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1.
J Pediatr Urol ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39317607

ABSTRACT

INTRODUCTION: Hypospadias is a common disease that affects approximately 1 in every 200 live male births in the United States, and long-term studies of individuals who have undergone repair demonstrate complication rates of 15%-70%. The Hypospadias-Specific Health-related Quality of Life (HRQOL) Conceptual Framework for youth and adults suggests that additional morbidity may be incurred from poor psychological, social, and sexual health. The current study sought to clarify hypospadias-specific HRQOL and care priorities in a pre-pubertal population. MATERIAL AND METHODS: This IRB-approved, semi-structured interview study used rigorous qualitative research methods. Eligible patients were English-speaking 8-12-year-old males with hypospadias and their parents. Families completed a demographic questionnaire and separate youth and parent 30-min telephone interviews. We used hybrid thematic analysis to develop an operational codebook, analyze participant responses, and generate conceptual themes. Mixed methods analysis was used to explore patterns of experiences across groups defined by socioeconomic level. RESULTS: We interviewed 10 parents and 8 children (Median age 9 years, Range 8-11). We generated three overarching themes: Penile Factors, Psychosocial Concerns, and Expectations of Surgery and the Healthcare Team. These highest-order themes were generated for youth, parent-proxy, and parent self-reported experiences, and there were different sub-themes for each participant type (Figure). Youth were focused on avoidance of disclosure and the psychological impact of self-comparisons and embarrassment, while the parental perspective centered on worries about future fertility, complications, psychological health, and normality. Some youth and parents from disadvantaged neighborhoods or those with public insurance indicated a need for more education on normal penile functions and provision of strategies for long-term self-monitoring and facilitation of long-term follow-up on mixed methods analysis. CONCLUSION: These findings add insight into the multifaceted experiences of pre-pubertal youth and families dealing with hypospadias, and underscore the consistent, wide-ranging interplay between medical, psychological, and social concerns. Patterns in themes across socioeconomic status and insurance coverage suggest that access to information and quality care may vary significantly and could contribute to health disparities. Urologists should employ an individualized approach to counseling and care delivery. Future studies will seek to characterize care priorities in pubertal and post-pubertal age groups to design developmentally adjusted support tools for youth and adults with hypospadias and their families.

2.
Inorg Chem ; 63(33): 15311-15322, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39115455

ABSTRACT

The widespread use and contamination of natural sources by new-generation drugs and pesticides have enhanced concern about environmental pollution. Understanding the above importance, we developed a superhydrophobic metal-organic framework (MOF) (SHMOF': [Zr6O4(OH)4(BDC-NH-CO-R)2.4(BDC-NH2)0.6(CF3COO)6]·2.5H2O·4DMF) for ecological remediation via adsorption-based separation of hydrophobic drugs (flurbiprofen) and pesticides (fluazinam). The newly developed SHMOF' has a high adsorption capacity toward flurbiprofen and fluazinam, i.e., 435 and 575 mg/g, respectively. The adsorption equilibrium time of the MOF is very short (15 and 10 min for flurbiprofen and fluazinam, respectively). The outstanding superhydrophobic nature of the MOF was employed to separate flurbiprofen and fluazinam from highly alkaline and acidic media and environmental water samples. The SHMOF' has excellent selectivity toward the adsorption-based separation of flurbiprofen and fluazinam in the coexistence of common analytes. Again, we developed a polypropylene (PP) fabric-based composite of SHMOF' (SHMOF'@PP) to separate the hydrophobic targeted analytes by using a zero-energy-consuming filtration-based separation method, which made this separation process cost-efficient and user-friendly. Moreover, Ag nanoparticles were doped to the superhydrophobic composite. The Ag-doped reusable SHMOF'@PP@Ag composite exhibited excellent bacterial antiadhesion and antibacterial properties toward Staphylococcus aureus bacteria.


