Organ Systems Research Articles

Nomogram for predicting early hypophosphatemia in term infants

Abstract Background Physiological processes rely on phosphate, which is an essential component of adenosine triphosphate (ATP). Hypophosphatasia can affect nearly every organ system in the body. It is crucial to monitor newborns with risk factors for hypophosphatemia and provide them with the proper supplements. We aimed to evaluate the risk factors and develop a nomogram for early hypophosphatemia in term infants. Methods We conducted a retrospective study involving 416 term infants measured serum phosphorus within three days of birth. The study included 82 term infants with hypophosphatemia (HP group) and 334 term infants without hypophosphatemia (NHP group). We collected data on the characteristics of mothers, newborn babies, and childbirth. Furthermore, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for hypophosphatemia in term infants, and a nomogram was developed and validated based on the final independent risk factors. Results According to our analysis, the multivariate logistic regression analysis showed that male, maternal diabetes, cesarean delivery, lower serum magnesium, and lower birth weight were independent risk factors for early hypophosphatemia in term infants. In addition, the C-index of the developed nomogram was 0.732 (95% CI = 0.668–0.796). Moreover, the calibration curve indicated good consistency between the hypophosphatemia diagnosis and the predicted probability, and a decision curve analysis (DCA) confirmed the clinical utility of the nomogram. Conclusions The analysis revealed that we successfully developed and validated a nomogram for predicting early hypophosphatemia in term infants.

Piezo1 and Piezo2 collectively regulate jawbone development.

Piezo1 and Piezo2 are novel mechanosensory ion channels that transduce mechanical stimuli from the environment into intracellular biochemical signals in various tissues and organ systems. Here, we showed that Piezo1 and Piezo2 displayed a robust expression during jawbone development. Deletion of Piezo1 in neural crest cells caused jawbone malformations in a small but significant number of mice. We further demonstrated that disruption of Piezo1 and Piezo2 in neural crest cells caused more striking defects in jawbone development than any single knockout, suggesting essential but partially redundant roles of Piezo1 and Piezo2. In addition, we observed defects in other neural crest derivatives such as malformation of the vascular smooth muscle in double knockout mice. Moreover, TUNEL examinations revealed excessive cell death in osteogenic cells of the maxillary and mandibular arches of the double knockout mice, suggesting that Piezo1 and Piezo2 together regulate cell survival during jawbone development. We further demonstrated that Yoda1, a Piezo1 agonist, promotes mineralization in the mandibular arches. Altogether, these data firmly establish that Piezo channels play important roles in regulating jawbone formation and maintenance.

Exploring clinical variability in gelsolin amyloidosis: Brazilian family case study with confocal microscopy.

Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked by amyloid fibrils composed of misfolded gelsolin fragments. We present three sisters with AGel amyloidosis, illustrating its clinical diversity. Patient 1, a 51-year-old, had bilateral ptosis, ocular discomfort, and dry eye syndrome due to cranial nerve involvement. Patient 2, a 53-year-old, experienced progressive bilateral visual impairment. Patient 3, a 50-year-old, exhibited right eye ectropion. Genetic analysis, with the identical mutation, heterozygous c.640G > A (p.Asp214Asn) mutation, confirmed AGel amyloidosis diagnoses, with common findings including lattice corneal amyloidosis, reduced corneal sensitivity, and recurrent corneal erosions. Neurological manifestations included ataxia and peripheral neuropathy, with skin abnormalities observed in patient 1. Ocular involvement severity and distribution varied among patients. Common ocular and neurological manifestations validated AGel amyloidosis diagnoses, reinforcing its hereditary basis. Neurological symptoms highlighted the disorder's impact on various organ systems, while skin abnormalities contributed to ocular discomfort. Variable ocular involvement emphasized the disorder's heterogeneity. These patients emphasize hereditary gelsolin amyloidosis's clinical diversity and suggest potential environmental influences on disease expression. Genetic confirmation and confocal microscopy findings reaffirm the genetic basis while raising questions about assessing systemic disease severity, necessitating further investigation in larger cohorts. Ophthalmologists' specialized care is crucial for managing ocular symptoms, given the absence of a universal cure.

Total hip arthroplasty outcomes in Ehlers-Danlos patients: data from the Statewide Planning and Research Cooperative System.

