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1.
Cell Mol Life Sci ; 81(1): 169, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589732

RESUMO

Rhes (Ras homolog enriched in the striatum), a multifunctional protein that regulates striatal functions associated with motor behaviors and neurological diseases, can shuttle from cell to cell via the formation of tunneling-like nanotubes (TNTs). However, the mechanisms by which Rhes mediates diverse functions remain unclear. Rhes is a small GTPase family member which contains a unique C-terminal Small Ubiquitin-like Modifier (SUMO) E3-like domain that promotes SUMO post-translational modification of proteins (SUMOylation) by promoting "cross-SUMOylation" of the SUMO enzyme SUMO E1 (Aos1/Uba2) and SUMO E2 ligase (Ubc-9). Nevertheless, the identity of the SUMO substrates of Rhes remains largely unknown. Here, by combining high throughput interactome and SUMO proteomics, we report that Rhes regulates the SUMOylation of nuclear proteins that are involved in the regulation of gene expression. Rhes increased the SUMOylation of histone deacetylase 1 (HDAC1) and histone 2B, while decreasing SUMOylation of heterogeneous nuclear ribonucleoprotein M (HNRNPM), protein polybromo-1 (PBRM1) and E3 SUMO-protein ligase (PIASy). We also found that Rhes itself is SUMOylated at 6 different lysine residues (K32, K110, K114, K120, K124, and K245). Furthermore, Rhes regulated the expression of genes involved in cellular morphogenesis and differentiation in the striatum, in a SUMO-dependent manner. Our findings thus provide evidence for a previously undescribed role for Rhes in regulating the SUMOylation of nuclear targets and in orchestrating striatal gene expression via SUMOylation.


Assuntos
Proteínas Nucleares , Ubiquitina , Ubiquitina/metabolismo , Proteínas Nucleares/metabolismo , Processamento de Proteína Pós-Traducional , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinas/genética , Sumoilação , Expressão Gênica , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
2.
Chem Commun (Camb) ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619439

RESUMO

Herein, we present an efficient Pd-catalysed method for stereoselective synthesis of chromone C-glycosides from various glycals. We successfully applied this method to various glycals with different protecting groups, yielding the corresponding glycosides in 41-78% yields. Additionally, we investigated the potential of this approach for the late-stage modification of natural products and pharmaceutical compounds linked to glycals, leading to the synthesis of their respective glycosides. Furthermore, we extended our research to gram-scale synthesis and demonstrated its applicability in producing various valuable products, including 2-deoxy-chromone C-glycosides. In summary, our work introduces a novel library of chromone glycosides, which holds promise for advancing drug discovery efforts.

3.
Mol Cell Proteomics ; 23(4): 100746, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38447791

RESUMO

Huntington disease (HD) is caused by an expanded polyglutamine mutation in huntingtin (mHTT) that promotes prominent atrophy in the striatum and subsequent psychiatric, cognitive deficits, and choreiform movements. Multiple lines of evidence point to an association between HD and aberrant striatal mitochondrial functions; however, the present knowledge about whether (or how) mitochondrial mRNA translation is differentially regulated in HD remains unclear. We found that protein synthesis is diminished in HD mitochondria compared to healthy control striatal cell models. We utilized ribosome profiling (Ribo-Seq) to analyze detailed snapshots of ribosome occupancy of the mitochondrial mRNA transcripts in control and HD striatal cell models. The Ribo-Seq data revealed almost unaltered ribosome occupancy on the nuclear-encoded mitochondrial transcripts involved in oxidative phosphorylation (SDHA, Ndufv1, Timm23, Tomm5, Mrps22) in HD cells. By contrast, ribosome occupancy was dramatically increased for mitochondrially encoded oxidative phosphorylation mRNAs (mt-Nd1, mt-Nd2, mt-Nd4, mt-Nd4l, mt-Nd5, mt-Nd6, mt-Co1, mt-Cytb, and mt-ATP8). We also applied tandem mass tag-based mass spectrometry identification of mitochondrial proteins to derive correlations between ribosome occupancy and actual mature mitochondrial protein products. We found many mitochondrial transcripts with comparable or higher ribosome occupancy, but diminished mitochondrial protein products, in HD. Thus, our study provides the first evidence of a widespread dichotomous effect on ribosome occupancy and protein abundance of mitochondria-related genes in HD.

