A handy way for forming N-doped TiO2/carbon from pectin and d,l-serine hydrazide hydrochloride.

N-doped TiO2/carbon composites (N-TiPC) have shown excellent photodegradation performances to the organic contaminants but are limited by the multistage preparation (i.e., preparation of porous carbon, preparation of N-doped TiO2, and loading of N-doped TiO2 on porous carbon). Here, we develop a handy way by combining the Pickering emulsion-gel template route and chelation reaction of polysaccharides. The N-TiPC is obtained by calcinating pectin/Dl-serine hydrazide hydrochloride (SHH)-Ti4+ chelate and is further described by modern characterization techniques. The results show that the N atom is successfully doped into the TiO2 lattice, and the bandgap value of N-TiPC is reduced to 2.3 eV. Moreover, the particle size of N-TiPC remains about 10 nm. The configurations of the composites are simulated using DFT calculation. The photocatalytic experiments show that N-TiPC has a high removal efficiency for methylene blue (MB) and oxytetracycline hydrochloride (OTC-HCL). The removal ratios of MB (20 mg/L, 50 mL) and OTC-HCL (30 mg/L, 50 mL) are 99.41 % and 78.29 %, respectively. The cyclic experiments show that the photocatalyst has good stability. Overall, this study provides a handy way to form N-TiPC with enhanced photodegradation performances. It can also be promoted to other macromolecules such as cellulose and its derivatives, sodium alginate, chitosan, lignin, etc.

Modulating alginate-polyurethane elastomer properties: Influence of NCO/OH ratio with aliphatic diisocyanate.

This research addresses the need for enhanced biomaterials by investigating the influence of the NCO/OH ratio on sodium alginate-based polyurethane elastomers(Al-PUEs), offering novel insights into their structural, thermal, mechanical and swelling behavior. Al-PUEs were prepared by blending the chain extenders with key ingredients in a specific molar ratio using aliphatic HMDI and HTPB monomers. The chemical linkages, crystalline behavior, homogeneity, and surface morphology of PUEs were evaluated by FT-IR, XRD, SEM, and EDX analysis. Thermo-mechanical studies were performed using TGA, DSC and tensile testing. Swelling behavior and absorption analysis were analyzed in DMSO and water. The analysis indicated that the hydrophilicity and swelling behavior of the prepared PUEs were affected by the addition of sodium alginate content. The results exhibit the tailor-made network structure of Al-PUEs, resulting in better thermal stability, elasticity of materials via stress-strain behavior and marvelous characteristic features than traditional high-tech yields. Furthermore, the resulting Al-PUEs are potential candidates for biomedical implants.

Transformative enhancement of cellulosic textile properties via metallic oxide deposition: Comprehensive analysis of structural, optical, and thermoelectric traits.

This novel research addresses the critical need for sustainable and efficient materials, aiming to enhance the optical and thermoelectric properties of Aluminum doped Zinc Oxide (Al-doped ZnO) on cellulose fabric for diverse applications. At first stage, Cellulosic fabric of Al-doped ZnO were experimentally studied in detail with respect to varying levels of annealing temperature. Structural analysis unveiled structural evolution in hexagonal crystal formations with a reduction in particle size up to 27.5 % on average, with increased temperature. Further, Raman spectroscopy revealed the doping effects on the vibrational modes of ZnO, potentially due to alterations in lattice structure. The ZnO optical modes are found as E2 (low) = 110 cm-1 with observed phonon frequency in the Raman spectra of ZnO at A1 (TO) = 364 cm-1. Fourier transform infrared spectroscopy (FTIR) revealed the presence of characteristic stretching of developed material. Furthermore, the optical characters revealed a decrement of 43.22 % in bandgap values with increasing annealing temperature. The analysis of thermoelectric attributes documented that the prominent sample annealed at 300°C exhibited the maximum Seebeck coefficient and power factor of 2.1 × 10-3 µV/oC and 5.8 × 10-21 Wm-1 K-2, respectively. At second stage the optical characteristics of experimentally optimized sample were rigorously studied through the application of Material Studio software, while varying the doping ratio.

