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1.
Cureus ; 16(6): e61629, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38966440

ABSTRACT

Aim The study aims to analyze the imaging findings of invasive rhino-orbital-cerebral mucormycosis (ROCM) in patients who had COVID-19. Materials and methods This retrospective descriptive study was done on confirmed (culture and histopathology) patients who had a COVID-19 infection. The data was collected from the record section from May 2021 to June 2021. Imaging data were analyzed, and findings were tabulated according to statistical methods. Results Radiological evaluation, including CT and MRI, was done in 48 cases. The ethmoid sinus was the most common sinus involved in 60.41% of cases, followed by the maxillary sinus (52.09%). Unilateral pansinusitis was observed in 21 cases (43.75%). Among periantral extensions, retroantral fat involvement was the most common finding, seen in 24 cases (50%). Lamina papyracea and the walls of the maxillary sinus were involved in eight cases (16.67%). A total of 38 cases (79.17%) exhibited involvement of the extraconal compartment, while 32 cases (66.67%) showed involvement of the intraconal compartment. In intracranial involvement, infarct was noted in 13 cases (27%), and cavernous sinus involvement in nine cases (18.75%). Conclusions ROCM is a life-threatening fungal infection in immunocompromised patients, especially diabetics. Imaging of ROCM plays a pivotal role in early diagnosis, the extent of disease, surgical planning, prognosis, and the response to treatment. Radiologists must know the imaging features and patterns of extension of ROCM.

2.
Inorg Chem ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981070

ABSTRACT

The extensive growth of nuclear power plants has a severe detrimental effect on human health and the surroundings due to the uncontrolled and unfiltered release of radioactive wastes into the environment. One such radioactive waste is 129I which has a fatal effect when released into the air or water bodies. Hence, molecular and ionic iodine capture from multimedia has become an important area of interest in the recent past. This work is aimed at introducing two 2D metal-organic frameworks with a fused cis-decalin conformation, {[Zn2(tpbn)(fdc)2]·6H2O}n (1) and {[Cd2(tpbn)(fdc)2(H2O)2]·2H2O}n (2), synthesized at room temperature utilizing a combination of M(OAc)2·2H2O (M: Zn/Cd), a neutral flexible ligand, tpbn, and a simple commercially available furan dicarboxylate, fdc2-, for the target application. The polarizing nature of the furan moieties and the oxygen rich pores in 1 and 2 facilitate the easy capture of molecular iodine from both the vapor phase and aqueous media with high uptake values. Furthermore, their efficiency was tested for the practical application under real-world conditions using river and seawater. In addition to confirming their recyclability with the retention of structural integrity, the interaction between 1 and 2 with iodine has also been established with experimental and theoretical calculations.

3.
Cureus ; 16(6): e61726, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975482

ABSTRACT

Kawasaki disease (KD), formerly called mucocutaneous lymph node syndrome, is one of the common vasculitides of childhood. KD most commonly occurs in children over six months up to five years of age, although it can occur in young infants, older children, and adults. Early diagnosis is critical to achieving optimal treatment. We present a case of a three-year-old female child who was admitted with a fever for five days and fulfilled the diagnostic clinical criteria for KD. She was given intravenous immunoglobulin (IVIG) and aspirin. However, the fever persisted, and a urine culture showed the growth of Klebsiella pneumoniae. We started an antibiotic based on her sensitivity. Since fever spikes were not subsiding, she was given a repeat dose of IVIG along with an oral corticosteroid for refractory KD, after which she showed clinical improvement. This case highlighted that refractory KD can coexist with infection.

4.
Article in English | MEDLINE | ID: mdl-38973017

ABSTRACT

Metal Organic Frameworks (MOFs) are an evolving category of crystalline microporous materials that have grabbed the research interest for quite some time due to their admirable physio-chemical properties and easy fabrication methods. Their enormous surface area can be a working ground for innumerable molecular adhesions and site for potential sensor matrices. They have been explored in the last decade for incorporation in electrochemical sensor matrices as diagnostic solutions for a plethora of diseases. This review emphasizes on some of the recent advancements in the area of MOF-based electrochemical biosensors with focus on various important diseases and their significance in upgrading the sensor performance. It summarizes MOF-based biosensors for monitoring biomarkers relevant to diabetes, viral and bacterial sepsis infections, neurological disorders, cardiovascular diseases, and cancer in a wide range of real matrices. The discussion has been supplemented with extensive tables elaborating recent trends in the field of MOF-composite probe fabrication strategies with their respective sensing parameters. The article sums up the future scope of these materials in the field of biosensors and enlightens the reader with recent trends for future research scope. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Humans , Animals
5.
PLoS One ; 19(7): e0303395, 2024.
Article in English | MEDLINE | ID: mdl-38968223

ABSTRACT

BACKGROUND: Phenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcus aureus infections (SAIs) has been done leaving potential novel risk factors or complications undiscovered. METHOD AND COHORTS: We tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively. RESULTS: Forty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria. CONCLUSIONS: The PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation.


