A direct link between renal impairment and TEMPI syndrome is not currently established; cytokine deregulation could potentially be involved in the ischemic changes observed in the renal biopsy of our patient.

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

BACKGROUND: With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. AIMS: The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. METHODS: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. RESULTS: This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. CONCLUSIONS: IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Diversity, equity, and inclusion in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy Position Statement.

1: The European Society of Gastrointestinal Endoscopy (ESGE) adheres to the overarching principles of equality of opportunity, fair treatment, nondiscrimination, and diversity of health care professionals. 2: ESGE strongly supports the creation of collaborations within and between national and international endoscopy societies to disseminate the principles of diversity, equality, and inclusion (DEI) in the field of gastrointestinal (GI) endoscopy. 3: ESGE aims to reflect the diversity of its membership in all its scientific and educational activities. 4: ESGE supports the fostering of collaborative work settings that empower all members of the endoscopy team to reach their full potential. 5: ESGE supports international and national endoscopy societies in promoting equitable access to high quality endoscopy training. 6: ESGE recommends the implementation of ergonomic principles in endoscopy units to prevent injuries and to provide adapted workplace conditions for personnel with disabilities and/or special needs. 7: ESGE recommends comprehensive mentorship, that includes diverse backgrounds, and equitable sponsorship for professional development, training, and academic excellence. 8: ESGE recommends that endoscopists actively identify, discuss, and attempt to accommodate reasonable patient preferences and expectations regarding endoscopy procedures. 9: ESGE advocates for educational and awareness campaigns targeting both health care professionals and patients, as well as the adoption of cost-effective health care strategies to address disparities and enhance equity in endoscopy care. 10: ESGE is committed to increasing support for underrepresented scholars and minorities pursuing research in endoscopy. 11: ESGE identifies mentorship and sponsorship as factors that may mitigate the barriers to academic careers for underrepresented endoscopy scholars. 12: ESGE recognizes the need to increase awareness of diversity, equity, and inclusion (DEI) in the field of endoscopy and supports publications on these topics.

Levels of IgE sensitization drive symptom thresholds in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications that polysensitization is associated with more severe disease. However, the extent to which the level of sensitization is associated with clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known. OBJECTIVE: To evaluate phenotypical differences between monosensitized and polysensitized patients with AR and to quantify their symptomatic variability. METHODS: A total of 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. Of those, 155 were monosensitized and 410 were polysensitized. Interactions between sensitization levels and the reporting of different symptoms of AR and co-morbidities, disease duration, and impact were assessed. Furthermore, patients were stratified into monosensitized, oligosensitized, and polysensitized to assess whether the effect of sensitization on the phenotype was ranked. RESULTS: Polysensitized patients reported itchy eyes significantly more often (P = .001) and had a higher number of ocular (P = .005), itch-related (P = .036), and total symptoms (P = .007) than monosensitized patients. In addition, polysensitized adults and children more often reported wheeze (P = .015) and throat-clearing (P = .04), respectively. Polysensitization was associated with more burdensome AR based on a visual analog scale (P = .005). Increased sensitization level was reflected in more itchy eyes, a higher number of ocular, itch-related, and total number of symptoms, and disease burden. CONCLUSION: With an increasing number of sensitizations, patients with AR experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.

Experimental and Theoretical Investigation of the Mechanism of the Reduction of O2 from Air to O22- by VIVO2+-N,N,N-Amidate Compounds and Their Potential Use in Fuel Cells.

The two-electron reductive activation of O2 to O22- is of particular interest to the scientific community mainly due to the use of peroxides as green oxidants and in powerful fuel cells. Despite of the great importance of vanadium(IV) species to activate the two-electron reductive activation of O2, the mechanism is still unclear. Reaction of VIVO2+ species with the tridentate-planar N,N,N-carboxamide (ΗL) ligands in solution (CH3OH:H2O) under atmospheric O2, at room temperature, resulted in the quick formation of [VV(═O)(η2-O2)(κ3-L)(H2O)] and cis-[VV(═O)2(κ3-L)] compounds. Oxidation of the VIVO2+ complexes with the sterically hindered tridentate-planar N,N,N-carboxamide ligands by atmospheric O2 gave only cis-[VV(═O)2(κ3-L)] compounds. The mechanism of formation of [VV(═O)(η2-O2)(κ3-L)(H2O)] (I) and cis-[VV(═O)2(κ3-L)] (II) complexes vs time, from the interaction of [VIV(═O)(κ3-L)(Η2Ο)2]+ with atmospheric O2, was investigated with 51V, 1H NMR, UV-vis, cw-X-band EPR, and 18O2 labeling IR and resonance Raman spectroscopies revealing the formation of a stable intermediate (Id). EPR, MS, and theoretical calculations of the mechanism of the formation of I and II revealed a pathway, through a binuclear [VIV(═O)(κ3-L)(H2O)(η1,η1-O2)VIV(═O)(κ3-L)(H2O)]2+ intermediate. The results from cw-EPR, 1H NMR spectroscopies, cyclic voltammetry, and the reactivity of the complexes [VIV(═O)(κ3-L)(Η2Ο)2]+ toward O2 reduction fit better to an intermediate with a binuclear nature. Dynamic experiments in combination with computational calculations were undertaken to fully elucidate the mechanism of the O2 reduction to O22- by [VIV(═O)(κ3-L)(Η2Ο)2]+. The galvanic cell {Zn|VIII,VII||Id, [VIVO(κ3-L)(H2O)2]+|O2|C(s)} was manufactured, demonstrating the important applicability of this new chemistry to Zn|H2O2 fuel cells technology generating H2O2 in situ from the atmospheric O2.