4.
Environ Monit Assess ; 196(4): 342, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438750

RESUMO

Air pollution is growing at alarming rates on regional and global levels, with significant consequences for human health, ecosystems, and change in climatic conditions. The present 12 weeks (4 October 2021, to 26 December 2021) study revealed the different ambient air quality parameters, i.e., PM2.5, PM10, SO2, NO2, and O3 over four different sampling stations of Delhi-NCR region (Dwarka, Knowledge park III, Sector 125, and Vivek Vihar), India, by using satellite remote sensing data (MERRA-2, OMI, and Aura Satellite) and different ground-based instruments. The ground-based observation revealed the mean concentration of PM2.5 in Dwarka, Knowledge park III, Sector 125, and Vivek Vihar as 279 µg m-3, 274 µg m-3, 294 µg m-3, and 365 µg m-3, respectively. The ground-based instrumental concentration of PM2.5 was greater than that of satellite observations, while as for SO2 and NO2, the mean concentration of satellite-based monitoring was higher as compared to other contaminants. Negative and positive correlations were observed among particulate matter, trace gases, and various meteorological parameters. The wind direction proved to be one of the prominent parameter to alter the variation of these pollutants. The current study provides a perception into an observable behavior of particulate matter, trace gases, their variation with meteorological parameters, their health hazards, and the gap between the measurements of satellite remote sensing and ground-based measurements.


Assuntos
Poluentes Atmosféricos , Humanos , Dióxido de Nitrogênio , Ecossistema , Monitoramento Ambiental , Material Particulado , Gases
5.
J Biomol Struct Dyn ; : 1-16, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38444340

RESUMO

Protein structure prediction (PSP) is a key concern in computational biology, which is considered a challenging task that is vital to determine the structure and the protein function since each protein possesses a definite shape, whereas the protein secondary structure prediction (PSSP) is the foundation for three-dimensional PSP. An Advanced hybrid ensemble deep predictor is utilized for predicting the structure of a protein using Long-Short Term Memory (LSTM), in which the performance of the predictor is improved for obtaining the features through the Salp-J Colony Optimization, which is developed by integrating the features of three optimizations the exploration behavior of Ulmaris, the immune system of virus colony and the teamwork of salp for solution update that helps to predict the accurate protein structure. The proposed method achieved the value of 99.1% accuracy, 99.5% sensitivity, 98.85% specificity, and 0.9% error at the 80% of training percentage 90 using CullPDB. Similarly, in Protein Net, the attained value of accuracy is 97.27%, sensitivity is 98.13%, specificity is 97%, and error is 2.7% concerning training percentage 90%.Communicated by Ramaswamy H. Sarma.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38446299

RESUMO

A convenient synthesis of a novel 1,3,4-oxadiazole derivative, specifically known as, 2-(5-methylthiophen-2-yl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (MTPO), is reported along with a comprehensive evaluation of its ability to inhibit the corrosion of mild steel (MS) in a 1 N HCl environment using weight loss, EIS, PDP, SEM, EDX, and UV-Vis spectroscopy. The investigated inhibitor expressed excellent inhibition efficiency (99.05% at 500 ppm, 298 K) with a mixed-type inhibitory mechanism as demonstrated by the PDP technique. Furthermore, MTPO followed Langmuir adsorption isotherm, which provides insights into the adsorption phenomena, demonstrating that it exhibits superior adsorption behavior on the MS surface compared. In silico investigations, using DFT computation and MD simulation complements the experimental outcomes revealing strong adsorbing attributes of the MTPO hybrid with the ω - and ω + values of 8.8882 eV and 4.4787 eV, respectively. In addition, the radial distribution function also addressed the chemisorption behavior of MTPO. This article also takes into consideration the various ways in which the inhibitor interacts with the mild steel, offering potential insights for developing strategies to mitigate metal dissolution in acidic environments.