Subject(s)
Phenotype , Staphylococcal Infections , Staphylococcus aureus , Humans , Staphylococcal Infections/microbiology , Staphylococcal Infections/genetics , Staphylococcus aureus/genetics , Male , Female , Middle Aged , Adult , Aged , Phenomics , Genome-Wide Association Study , Adolescent , Risk Factors , Young Adult , Child
6.
Article in English | MEDLINE | ID: mdl-39007979

ABSTRACT

The detection of uranium in drinking water has ignited concerns among the public, regulators, and policymakers, particularly as around 1% of the 55,554 water samples in India have shown uranium levels surpassing the 60 µg/l guideline established by the Atomic Energy Regulatory Board (AERB) based on radiological toxicity. Further, the Bureau of Indian Standard (BIS), has given a limit of 30 µg/l, which is derived from World Health Organization (WHO) guidelines. Besides the chemical and radiological aspects associated with uranium, factors such as technological constraints in water purification, waste management, environmental factors, and socio-economic conditions significantly influence these guideline values, which are often overlooked. This manuscript explores the variations in approaches for establishing guideline values and highlights the uncertainties arising from dependence on various variables such as intake and usage patterns, inter- and intra-species distinctions, and epidemiological data. A critical analysis indicates that adherence to global guidelines may result in some undesirable environmental issues. By considering factors such as population dynamics, socio-economic conditions, and geological influences, we suggest that limit of 60 µg/l for uranium in drinking water is appropriate for India.

7.
J Nucl Med ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960711

ABSTRACT

Despite the recent advances in understanding the mechanisms of olfaction, no tools are currently available to noninvasively identify loss of smell. Because of the substantial increase in patients presenting with coronavirus disease 2019-related loss of smell, the pandemic has highlighted the urgent need to develop quantitative methods. Methods: Our group investigated the use of a novel fluorescent probe named Tsp1a-IR800P as a tool to diagnose loss of smell. Tsp1a-IR800P targets sodium channel 1.7, which plays a critical role in olfaction by aiding the signal propagation to the olfactory bulb. Results: Intuitively, we have identified that conditions leading to loss of smell, including chronic inflammation and coronavirus disease 2019, correlate with the downregulation of sodium channel 1.7 expression in the olfactory epithelium, both at the transcript and at the protein levels. We demonstrated that lower Tsp1a-IR800P fluorescence emissions significantly correlate with loss of smell in live animals-thus representing a potential tool for its semiquantitative assessment. Currently available methods rely on delayed subjective behavioral studies. Conclusion: This method could aid in significantly improving preclinical and clinical studies by providing a way to objectively diagnose loss of smell and therefore aid the development of therapeutic interventions.

8.
Article in English | MEDLINE | ID: mdl-39001729

ABSTRACT

BACKGROUND: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters. OBJECTIVES: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM. METHODS: A total of 758 patients with HCM (67% male; aged 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation-related stroke. RESULTS: MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, -17.3% for GCS). CONCLUSIONS: ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM.

