Disparities in Access to Timely Waitlisting Among Pediatric Kidney Transplant Candidates.

BACKGROUND AND OBJECTIVES: Kidney transplantation with minimal or no dialysis exposure provides optimal outcomes for children with end-stage kidney disease. We sought to understand disparities in timely access to transplant waitlisting. METHODS: We conducted a retrospective, registry-based cohort study of candidates ages 3 to 17 added to the US kidney transplant waitlist 2015 to 2019. We defined "preemptive waitlisting" as waitlist addition before receiving dialysis and compared demographics of candidates based on preemptive status. We used competing risk regression to determine the association between preemptive waitlisting and transplantation. We then identified waitlist additions age >18 who initiated dialysis as children, thereby missing pediatric allocation prioritization, and evaluated the association between waitlisting with pediatric prioritization and transplantation. RESULTS: Among 4506 pediatric candidates, 48% were waitlisted preemptively. Female sex, Hispanic ethnicity, Black race, and public insurance were associated with lower adjusted relative risk of preemptive waitlisting. Preemptive listing was not associated with time from waitlist activation to transplantation (adjusted hazard ratio 0.94, 95% confidence interval 0.87-1.02). Among transplant recipients waitlisted preemptively, 68% had no pretransplant dialysis, whereas recipients listed nonpreemptively had median 1.6 years of dialysis at transplant. Among 415 candidates initiating dialysis as children but waitlisted as adults, transplant rate was lower versus nonpreemptive pediatric candidates after waitlist activation (adjusted hazard ratio 0.54, 95% confidence interval 0.44-0.66). CONCLUSIONS: Disparities in timely waitlisting are associated with differences in pretransplant dialysis exposure despite no difference in time to transplant after waitlist activation. Young adults who experience delays may miss pediatric prioritization, highlighting an area for policy intervention.

Polygonum bistorta Linn. as a green source for synthesis of biocompatible selenium nanoparticles with potent antimicrobial and antioxidant properties.

Here, we report for the first time, green-synthesized selenium nanoparticles (SeNPs) using pharmacologically potent herb of Polygonum bistorta Linn. for multiple biomedical applications. In the study, a facile and an eco-friendly approach is utilized for synthesis of SeNPs using an aqueous roots extract of P. bistorta Linn. followed by extensive characterization via Fourier transform infrared spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Energy Dispersive X-Ray (EDX) analysis. The XRD and FTIR data determine the phase composition and successful capping of plant extract onto the surface of NPs while SEM and TEM micrographic examination reveals the elliptical and spherical morphology of the particles with a mean size of 69 ± 23 nm. After comprehensive characterization, the NPs are investigated for antifungal, antibacterial, antileishmanial, antioxidant, and biocompatibility properties. The study reveals that Polygonum bistorta Linn. synthesized SeNPs exhibit significant antibacterial and antifungal activities with Staphylococcus aureus and Fusarium oxysporum inducing the highest zone of inhibition of 14 ± 1.0 mm and 20 ± 1.2 mm, respectively at the concentration of 40 mg/mL. The NPs are also found to have antiparasitic potential against promastigote and amastigote forms of Leishmania tropica. Furthermore, the NPs are discovered to have excellent potential in neutralizing harmful free radicals thus exhibiting considerable antioxidant potential. Most importantly, Polygonum bistorta Linn. synthesized SeNPs showed substantial compatibility against blood cells in vitro studies, which signifies the nontoxic nature of the NPs. The study thus concludes that medicinally important Polygonum bistorta Linn. roots can be utilized as an eco-friendly, sustainable, and green source for the synthesis of pharmacologically potent selenium nanoparticles.

Polypharmacy to Clozapine Monotherapy in Treatment-Resistant Schizophrenia: A Case Report and Review of the Literature.

This case report discusses a 25-year-old Middle Eastern female with a 14-year history of schizophrenia, managed as an inpatient for nearly eight years. Initially referred to a psychiatrist at age 12, with one-year-long concerns about preoccupation with the idea of having a serious illness, depressed mood, decreased appetite, social withdrawal, and aggression, she underwent multiple admissions, various medication combinations, and electroconvulsive therapy but remained resistant to treatment until clozapine monotherapy was initiated in 2023. After starting clozapine, improvements were noted in speech, communication, and eye contact, though negative symptoms and bouts of aggression persisted. This case highlights the efficacy of clozapine monotherapy in managing treatment-resistant schizophrenia after years of ineffective polypharmacy treatment. The importance of clozapine in treating treatment-resistant schizophrenia cannot be understated. Despite its efficacy, clozapine is often underutilised globally due to concerns about adverse effects and the need for blood monitoring, leading to the overuse of antipsychotic polypharmacy. This polypharmacy is associated with higher adverse event rates, increased costs, and uncertain long-term safety. This case report demonstrates the successful management of treatment-resistant schizophrenia with clozapine monotherapy. The patient's significant improvement supports the need to prioritise clozapine, highlighting its benefits over polypharmacy and advocating for its broader use to enhance patient outcomes.