7.
Invest New Drugs ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483782

RESUMO

MEK inhibitors have immunomodulatory activity and potential for synergistic activity when combined with PD-1 inhibitors. We evaluated selumetinib (inhibitor of MEK1/2) plus pembrolizumab (anti‒PD-1 antibody) in patients with advanced/metastatic solid tumors. In this phase 1b study, adults with previously treated advanced/metastatic solid tumors received pembrolizumab 200 mg intravenously every 3 weeks plus selumetinib on days 1‒14 per 3-week cycle (2 weeks on/1 week off); selumetinib dosing began at 50 mg orally twice daily with escalation in 25 mg increments for ≤ 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. Thirty-two patients were enrolled. Dose escalation was completed up to selumetinib 125 mg twice daily. The target DLT rate of 30% was not reached at any dose level. In the selumetinib 100 mg group, 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis). Dose-related changes in pharmacokinetic exposures were observed for selumetinib and N-desmethyl selumetinib up to 100 mg (saturation at 125 mg). Two patients achieved partial responses (1 each with selumetinib 75 mg and 125 mg) for an objective response rate of 6%. The study was stopped early because of insufficient efficacy. Although the target DLT rate was not reached at any dose level and no new safety signals were identified, selumetinib plus pembrolizumab had limited antitumor activity in this population. Trial registration: ClinicalTrials.gov , NCT03833427.

8.
J Immunother Cancer ; 12(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38458639

RESUMO

BACKGROUND: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors. METHODS: CA186-018: Patients with metastatic colorectal cancer or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated in a dose-evaluation phase with urelumab 0.1 mg/kg (urelumab-0.1) every 3 weeks (Q3W)+cetuximab 250 mg/m2 (cetuximab-250) weekly; and in a dose-expansion phase with urelumab 8 mg flat dose (urelumab-8) Q3W+cetuximab-250 weekly. CA186-107: The dose-escalation phase included patients with previously treated advanced solid tumors (or treated or treatment-naive melanoma); patients received urelumab 3 mg flat dose (urelumab-3) or urelumab-8 every 4 weeks+nivolumab 3 mg/kg (nivolumab-3) or 240 mg (nivolumab-240) every 2 weeks. In the expansion phase, patients with melanoma, non-small cell lung cancer, or SCCHN were treated with urelumab-8+nivolumab-240. Primary endpoints were safety and tolerability, and the secondary endpoint included efficacy assessments. RESULTS: CA186-018: 66 patients received study treatment. The most frequent treatment-related adverse events (TRAEs) were fatigue (75%; n=3) with urelumab-0.1+cetuximab-250 and dermatitis (45%; n=28) with urelumab-8+cetuximab-250. Three patients (5%) discontinued due to TRAE(s) (with urelumab-8+cetuximab-250). One patient with SCCHN had a partial response (objective response rate (ORR) 5%, with urelumab-8+cetuximab-250).CA186-107: 134 patients received study treatment. Fatigue was the most common TRAE (32%; n=2 with urelumab-3+nivolumab-3; n=1 with urelumab-8+nivolumab-3; n=40 with urelumab-8+nivolumab-240). Nine patients (7%) discontinued due to TRAE(s) (n=1 with urelumab-3+nivolumab-3; n=8 with urelumab-8+nivolumab-240). Patients with melanoma naive to anti-PD-1 therapy exhibited the highest ORR (49%; n=21 with urelumab-8+nivolumab-240). Intratumoral gene expression in immune-related pathways (CD3, CD8, CXCL9, GZMB) increased on treatment with urelumab+nivolumab. CONCLUSIONS: Although the addition of urelumab at these doses was tolerable, preliminary response rates did not indicate an evident additive benefit. Nevertheless, the positive pharmacodynamics effects observed with urelumab and the high response rate in treatment-naive patients with melanoma warrant further investigation of other anti-CD137 agonist agents for treatment of cancer. TRIAL REGISTRATION NUMBERS: NCT02110082; NCT02253992.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Melanoma , Humanos , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Neoplasias Pulmonares/induzido quimicamente , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico
9.
J Biol Chem ; 300(4): 105778, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38395307