The ras-related protein RAB22A interacts with hypoxia-inducible factor 1-alpha (HIF-1α) in MDA-MB-231 breast cancer cells in hypoxia.

BACKGROUND: Recent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1α) and the small GTPase protein Ras-related protein Rab-22 A (RAB22A) may be colocalized in the cytoplasm and that as a conequence they may enhance the formation of microvesicles in breast cancer cells under hypoxia. Therefore, we sought to determine whether these two proteins are present in intracellular complexes in breast carcinoma cells. METHODS AND RESULTS: Evaluation using molecular docking indicated that HIF-1α and RAB22A interact with each other. Co-immunoprecipitation of endogenous or ectopically expressed HIF-1α and RAB22A proteins in MDA-MB-231 breast cancer cells or HEK-293T cells demonstrated that endogenous HIF-1α and RAB22A can form an intracellular complex; however, transiently expressed HIF-1α and RAB22A failed to interact. Investigating RAB22A and HIF-1α interactions in various cancer cell lines under hypoxia may shed light on their roles in cancer cell survival and progression through regulation of intracellular trafficking by HIF-1α under hypoxic conditions. CONCLUSIONS: Our study is the first to reveal the potential involvement of HIF-1α in intracellular trafficking through physical interactions with the small GTPase protein RAB22A. We discuss the implications of our work on the role of exosomes and microvesicles in tumor invasiveness.

The impact of continuous lenalidomide maintenance treatment on people living with multiple myeloma-a single-centre, qualitative service evaluation study.

PURPOSE: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients. METHODS: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis. RESULTS: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients' preferences when making treatment decisions. CONCLUSION: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

Prevalence of cannabis use disorder and perioperative outcomes in adult colectomy patients: A propensity score-matched analysis.

BACKGROUND: The decriminalization of cannabis across the United States has led to an increased number of patients reporting cannabis use prior to surgery. However, it is unknown whether preoperative cannabis use disorder (CUD) increases the risk of postoperative complications among adult colectomy patients. METHODS: Adult patients undergoing an elective colectomy were retrospectively analyzed from the National Inpatient Sample database (2004-2018). To control for potential confounders, patients with CUD, defined using ICD-9/10 codes, were propensity score matched to patients without CUD in a 1:1 ratio. The association between preoperative CUD and composite morbidity, the primary outcome of interest, was assessed. Subgroup analyses were performed after stratification by age (≥50 years). RESULTS: Among 432,018 adult colectomy patients, 816 (0.19%) reported preoperative CUD. The prevalence of CUD increased nearly three-fold during the study period from 0.8/1000 patients in 2004 to 2.0/1000 patients in 2018 (P-trend<0.001). After propensity score matching, patients with CUD exhibited similar rates of composite morbidity (140 of 816; 17.2%) as those without CUD (151 of 816; 18.5%) (p = 0.477). Patients with CUD also had similar anastomotic leak rates (CUD: 5.64% vs. No CUD: 6.25%; p = 0.601), hospital lengths of stay (CUD: 5 days, IQR 4-7 vs. No CUD: 5 days, IQR 4-7) (p = 0.415), and hospital charges as those without CUD. Similar findings were seen among patients aged ≥50 years in the subgroup analysis. CONCLUSIONS: Though the prevalence of CUD has increased drastically over the past 15 years, preoperative CUD was not associated with an increased risk of composite morbidity among adult patients undergoing an elective colectomy.