Following hip fracture, hospital organizational factors associated with prescription of anti-osteoporosis medication on discharge, to address imminent refracture risk: a record-linkage study.

Patients who sustain a hip fracture are known to be at imminent refracture risk. Their complex multidisciplinary rehabilitation needs to include falls prevention and anti-osteoporosis medication (AOM) to prevent such fractures. This study aimed to determine which hospital-level organizational factors predict prescription of post-hip fracture AOM and refracture risk. A cohort of 178 757 patients aged ≥60 yr who sustained a hip fracture in England and Wales (2016-2019) was examined and followed for 1 yr. Patient-level hospital admission datasets from 172 hospitals, the National Hip Fracture Database, and mortality data were linked to 71 metrics extracted from 18 hospital-level organizational reports. Multilevel models determined organizational factors, independent of patient case-mix, associated with (1) AOM prescription and (2) refracture (by ICD10 coding). Patients were mean (SD) 82.7 (8.6) yr old, 71% female, with 18% admitted from care homes. Overall, 101 735 (57%) were prescribed AOM during admission, while 50 354 (28%) died during 1-yr follow-up, 12 240 (7%) refractured. Twelve organizational factors were associated with AOM prescription, for example, orthogeriatrician-led care compared to traditional care models (odds ratio [OR] 4.65 [95% CI, 2.25-9.59]); AOM was 9% (95% CI, 6%-13%) more likely to be prescribed in hospitals providing routine bone health assessment to all patients. Refracture occurred at median 126 d (IQR 59-234). Eight organizational factors were associated with refracture risk; hospitals providing orthogeriatrician assessment to all patients within 72 h of admission had an 18% (95% CI, 2%-31%) lower refracture risk, weekend physiotherapy provision had an 8% (95% CI, 3%-14%) lower risk, and where occupational therapists attended clinical governance meetings, a 7% (95% CI, 2%-12%) lower risk. Delays initiating post-discharge community rehabilitation were associated with a 15% (95% CI, 3%-29%) greater refracture risk. These novel, national findings highlight the importance of orthogeriatrician, physiotherapist, and occupational therapist involvement in secondary fracture prevention post hip fracture; notably, fracture risk reductions were seen within 12 mo of hip fracture.

Patients who have broken (fractured) a hip are at risk of having another fracture soon after. They have complex needs to avoid more fractures, which include being prescribed bone-strengthening medicines and taking measures to prevent falls. This study looked at which of the measurements, that describe how well a hospital is organized, are associated with whether bone-strengthening medicine is prescribed and the chance of having another fracture. We used data from 178 757 patients aged over 60 yr who had a hip fracture at 172 English and Welsh hospitals, linked to their hospital records, and other datasets that describe hospital services. Overall, 57% of patients were prescribed bone-strengthening medicines, and 7% went on to have another fracture. Bone-strengthening medicines were more likely to be prescribed in hospitals where patient care was led by a consultant specializing in the care of older people with fractures (called orthogeriatricians) and in hospitals which routinely checked patients' bone health. Patients attending hospitals that provided orthogeriatrician assessment to all patients within 72 h of being admitted, physiotherapy services at the weekend, or where occupational therapists attended meetings aimed at improving hospital services had a lower chance of having another fracture.

Longitudinal assessment of physical function in adults with X-linked hypophosphatemia following initiation of burosumab therapy.