Pleomorphic adenoma and carcinoma ex-pleomorphic adenoma tumorigenesis: A proteomic analysis.

OBJECTIVES: To conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex-pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry. METHODS: Six normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation. RESULTS: Comparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up-regulated in CXPA compared to PA. Decorin was markedly up-regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA. CONCLUSIONS: Proteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.

C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation.

Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. Methods: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. Results: During a median (interquartile range) follow-up period of 37 (18­56) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13­141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. Conclusions: Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.

Correction: The hidden costs of inflation: A critical analysis of industrial development and environmental consequences.

[This corrects the article DOI: 10.1371/journal.pone.0297413.].

The hidden costs of inflation: A critical analysis of industrial development and environmental consequences.

The study draws attention to the associations between monetary and economic elements and their potential environmental impacts. The study uses time series data from 1960 to 2022 to examine the connection between CO2 emissions, industrial growth, GNE, and inflation in China. The researchers utilized the well-known econometric technique of nonlinear autoregressive distributed lag (NARDL) to examine nonlinear correlations between these variables. The results reveal that GDP, inflation, and economic development influence long-term CO2 emissions. The strong positive correlation between gross national expenditures and economic activity increases CO2 emissions. In the short run, CO2 emissions are positively and statistically significantly affected by inflation. While inflation temporarily affects CO2 emissions, this effect dissipates with time. Industrial activity increases CO2 emissions, and China's fast industrialization has damaged the environment. The energy-intensive fertiliser manufacturing process and fossil fuels increase CO2 emissions. The research shows how government officials and academics may collaborate to create tailored measures to alleviate the environmental impacts of economic activity.

Identification and mapping of groundwater recharge zones using multi influencing factor and analytical hierarchy process.

The management of groundwater systems is essential for nations that rely on groundwater as the principal source of communal water supply (e.g., Mohmand District of Pakistan). The work employed Remote Sensing and GIS datasets to ascertain the groundwater recharge zones (GWRZ) in the Mohmand District of Pakistan. Subsequently, a sensitivity analysis was conducted to examine the impact of geology and hydrologic factors on the variability of the GWRZ. The GWRZ was determined by employing weighted overlay analysis on thematic maps derived from datasets about drainage density, slope, geology, rainfall, lineament density, land use/land cover, and soil types. The use of multi-criteria decision analysis (MCDA) involves the utilization of the multi-influencing factor (MIF) and analytical hierarchy procedure (AHP) to allocate weights to the selected influencing factors. The MIF data found that very high groundwater recharge spanned 1.20%, high zones covered 40.44%, moderate zones covered 50.81%, and low zones covered 7.54%. In comparison, the AHP technique results suggest that 1.81% of the whole area is very high, 33.26 is high, 55.01% is moderate, and 9.92% has low groundwater potential. The geospatial-assisted multi-influencing factor approach helps increase conceptual knowledge of groundwater resources and evaluate possible groundwater zones.

Orbital malignant peripheral nerve sheath tumor: A case report and review.

Malignant peripheral nerve sheath tumor of the orbit is an exceedingly rare entity. These tumors exhibit locally aggressive behavior, recurrences, distant metastasis, and poor response to existing treatment protocols. Orbital nerve sheath tumors are often associated with neurofibromatosis 1, and malignant transformation of neurofibroma into malignant nerve sheath tumor has also been seen. The recommended treatment for localized disease is radical or wide surgical excision to achieve negative margins followed by chemoradiation. For extensive disease, chemotherapy and radiotherapy can be utilized to stabilize the disease. Due to poor response and outcomes with current regimens, the focus has been shifted to approaches utilizing molecular targets and immunological agents. Despite all the advancements, the outcomes still remain discouraging for moderate- to high-grade lesions and thus necessitate studies to design promising treatment modalities.

Pure Hereditary Spastic Paraplegia in a Patient With a Novel Heterozygous KIDINS220 Gene Mutation.

This case presents a somewhat unique and different phenotype of hereditary spastic paraplegia from previously reported kinase D-interacting substrate of 220 kDa (KIDINS220) gene mutation-related disease. We report a unique putative causative heterozygous mutation in KIDINS220 in a pure hereditary spastic paraplegia (HSP) patient expanding the HSP group further. We also deliberate on how our case was different from prior KIDINS220-related pathologies including spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, and the observation of KIDINS220 and aquaporin-4 (AQP4) downregulation in the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. These findings warrant further investigations of the biology of KIDINS220. With the advent of new gene editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), variants such as ours provide an opportunity for targeted precision medicine.

Bridging sustainability and industry through resourceful utilization of pea pods- A focus on diverse industrial applications.