Subject(s)
Anti-Bacterial Agents , Hydrophobic and Hydrophilic Interactions , Metal-Organic Frameworks , Pesticides , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Pesticides/isolation & purification , Pesticides/chemistry , Pesticides/pharmacology , Adsorption , Staphylococcus aureus/drug effects , Water Pollutants, Chemical/isolation & purification , Water Pollutants, Chemical/chemistry , Microbial Sensitivity Tests , Surface Properties , Flurbiprofen/chemistry , Flurbiprofen/pharmacology , Flurbiprofen/isolation & purification , Molecular Structure
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124731, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-38955074

ABSTRACT

Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles. In a bid to surmount this obstacle, researchers embarked on a journey to develop ibrutinib-loaded NLCs (Nanostructured Lipid Carriers) using a methodology steeped in complexity: a Design of Experiments (DoE)-based hot melted ultrasonication approach. Despite a plethora of methods for analyzing ibrutinib in various matrices, the absence of a spectrofluorimetric method for assessing it in rat plasma added to the enigma. Thus emerged a spectrofluorimetric method, embodying principles of white analytical chemistry and analytical quality by design, employing a Placket-Burman design for initial method exploration and a central composite design for subsequent refinement. This method underwent rigorous validation in accordance with ICH guidelines, paving the way for its application in scrutinizing the in-vivo pharmacokinetics of ibrutinib-loaded NLCs, juxtaposed against commercially available formulations. Surprisingly, the optimized NLCs exhibited a striking 1.82-fold boost in oral bioavailability, shedding light on their potential efficacy. The environmental impact of this method was scrutinized using analytical greenness tools, affirming its eco-friendly attributes. In essence, the culmination of these efforts has not only propelled advancements in drug bioavailability but also heralded the dawn of a streamlined and environmentally conscious analytical paradigm.


Subject(s)
Adenine , Lipids , Piperidines , Pyrimidines , Spectrometry, Fluorescence , Animals , Adenine/analogs & derivatives , Adenine/pharmacokinetics , Adenine/chemistry , Adenine/blood , Piperidines/pharmacokinetics , Piperidines/chemistry , Piperidines/blood , Lipids/chemistry , Male , Spectrometry, Fluorescence/methods , Rats , Pyrimidines/pharmacokinetics , Pyrimidines/chemistry , Pyrimidines/blood , Drug Carriers/chemistry , Nanostructures/chemistry , Pyrazoles/pharmacokinetics , Pyrazoles/chemistry , Pyrazoles/blood , Pyrazoles/administration & dosage , Reproducibility of Results , Rats, Wistar
4.
Cureus ; 16(4): e58192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38741847

ABSTRACT

Lemierre-like syndrome is a rare, systemic sequelae following a persistent oropharyngeal infection, leading to septic thrombophlebitis of the internal jugular vein (IJV). Lemierre syndrome is caused by the obligate anaerobic organism Fusobacterium necrophorum, innate to the oropharyngeal tract. Lemierre-like syndrome is due to infections caused by other organisms, including methicillin-resistant Staphylococcus aureus (MRSA). We are reporting a case of a five-month-old male who presented with one week of fever that was not alleviated by acetaminophen, bilateral otitis media, and left-sided cervical lymphadenopathy not alleviated with medical therapy. The patient's clinical course continued to deteriorate as he developed respiratory distress that progressed to acute respiratory failure requiring mechanical ventilation support. Extensive laboratory investigation ruled out the causes of primary and secondary immunodeficiencies. Blood cultures were positive for MRSA, and he was treated initially with vancomycin, then switched to linezolid per ENT recommendations, and ultimately needed daptomycin and ceftaroline therapy. A computed tomography (CT) scan of the neck and chest showed deep neck space infection, bilateral loculated pleural empyema, and mediastinitis. The patient required a decortication video-assisted thoracoscopic surgery (VATS), multiple drains, and a mediastinal washout to control the MRSA infection. This report emphasizes that the rapid progression and spread of septic thrombus can become detrimental to a patient's recovery and survival; therefore, it should be recognized early and treated promptly.