RESUMO

The mechanistic target of rapamycin (mTOR) signaling is influenced by multiple regulatory proteins and post-translational modifications; however, underlying mechanisms remain unclear. Here, we report a novel role of small ubiquitin-like modifier (SUMO) in mTOR complex assembly and activity. By investigating the SUMOylation status of core mTOR components, we observed that the regulatory subunit, GßL (G protein ß-subunit-like protein, also known as mLST8), is modified by SUMO1, 2, and 3 isoforms. Using mutagenesis and mass spectrometry, we identified that GßL is SUMOylated at lysine sites K86, K215, K245, K261, and K305. We found that SUMO depletion reduces mTOR-Raptor (regulatory protein associated with mTOR) and mTOR-Rictor (rapamycin-insensitive companion of mTOR) complex formation and diminishes nutrient-induced mTOR signaling. Reconstitution with WT GßL but not SUMOylation-defective KR mutant GßL promotes mTOR signaling in GßL-depleted cells. Taken together, we report for the very first time that SUMO modifies GßL, influences the assembly of mTOR protein complexes, and regulates mTOR activity.

10.
Heliyon ; 10(4): e26525, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404771

RESUMO

Bael is a medicinal cum fruit tree with multipurpose utility and propagated mostly through seeds. The present study aimed to assess and analyse the morpho-pomological and biochemical traits of eighty seedlings grown bael genotypes comparison with two commercial cultivars (NB-5 and NB-9) of bael. The significant differences were detected among the genotypes based on the measured morpho-pomological and biochemical traits. The morpho-pomological and biochemical traits of bael exhibited variation ranging from 6.17% to 133.65%. Trunk girth ranged from 29.50 to 63.40 cm and tree spread (N-S) varied 1.00-6.30 m. Fruit length ranged from 4.60 to 12.05 cm and fruit width ranged from 4.64 to 11.72 cm. Moreover, fruit weight ranged from 56.33 to 917.65 g and pulp percentage varied from 58.64 to 81.38%. Soluble Solid Content ranged from 25.90 to 36.77 0brix and ascorbic acid varied from 14.38 to 25.45 mg/100 g. Fruit length was positively correlated with fruit width, fruit weight, pulp percentage, seed length, seed diameter and number of seeds per fruit, while it was negatively correlated with fruit surface and total number of fruit per plant. Principal component analysis showed that 76.66% of the variability observed was explained by the 13 components. Ward cluster analysis using Euclidean distance classified the genotypes into two main clusters. These findings contribute to a better understanding of the diversity and relationships among the studied genotypes, aiding future breeding and selection programs for improved bael cultivation.

11.
Heliyon ; 10(4): e26398, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404786

RESUMO

Brain implantable wireless microsystems has potential to treat neurological diseases and maintain the quality of life. Highly efficient miniaturized antenna is the fundamental part of BID (brain implantable device) for reliable signaling of data through dissipative intracranial material. In this paper, a patch antenna with L-shaped defected ground is demonstrated. L-shaped radiator contributed to achieve the resonance at 2.45 GHz industrial scientific and medical (ISM) band. Antenna size is reduced to 10 × 10 × 0.25 mm3. The proposed L-shaped ground plane geometry is contributing in improving the radiation performance. |S11| value shifts from 15 dB to 30 dB after modifying the ground plane. Proposed structure attained the gain of -14 dBi when located between the Dura and CSF layers at the depth of 12 mm in human brain model. Full wave simulated antenna prototype is fabricated and measured for performance verification. Impedance bandwidth of 270 MHz and broadside radiation pattern (for transferring maximum electromagnetic energy away from tissue) are maintained by the proposed antenna. Brain tissue safety is ensured by specific absorption rate which is 0.709 W/kg and in compliance with the safety limits of 1.6 W/kg for 1-g averaged tissue. Proposed antenna structure is the promising candidate for medical implant technology.

