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1.
Parkinsons Dis ; 2024: 6111483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220822

RESUMO

Alzheimer's disease is a chronic clinical condition that is predominantly seen in age groups above 60 years. The early detection of the disease through image classification aids in effective diagnosis and suitable treatment. The magnetic resonance imaging (MRI) data on Alzheimer's disease have been collected from Kaggle which is a freely available data source. These datasets are divided into training and validation sets. The present study focuses on training MRI datasets using TinyNet architecture that suits small-scale image classification problems by overcoming the disadvantages of large convolutional neural networks. The architecture is designed such that convergence time is reduced and overall generalization is improved. Though the number of parameters used in this architecture is lesser than the existing networks, still this network can provide better results. Training MRI datasets achieved an accuracy of 98% with the method used with a 2% error rate and 80% for the validation MRI datasets with a 20% error rate. Furthermore, to validate the model-supporting data collected from Kaggle and other open-source platforms, a comparative analysis is performed to substantiate TinyNet's applicability and is projected in the discussion section. Transfer learning techniques are employed to infer the differences and to improve the model's efficiency. Furthermore, experiments are included for fine-tuning attempts at the TinyNet architecture to assess how the nuances in convolutional neural networks have an impact on its performance.

2.
J Mater Chem B ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225172

RESUMO

Temporal control over self-assembly processes is a highly desirable attribute that is efficiently exhibited by biological systems, such as actin filaments. In nature, various proteins undergo enzymatically catalysed chemical reactions that kinetically govern their structural and functional properties. Consequently, any stimuli that can alter their reaction kinetics can lead to a change in their growth or decay profiles. This underscores the urgent need to investigate bioinspired, adaptable and controllable synthetic materials. Herein we intend to develop a general strategy for controlling the growth and decay of self-assembled systems via enzymatically coupled reactions. We achieve this by the coupling of enzymes phosphokinase/phosphatase with a bolaamphiphilic cationic chromophore (PDI) which selectively self-assembles with ATP and disassembles upon its enzymatic hydrolysis. The aggregation process is efficiently regulated by the controlled in situ generation of ATP, through enzymatic reactions. By carefully managing the ATP generating components, we realize precise control over the self-assembly process. Moreover, we also show self-assembled structures with programmed temporal decay profiles through coupled enzymatic reactions of ATP generation and hydrolysis, essentially rendering the process dissipative. This work introduces a novel strategy to generate a reaction-coupled one-dimensional nanostructure with controlled dimensions inspired by biological systems.

3.
Clin Rehabil ; : 2692155241278949, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39257067

RESUMO

OBJECTIVE: To compare the efficacy of interferential current (IFC) therapy combined with quadriceps strengthening exercise versus sham IFC plus exercise for pain relief and functional improvement in patients with knee osteoarthritis. STUDY DESIGN: Double-blind randomised controlled trial. SETTING: Outpatient rehabilitation clinic. SUBJECTS: Knee osteoarthritis patients aged 50-85 years with a pain score ≥4/10. METHODS: One hundred forty-four participants were randomly allocated into the study and control groups. The study group received 20 min of IFC therapy (carrier frequency: 4000 Hz, beat frequency: 100 Hz) five times per week for three weeks, while the control group received sham IFC following the same protocol, followed by 10 min of exercise in both groups. Outcome measures included Numeric Rating Scale for Pain, Western Ontario and McMaster Universities Index (WOMAC) score, gait speed, and EuroQol-Five Dimensions-Five Levels questionnaire assessed at baseline, Week 3, and Week 6. Adverse events and patient satisfaction were evaluated at Week 3. RESULTS: At Week 3, the study group demonstrated statistical improvement compared to the control group for Numeric Rating Scale for Pain, WOMAC Total, WOMAC Pain, and WOMAC Stiffness. The mean difference (95% confidence interval) between groups was 0.76 (0.21-1.30), 0.49 (0.03-0.95), 0.63 (0.13-1.13), and 0.62 (0.04-1.20), respectively. However, the mean differences between groups were below the Minimally Clinically Important Difference values for each outcome. Additionally, there were no significant differences between groups at Week 6 for any outcome measure. CONCLUSION: IFC had no effect on pain reduction and functional improvement in patients with mild to moderate knee osteoarthritis.