The focus on sustainable utilization of agricultural waste is currently a leading area of scientific research, driving significant advancements in technology and circular economy models. The fundamental capacity of bio-based products, bioprocessing techniques, and the crucial involvement of microbial treatments are opening opportunities for efficient solutions in various industries. One of the most popular green vegetables, peas are members of the Fabaceae family and have a pod-like structure. Every year, a significant amount of pea pods is discarded as waste products of peas that have negative impacts on our environment. In this comprehensive review, we explore innovative methods for utilizing pea pods to minimize their environmental footprint and optimize their viability across multiple industries. A large portion of the pea processing industry's output consists of pea pods. Variety of proteins, with major classes being globulin and albumin (13%), dietary fiber (43-58%), and minerals are abundant in these pods. Because of their diverse physiochemical properties, they find applications in many diverse fields. The porous pea pods comprised cellulose (61.35%) and lignin (22.12%), which could make them superior adsorbents. The components of these byproducts possess valuable attributes that make them applicable across treatment of wastewater, production of biofuels, synthesis of biocolors, development of nutraceuticals, functional foods, and enzymes for the textile industry, modification of oil, and inhibition of steel corrosion.

Neuropsychological complications of hypoprolactinemia.

Prolactin (PRL) is primarily produced by the pituitary lactotrophic cells and while initially named for its role in lactation, PRL has several other biological roles including immunomodulation, osmotic balance, angiogenesis, calcium metabolism, and appetite regulation. Most of the PRL-related literature has traditionally focused on hyperprolactinemia, whereas hypoprolactinemia has received little attention. There is evidence to suggest that PRL receptors are widely distributed within the central nervous system including the limbic system. Furthermore, PRL has been shown to play key role in the stress regulation pathway. Recent data also suggest that hypoprolactinemia may be associated with increased sexual dysfunction, anxiety, and depression. In this paper we discuss the current understanding regarding the neuropsychological impact of hypoprolactinemia and highlight the need for adequately defining hypoprolactinemia as an entity and consideration for future replacement therapies.

The Value of Labial Gland Biopsies as a Diagnostic Test for Sjögren's Syndrome.

PURPOSE: There are a number of diagnostic criteria that can be used to support a diagnosis of Sjögren's syndrome (SS), a chronic autoimmune condition often characterised by xerostomia and xerophthalmia. Of the available investigations, the most invasive is the labial gland biopsy (LGB) for histopathology, which is associated with a risk of long-term altered sensation to the lip. A positive histological diagnosis is currently considered to be one of the most objective criteria, however there is debate about the interobserver agreement between pathologists, as well as the sensitivity and specificity of this test. We aim to determine if the diagnostic value of the LGB is significant enough to warrant the surgical procedure and its associated risks. METHODS: This study involved assessing the degree of agreement between members of a pathology team for a cohort of 50 LGBs taken for the purpose of confirming or excluding SS. The Tarpley system was used, which involves the allocation of a 'focus score'. Additionally, the histological diagnoses were compared to the relevant serological findings where available. RESULTS: All cases within the cohort had adequate tissue for assessment. 84% agreement (Cohen's Kappa = 0.585) was seen between the current team's consensus and the original reporting pathologist on whether the appearance was supportive of SS. However, only 58% agreement was seen for focus scores (Weighted Kappa = 0.496). The agreement between the serology result and whether the histology was supportive of SS was 79% (Cohen's Kappa = 0.493). CONCLUSION: The findings raise the possibility that undue emphasis is placed on the value of a histological SS diagnosis. The current system for assessing and grading these biopsies is ambiguous in nature, with a low threshold considered indicative of SS. Due to the risk of complications associated with a LGB, alternative minimally invasive investigations should always be considered. The histological findings in isolation, particularly when a low focus score is seen, may not be predictive of a diagnosis of SS.

The Effects of Whole-Body Vibration Therapy in Weight-Bearing and Non-Weight-Bearing Positions for Upper and Lower Extremities on Balance and Function in Cerebral Palsy Children: A Randomized Controlled Trial.

Background and objective Cerebral palsy (CP) is one of the most prevalent neurological conditions affecting children; it is characterized by poor motor control, restricted range of motion (ROM), and poor balance. While whole-body vibration therapy (WBVT) has been used to treat these symptoms, its efficacy in different configurations remains unexplored. Hence, this study aimed to determine and compare the effects of WBVT applied to either the upper extremities, lower extremities, or both upper and lower extremities in weight-bearing and non-weight-bearing positions on ROM (shoulders, elbows, wrists, hips, knees, and ankle joints), balance, and function in children with spastic hemiplegic CP. Methods This randomized clinical trial involved 60 hemiplegic spastic CP children aged 5-15 years. After randomization, all the participants were divided into six groups of equal size based on the WBVT application for upper extremities, lower extremities, or both in weight-bearing or non-weight-bearing positions. The therapy was applied three times per week for four consecutive weeks. The outcome measures were ROM, hand grip strength, balance quantification score using My Fitness Trainer (MFT) 2.0, and timed up and go (TUG) scores. Results While all the groups were homogenous before treatment, after treatment, it was observed that all the ranges improved significantly in all groups. The same was observed for hand grip strength, balance score, and TUG test scores (p<0.05). The post-hoc analysis revealed that the weight-bearing position for the upper and lower extremities combined showed the highest level of improvement. Conclusions Based on our findings, WBVT in weight-bearing positions produces more significant results than in non-weight-bearing positions. We also observed that when WBVT is applied to the upper extremities, it can improve the function of the lower extremities and vice versa.