12.
Clin Ther ; 46(3): 228-238, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38423866

RESUMO

PURPOSE: The poly (ADP-ribose) polymerase inhibitor niraparib is indicated as maintenance treatment in patients with certain subtypes of advanced ovarian cancer, and is being investigated in patients with other solid tumors. Niraparib is available in 100-mg capsules with a starting dosage of 200 or 300 mg/d. This study assessed the relative bioavailability (BA) and bioequivalence (BE) between a 1 × 300-mg tablet relative to 3 × 100-mg niraparib capsules. In addition, the food effect (FE) of a high-fat meal on the pharmacokinetic (PK) properties of tablet-formulated niraparib was investigated. METHODS: This was a US-based, 3-stage, open-label, multicenter, single-crossover, randomized-sequence study. Enrolled patients were 18 years and older, with histologically or cytologically confirmed advanced solid tumors (metastatic or local) and disease progression despite standard therapy. Patients were randomly assigned 1:1 to receive niraparib 1 × 300-mg tablet or 3 × 100-mg capsules in the BA and BE stages or 1 × 300-mg tablet in a fasted or fed (high-fat meal) state in the FE stage. Across all study stages, PK parameters were assessed for 7 days after each dose (tablet or capsule) or prandial state (fasted or fed). In the BA stage, patients crossed over to the other treatment after a 7-day washout period, which was extended to 14 days in the BE and FE stages. Tolerability was assessed for patients who received any amount of niraparib. FINDINGS: The BA-, BE-, and FE-evaluable populations comprised 23, 108, and 19 patients, respectively, who completed both treatment periods in each study stage, had sufficient concentration data to accurately estimate PK parameters without niraparib carryover, and did not experience disqualifying events. PK parameters were similar after dosing with tablet or capsule formulations; the 90% CIs of the geometric least square means for Cmax, AUC0-t, and AUC0-∞ were within the 0.80 to 1.25 BE limits. In the FE stage, Cmax, AUC0-t, and AUC0-∞ were 11%, 32%, and 28% higher, respectively, in the fed versus fasted state. The safety population included 29, 168, and 28 patients in the BA, BE, and FE stages, respectively, who received niraparib. No new safety signals were identified. IMPLICATIONS: Niraparib tablets were found to be bioequivalent to capsules. A modest (≤32%) FE was observed with a high-fat meal, but was not considered to be clinically meaningful, given niraparib's PK variability. CLINICALTRIALS: gov identifier: NCT03329001. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.


Assuntos
Antineoplásicos , Indazóis , Neoplasias , Piperidinas , Humanos , Equivalência Terapêutica , Disponibilidade Biológica , Comprimidos/farmacocinética , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Jejum , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Estudos Cross-Over , Área Sob a Curva
13.
Cureus ; 16(1): e53175, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38420093

RESUMO

INTRODUCTION: Traumatic mandibular fractures are the most common fractures of the facial region and are associated with loss of neurosensation in the inferior alveolar nerve (IAN). The present study aimed to compare IAN recovery after traumatic mandibular fractures between the open and closed reduction methods. MATERIALS AND METHODS: The study included 90 patients with traumatic mandibular fractures of the body, angle, and symphysis, divided into two groups of 45 patients: group 1 was treated with closed reduction and fixation with rich arch-bar fixation under local anesthesia, and group 2 was treated with open reduction and rigid internal fixation with 2-mm titanium mini plates and monocortical screws (6 mm), and the plate was fixed to the fractured bony fragments. All patients underwent neurosensory testing using the Zuniga and Essick algorithm at baseline (preoperative), one week after surgery (postoperative), at three months, and at six months of follow-up. RESULTS: No statistically significant differences were observed in IAN recovery between the groups. The most common site of fracture was the body (44% in group 1 and 56% in group 2). The maximum recovery was observed in the younger age group (25-30 years). At baseline, functional nerve recovery was observed in 40 cases (88%) in group 1 and 38 cases (84%) in group 2, and the difference was not statistically significant. Levels A and B tests were affected by surgical management and improved after three months. The total recovery in group 1 ranged from 60% to 80%, and that in group 2 ranged from 56% to 72%. CONCLUSION: Based on the findings of the current study, both methods are recommended for surgical management of traumatic mandibular fractures with IAN recovery in 60-80% of cases six months postoperatively.