9.
Cell Signal ; : 111299, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39004324

ABSTRACT

The lack of therapeutics along with complex pathophysiology made non-alcoholic fatty liver disease (NAFLD) a research hotspot. Studies showed that the deficiency of Vitamin D plays a vital role in NAFLD pathogenesis. While several research studies focused on vitamin D supplementation in NAFLD, there is still a need to understand the regulatory mechanism of direct vitamin D receptor activation in NAFLD. In the present study, we explored the role of direct Vitamin D receptor activation using paricalcitol in choline-deficient high-fat diet-induced NAFLD rat liver and its modulation on protein acetylation. Our results showed that paricalcitol administration significantly reduced the fat accumulation in HepG2 cells and the liver of NAFLD rats. Paricalcitol attenuated the elevated serum level of alanine transaminase, aspartate transaminase, insulin, low-density lipoprotein, triglyceride, and increased high-density lipoprotein in NAFLD rats. Paricalcitol significantly decreased the increased total protein acetylation by enhancing the SIRT1 and SIRT3 expression in NAFLD liver. Further, the study revealed that paricalcitol reduced the acetylation of NFκB and FOXO3a in NAFLD liver along with a decrease in the mRNA expression of IL1ß, NFκB, TNFα, and increased catalase and MnSOD. Moreover, total antioxidant activity, glutathione, and catalase were also elevated, whereas lipid peroxidation, myeloperoxidase, and reactive oxygen species levels were significantly decreased in the liver of NAFLD after paricalcitol administration. The study concludes that the downregulation of SIRT1 and SIRT3 in NAFLD liver was associated with an increased acetylated NFκB and FOXO3a. Paricalcitol effectively reversed hepatic inflammation and oxidative stress in NAFLD rats through transcriptional regulation of NFκB and FOXO3a, respectively, by inhibiting their acetylation.

10.
Indian J Microbiol ; 64(2): 445-456, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39011010

ABSTRACT

Hydrogen (H2), a clean and versatile energy carrier, has recently gained significant attention as a potential solution for reducing carbon emissions and promoting sustainable energy systems. The yield and efficiency of the biological H2 production process primarily depend on sterilization conditions. Various strategies, such as heat inactivation and membrane-based sterilization, have been used to achieve desirable yields via microbial fermentation. Almost every failed biotransformation process is linked to nonsterile conditions at any reaction stage. Therefore, the production of renewable biofuels as alternatives to fossil fuels is more attractive. Pure sugars have been widely documented as a costly feedstock for H2 production under sterile conditions. Biotransformation under nonsterile conditions is more desirable for stable and sustainable operation. Low-cost feeds, such as biowaste, are considered suitable alternatives, but they require appropriate sterilization to overcome the limitations of inherited or contaminating microbes during H2 production. This article describes the status of microbial fermentative processes for H2 production under nonsterile conditions and discusses strategies to improve such processes for sustainable, cleaner production.

11.
Eur Heart J ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011630

ABSTRACT

BACKGROUND AND AIMS: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. METHODS: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). RESULTS: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. CONCLUSIONS: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.

12.
Sci Rep ; 14(1): 14743, 2024 06 26.
Article in English | MEDLINE | ID: mdl-38926411

ABSTRACT

Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (ßCAC = - 0.14, P = 0.23; ßcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Plaque, Atherosclerotic , Vitamin D Deficiency , Vitamin D , Humans , Vitamin D/blood , Vitamin D/analogs & derivatives , Vitamin D Deficiency/genetics , Vitamin D Deficiency/complications , Plaque, Atherosclerotic/genetics , Carotid Artery Diseases/genetics , Polymorphism, Single Nucleotide , Risk Factors , Genetic Predisposition to Disease , Female , Male , Carotid Arteries/pathology , Carotid Arteries/diagnostic imaging
13.
Plants (Basel) ; 13(11)2024 May 25.
Article in English | MEDLINE | ID: mdl-38891273

ABSTRACT

Legume-rhizobia symbiosis is the most important plant-microbe interaction in sustainable agriculture due to its ability to provide much needed N in cropping systems. This interaction is mediated by the mutual recognition of signaling molecules from the two partners, namely legumes and rhizobia. In legumes, these molecules are in the form of flavonoids and anthocyanins, which are responsible for the pigmentation of plant organs, such as seeds, flowers, fruits, and even leaves. Seed-coat pigmentation in legumes is a dominant factor influencing gene expression relating to N2 fixation and may be responsible for the different N2-fixing abilities observed among legume genotypes under field conditions in African soils. Common bean, cowpea, Kersting's groundnut, and Bambara groundnut landraces with black seed-coat color are reported to release higher concentrations of nod-gene-inducing flavonoids and anthocyanins compared with the Red and Cream landraces. Black seed-coat pigmentation is considered a biomarker for enhanced nodulation and N2 fixation in legumes. Cowpea, Bambara groundnut, and Kersting's bean with differing seed-coat colors are known to attract different soil rhizobia based on PCR-RFLP analysis of bacterial DNA. Even when seeds of the same legume with diverse seed-coat colors were planted together in one hole, the nodulating bradyrhizobia clustered differently in the PCR-RFLP dendrogram. Kersting's groundnut, Bambara groundnut, and cowpea with differing seed-coat colors were selectively nodulated by different bradyrhizobial species. The 16S rRNA amplicon sequencing also found significant selective influences of seed-coat pigmentation on microbial community structure in the rhizosphere of five Kersting's groundnut landraces. Seed-coat color therefore plays a dominant role in the selection of the bacterial partner in the legume-rhizobia symbiosis.