Adult dietary patterns with increased bean consumption are associated with greater overall shortfall nutrient intakes, lower added sugar, improved weight-related outcomes and better diet quality.

BACKGROUND: Limited evidence is available that focuses on beans within American dietary patterns and health. The purpose of this study was to identify commonly consumed adult dietary patterns that included beans and compare shortfall nutrient intakes and diet quality, relative to adults whose typical dietary pattern did not include beans. METHODS: The analyses used data from the National Health and Nutrition Examination Survey, 2001-2018. Cluster analysis was used to identify bean patterns of consumption, while the USDA food coding system defined daily beans consumed. Five bean dietary patterns of consumption were identified, of which four patterns included both canned beans and dry beans, while one pattern had no bean consumption. Bean consumption was defined as those consuming kidney beans, black beans, chickpeas, and/or pinto beans. RESULTS: Adults consuming Bean Dietary Patterns 1, 2, 3 and 4 had significantly higher diet quality scores (as assessed by USDA's Healthy Eating Index-2015) compared to the no-bean pattern (61.2 ± 0.5, 58.9 ± 0.5, 55.2 ± 0.4 and 56.5 ± 0.8 vs 48.8 ± 0.2 p's < 0.0001). Bean consumers also had significantly higher intakes of several shortfall nutrients (choline, alpha-linolenic acid, folate, iron, magnesium and vitamin E) relative to non-consumers of beans. Similarly, intake of dietary fiber, potassium and calcium, all nutrients of public health concern were significantly higher in bean patterns compared to no-beans. Bean Dietary Pattern 1 (~ 13.5% of total daily kcal from beans or ~ 2 servings of beans/day) and 2 (~ 9.5% of total daily kcal from beans or ~ 1.7 servings of beans/day) were significantly associated with lower BMI, decreased body weight and improved waist circumference relative to no-beans. CONCLUSIONS: Dietary patterns that are rich in canned and dry beans were associated with significantly higher diet quality scores and greater intake of shortfall nutrients, including nutrients of public health concern. Bean dietary patterns were also associated with improved weight-related outcomes. Dietary guidance should consider the nutrient and health benefits associated with the promotion of increased canned and dry bean consumption in American dietary patterns.

Diastasis Recti Abdominis Rehabilitation in the Postpartum Period: A Scoping Review of Current Clinical Practice.

INTRODUCTION AND HYPOTHESIS: Despite exercise being the standard approach to diastasis recti abdominis (DRA) rehabilitation, there is no consensus on the most effective exercise routine and adjunct modalities for reducing DRA and improving functional parameters. The present study is aimed at investigating evidence for DRA rehabilitation in postpartum women, as well as knowledge gaps and areas for future research. METHODS: For this scoping review a systematic search was conducted in MEDLINE, AMED, CINAHL, Embase, ScienceDirect, Scopus, and PEDro up to November 2022. Selection criteria included studies investigating exercise therapy interventions both with and without adjunct modalities for postpartum DRA. Sample characteristics, diagnostic criteria, program design, and outcome measures were recorded. Critical appraisal of clinical trials was performed using PEDro classification. RESULTS: Twenty-eight studies were included: 14 clinical trials, 3 case series, and 11 observational studies. DRA exercises that focused on deep and superficial muscles, pelvic floor muscles, respiratory maneuvers, functional exercises, or alternative interventions (yoga, suspension training, hypopressive exercise) and adjunct modalities showed promising results in reducing the inter-recti distance and related dysfunction. However, there was great variability in diagnostic criteria and methods, DRA severity, time post-birth, and exercise program design. CONCLUSIONS: Reviewed studies provide valuable insights into exercise therapy, but it is important to recognize their limitations, as variability in diagnostic criteria, sample characteristics, and exercise program design hinder the generalizability of the findings. Further high-quality research is needed to strengthen the evidence in this area and provide reliable recommendations for clinical practice.

Anterior Subtenon Triamcinolone Injection for Refractory Macular Edema: A Retrospective Case Series.