Ehlers-Danlos syndromes (EDS) are genetic connective tissue disorders affecting multiple organ systems that frequently result in connective tissue hyperlaxity and early osteoarthritis. Short- and long-term outcomes after primary total hip arthroplasty (THA) in this patient population remain poorly characterised. The primary purpose of this study is to compare postoperative outcomes and survivorship after primary THA in patients with and without EDS. The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for all patients undergoing primary elective THA between September 2009 and December 2020. Patients with EDS were identified using ICD9 and ICD10 diagnosis codes. Given the relatively low incidence of EDS in this patient population, the cohort was propensity-matched 1:10 to patients without diagnosis of EDS based on demographics characteristics and medical comorbidities as measured by the Elixhauser Comorbidity Index. A total of 66 THA patients with and 660 without EDS were included in each group after 1:10 propensity-matching. There were no significant differences in baseline characteristics or THA indications. Early postoperative outcomes such as length of hospital stay and discharge disposition were similar. Emergency Room visits and inpatient readmission rates at 3 months postoperatively did not significantly differ between groups. Patients with EDS had a higher overall revision rate compared to those without (15.0% vs. 3.2%, p < 0.001). Revision free survival after primary THA in patients with EDS was significantly lower than those without EDS at 9-year follow-up. Cox proportional hazard regression demonstrated EDS patients had 7-times higher risk of revision (hazard ratio [HR] 7.43; 95% CI, 3.46-16.00; p < 0.001). Lastly, revision due to instability insignificantly trended higher in the EDS cohort (HR 2.29; 95% CI, 0.95-5.49; p = 0.063). EDS patients undergoing primary THA have increased rate of all cause revision and demonstrate decreased revision free survival compared to non-EDS THA patients.

Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management.

Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.

Value of preclinical systematic reviews and meta-analyses in pediatric research.

Similar to systematic reviews (SRs) in clinical fields, preclinical SRs address a specific research area, furnishing information on current knowledge, possible gaps, and potential methodological flaws of study design, conduct, and report. One of the main goals of preclinical SRs is to identify aspiring treatment strategies and evaluate if currently available data is solid enough to translate to clinical trials or highlight the gaps, thus justifying the need for new studies. It is imperative to rigorously follow the methodological standards that are widely available. These include registration of the protocol and adherence to guidelines for assessing the risk of bias, study quality, and certainty of evidence. A special consideration should be made for pediatric SRs, clinical and preclinical, due to the unique characteristics of this age group. These include rationale for intervention and comparison of primary and secondary outcomes. Outcomes measured should acknowledge age-related physiological changes and maturational processes of different organ systems. It is crucial to choose the age of the animals appropriately and its possible correspondence for specific pediatric age groups. The findings of well-conducted SRs of preclinical studies have the potential to provide a reliable evidence synthesis to guide the design of future preclinical and clinical studies. IMPACT: This narrative review highlights the importance of rigorous design, conduct and reporting of preclinical primary studies and systematic reviews. A special consideration should be made for pediatric systematic reviews of preclinical studies, due to the unique characteristics of this age group.

Review of Virulence Factors in Candida

Candida albicans is a prevalent commensal fungus that inhabits various anatomical regions, including the oropharyngeal cavity, gastrointestinal and vaginal tract, as well as the skin of persons in good condition. C. albicans is present in the normal flora of the microbiota in around 50% of the population. The clinical presentations of Candida species encompass a spectrum of symptoms, spanning from localized. The spectrum of mucocutaneous issues ranges from superficial to invasive disorders that impact many organ systems and present a substantial threat to human life. Disruptions in the normal homeostasis of Candida can be attributed to a range of reasons, encompassing systemic and local factors as well as genetic and environmental influences.&#x0D; These disruptions ultimately lead to a shift from a state of normal flora to the development of Infections caused by pathogens and opportunistic agents. The initiation and advancement of infection are regulated by the virulence characteristics of Candida, which play a role in the emergence of candidiasis. Oral candidiasis presents with a wide range of symptoms, which can be classified into major and minor types. The gastrointestinal tract is the main reservoir for Candida albicans in the human body. Infection occurs due to an imbalance in the local microbiota, impaired immune function, and damage to the intestinal mucosal barrier. Candidaemia, a term used to describe invasive infections caused by candida, is associated with the presence of Candida albicans in the bloodstream. The mutual relationship remains intact by maintaining a balance between the host immune system and C. albicans virulence factors. This study investigates the virulence traits exhibited by Candida albicans. These components have a significant impact on the development of disorders.