14.
Med Eng Phys ; 124: 104107, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38418014

RESUMO

Today, depression is a common problem that affects many people all over the world. It can impact a person's mood and quality of life unless identified and treated immediately. Due to the hectic and stressful modern life seems to be, depression has become a leading cause of mental health illnesses. Signals from electroencephalograms (EEG) are frequently used to detect depression. It is difficult, time-consuming, and highly skilled to manually detect depression using EEG data analysis. Hence, in the proposed study, an automated depression detection system using EEG signals is proposed. The proposed study uses a clinically available dataset and dataset provided by the Department of Psychiatry at the Government Medical College (GMC) in Kozhikode, Kerala, India which consisted of 15 depressed patients and 15 healthy subjects and a publically available Multi-modal Open Dataset (MODMA) for Mental-disorder Analysis available at UK Data service reshare that consisted of 24 depressed patients and 29 healthy subjects. In this study, we have developed a novel Deep Wavelet Scattering Network (DWSN) for the automated detection of depression EEG signals. The best-performing classifier is then chosen by feeding the features into several machine-learning algorithms. For the clinically available GMC dataset, Medium Neural Network (MNN) achieved the highest accuracy of 99.95% with a Kappa value of 0.999. Using the suggested methods, the precision, recall, and F1-score are all 1. For the MODMA dataset, Wide Neural Network (WNN) achieved the highest accuracy of 99.3% with a Kappa value of 0.987. Using the suggested methods, the precision, recall, and F1-score are all 0.99. In comparison to all current methodologies, the performance of the suggested research is superior. The proposed method can be used to automatically diagnose depression both at home and in clinical settings.


Assuntos
Depressão , Qualidade de Vida , Humanos , Depressão/diagnóstico , Redes Neurais de Computação , Algoritmos , Aprendizado de Máquina , Eletroencefalografia/métodos
15.
World J Pediatr Congenit Heart Surg ; : 21501351231215257, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263667

RESUMO

Background: Treatment of congenital heart disease (CHD), being the most common congenital anomaly, puts immense financial burden in low- and middle-income countries (LMICs) and contributes significantly to infant mortality. We report experiences of treatment of CHD in the Indian state of West Bengal by a public-private partnership (PPP) model. Methods: Under the Rashtriya Bal Swasthya Karyakram, the government of the state of West Bengal in India launched a program called the "Sishu Sathi Scheme" to provide free treatment to children who need heart surgeries, irrespective of economic status. Treatment was provided in selected private hospitals and some public hospitals in a reimbursement model where government compensated the hospitals. Data were collected on such procedures from 2013 to 2022 and analyzed. Results: A total of 27,844 patients with CHD received treatment under the Sishu Sathi Scheme from August 2013 to December 2022. The average number of patients per year was 3,093. Detailed data of procedures from January 2016 to December 2022 showed a total of 22,572 procedures (6,249 device interventions, 4,840 cardiac catheterizations, and 11,483 surgical interventions). The in-hospital mortality of surgical procedures and catheterization lab procedures were 5.2% and 0.9%, respectively. Conclusions: A large number of patients with CHD were successfully treated under a PPP in the state of West Bengal in India. In spite of its inherent challenges, this model is of special relevance in LMICs where access and affordability for treatment of CHD always remain a challenge.