4.
Clin Pathol ; 17: 2632010X241278180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246689

RESUMO

COVID-19 infection is still a mystery in terms of its long-term effect on health and its consequences on hematological disorders. Prior studies including ours have shown the abnormal changes in hematopoietic cells in COVID-19 patients. In this article, we are presenting 2 cases of pediatric B-lymphoblastic leukemia (B-ALL) with a previous history of COVID-19 infection. The first case describes a 22-month-old boy presenting with lymphadenopathy, neutropenia, and anemia with concurrent COVID-19 infection without any evidence of a hematolymphoid neoplasm as per bone marrow and lymph node biopsy. However, he presented after 2 months with bone marrow biopsy confirming B-ALL. The second case is that of a 4-year-old girl presenting with B-ALL who has had asymptomatic COVID-19 infection 5 months before this current presentation. Both the cases had complete resolution of COVID-19 infection during the time of presentation with acute leukemia. There were notably 2 rare findings along the course of the patients' illnesses. First, the unusual plasmacytosis in the marrow during active COVID-19 infection in the first patient and the second, is predilection of development of B-ALL following COVID-19. In both the cases the fluorescence in situ hybridization (FISH) studies showed pathologic alteration of the RUNX1 gene. Overall, there are no literature to support a causal association between acute B-ALL and COVID-19. The diagnosis of B-ALL in these patients after COVID-19 infection may be totally unrelated. However, if we consider Greaves proposed 2-hit model for childhood acute leukemia, that an infectious agent can precipitate development of B-ALL in a genetically susceptible individual. Alteration of the RUNX1 gene in both the patients, opens a door for further exploration of the "second-hit" hypothesis regarding an infectious agent precipitating development of B-ALL in a genetically susceptible individual.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39242411

RESUMO

BACKGROUND: Pantoea agglomerans is a gram negative, aerobic/facultative anaerobic, rod shaped bacilli commonly isolated from plants, soil, food and faeces.(1) It is a rare cause of opportunistic infections in humans acquired mainly via two major routes being, wound infection or hospital acquired. CASE REPORT: Here, we encountered a landmark, first of its kind, head and neck manifestation of a cervical soft tissue abscess with Pantoea agglomerans being the miscreant. The patient presented with complaints of a left sided neck swelling, which was radiologically suggestive of a cold abscess, however clinical suscpicion encouraged us to perform an incision and drainage, culture of which revealed this notorious phytogenic bacterium. DISCUSSION: Commonly encountered Pantoea infected cases documented in literature have shown a clinical picture of endophthalmitis, acute unilateral dacryocystitis, periostitis, endocarditis, osteomyelitis and a tumour like muscle cyst of the thigh with many of them eventually leading to septicemia while a few also resolved with targeted antibiotics.(2) Remarkably, no ENT or head and neck presentations have been reported in literature till date. History of trauma by brushing against a mango tree was confirmed retrospectively, which was found to be the missing piece of the puzzle.

6.
World J Otorhinolaryngol Head Neck Surg ; 10(3): 193-199, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39233860

RESUMO

Purpose: To assess the potential benefit of impregnating Merocel (a non-absorbable nasal dressing) with a topical steroid solution, for use as a direct and slow local delivery system of steroids after sinus surgery to improve postoperative wound healing. Methods: In this randomized controlled trial, 40 patients with bilateral chronic rhinosinusitis with nasal polyposis were subjected to functional endoscopic sinus surgery. Following the completion of the surgery, Merocel packs were inserted in the bilateral nasal cavities and infiltrated with 4 mL triamcinolone (40 mg/mL) in one nasal cavity (treatment group) and 4 mL normal saline in the other (control group). Nasal packs were removed on the third postoperative day and postoperative healing assessment was done on postoperative Weeks 1, 2, 4, and 12. The findings were noted as per Lund Kennedy (LKES) and perioperative sinus endoscopy (POSE) scores and compared on both sides. Results: Significant (P < 0.05) improvement was noted in Lund Kennedy score for crusting and polyp at Week 12, for edema at Week 1, and nasal discharge at Weeks 1 and 12, but there was no significant improvement in scarring at any week. Overall, the difference between the treatment and control arms was statistically significant at all postoperative visits except at Week 4. Also, there was a significant improvement in POSE scores at Weeks 1, 2, and 12 but not at Week 4. Conclusion: This study positively concludes that the nasal cavity packed with drug-soaked packs had less scarring and edema in the postoperative period and the overall wound healing was much better as compared to saline-soaked packs.