5.
Comput Med Imaging Graph ; 112: 102326, 2024 03.
Article in English | MEDLINE | ID: mdl-38211358

ABSTRACT

Micro-ultrasound (micro-US) is a novel 29-MHz ultrasound technique that provides 3-4 times higher resolution than traditional ultrasound, potentially enabling low-cost, accurate diagnosis of prostate cancer. Accurate prostate segmentation is crucial for prostate volume measurement, cancer diagnosis, prostate biopsy, and treatment planning. However, prostate segmentation on micro-US is challenging due to artifacts and indistinct borders between the prostate, bladder, and urethra in the midline. This paper presents MicroSegNet, a multi-scale annotation-guided transformer UNet model designed specifically to tackle these challenges. During the training process, MicroSegNet focuses more on regions that are hard to segment (hard regions), characterized by discrepancies between expert and non-expert annotations. We achieve this by proposing an annotation-guided binary cross entropy (AG-BCE) loss that assigns a larger weight to prediction errors in hard regions and a lower weight to prediction errors in easy regions. The AG-BCE loss was seamlessly integrated into the training process through the utilization of multi-scale deep supervision, enabling MicroSegNet to capture global contextual dependencies and local information at various scales. We trained our model using micro-US images from 55 patients, followed by evaluation on 20 patients. Our MicroSegNet model achieved a Dice coefficient of 0.939 and a Hausdorff distance of 2.02 mm, outperforming several state-of-the-art segmentation methods, as well as three human annotators with different experience levels. Our code is publicly available at https://github.com/mirthAI/MicroSegNet and our dataset is publicly available at https://zenodo.org/records/10475293.


Subject(s)
Deep Learning , Prostatic Neoplasms , Male , Humans , Prostate/diagnostic imaging , Prostate/pathology , Ultrasonography/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Urinary Bladder , Image Processing, Computer-Assisted/methods
6.
Diabetol Metab Syndr ; 16(1): 8, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178175

ABSTRACT

BACKGROUND: Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. OBJECTIVE: To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. METHODS: Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. RESULTS: Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference - 0.03, 95% CI 0.06, - 0.01; I2 58.69%), inositol (risk difference - 0.19, 95% CI 0.33, - 0.06; I2 92.19%), and vitamin D supplements (risk difference - 0.16, 95% CI 0.25, - 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference - 0.16, 95% CI 0.25, - 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference - 0.17, 95% CI 0.22, - 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. CONCLUSIONS: This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted.

7.
Adv Healthc Mater ; 13(6): e2302790, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37909063

ABSTRACT

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA-SS-HA-encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity reveals that HA-SS-HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics-encapsulated HA-SS-HA hydrogel can effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA can be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacteria.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , United States , Animals , Mice , Anti-Bacterial Agents/pharmacology , Hyaluronic Acid/pharmacology , Hydrogels/pharmacology , Staphylococcus aureus , Bacteria , Drug Carriers/pharmacology , Polymers
8.
Hepatol Commun ; 7(12)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38055623

ABSTRACT

BACKGROUND: There are no immunological biomarkers that predict control of chronic hepatitis B (CHB). The lack of immune biomarkers raises concerns for therapies targeting PD-1/PD-L1 because they have the potential for immune-related adverse events. Defining specific immune functions associated with control of HBV replication could identify patients likely to respond to anti-PD-1/PD-L1 therapies and achieve a durable functional cure. METHODS: We enrolled immunotolerant, HBeAg+ immune-active (IA+), HBeAg- immune-active (IA-), inactive carriers, and functionally cured patients to test ex vivo PD-1 blockade on HBV-specific T cell functionality. Peripheral blood mononuclear cells were stimulated with overlapping peptides covering HBV proteins +/-α-PD-1 blockade. Functional T cells were measured using a 2-color FluoroSpot assay for interferon-γ and IL-2. Ex vivo functional restoration was compared to the interferon response capacity assay, which predicts overall survival in cancer patients receiving checkpoint inhibitors. RESULTS: Ex vivo interferon-γ+ responses did not differ across clinical phases. IL-2+ responses were significantly higher in patients with better viral control and preferentially restored with PD-1 blockade. Inactive carrier patients displayed the greatest increase in IL-2 production, which was dominated by CD4 T cell and response to the HBcAg. The interferon response capacity assay significantly correlated with the degree of HBV-specific T cell restoration. CONCLUSIONS: IL-2 production was associated with better HBV control and superior to interferon-γ as a marker of T cell restoration following ex vivo PD-1 blockade. Our study suggests that responsiveness to ex vivo PD-1 blockade, or the interferon response capacity assay, may support stratification for α-PD-1 therapies.