14.
Am J Gastroenterol ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916226

ABSTRACT

INTRODUCTION: To study digestive system cancer risks in inflammatory bowel diseases (IBD) in the biologic era. METHODS: We used population-level administrative and cancer registry data from Ontario, Canada (1994 - 2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths. RESULTS: Among 110,919 IBD and 1,109,190 controls, colorectal cancer (CRC) incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change (AAPC) -1.81; 95% CI, -2.48, -1.156) and controls (AAPC -2.79; 95% CI, -3.44, -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI, 2.51, 17.3) than controls (AAPC 3.64; 95% CI, 1.52, 5.80). Extra-intestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI, 1.83, 4.73) than controls (AAPC -1.87; 95% CI, -2.33, -1.42), particularly for liver (IBD AAPC 8.48; 95% CI, 4.11, 13.1) and bile duct (IBD AAPC 7.22; 95 % CI, 3.74, 10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI, 1.46, 1.75), small bowel (4.10; 95% CI 3.37, 4.99), bile duct (2.33; 95% CI 1.96, 2.77) and pancreatic (1.19; 95% CI, 1.00, 1.40) cancers, were higher in people with IBD. DISCUSSION: Cancer incidence is declining for CRC and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in IBD than controls for colorectal, small bowel, bile duct and pancreatic cancers.

16.
Cureus ; 16(3): e57335, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38690458

ABSTRACT

Background Central nervous system (CNS) tumors cause significant mortality and morbidity in all age groups. There was no data about the histological spectrum of all CNS tumors in the tertiary care center serving primarily the rural population of Uttar Pradesh. Aims and objectives The present study aimed to describe the histopathological spectrum of all CNS tumors reported in a rural tertiary care center at Saifai, Uttar Pradesh. It also aimed to provide an overview of the descriptive epidemiology of CNS tumors. Material and methods This was a retrospective, cross-sectional study. The study duration was three years. A total of 115 cases of CNS tumors were studied during that period. Cases were classified according to their histological types, and results were analyzed. Results The most common histological group was neuroepithelial tumors, with 53 cases (46.08%). This group had 36 cases of astrocytic tumors (31.3%), three cases of oligodendroglial tumors (2.6%), five cases of oligoastrocytic tumors (4.34%), five cases of ependymal tumors (4.34%), and four cases of embryonal tumors (3.47%). The second most common tumor was meningeal tumors, with 32 cases (27.82%). The male/female ratio (M/F) ratio was 0.7. Females were found to be more affected by almost all histologic categories. Most meningiomas (89.6%) were of World Health Organization (WHO) grade I (26 cases out of 29). Astrocytic tumors showed WHO grade I, II, III, and IV tumors in two cases (5.5%), twelve cases (33.3%), four cases (11.1%), and eighteen cases (50%), respectively. In the younger age group (0-20 years), ependymoma and medulloblastoma were most common, followed by pilocytic astrocytoma and schwannoma. Conclusion In this region, neuroepithelial tumors were seen more commonly than meningioma. Females were found to be more affected by CNS tumors. This study has provided relevant data, which can be used for research and better patient management. Further studies with the incorporation of advanced radiological investigation and immunohistochemistry have been recommended.