Tuneable Current Rectification Through a Designer Graphene Nanoribbon.

Unimolecular current rectifiers are fundamental building blocks in organic electronics. Rectifying behavior has been identified in numerous organic systems due to electron-hole asymmetries of orbital levels interfaced by a metal electrode. As a consequence, the rectifying ratio (RR) determining the diode efficiency remains fixed for a chosen molecule-metal interface. Here, wepresent a mechanically tunable molecular diode exhibiting an exceptionally large rectification ratio (>105) and reversible direction. The molecular system comprises a 7-armchair graphene nanoribbon (GNR) doped with a single unit of substitutional diboron within its structure, synthesized with atomic precision on a gold substrate by on-surface synthesis. The diboron unit creates half-populated in-gap bound states and splits the GNR frontier bands into two segments, localizing the bound state in a double barrier configuration. By suspending these GNRs freely between the tip of a low-temperature scanning tunneling microscope and the substrate, wedemonstrate unipolar hole transport through the boron in-gap state's resonance. Strong current rectification is observed, associated with the varying widths of the two barriers, which can be tuned by altering the distance between tip and substrate. This study introduces an innovative approach for the precise manipulation of molecular electronic functionalities, opening new avenues for advanced applications in organicelectronics. This article is protected by copyright. All rights reserved.

Treatment with Digoxin – is it a clinical challenge? A Retrospective Analysis of Hospitalizations due to Digoxin intoxication

Introduction and purpose: Digoxin, a cardiac glycoside derived from Digitalis lanata, has stood as a cornerstone in the treatment of various cardiovascular disorders for centuries. This study aims to delve into the demographic aspects, clinical characteristics, and outcomes associated with Digoxin poisoning. By drawing upon a dataset involving 22 patients hospitalized for Digoxin intoxication at the Clinical Department of Toxicology and Cardiology in Lublin, Poland, spanning from April 2014 to December 2023, our investigation seeks to provide an understanding of this issue.Brief description of the state of knowledge: Despite the efficacy of Digoxin, the potential risk of intoxication, especially in the elderly, necessitate a comprehensive examination. Age-related changes, such as declining renal function,  electrolyte imbalances, comorbidities and polypharmacy affect how drugs like Digoxin work. The symptoms of Digoxin poisoning can manifest in various organ systems such as cardiovascular, gastrointestinal, nervous system, highlighting the importance of prompt recognition to seek medical attention.Methods and results: In our study, we analyzed data from 22 patients hospitalized due to Digoxin intoxication, focusing on demographic aspects, clinical characteristics and outcomes. The cases of Digoxin poisoning were categorized according to several factors, including the quantity and nature of substances consumed, the cause of intoxication, gender, age brackets, health conditions, peak serum Digoxin levels, length and outcomes of hospitalization.Conclusions: Our study provides insights into the characteristics and outcomes of patients hospitalized due to Digoxin intoxication. The findings underscore the association of Digoxin poisoning, and emphasize the importance of monitoring serum levels to prevent adverse outcomes. As Digoxin continues to be relevant in treating cardiovascular conditions, our study calls for careful management and monitoring.

Monolithically Defined Wireless Fully Implantable Nervous System Interfaces.