16.
Physiol Meas ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38237198

RESUMO

Insomnia is a prevalent sleep disorder characterized by difficulties in initiating sleep or experiencing non-restorative sleep. It is a multifaceted condition that impacts both the quantity and quality of an individual's sleep. Recent advancements in machine learning (ML), and deep learning (DL) have enabled automated sleep analysis using physiological signals. This has led to the development of technologies for more accurate detection of various sleep disorders, including insomnia. This paper explores the algorithms and techniques for automatic insomnia detection. Methods: We followed the recommendations given in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) during our process of content discovery. Our review encompasses research papers published between 2015 and 2023, with a specific emphasis on automating the identification of insomnia. From a se- lection of well-regarded journals, we included more than 30 publications dedicated to insomnia detection. In our analysis, we assessed the performance of various meth- ods for detecting insomnia, considering different datasets and physiological signals. A common thread across all the papers we reviewed was the utilization of artificial intel- ligence (AI) models, trained and tested using annotated physiological signals. Upon closer examination, we identified the utilization of 15 distinct algorithms for this de- tection task. Results: Result: The major goal of this research is to conduct a thorough study to categorize, compare, and assess the key traits of automated systems for identifying insomnia. Our analysis offers complete and in-depth information. The essential com- ponents under investigation in the automated technique include the data input source, objective, machine learning (ML) and deep learning (DL) network, training framework, and references to databases. We classified pertinent research studies based on ML and DL model perspectives, considering factors like learning structure and input data types. Conclusion: Based on our review of the studies featured in this paper, we have identi- fied a notable research gap in the current methods for identifying insomnia and oppor- tunities for future advancements in the automation of insomnia detection. While the current techniques have shown promising results, there is still room for improvement in terms of accuracy and reliability. Future developments in technology and machine learning algorithms could help address these limitations and enable more effective and efficient identification of insomnia. .

17.
AJNR Am J Neuroradiol ; 45(2): 198-204, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38176729

RESUMO

BACKGROUND AND PURPOSE: Non-EPI-based DWI has shown better performance in head and neck pathologies owing to lesser susceptibility artifacts compared with EPI-DWI. However, only sporadic studies have investigated the feasibility of non-EPI-based DWI in retinoblastoma (RB). We qualitatively and quantitively compared EPI-DWI and HASTE-DWI in RB and correlated the tumor ADC values obtained from these 2 techniques with histopathologic markers. MATERIALS AND METHODS: Twenty-one treatment-naive patients with RB underwent 1.5T orbital MR imaging. EPI-DWI and HASTE-DWI were acquired at 3 b-values (0, 500, and 1000 s/mm2). All patients subsequently underwent surgical enucleation. For qualitative image assessment, scoring of overall image quality, artifacts, tumor sharpness, and tumor conspicuity was done by using a 5-point Likert scale. Quantitative assessment included calculations of SNR, contrast-to-noise ratio (CNR), geometric distortion, and ADC. Qualitative scores were compared by using the Wilcoxon signed-rank test, and quantitative parameters were analyzed with a t test. RESULTS: All 21 patients had unilateral RB; 15 were male and 6 were female with a median age of 36 months (range, 9-72 months). On histopathology, patients had either poorly differentiated (n = 13/21) or moderately differentiated (n = 8/21) RB. Other poor prognostic markers evaluated were optic nerve invasion (n = 10/21), choroidal invasion (n = 12/21), and anterior eye segment enhancement on MRI (n = 6/21). HASTE-DWI demonstrated higher image quality scores than EPI-DWI (P < .01), except for tumor conspicuity score, which was higher for EPI-DWI (P < .001). HASTE-DWI showed lower SNR, CNR, and geometric distortion than EPI-DWI (P < .001). The average acquisition times of EPI-DWI and HASTE-DWI were ∼1 and 14 minutes, respectively. The mean tumor ADC value on EPI-DWI was 0.62 ± 0.14 × 10-3 mm2/s and on HASTE-DWI was 0.83 ± 0.17 × 10-3 mm2/s. A significant correlation between EPI-DWI and HASTE-DWI ADC values (r = 0.8; P = .01) was found. Lower ADC values were found in tumors with poor prognostic markers, but none reached a statistically significant difference. CONCLUSIONS: HASTE-DWI shows improved overall image quality; however, it lacks in terms of tumor conspicuity, SNR, CNR, and longer acquisition time compared with EPI-DWI. ADC values derived from HASTE-DWI show no advantage over EPI-DWI in correlation with histopathologic prognostic markers.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Retinoblastoma/diagnóstico por imagem , Prognóstico , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Reprodutibilidade dos Testes , Neoplasias da Retina/diagnóstico por imagem
18.
Langmuir ; 40(1): 541-553, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38109877