PURPOSE: To evaluate the effectiveness of anterior subtenon triamcinolone (AST) injections in the management of refractory macular edema. METHODS: This is a retrospective case series of consecutive eyes with refractory macular edema treated with AST at a single vitreoretinal surgeon's practice at Toronto Western Hospital, University of Toronto, Canada in 2018-2023. Refractory was defined as persistent macular edema with a central subfield thickness of 250µm or greater over a 24-week period, receiving at least four intravitreal anti-VEGF injections. Vision outcomes and optical coherence tomography features for all eyes were compared for three visits pre-AST treatment and two visits post-AST treatment. RESULTS: Ninety-three patients (119 eyes; diabetic macular edema (26%), and pseudophakic CME (74%), with a mean follow-up duration of 161 days were included. The presence of subretinal fluid (p=0.0013), central subfield macular thickness (p<0.0001), cube average thickness (p=0.0024) and macular cube volume (p= 0.0017) significantly improved from pre-AST to post-AST treatment. Visual acuity also significantly improved from pre-AST treatment to post-AST treatment (p<0.0001). There was no significant change in the intraocular pressures from pre-AST to post-AST (p=0.7920) and no complications were noted throughout the follow-up period. CONCLUSION: The findings from this study suggest that AST injections show modest improvement in anatomical and functional outcomes, and are safe for the treatment and management of refractory macular edema.

Recovery kinetics following sprint training: resisted versus unresisted sprints.

PURPOSE: To determine the recovery kinetics of performance and exercise-induced muscle damage following different sprint-training protocols. METHODS: In a crossover design, ten male and female athletes (20.6 ± 2.4 years) performed 2 × (3 × 20 m: 2 min rest) and 1× (3 × 30 m: 3 min rest) of: (a) unresisted sprints (UST), (b) resisted sprints with 10% of body mass (BM) load (RST10), (c) resisted sprints with 20% BM load (RST20), against a control trial (no-training). RESULTS: Blood lactate (mmol/L) increased post-training versus pre-training in all sprint-training trials (6.7 ± 2.4 vs 1.2 ± 0.2, 5.6 ± 2.4 vs 1.3 ± 0.3, 7.3 ± 2.7 vs 1.2 ± 0.3, in UST, RST10, RST20, respectively), as did creatine kinase (U/L) 24 h, 48 h and 72 h post-training (UST: 251 ± 173, 238 ± 154, 209 ± 115 vs 155 ± 9, RST10: 252 ± 134, 240 ± 83, 218 ± 103 vs 164 ± 106; RST20: 237 ± 133, 323 ± 303, 262 ± 184 vs 179 ± 106, respectively). DOMS of knee-extensors (KE) and knee-flexors (KF) increased post-training up to 72 h in all sprint-training trials versus pre-training (ranging from 1.6 ± 1.3 to 3.8 ± 2.8 vs 1.0 ± 0, respectively). Eccentric torque (N m) of the KE of the non-dominant limb, decreased 24 h post-training versus pre-training in all sprint-training trials (UST: 249 ± 49 vs 266 ± 54; RST10: 229 ± 52 vs 273 ± 72; RST20: 253 ± 6 vs 262 ± 56), as did that of the KF of the dominant limb (UST: 135 ± 29 vs 144 ± 26; RST10: 130 ± 29 vs 140 ± 25; RST20: 139 ± 33 vs 142 ± 26). 10-m sprint-time (s) increased 48 h post-training versus pre-training (1.81 ± 0.15 vs 1.77 ± 0.11), and 30-m sprint-time increased 24 h, 48 h, 72 h post-training versus pre-training (4.35 ± 0.36, 4.40 ± 0.44, 4.33 ± 0.41 vs 4.21 ± 0.34, respectively), only in RST20. CONCLUSIONS: Unresisted and resisted sprint-training induces prolonged reduction of muscle strength (24 h), and sprinting performance (72 h), associated with prolonged increase of DOMS and CK (72 h).

Understanding priorities and needs for child and adolescent mental health in Greece from multiple informants: an open resource dataset.

The Child and Adolescent Mental Health Initiative (CAMHI) aims to enhance mental health care capacity for children and adolescents across Greece. Considering the need for evidence-based policy, the program developed an open-resource dataset for researching the field within the country. A comprehensive, mixed-method, community-based research was conducted in 2022/2023 assessing the current state, needs, barriers, and opportunities according to multiple viewpoints. We surveyed geographically distributed samples of 1,756 caregivers, 1,201 children/adolescents, 404 schoolteachers, and 475 health professionals using validated instruments to assess mental health symptoms, mental health needs, literacy and stigma, service use and access, professional practices, training background, and training needs and preferences. Fourteen focus groups were conducted with informants from diverse populations (including underrepresented minorities) to reach an in-depth understanding of those topics. A dataset with quantitative and qualitative findings is now available for researchers, policymakers, and society [ https://osf.io/crz6h/ and https://rpubs.com/camhi/sdashboard ]. This resource offers valuable data for assessing the needs and priorities for child and adolescent mental health care in Greece. It is now freely available to consult, and is expected to inform upcoming research and evidence-based professional training. This initiative may inspire similar ones in other countries, informing methodological strategies for researching mental health needs.