We assessed multiple components of muscle function in ten adults with X-linked hypophosphatemia (XLH) receiving burosumab treatment. Lower limb power (+ 9%), short physical performance battery (SPPB) score (+ 1.2 points), and physical activity (+ 65%) increased following 6 months of treatment, and hand grip increased (+ 10%) between 6 and 12 months of treatment. PURPOSE: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism. Burosumab is a monoclonal antibody treatment shown to improve phosphate homeostasis and improve symptoms as well as fracture healing when used as a therapy for XLH in adults. However, little is known about its effects on the large deficits in multiple components of physical function previously reported in XLH. METHODS: Ten adults (6 females, age 41.1 ± 15.7 y) were recruited from specialist centres in London and Bristol. During clinical visits for initial burosumab treatment and at 6-month and 12-month follow-up, physical function, and physical activity (PA) assessments were performed. In detail, lower limb power was assessed by mechanography via a countermovement jump, mobility by short physical performance battery (SPPB), functional capacity by 6-min walk test (6MWT), upper limb strength by hand grip dynamometry, and PA via an International Physical Activity Questionnaire (IPAQ). Differences between baseline and 6-month follow-up, and in a subset of 5 patients between 6- and 12-month follow-up, were assessed. RESULTS: Lower limb power increased by 9% (P = 0.049) from baseline to 6 months, as did SPPB score (+ 1.2 points, P = 0.033) and total PA (+ 65%, P = 0.046) although hand grip and 6MWT did not differ. Only for hand grip was a significant improvement (+ 10%, P = 0.023) seen between 6 and 12 months. CONCLUSIONS: Burosumab treatment is associated with improved lower limb function and mobility at 6 months, with improvement in hand grip strength at 12 months. Future studies should explore the underlying mechanisms and describe on function and other patient outcomes.

Setrusumab for the Treatment of Osteogenesis Imperfecta: 12-Month Results from the Phase 2b Asteroid Study.

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20 mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-month treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20 mg/kg open label. Therefore, only results from the 2, 8, and 20 mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular vBMD from baseline at Month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro finite element-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12 months, there was a significant increase in mean (SE) failure load in the 20 mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20 mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p > 0.05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20 mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation.

Osteogenesis imperfecta, or OI, is a rare disorder affecting patients' bones causing pain and an increased chance of the bone breaking. Setrusumab is a possible treatment for OI being studied in a clinical trial called Asteroid. The goal of Asteroid was to determine which dose of setrusumab helped adults with OI the most: 2, 8, or 20 mg/kg. Researchers looked at the density of patients' bones and estimated how strong their bones were before setrusumab and again after 12 months of treatment to see how they improved with treatment. Researchers could compare these improvements to see which dose of setrusumab helped patients the most. Patients on the highest dose of setrusumab (20 mg/kg) experienced improvements in the density of their arm bones (radius) and leg bones (tibia) after 12 months. The strength of these bones also improved. The density of other bones including the spine, hip, and the overall skeleton (total body) also improved with treatment. Of patients who had side effects after receiving setrusumab, most were mild or moderate intensity. Overall, setrusumab improved the bones of patients with OI with no serious safety concerns. More studies will include even more patients to see how setrusumab can improve their bones.

Demystifying normal-anion-gap metabolic acidosis: pathophysiology, aetiology, evaluation and diagnosis.

Normal-anion-gap metabolic acidosis (NAGMA) is a common but often under-recognised and poorly understood condition, especially by less-experienced clinicians. In adults, NAGMA might be an initial clue to a more significant underlying pathology, such as autoimmune diseases, hypergammaglobulinemia or drug toxicities. However, identifying the aetiology can be challenging due to the diverse processes involved in the development of acidosis. A better understanding of the pathophysiology of NAGMA can help treating physicians suspect and evaluate the condition early and reach the correct diagnosis. This article provides an overview of renal acid-base regulation, discusses the pathophysiological processes involved in developing NAGMA and provides a framework for evaluation to reach an accurate diagnosis.

Green-synthesized lignin nanoparticles enhance Zea mays resilience to salt stress by improving antioxidant metabolism and mitigating ultrastructural damage.