ConspectusEvolution of implantable neural interfaces is critical in addressing the challenges in understanding the fundamental working principles and therapeutic applications for central and peripheral nervous systems. Traditional approaches utilizing hermetically sealed, rigid electronics and detached electrodes face challenges in power supply, encapsulation, channel count, dispersed application location, and modality. Employing thin-film, wirelessly powered devices is promising to expand capabilities. Devices that forego bulky power supplies, favoring a configuration where electronics are integrated directly onto thin films, reduce displacement volumes for seamless, fully implantable interfaces with high energy availability and soft mechanics to conform to the neuronal target. We discuss 3 device architectures: (1) Highly miniaturized devices that merge electronics and neural interfaces into a single, injectable format; (2) Interfaces that consolidate power, computation, and neural connectivity on a thin sheet applied directly to the target area; (3) A spatially dislocated approach where power and computation are situated subdermally, connected via a thin interconnect to the neural interface.Each has advantages and constraints in terms of implantation invasiveness, power capturing efficiency, and directional sensitivity of power delivery. In powering these devices, near-field power delivery emerges as the most implemented technique. Key parameters are size and volume of primary and secondary antennas, which determine coupling efficiency and power delivery. Based on application requirements, ranging from small to large animal models, subjects require system level designs. Material strategies play a crucial role; monolithic designs, with materials like polyimide substrates, enable scalability with high performance. This contrasts with established hermetic encapsulation approaches that use a stainless steel or titanium box with passthroughs that result in large tissue displacements and prohibit intimate integration with target organ systems. Encapsulation, particularly with parylene, enables longevity and effectiveness; more research is needed to enable human lifetime operation. Implant-to-ambient device communication, focusing on strategies compatible with well-established standards and off-the-shelf electronics, is discussed with the goal of enabling seamless system integration, reliability, and scalability. The interface with the central nervous system is explored through various wireless, battery-free devices capable of both stimulation (electrical and optogenetic) and recording (photometric and electrochemical). These devices show advanced capabilities for chronic studies and insights into neural dynamics. In the peripheral nervous system, stimulation devices for applications, such as spinal and muscle stimulation, are discussed. The challenges lie in the mechanical and electrochemical durability. Examples that successfully navigate these challenges offer solutions for chronic studies in this domain. The potential of wireless, fully implantable nervous system interfaces using near field resonant power transfer is characterized by monolithically defined device architecture, providing a significant leap toward seamless access to the central and peripheral nervous systems. New avenues for research and therapeutic applications supporting a multimodal and multisite approach to neuromodulation with a high degree of connectivity and a holistic approach toward deciphering and supplementing the nervous system may enable recovery and treatment of injury and chronic disease.

Impact of Elevated Body Mass Index (BMI) on Cognitive Functioning and Inflammation in Persons with Post-COVID-19 Condition: A Secondary Analysis.

Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterized by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC. This is a post-hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impacts of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Complete data from 70 participants were statistically analyzed and adjusted for age and sex. BMI is negatively correlated with performance on the DSST (β=-0.003, p=0.047), TMT-A (β=-0.006, p=0.025), and TMT-B (β=-0.006, p=0.002). BMI is positively correlated with serum CRP (unstandardized β=0.193, standardized β=0.612, p<0.001) and ESR (β=0.039, p<0.001) levels. We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.

Association of hematological parameters on polymorphisms of HFE gene (rs1800562, rs1800730, rs1799945) in non-alcoholic fatty liver disease

Background. Non-alcoholic fatty liver disease and its associated metabolic syndrome are one of the most common chronic liver diseases among adults worldwide. One of the reasons associated with unfavorable course may be an abnormalities of iron metabolism associated with of fatty liver degeneration, caused by the presence of a certain polymorphic locus of the HFE gene.&#x0D; Aim. Study the dependence of changes in hematological parameters on HFE gene polymorphisms among patients with non-alcoholic fatty liver disease with metabolic syndrome and normal body weight.&#x0D; Materials and methods. The study included 173 patients, of which 85 people had NAFLD and normal body weight, 88 people had NAFLD and metabolic syndrome. All patients underwent genotyping of the rs1800562, rs1800730, rs1799945 polymorphisms of the HFE gene, as well as assessment of hematological parameters. Statistical analysis was performed out using the Statistica 10 package.&#x0D; Results. Patients with NAFLD and normal body weight were characterized by the presence of the AT genotype of the rs1800730 polymorphism and the CG and GG genotypes of the rs1799945 polymorphism. In patients with NAFLD and metabolic syndrome, genotypes AA and TT of the rs1800730 polymorphism and CC of the rs1799945 polymorphism were more common.&#x0D; Changes in hematological parameters were noted in both groups. In patients with normal body weight, an increase in ESR and monocytosis was observed. Patients with metabolic syndrome had anemia, increased ESR and pancytopenia.&#x0D; Conclusion. Patients with NAFLD and normal body weight are characterized by the AT genotypes of the rs1800730 polymorphism and the CG and GG genotypes of the rs1799945 polymorphism. In patients with metabolic syndrome, variants of the AA polymorphism rs1800730 and CC polymorphism rs1799945 are more common. The rs1800562 polymorphism did not show significant differences in prevalence when compared between groups.&#x0D; In patients with normal body weight, changes in hematological parameters are less pronounced, an increase in ESR and monocytosis is noted. In patients with metabolic syndrome, on the contrary, disturbances in hematological parameters are more pronounced; panleukopenia, increased ESR, and anemia are noted.&#x0D; The changes we discovered may be evidence that in patients with NAFLD and normal body weight, steatosis and chronic inflammation predominated, and in patients with metabolic syndrome and NAFLD, steatohepatitis, which has a negative effect on organ systems. One of the risk factors for its development was the AA genotype of the rs800730 polymorphism and the CC genotype of the rs1799945 polymorphism.