RESUMO

Effluent from nuclear power plants, rocks, and minerals contains hazardous radionuclides that adversely affect human health and seriously threaten the environment. To address this issue, simple, economic, and sustainable magnetite nanoparticle loaded sodium alginate copper metal-organic framework composite beads (MNPs-SA@Cu MOF composite beads) have been designed, and their performance has been evaluated under varying conditions of pH, time, adsorbent dose, and initial concentration and have been studied by batch adsorption studies for optimizing the adsorption conditions. In this work, MNPs-SA@Cu MOF composite beads have been prepared in situ for the adsorptive removal of uranium [U(VI)] and thorium [Th(IV)] ions from an aqueous solution. The synthesized MNPs-SA@Cu MOF composite beads were characterized by model analytical techniques like Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, Brunauer-Emmett-Teller, and thermal gravimetric analysis. Here, 6 mg of adsorbent with 10 mL of 50 mg/L uranium and thorium ion solution at pH 5 was capable of removing the U(VI) and Th(IV) ions with 99.9 and 97.7% removal efficiencies, respectively. The obtained results showed that the adsorption behavior of the adsorbent for U(VI) and Th(IV) follows pseudo-second-order kinetics, and Langmuir isotherm fitted well with a maximum adsorption capacity of 454.54 and 434.78 mg/g, respectively. The adsorption mechanism indicated that electrostatic interaction and hydrogen bonding are the main driving forces for removing the U(VI) and Th(IV) ions. It can be reused for up to 10 adsorption-desorption cycles with minimal loss of removal efficiency. The easy synthesis method of MNPs-SA@Cu MOF composite beads and the high removal efficiency of U(VI) and Th(IV) ions reveal that they can potentially treat radionuclide waste effectively.

19.
Med Int (Lond) ; 3(6): 63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074620

RESUMO

Ameloblastic fibro-odontoma (AFO) is a rare, slow-growing neoplastic lesion classified as a benign, epithelial odontogenic mesenchymal tumor. This tumor exhibits histological features characteristic of both ameloblastic fibromas and complex odontomas. The clinical manifestation of AFO is typically characterized by the asymptomatic enlargement of the jawbones. Radiographically, it presents as a distinct radiolucent region, indicating the presence of radiopaque substances with varying degrees of irregularities in size and morphology. Standard therapeutic intervention involves enucleation. Despite its benign nature, AFO can cause significant morbidity if left untreated. Therefore, prompt diagnosis and appropriate management are essential to ensure optimal patient outcomes. The present study describes the case (clinical presentation and management) of an 18-year-old male patient with an AFO lesion located in the posterior mandible. This particular case was treated with conservative measures involving surgical enucleation along with the extraction of the impacted tooth and the curettage of residual bone.

20.
Cureus ; 15(11): e48706, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38094540

RESUMO

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) is the main host cell receptor for coronavirus disease 2019 (COVID-19) and is highly expressed in the tongue and buccal mucosa. Therefore, the present study was conducted to investigate genotoxic changes in epithelial cells of the buccal and tongue mucosa following COVID-19 infection. MATERIALS AND METHODS: This study included 40 patients aged 25-40 years, divided into two groups: Group 1 (control group) included 20 healthy individuals with no prior history of COVID-19 infection subdivided into Group 1a (buccal mucosa), and Group 1b (tongue mucosa); Group 2 (case group) included 20 patients with a history of mild to moderate COVID-19 infection subdivided into Group 2a (buccal mucosa) and Group 2b (tongue mucosa). Genotoxic biomarkers, such as the number of micronuclei, pyknosis, karyolysis, and karyorrhexis, were assessed in epithelial cells from the buccal mucosa and the ventral surface of the tongue. Analysis of variance was used for intragroup comparisons, followed by post-hoc analysis using Tukey's test. RESULTS: The mean age of the patients was 27.4±6.52 years. Statistically significant differences were observed between cases and controls in the number of micronuclei, pyknosis, karyolysis, and karyorrhexis in the epithelial cells of the buccal and tongue mucosa (p = 0.05). CONCLUSION: SARS-CoV-2 has pronounced genotoxic effects on the epithelium of the ventral surface of the tongue in comparison to the buccal mucosa Therefore, patients with COVID-19 should be monitored regularly to develop future carcinomas, particularly those with habits of smoking, alcohol consumption, and tobacco usage.

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