Soil salinity poses a substantial threat to agricultural productivity, resulting in far-reaching consequences. Green-synthesized lignin nanoparticles (LNPs) have emerged as significant biopolymers which effectively promote sustainable crop production and enhance abiotic stress tolerance. However, the defensive role and underlying mechanisms of LNPs against salt stress in Zea mays remain unexplored. The present study aims to elucidate two aspects: firstly, the synthesis of lignin nanoparticles from alkali lignin, which were characterized using Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Fourier Infrared Spectroscopy (FT-IR) and Energy Dispersive X-Ray Spectroscopy (EDX). The results confirmed the purity and morphology of LNPs. Secondly, the utilization of LNPs (200 mg/L) in nano priming to alleviate the adverse effects of NaCl (150 mM) on Zea mays seedlings. LNPs significantly reduced the accumulation of Na+ (17/21%) and MDA levels (21/28%) in shoots/roots while increased lignin absorption (30/31%), resulting in improved photosynthetic performance and plant growth. Moreover, LNPs substantially improved plant biomass, antioxidant enzymatic activities and upregulated the expression of salt-tolerant genes (ZmNHX3 (1.52 & 2.81 FC), CBL (2.83 & 3.28 FC), ZmHKT1 (2.09 & 4.87 FC) and MAPK1 (3.50 & 2.39 FC) in both shoot and root tissues. Additionally, SEM and TEM observations of plant tissues confirmed the pivotal role of LNPs in mitigating NaCl-induced stress by reducing damages to guard cells, stomata and ultra-cellular structures. Overall, our findings highlight the efficacy of LNPs as a practical and cost-effective approach to alleviate NaCl-induced stress in Zea mays plants. These results offer a sustainable agri-environmental strategy for mitigating salt toxicity and enhancing crop production in saline environments.

Exploring Roemheld syndrome: a comprehensive review with proposed diagnostic criteria.

Roemheld syndrome (RS) is a condition that triggers cardiac symptoms due to gastrointestinal compression of the heart. It is often misdiagnosed as other types of cardiac or digestive disorders, leading to unnecessary treatments and reduced quality of life. Here, we provide a thorough review of RS, covering its pathogenesis, etiology, diagnosis, treatment, and outcome. We found that a number of conditions, including gallstones, hiatal hernia, excessive gas, and gastroesophageal reflux syndrome, can cause RS. The symptoms of RS can include chest pain, palpitations, shortness of breath, nausea, vomiting, bloating, and abdominal pain. Clinical history, physical examination, electrocardiograms, and improvement in symptoms following gastrointestinal therapy can all be used to identify RS. We also propose a set of criteria, the IKMAIR criteria, to improve the diagnostic approach for this condition. Dietary changes, lifestyle adjustments, pharmaceutical therapies, and surgical procedures can all be used to control RS. Depending on the underlying etiology and the outcome of treatment, RS has a varying prognosis. We conclude that RS is a complicated and understudied disorder that needs more attention from researchers and patients as well as from medical professionals. We recommend the inclusion of RS in the differential diagnosis for individuals with gastrointestinal problems and unexplained cardiac symptoms. Additionally, we advise treating RS holistically by attending to its cardiac and gastrointestinal components.

Influence of brassinosteroid and silicon on growth, antioxidant enzymes, and metal uptake of leafy vegetables under wastewater irrigation.

Vegetable cultivation under sewage irrigation is a common practice mostly in developing countries due to a lack of freshwater. Long-term usage provokes heavy metals accumulation in soil and ultimately hinders the growth and physiology of crop plants and deteriorates the quality of food. A study was performed to investigate the role of brassinosteroid (BRs) and silicon (Si) on lettuce, spinach, and cabbage under lead (Pb) and cadmium (Cd) contaminated sewage water. The experiment comprises three treatments (control, BRs, and Si) applied under a completely randomized design (CRD) in a growth chamber. BRs and Si application resulted in the highest increase of growth, physiology, and antioxidant enzyme activities when applied under canal water followed by distilled water and sewage water. However, BRs and Si increased the above-determined attributes under the sewage water by reducing the Pb and Cd uptake as compared to the control. It's concluded that sewerage water adversely affected the growth and development of vegetables by increasing Pb and Cd, and foliar spray of Si and BRs could have great potential to mitigate the adverse effects of heavy metals and improve the growth. The long-term alleviating effect of BRs and Si will be evaluated in the field conditions at different ecological zones.