7.
Hum Mol Genet ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39239979

RESUMO

Common variants in the MicroRNA 137 host gene MIR137HG and its adjacent gene DPYD have been associated with schizophrenia risk and the latest Psychiatric Genomics Consortium (PGC). Genome-Wide Association Study on schizophrenia has confirmed and extended these findings. To elucidate the association of schizophrenia risk-associated SNPs in this genomic region, we examined the expression of both mature and immature transcripts of the miR-137 host gene (MIR137HG) in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of postmortem brain samples of donors with schizophrenia and psychiatrically-unaffected controls using qPCR and RNA-Seq approaches. No differential expression of miR-137, MIR137HG, or its transcripts was observed. Two schizophrenia risk-associated SNPs identified in the PGC study, rs11165917 (DLPFC: P = 2.0e-16; sgACC: P = 6.4e-10) and rs4274102 (DLPFC: P = 0.036; sgACC: P = 0.002), were associated with expression of the MIR137HG long non-coding RNA transcript MIR137HG-203 (ENST00000602672.2) in individuals of European ancestry. Carriers of the minor (risk) allele of rs11165917 had significantly lower expression of MIR137HG-203 compared with those carrying the major allele. However, we were unable to validate this result by short-read sequencing of RNA extracted from DLPFC or sgACC tissue. This finding suggests that immature transcripts of MIR137HG may contribute to genetic risk for schizophrenia.

8.
Nature ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261728

RESUMO

DNA double-strand break (DSB) repair by homologous recombination is initiated by DNA end resection, a process involving the controlled degradation of the 5'-terminated strands at DSB sites1,2. The breast cancer suppressor BRCA1-BARD1 not only promotes resection and homologous recombination, but it also protects DNA upon replication stress1,3-9. BRCA1-BARD1 counteracts the anti-resection and pro-non-homologous end-joining factor 53BP1, but whether it functions in resection directly has been unclear10-16. Using purified recombinant proteins, we show here that BRCA1-BARD1 directly promotes long-range DNA end resection pathways catalysed by the EXO1 or DNA2 nucleases. In the DNA2-dependent pathway, BRCA1-BARD1 stimulates DNA unwinding by the Werner or Bloom helicase. Together with MRE11-RAD50-NBS1 and phosphorylated CtIP, BRCA1-BARD1 forms the BRCA1-C complex17,18, which stimulates resection synergistically to an even greater extent. A mutation in phosphorylated CtIP (S327A), which disrupts its binding to the BRCT repeats of BRCA1 and hence the integrity of the BRCA1-C complex19-21, inhibits resection, showing that BRCA1-C is a functionally integrated ensemble. Whereas BRCA1-BARD1 stimulates resection in DSB repair, it paradoxically also protects replication forks from unscheduled degradation upon stress, which involves a homologous recombination-independent function of the recombinase RAD51 (refs. 4-6,8). We show that in the presence of RAD51, BRCA1-BARD1 instead inhibits DNA degradation. On the basis of our data, the presence and local concentration of RAD51 might determine the balance between the pronuclease and the DNA protection functions of BRCA1-BARD1 in various physiological contexts.

9.
Nanoscale ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264375

RESUMO

Sulfur dots (S-QDs) hold promise as a new category of metal-free, luminescent nanomaterials, yet their practical application faces challenges primarily due to a limited understanding of their structure and its impact on their optical properties. Herein, by employing a spectrum of aliphatic and aromatic ligands, we identify the surface structure and composition of S-QDs while delineating the pivotal role of ligands in inducing photoluminescence. Thiol-functionalized ligands, such as 4-mercapto benzoic acid and glutathione, notably promote the formation of both green and blue luminescent S-QDs, boosting a high quantum yield of up to 56%. Further investigation on the synthesis of S-QDs with 4-mercapto benzoic acid unveils the dual role of H2O2: etching sulfur powder and oxidizing the -SH group to -SO2H. These oxidized ligands passivate the S-QD surface through hydrogen bonding. Electrospray ionization mass spectrometry analysis unveils the presence of distinct sulfur species such as [S4(C6H5SO2H)4(H2O)2H]+ and [S6(C6H5SO2H)6(H2O)3H]+, while XPS analysis confirms the existence of zerovalent sulfur and oxidized sulfur species including SO32- and SO42-. Further detailed spectroscopic examination demonstrates that S-QDs predominantly exist as aggregated entities, with the emission wavelength correlating with the degree of aggregation. The absence of photoluminescence in aggregations devoid of ligands underscores the critical role of ligands in the photoluminescence genesis of S-QDs.