Successful treatment with fludarabine and cyclophosphamide in a VEXAS syndrome patient with associated myelodysplastic syndrome: a case report and systematic review

Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.

Trade-offs in the externalities of pig production are not inevitable.

Farming externalities are believed to co-vary negatively, yet trade-offs have rarely been quantified systematically. Here we present data from UK and Brazilian pig production systems representative of most commercial systems across the world ranging from 'intensive' indoor systems through to extensive free range, Organic and woodland systems to explore co-variation among four major externality costs. We found that no specific farming type was consistently associated with good performance across all domains. Generally, systems with low land use have low greenhouse gas emissions but high antimicrobial use and poor animal welfare, and vice versa. Some individual systems performed well in all domains but were not exclusive to any particular type of farming system. Our findings suggest that trade-offs may be avoidable if mitigation focuses on lowering impacts within system types rather than simply changing types of farming.

Lentil Cultivar Evaluation in Diverse Organic Mediterranean Environments

Lentil (Lens culinaris Medik.) production faces challenges due to shifting environmental conditions, potentially leading to a transition towards cooler or highland Mediterranean environments. This study assessed the responses of five lentil genotypes across five diverse locations (L1–L5) managed under organic cropping systems over two seasons, focusing on key parameters including seed yield (SY), crude protein (CP), cooking time (CT), seed loss percentage (SL), and yield loss per hectare (YL) caused by bruchid (Bruchus sp.). Excessive seasonal rainfall (500 mm), low winter temperatures (−17.9 °C), bruchid SL, and spring sowing were identified as crucial, particularly in challenging environments like highlands. Genotype selection was highlighted as essential for balancing yield and stability, with the small-seeded cultivar ‘Dimitra’ demonstrating lower YL due to bruchid. Additionally, increased CP was noted in response to heightened bruchid infestations. Specific recommendations were proposed for different environments: In productive lowland areas with low bruchid pressure and high CTs (L1), prioritizing cultivars like ‘Samos’, ‘Dimitra’, and ‘Thessalia’ enhances quality. Locations with high bruchid populations (L4) were not favored organic production but can serve as genetic resistance screening sites. High-elevation environments (L3, L5) proved significantly less productive, underscoring the requirement for earlier and winter-hardy cultivars. These insights guide lentil cultivation, emphasizing the need for tailored breeding strategies adaptable to changing environments.

Commercial Quality of Potato Tubers of Different Varieties from Organic and Conventional Production System

Research conducted at the Plant Breeding and Acclimatization Institute—NIR in Poland in 2020–2022 assessed the commercial quality of potato tubers depending on the production system (organic, conventional), variety, and weather conditions prevailing in the years of research. The tuber size distribution and the share of tuber defects was assessed. It was found that all tested factors influenced the commercial quality of the yield but to different extents. The production system had the greatest influence on most of the examined features, followed by weather conditions and the least influential factor being the variety. The production system had the greatest impact on such features as: tuber size distribution (all fractions), pest damage, scab infection, tuber deformations, and share of green tubers. Weather conditions had the greatest impact on scab infection, pest damage, deformation, cracks and share of large tubers. The variety factor had the greatest influence on such features as: deformations, cracks, green tubers, black scarf, and share of the smallest (non-commercial) tubers. In the conventional system, a significantly better tuber yield distribution was found. The share of tuber defects varied depending on the production system. In the organic system, a greater share of defects such as scab (68.3 and 41.3) and pest damage was found (6.8 and 0.2), while in the conventional system, a greater share of deformations (9.2 and 4.9), cracks (5.4 and 2.4), and rust spots (0.61 and 0.06) occurred.