Subject(s)
Hepatitis B, Chronic , Humans , T-Lymphocytes/metabolism , Hepatitis B virus , Interleukin-2 , Interferon-gamma , B7-H1 Antigen , Hepatitis B e Antigens , Programmed Cell Death 1 Receptor , Leukocytes, Mononuclear/metabolism , Biomarkers
9.
Curr Chin Sci ; 3(5): 386-395, 2023.
Article in English | MEDLINE | ID: mdl-37981909

ABSTRACT

Cerebral cavernous malformations (CCMs) are comprised of tissue matter within the brain possessing anomalous vascular architecture. In totality, the dilated appearance of the cavernomatakes on a mulberry-like shape contributed by the shape and relation to vascular and capillary elements. Analyzing its pathophysiology along with its molecular and genetic pathways plays a vital role in whether or not a patient receives GKRS, medical management, or Surgery, the most invasive of procedures. To avoid neurological trauma, microsurgical resection of cavernomas canbe guided by the novel clinical application of a 3D Slicer with Sina/MosoCam. When cavernomas present in deep lesions with poor accessibility, gamma knife stereotactic radiosurgery (GKSR) is recommended. For asymptomatic and non-multilobal lesions, medical and symptom management is deemed standard, such as antiepileptic therapy. The two-hit hypothesis serves to explain the mutations in three key genes that are most pertinent to the progression of cavernomas: CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10. Various exon deletions and frameshift mutations can cause dysfunction in vascular structure through loss and gain of function mutations. MEKK3 and KLF2/4 are involved in a protein kinase signaling cycle that promotes abnormal angiogenesis and cavernoma formation. In terms of potential treatments, RhoKinase inhibitors have shown to decrease endothelial to mesenchymal transition and CCM lesion development in mice models. All in all, understanding the research behind the molecular genetics in CCMs can foster personalized medicine and potentially create new neurosurgical and medicative treatments.

10.
Expert Rev Anticancer Ther ; 23(12): 1265-1279, 2023.
Article in English | MEDLINE | ID: mdl-38032181

ABSTRACT

INTRODUCTION: Artificial intelligence (AI) has the potential to transform oncologic care. There have been significant developments in AI applications in medical imaging and increasing interest in multimodal models. These are likely to enable improved oncologic care through more precise diagnosis, increasingly in a more personalized and less invasive manner. In this review, we provide an overview of the current state and challenges that clinicians, administrative personnel and policy makers need to be aware of and mitigate for the technology to reach its full potential. AREAS COVERED: The article provides a brief targeted overview of AI, a high-level review of the current state and future potential AI applications in diagnostic radiology and to a lesser extent digital pathology, focusing on oncologic applications. This is followed by a discussion of emerging approaches, including multimodal models. The article concludes with a discussion of technical, regulatory challenges and infrastructure needs for AI to realize its full potential. EXPERT OPINION: There is a large volume of promising research, and steadily increasing commercially available tools using AI. For the most advanced and promising precision diagnostic applications of AI to be used clinically, robust and comprehensive quality monitoring systems and informatics platforms will likely be required.


Subject(s)
Artificial Intelligence , Neoplasms , Humans , Diagnostic Imaging , Medical Oncology , Forecasting , Palliative Care , Neoplasms/diagnostic imaging , Neoplasms/therapy
11.
J Radiol Oncol ; 7(2): 26-32, 2023.
Article in English | MEDLINE | ID: mdl-37795208