Exploring the synergistic effect of carboxymethyl cellulose and chitosan in enhancing thermal stability of polyurethanes through statistical mixture design approach.

The thermal stability of polyurethanes, known for its limitations, was addressed in this research by seeking improvement through the introduction of carbohydrate-based chain extenders. In this research paper, we systematically sought to improve the thermal resistance of polyurethanes by incorporating carboxymethyl cellulose and chitosan, representing a pioneering application of the mixture design approach in their preparation. In this synthesis, hydroxyl-terminated polybutadiene and isophorone diisocyanate (IPDI) were reacted to prepare -NCO terminated prepolymer, which was subsequently reacted with varying mole ratios of CMC and CSN to develop a series of five PU samples. The prepared PU samples were characterized using the Fourier-transformed infrared spectroscopic technique. Thermal pyrolysis of PU samples was examined using thermal gravimetric analysis (TGA). It was observed that, among all the samples, PUS-3 showed remarkable thermal stability over a wide temperature range. A comprehensive statistical analysis was conducted to substantiate the experimental findings. It was estimated that CMC and CSN significantly enhance the thermal stability of the samples when involved in an interaction fashion. The ANOVA Table for the mixture design demonstrates that over 90 % of the total variation in thermal stability is explained by the mixture model across a wide temperature range. Moreover, PSU-3 exhibited 4 % more thermal stability over a wide range of temperatures on average, as compared to contemporary samples.

Development of lactic acid based chain extender and soybean oil-derived polyurethanes for ecofriendly sustained drug delivery systems.

In the present study, a range of sustainable, biocompatible and biodegradable polyurethanes (PU-1 to PU-4) were synthesized using different combinations of biobased polyol (obtained through the epoxidation of soybean oil, followed by ring opening with ethanol) and polyethylene glycol (PEG) and isophorone diisocyanate. The sustainable chain extender used in this study was synthesized by the esterification of lactic acid with ethylene glycol (EG). The synthesized PU samples were characterized through scanning electron microscopy (SEM), Fourier transformed infrared (FTIR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopy. Wetting ability and thermal degradation analysis (TGA) of the samples were also studied. Subsequently, these PUs were examined as potential drug delivery systems using Gabapentin as a model drug, which was loaded in the polymer matrix using the solvent evaporation method. The drug release studies were carried out in 0.06 N HCl as a release medium according to the method outlined in the United States Pharmacopeia. The maximum drug release was observed for sample PU-P1, which was found to be 53.0 % after 6 h. Moreover, a comparison of different PU samples revealed a trend wherein the values of drug release were decreased with an increase in the PEG content.

The synergistic potential of biochar and nanoparticles in phytoremediation and enhancing cadmium tolerance in plants.

Cadmium (Cd) is classified as a heavy metal (HM) and is found into the environment through both natural processes and intensified anthropogenic activities such as industrial operations, mining, disposal of metal-laden waste like batteries, as well as sludge disposal, excessive fertilizer application, and Cd-related product usage. This rising Cd disposal into the environment carries substantial risks to the food chain and human well-being. Inadequate regulatory measures have led to Cd bio-accumulation in plants, which is increasing in an alarming rate and further jeopardizing higher trophic organisms, including humans. In response, an effective Cd decontamination strategy such as phytoremediation emerges as a potent solution, with innovations in nanotechnology like biochar (BC) and nanoparticles (NPs) further augmenting its effectiveness for Cd phytoremediation. BC, derived from biomass pyrolysis, and a variety of NPs, both natural and less toxic, actively engage in Cd removal during phytoremediation, mitigating plant toxicity and associated hazards. This review scrutinizes the application of BC and NPs in Cd phytoremediation, assessing their synergistic mechanism in influencing plant growth, genetic regulations, structural transformations, and phytohormone dynamics. Additionally, the review also underscores the adoption of this sustainable and environmentally friendly strategies for future research in employing BC-NP microaggregates to ameliorate Cd phytoremediation from soil, thereby curbing ecological damage due to Cd toxicity.