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus

Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present a unique opportunity to delve into the intricacies of complex neurological disorders. Afflicting approximately one in a thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with a pronounced impact on the central and peripheral nervous system. In the pursuit of understanding RASopathies’ neurobiology and establishing phenotype–genotype relationships, in vivo non-mammalian models have emerged as indispensable tools. Species such as Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus species and Gallus gallus embryos have proven to be invaluable in shedding light on the intricate pathways implicated in RASopathies. Despite some inherent weaknesses, these genetic models offer distinct advantages over traditional rodent models, providing a holistic perspective on complex genetics, multi-organ involvement, and the interplay among various pathway components, offering insights into the pathophysiological aspects of mutations-driven symptoms. This review underscores the value of investigating the genetic basis of RASopathies for unraveling the underlying mechanisms contributing to broader neurological complexities. It also emphasizes the pivotal role of non-mammalian models in serving as a crucial preliminary step for the development of innovative therapeutic strategies.

Adoption of Cereal–Legume Double Cropping toward More Sustainable Organic Systems in the Mediterranean Area

Environmental benefits can be achieved by organic farming systems; however, weed pressure and timely crop nutrition remain important drawbacks for many field crops. Agroecological practices, such as double cropping (e.g., intercropping and relay cropping), using forage legume species can provide nitrogen (N) to the companion crop through biological N fixation and tackle weed issues by competing for light, water and land. The present study investigated the effect of intercropping (IC) and relay-cropping (RC) systems of durum wheat (Triticum turgidum subsp. durum (Desf.) Husn) and forage legumes (Trifolium subterraneum L., Medicago polymorpha L., and Lotus corniculatus L.) by varying organic N fertilization with the aim to reduce N-requirement and weed pressure and increase wheat grain yield and grain protein content in Mediterranean organic farming systems. N fertilizer significantly improved wheat grain yield and grain protein, while a null effect on legume and weed biomass yields was found. Double cropping (T. durum-M. polymorpha, and T. durum-L. corniculatus) enhanced wheat grain yield as compared to the control and the T. durum-T. subterraneum. IC significantly improved legume yield, grain protein and the land equivalent ratio (LER) and reduced weed dry biomass as compared with the RC and the control. Among legume species, T. subterraneum outperformed the others and was less affected by the wheat’s competitive performance. Nonetheless, M. polymorpha was as effective as T. subterraneum in controlling weeds. Weed dry biomass was linearly reduced by increasing legume yield; the relationship improved by cumulating wheat grain yield to legume yield. Overall, this study indicated that double cropping, especially IC, can be a suitable agroecological practice to tackle weed issues and reduce N-requirement in Mediterranean organic cereal-based systems.

Extracting Insoluble Inorganic Phosphorus from Organic Farm Soils in Mountains: Identifying Effective Organic Acid Extractants

Phosphorus, among others, is quite a vital nutrient for the life of a plant. Because of the dominance of iron and aluminium oxides in acidic soils, they facilitate the fixation of phosphorus which results into phosphorus deficiency in large amounts. Hence, proper replenishment of the soil phosphorus (P) is very much important to cater the need of plant P requirement for better yield and development. The agricultural soils of Meghalaya (India) are by default rich in organic contents and organic P pool contributes 15-80% of the total plant P nutrition. Moreover, a different nature of nutrient pools is present in organic farming system compared to the conventional farming system. Lack of knowledge of these pools results in an imbalanced manuring plan, which hinders successful production system. The dynamic fraction of P cannot represent the correct status of phosphorus in soils under organic production systems, as the conventional soil testing protocols do not take into account the potentially available inorganic pools of phosphorus. Hence, a different extractant that can extract such potentially available P in an acidic soil under organic production system is highly required. The mineralization, solubilization and extraction (of the potentially available P pool) by using various organic acids produced through the beneficial soil microorganisms can serve this purpose. Therefore, the present research work was carried out to identify the best suitable P extractant to extract such potentially available inorganic P pool. The result of the present investigation revealed that out of 6 different extractants selected, 2% citric acid and double lactate extractants were found to be strongly correlated to the total P of the selected sites. Conventional Bray 1 extractant was taken as a check extractant. The outcome of the research is to develop a proper recommendation of fertilizer dose and an appropriate soil testing protocol for phosphorus being used in organic cultivation.