ABSTRACT

Neurointerventional Radiology (NIR), encompassing neuroendovascular surgery, endovascular neurosurgery, and interventional neurology, is an innovative and rapidly evolving multidisciplinary specialty focused on minimally invasive therapies for a wide range of neurological disorders. This review provides a comprehensive overview of NIR, discussing the three routes into the field, highlighting their distinct training paradigms, and emphasizing the importance of unified approaches through organizations like the Society of Neurointerventional Surgery (SNIS). The paper explores the benefits of co-managed care and its potential to improve patient outcomes, as well as the role of interdisciplinary collaboration and cross-disciplinary integration in advancing the field. We discuss the various contributions of neurosurgery, radiology, and neurology to cerebrovascular surgery, aiming to inform and educate those interested in pursuing a career in neurointervention. Additionally, the review examines the adoption of innovative technologies such as robotic-assisted techniques and artificial intelligence in NIR, and their implications for patient care and the future of the specialty. By presenting a comprehensive analysis of the field of neurointervention, we hope to inspire those considering a career in this exciting and rapidly advancing specialty, and underscore the importance of interdisciplinary collaboration in shaping its future.

13.
Chem Commun (Camb) ; 59(71): 10624-10627, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37578258

ABSTRACT

Host-guest complexation-based suprasomes successfully deliver benzimidazolium amphiphiles. ß-CD and Zn2+ or an acidic environment act as the stimuli for the assembly and disassembly of suprasomes. The supramolecular nanomedicine developed by encapsulating tetracycline showed strong and tunable antibacterial activity and holds potential for the next-generation vesicle-based drug delivery system.


Subject(s)
Anti-Bacterial Agents , Drug Delivery Systems , Anti-Bacterial Agents/pharmacology
14.
Article in English | MEDLINE | ID: mdl-37601162

ABSTRACT

Theranostics in neurosurgery is a rapidly advancing field of precision medicine that combines diagnostic and therapeutic modalities to optimize patient outcomes. This approach has the potential to provide real-time feedback during therapy and diagnose a condition while simultaneously providing treatment. One such form of theranostics is focused ultrasound, which has been found to be effective in inducing neuroablation and neuromodulation and improving the efficacy of chemotherapy drugs by disrupting the blood-brain barrier. Targeted radionuclide therapy, which pairs positron emission tomography tracers with therapeutic effects and imaging modalities, is another promising form of theranostics for neurosurgery. Automated pathology analysis is yet another form of theranostics that can provide real-time feedback during the surgical resection of tumors. Electrical stimulation has also shown promise in optimizing therapies for patients with cerebral palsy. Overall, theranostics is a cost-effective way to optimize medical care for patients in neurosurgery. It is a relatively new field, but the advancements made so far show great promise for improving patient outcomes.

15.
J Med Chem ; 66(16): 11078-11093, 2023 08 24.
Article in English | MEDLINE | ID: mdl-37466499

ABSTRACT

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn2+ transport activities. Our findings showed that a potent QN-based Zn2+ transporter exhibits promising antibacterial properties against Gram-positive bacteria with reduced hemolytic activity and cytotoxicity to mammalian cells. Furthermore, this combination showed excellent in vivo efficacy against Staphylococcus aureus. Interestingly, this combination prevented bacterial resistance and restored susceptibility of gentamicin and methicillin-resistant S. aureus to commercially available ß-lactam and other antibiotics that had lost their activity against the drug-resistant bacterial strain. Our findings suggest that the transmembrane transport of Zn2+ by QN derivatives could be a promising strategy to combat bacterial infections and restore the activity of other antibiotics.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Quinolines , Staphylococcal Infections , Animals , Humans , Zinc , Ionophores/therapeutic use , Thiourea/pharmacology , Thiourea/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Quinolines/pharmacology , Quinolines/therapeutic use , Microbial Sensitivity Tests , Mammals
16.
Tomography ; 9(3): 1094-1109, 2023 05 29.
Article in English | MEDLINE | ID: mdl-37368542

ABSTRACT

Employing the full arsenal of therapeutics to treat brain tumors is limited by the relative impermeability of the blood-brain and blood-tumor barriers. In physiologic states, the blood-brain barrier serves a protective role by passively and actively excluding neurotoxic compounds; however, this functionality limits the penetrance of therapeutics into the tumor microenvironment. Focused ultrasound technology provides a method for overcoming the blood-brain and blood-tumor barriers through ultrasound frequency to transiently permeabilize or disrupt these barriers. Concomitant delivery of therapeutics has allowed for previously impermeable agents to reach the tumor microenvironment. This review details the advances in focused ultrasound in both preclinical models and clinical studies, with a focus on its safety profile. We then turn towards future directions in focused ultrasound-mediated therapies for brain tumors.