17.
J Pediatr Genet ; 13(2): 158-165, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38721578

ABSTRACT

Transient receptor potential vanilloid 4 channel ( TRPV4 ) gene mutations have been described in skeletal system and peripheral nervous system pathology. The case described here is a 9-year-old male child patient, born to a nonconsanguineous marriage with normal birth history who had difficulty in walking and stiffness of joints for the last 7 years, and progressive weakness of all four limbs and urine incontinence for 1 year following falls. Physical examination showed below-average weight and height and short trunk. Musculoskeletal examination revealed bony prominence bilaterally in the knee joints and contractures in knee and elbow joints with brachydactyly; muscle tone was increased, with brisk deep tendon reflexes. Skeletal survey showed platyspondyly with anterior beaking with metaphyseal dysplasia. Magnetic resonance imaging of the spine revealed atlantoaxial instability with hyperintense signal changes at a cervicomedullary junction and upper cervical cord with thinning and spinal canal stenosis suggestive of compressive myelopathy with platyspondyly and anterior beaking of the spine at cervical, thoracic and lumbar vertebrae. Exome sequencing revealed a heterozygous de novo variant c.2389G > A in exon 15 of TRPV4 , which results in the amino acid substitution p.Glu797Lys in the encoded protein. The characteristics observed indicated spondylometaphyseal dysplasia, Kozlowski type (SMD-K). The child underwent surgical intervention for compressive myelopathy by reduction of atlantoaxial dislocation with C1 lateral mass and C2 pars fusion using rib graft and fixation using screws and rods. To conclude, for any child presenting with progressive kyphoscoliosis, short stature, platyspondyly, and metaphyseal changes, a diagnosis of SMD-K should be considered and the patient and family should be advised to avoid spinal injuries.

18.
J Mater Chem B ; 12(21): 5098-5110, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38700289

ABSTRACT

The tunable properties of stimuli-responsive copolymers or hydrogels enable their application in different fields such as biomedical engineering, tissue engineering, or even drug release. Here we introduce a new PNIPAM-based triblock copolymer material comprising a controlled amount of a novel hydrophobic crosslinker 2,4'-diacryloyloxy benzophenone (DABP) and acrylic acid (AAc) to achieve lower critical solution temperature (LCST) between ambient and body temperatures. The dual stimuli-responsive p(NIPAM-co-DABP-co-AAc) triblock copolymer material and hydrogel were synthesized, and their temperature and pH-responsive behaviors were systematically investigated. The hydrogel exhibited excellent temperature and pH-responsive properties with an LCST of around 30 °C. Moreover, the synthesized copolymer has been demonstrated to be nontoxic both in vitro and in vivo. When the hydrogel was preloaded with the model drug 5-fluorouracil (5-FU), the designed hydrogel released the drug in a temperature and pH-controlled fashion. It was observed that the prepared hydrogel has the ability to entrap 5-FU, and the loading is more than 85%. In the case of temperature-controlled release, we observed almost complete release of 5-FU at lower temperatures and sustained release behavior at higher temperatures. In addition, the hydrogel matrix was able to retard the release of 5-FU in an acidic environment and selectively release 5-FU in a basic environment. By realizing how the hydrogel properties influence the release of drugs from preloaded hydrogels, it is possible to design new materials with myriad applications in the drug delivery field.


Subject(s)
Biocompatible Materials , Fluorouracil , Hydrogels , Temperature , Fluorouracil/pharmacology , Fluorouracil/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Hydrogels/pharmacology , Hydrogen-Ion Concentration , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/pharmacology , Animals , Humans , Drug Liberation , Mice , Drug Carriers/chemistry , Drug Carriers/chemical synthesis , Drug Delivery Systems
19.
Int J Biol Macromol ; 269(Pt 2): 132085, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723836

ABSTRACT

Non-biodegradable polyolefin based plastic mulch residues in agricultural fields after the end of a crop cycle have raised several concerns as an environmental pollutant in recent years. This study explores the potential of Poly (lactic acid) (PLA) and Poly (butylene adipate-co-terephthalate) (PBAT) based compostable films reactively blended with compatibilizers and chain extenders as a promising solution to environmental challenges associated with traditional plastic mulch films. Epoxidized soybean oil (ESO) and Epoxy-functionalized styrene acrylic copolymer (ESA) have been used as reactive compatibilizers and chain extenders respectively. In-depth analysis of the mechanical, thermal, and barrier properties of the developed films, revealed that the PLA/PBAT blend films at 75:25 weight ratio in the presence of 5 phr ESO and 0.5 phr ESA exhibit improved performance characteristics for application as mulch films. Furthermore, the films were subjected to 360-h UV exposure to gauge their stability under prolonged exposure, specifically investigating changes in the carbonyl index. Additionally, a rigorous real-time field trial of the mulch films spanning eight months with various crops was carried out to understand their performance in practical agricultural settings. The study also involved the identification of microorganisms responsible for the degradation of the developed mulch films employing 16S rRNA sequencing.


Subject(s)
Agriculture , Biodegradation, Environmental , Polyesters , Soil Microbiology , Polyesters/chemistry , Agriculture/methods , Microbiota , Soil/chemistry , Soybean Oil
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