Effect of salinity stress and surfactant treatment with zinc and boron on morpho-physiological and biochemical indices of fenugreek (Trigonella foenum-graecum).

Micronutrient application has a crucial role in mitigating salinity stress in crop plants. This study was carried out to investigate the effect of zinc (Zn) and boron (B) as foliar applications on fenugreek growth and physiology under salt stress (0 and 120 mM). After 35 days of salt treatments, three levels of zinc (0, 50, and 100 ppm) and two levels of boron (0 and 2 ppm) were applied as a foliar application. Salinity significantly reduced root length (72.7%) and shoot length (33.9%), plant height (36%), leaf area (37%), root fresh weight (48%) and shoot fresh weight (75%), root dry weight (80%) and shoot dry weight (67%), photosynthetic pigments (78%), number of branches (50%), and seeds per pod (56%). Fenugreek's growth and physiology were improved by foliar spray of zinc and boron, which increased the length of the shoot (6%) and root length (2%), fresh root weight (18%), and dry root weight (8%), and chlorophyll a (1%), chlorophyll b (25%), total soluble protein content (3%), shoot calcium (9%) and potassium (5%) contents by significantly decreasing sodium ion (11%) content. Moreover, 100 ppm of Zn and 2 ppm of B enhanced the growth and physiology of fenugreek by reducing the effect of salt stress. Overall, boron and zinc foliar spray is suggested for improvement in fenugreek growth under salinity stress.

Thromboembolic phenomena in patients with nephrotic syndrome: pathophysiology, risk factors, prophylaxis and treatment.

Thromboembolic events resulting from disturbances in the body's balance of thrombotic and antithrombotic abilities are among the most life-threatening complications of nephrotic syndrome. Certain causes of nephrotic syndrome leave the patient particularly susceptible to thromboembolism. The severity of proteinuria and degree of hypoalbuminaemia are other common predictors of risk. Timely initiation of prophylactic therapy can help prevent morbidity and mortality associated with this complication in patients with nephrotic syndrome. The duration of treatment and choice of therapeutic agent depends on several factors, including the degree of hypoalbuminaemia, risk factors for thrombosis and risk of bleeding. This article reviews current understanding of the pathophysiology and risk factors for thromboembolism associated with nephrotic syndrome, and summarises recommendations and strategies for preventing and treating thromboembolic events in patients with nephrotic syndrome.

Complements and Their Role in Systemic Disorders.

The complement system is critical to the body's innate defense against exogenous pathogens and clearance of endogenous waste, comprising the classical, alternative, and lectin pathways. Although tightly regulated, various congenital and acquired diseases can perturb the complement system, resulting in specific complement deficiencies. Systemic rheumatic, neurological, ophthalmological, renal, and hematological disorders are some prototypical complement-mediated diseases. An adequate understanding of the mechanisms of the normal complement system and the pathophysiology of complement dysregulation is critical for providing diagnostic clues and appropriately managing these conditions. This review guides clinicians in understanding the role of complement factors in systemic diseases and what diagnostic and therapeutic options are available for complement-mediated disorders.

Computing dominant metric dimensions of certain connected networks.