Dosimetric characterization of a new surface-conforming electron MLC prototype.

The purpose is to reduce normal tissue radiation toxicity for electron therapy through the creation of a surface-conforming electron multileaf collimator (SCEM). The SCEM combines the benefits of skin collimation, electron conformal radiotherapy, and modulated electron radiotherapy. An early concept for the SCEM was constructed. It consists of leaves that protrude towards the patient, allowing the leaves to conform closely to irregular patient surfaces. The leaves are made of acrylic to decrease bremsstrahlung, thereby decreasing the out-of-field dose. Water tank scans were performed with the SCEM in place for various field sizes for all available electron energies (6, 9, 12, and 15 MeV) with a 0.5 cm air gap to the water surface at 100 cm source-to-surface distance (SSD). These measurements were compared with Cerrobend cutouts with the field size-matched at 100 and 110 cm SSD. Output factor measurements were taken in solid water for each energy at dmax for both the cerrobend cutouts and SCEM at 100 cm SSD. Percent depth dose (PDD) curves for the SCEM shifted shallower for all energies and field sizes. The SCEM also produced a higher surface dose relative to Cerrobend cutouts, with the maximum being a 9.8% increase for the 3 cm × 9 cm field at 9 MeV. When compared to the Cerrobend cutouts at 110 cm SSD, the SCEM showed a significant decrease in the penumbra, particularly for lower energies (i.e., 6 and 9 MeV). The SCEM also showed reduced out-of-field dose and lower bremsstrahlung production than the Cerrobend cutouts. The SCEM provides significant improvement in the penumbra and out-of-field dose by allowing collimation close to the skin surface compared to Cerrobend cutouts. However, the added scatter from the SCEM increases shallow PDD values. Future work will focus on reducing this scatter while maintaining the penumbra and out-of-field benefits the SCEM has over conventional collimation.

Intravascular lithotripsy in peripheral lesions with severe calcification and its use in TAVI procedure - a meta-analysis.

Background: Heavily calcified peripheral artery lesions increase the risk of vascular complications, constituting a severe challenge for the operator during catheter-based cardiovascular interventions. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and represents a promising technique for plaque modification in patients with severe calcification in peripheral arteries. Purpose: Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified peripheral arteries and its use in Transcatheter Aortic Valve Implantation (TAVI). Patients and methods: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL in the peripheral vasculature. The diameter of the vessel lumen before and after IVL was estimated. The occurrence of peri-procedural complications was assessed using a random-effects model. Results: 20 studies with a total of 1,223 patients with heavily calcified peripheral lesions were analysed. The mean age of the cohort was 70.6 ± 17.4 years. Successful IVL delivery achieved in 100% (95% CI: 100%-100%, I2 = 0%), with an increase in the luminal diameter (SMD: 4.66, 95% CI: 3.41-5.92, I2 = 90.8%) and reduction in diameter stenosis (SMD: -4.15, 95% CI: -4.75 to -3.55, I2 = 92.8%), and a concomitant low rate of complications. The procedure was free from dissection in 97% (95% CI: 91%-100%, I2 = 81.4%) while dissections of any type (A, B, C, or D) were observed in 6% (95% CI: 2%-10%, I2 = 85.3%) of the patients. Several rare cases of abrupt closure, no-reflow phenomenon, perforation, thrombus formation, and distal embolization were recorded. Finally, the subgroup analysis of patients who underwent a TAVI with IVL assistance presented successful implantation in 100% (95% CI: 100%-100%, I2 = 0%) of the cases, with only 4% (95% CI: 0%-12%, I2 = 68.96%) presenting dissections of any sort. Conclusions: IVL seems to be an effective and safe technique for modifying severely calcified lesions in peripheral arteries and it is a promising modality in TAVI settings. Future prospective studies are needed to validate our results.

Reactive Oxygen Species Mechanisms that Regulate Protein-Protein Interactions in Cancer.

Reactive oxygen species (ROS) are produced during cellular metabolism and in response to environmental stress. While low levels of ROS play essential physiological roles, excess ROS can damage cellular components, leading to cell death or transformation. ROS can also regulate protein interactions in cancer cells, thereby affecting processes such as cell growth, migration, and angiogenesis. Dysregulated interactions occur via various mechanisms, including amino acid modifications, conformational changes, and alterations in complex stability. Understanding ROS-mediated changes in protein interactions is crucial for targeted cancer therapies. In this review, we examine the role that ROS mechanisms in regulating pathways through protein-protein interactions.

The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.

The DNA damage response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway as well as abnormalities in the DDR/MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.