Subject(s)
Brain Neoplasms , Humans , Brain Neoplasms/therapy , Brain Neoplasms/drug therapy , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/pathology , Ultrasonography , Magnetic Resonance Imaging/methods , Tumor Microenvironment
17.
Cureus ; 15(5): e38728, 2023 May.
Article in English | MEDLINE | ID: mdl-37292561

ABSTRACT

Neonatal alloimmune thrombocytopenia (NAIT) is a condition in which maternal IgG antibodies are directed against fetal platelets and cross the placenta, destroying fetal thrombocytes. It is typically caused by maternal alloimmunization to human leukocyte antigens (HLA). ABO incompatibility, on the other hand, is a rare cause of NAIT due to the variable expression of ABO antigens on platelets. Here, we present the case of a first-time mother (O+) who delivered a 37-week 0-day gestation newborn (B+) that was anemic and jaundiced with critically high total bilirubin levels. This required the initiation of phototherapy and intravenous immunoglobulins. Despite treatment, jaundice was slow to improve. Given infectious concerns, a complete white blood cell count was ordered. Incidentally, it revealed severe thrombocytopenia. Platelet transfusions were administered, although only minimal improvement was observed. This warranted maternal testing for antibodies to HLA-Ia/IIa, HLA-IIb/IIIa, and HLA-Ib/IX antigens given suspected NAIT. Results returned negative. Due to the severity of the condition, patient care was continued at a tertiary facility. When screening for NAIT, special consideration should be given to type O mothers with ABO incompatibility to their fetus - they can uniquely make IgG against A or B antigens, which, unlike IgM and IgA, can cross the placenta and cause potential sequelae harming the newborn. Early recognition and timely management of NAIT are important to prevent certain complications, such as fatal intracranial hemorrhage and developmental delay.

18.
J Pers Med ; 13(5)2023 May 19.
Article in English | MEDLINE | ID: mdl-37241023

ABSTRACT

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas.

19.
Inorg Chem ; 62(18): 6970-6980, 2023 May 08.
Article in English | MEDLINE | ID: mdl-37104732

ABSTRACT

In the current scenario, one of the crucial reaction conversions is the synthesis of renewable biofuels and value-added chemicals from the hydrogenation of biomass. Therefore, in the present work, we are proposing aqueous phase conversion of levulinic acid to γ-valerolactone via hydrogenation using formic acid as a sustainable green hydrogen source over a sustainable heterogeneous catalyst. The catalyst based on Pd nanoparticles stabilized by lacunary phosphomolybdate (PMo11Pd) was designed for the same and characterized by EDX, FT-IR, 31P NMR, powder XRD, XPS, TEM, HRTEM, and HAADF-STEM analyses. A detailed optimization study was done to achieve maximum conversion (95% conversion), using a very small amount of Pd (1.879 × 10-3 mmol) with notable TON (2585) at 200 °C in 6 h. The regenerated catalyst was found to be workable (reusable) up to three cycles without any change in activity. Also, a plausible reaction mechanism was proposed. The catalyst exhibits superior activity against reported catalysts.

20.
Oxygen (Basel) ; 3(2): 163-178, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37082315

ABSTRACT

Mitochondrial oxidative stress has been implicated in various forms of brain injury, both traumatic and non-traumatic. Due to its oxidative demand, the brain is intimately dependent on its mitochondrial functioning. However, there remains appreciable heterogeneity in the development of these injuries regarding ROS and their effect on the sequelae. These include traumatic insults such as TBIs and intracranial hemorrhaging secondary to this. In a different vein, such injuries may be attributed to other etiologies such as infection, neoplasm, or spontaneous hemorrhage (strokes, aneurysms). Clinically, the manner of treatment may also be adjusted in relation to each injury and its unique progression in the context of ROS. In the current review, then, the authors highlight the role of mitochondrial ROS in various forms of brain injury, emphasizing both the collective and unique elements of each form. Lastly, these narratives are met with the current therapeutic landscape and the role of emerging therapies in treating reactive oxygen species in brain injuries.

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