In the studies of the connected networks, metric dimension being a distance-based parameter got much more attention of the researches due to its wide range of applications in different areas of chemistry and computer science. At present its various types such as local metric dimension, mixed metric dimension, solid metric dimension, and dominant metric dimension have been used to solve the problems related to drug discoveries, embedding of biological sequence data, classification of chemical compounds, linear optimization, robot navigation, differentiating the interconnected networks, detecting network motifs, image processing, source localization and sensor networking. Dominant resolving sets are better than resolving sets because they carry the property of domination. In this paper, we obtain the dominant metric dimension of wheel, gear and anti-web wheel network in the form of integral numbers. We observe that the aforesaid networks have bounded dominant metric dimension as the order of the network increases. In particular, we also discuss the importance of the obtained results for the robot navigation networking.

Diagnostic journey for individuals with fibrous dysplasia / McCune albright syndrome (FD/MAS).

BACKGROUND: Reducing delayed diagnosis is a significant healthcare priority for individuals with rare diseases. Fibrous Dysplasia/ McCune Albright Syndrome (FD/MAS) is a rare bone disease caused by somatic activation mutations of NASA. FD/MAS has a broad clinical phenotype reflecting variable involvement of bone, endocrine and other tissues, distribution and severity. The variable phenotype is likely to prolong the diagnostic journey for patients further. AIM: To describe the time from symptom onset to final diagnosis in individuals living with FDMAS. METHODS: We used the UK-based RUDY research database ( www.rudystudy.org ), where patients self-report their diagnosis of FD/MAS. Participants are invited to complete the diagnostic journey based on the EPIRARE criteria. RESULTS: 51 individuals diagnosed with FD/MAS were included in this analysis. Among them, 70% were female, and the median age was 51.0 years (IQR 34.5-57.5]. 12 (35%) individuals reported McCune Albright Syndrome, 11 (21.6%) craniofacial and 11(21.6%) for each of poly- and mono-ostotic FD and 6 (11.8%) did not know their type of FD/MAS. Pain was the commonest first symptom (58.8%), and 47.1% received another diagnosis before the diagnosis of FD/MAS. The median time to final diagnosis from the first symptom was two years with a wide IQR (1,18) and range (0-59 years). Only 12 (23.5%) of individuals were diagnosed within 12 months of their first symptoms. The type of FD/MAS was not associated with the reported time to diagnosis. Significant independent predictors of longer time to final diagnosis included older current age, younger age at first symptom and diagnosis after 2010. CONCLUSION: Individuals with FDMAS have a variable time to diagnosis that can span decades. This study highlights the need for further research on how to improve diagnostic pathways within Orthopaedic and Ear, Nose and Throat (ENT)/Maxillofacial services. Our data provides a baseline to assess the impact of novel NHS diagnostic networks on reducing the diagnostic odyssey.

Melatonin as a master regulatory hormone for genetic responses to biotic and abiotic stresses in model plant Arabidopsis thaliana: a comprehensive review.

Melatonin is a naturally occurring biologically active amine produced by plants, animals and microbes. This review explores the biosynthesis of melatonin in plants, with a particular focus on its diverse roles in Arabidopsis thaliana , a model species. Melatonin affects abiotic and biotic stress resistance in A. thaliana . Exogenous and endogenous melatonin is addressed in association with various conditions, including cold stress, high light stress, intense heat and infection with Botrytis cinerea or Pseudomonas , as well as in seed germination and lateral root formation. Furthermore, melatonin confers stress resistance in Arabidopsis by initiating the antioxidant system, remedying photosynthesis suppression, regulating transcription factors involved with stress resistance (CBF, DREB, ZAT, CAMTA, WRKY33, MYC2, TGA) and other stress-related hormones (abscisic acid, auxin, ethylene, jasmonic acid and salicylic acid). This article additionally addresses other precursors, metabolic components, expression of genes (COR , CBF , SNAT , ASMT , PIN , PR1 , PDF1.2 and HSFA ) and proteins (JAZ, NPR1) associated with melatonin and reducing both biological and environmental stressors. Furthermore, the future perspective of melatonin rich agri-crops is explored to enhance plant tolerance to abiotic and biotic stresses, maximise crop productivity and enhance nutritional worth, which may help improve food security.