10.
Chemosphere ; 364: 143293, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245217

RESUMO

Severe toxic effects of arsenic on human physiology have been of immense concern worldwide. Arsenic causes irrevocable structural and functional disruption of tissues, leading to major diseases in chronically exposed individuals. However, it is yet to be resolved whether the effects result from direct deposition and persistence of arsenic in tissues, or via activation of indirect signaling components. Emerging evidences suggest that gut inhabitants play an active role in orchestrating various aspects of brain physiology, as the gut-brain axis maintains cognitive health, emotions, learning and memory skills. Arsenic-induced dysbiosis may consequentially evoke neurotoxicity, eventually leading to anxiety and depression. To delineate the mechanism of action, mice were exposed to different concentrations of arsenic. Enrichment of Gram-negative bacteria and compromised barrier integrity of the gut enhanced lipopolysaccharide (LPS) level in the bloodstream, which in turn elicited systemic inflammation. Subsequent alterations in neurotransmitter levels, microglial activation and histoarchitectural disruption in brain triggered onset of anxiety- and depression-like behaviour in a dose-dependent manner. Finally, to confirm whether the neurotoxic effects are specifically a consequence of modulation of gut microbiota (GM) by arsenic and not arsenic accumulation in the brain, fecal microbiota transplantations (FMT) were performed from arsenic-exposed mice to healthy recipients. 16S rRNA gene sequencing indicated major alterations in GM population in FMT mice, leading to severe structural, functional and behavioural alterations. Moreover, suppression of Toll-like receptor 4 (TLR4) using vivo-morpholino oligomers (VMO) indicated restoration of the altered parameters towards normalcy in FMT mice, confirming direct involvement of the GM in inducing neurotoxicity through the arsenic-gut-brain axis. This study accentuates the potential role of the gut microbiota in promoting neurotoxicity in arsenic-exposed mice, and has immense relevance in predicting neurotoxicity under altered conditions of the gut for designing therapeutic interventions that will target gut dysbiosis to attenuate arsenic-mediated neurotoxicity.

11.
Peptides ; 181: 171293, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244091

RESUMO

Asprosin is a recently discovered adipokine reported to be involved in the modulation of mammalian gonadal functions. Preliminary investigations suggest its role in regulation of ovarian functions in rodents as well as bovids. In addition, increased levels of the adipokine during human ovarian pathophysiologies implicate it in disease progression and severity. The present study evidenced high expression of asprosin in ovaries of juvenile, pubertal and adult mice while expression was significantly low in ageing ovaries. Further, asprosin stimulated expression of markers for ovarian folliculogenesis (Scf, c-Kit, Gdf9, Bmp6, Fshr, Lhr) and steroidogenesis (3ß-Hsd) in adult mice. In addition to exploring concentration-dependent effect of asprosin, the study implicates asprosin as an age-dependent modulator of ovarian functions as treatment of ovaries with asprosin led to upregulation of Fshr, c-Kit, Bmp6, and Gdf9 in both adult and juvenile ovaries, Lhr only in adults while that of Scf only in juvenile ovaries. The current study is first to report an age-dependent expression and role of asprosin in murine ovaries.

12.
Heliyon ; 10(16): e36163, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39247292

RESUMO

Background: Protozoal pathogens pose a considerable threat, leading to notable mortality rates and the ongoing challenge of developing resistance to drugs. This situation underscores the urgent need for alternative therapeutic approaches. Antimicrobial peptides stand out as promising candidates for drug development. However, there is a lack of published research focusing on predicting antimicrobial peptides specifically targeting protozoal pathogens. In this study, we introduce a successful machine learning-based framework designed to predict potential antiprotozoal peptides effective against protozoal pathogens. Objective: The primary objective of this study is to classify and predict antiprotozoal peptides using diverse negative datasets. Methods: A comprehensive literature review was conducted to gather experimentally validated antiprotozoal peptides, forming the positive dataset for our study. To construct a robust machine learning classifier, multiple negative datasets were incorporated, including (i) non-antimicrobial, (ii) antiviral, (iii) antibacterial, (iv) antifungal, and (v) antimicrobial peptides excluding those targeting protozoal pathogens. Various compositional features of the peptides were extracted using the pfeature algorithm. Two feature selection methods, SVC-L1 and mRMR, were employed to identify highly relevant features crucial for distinguishing between the positive and negative datasets. Additionally, five popular classifiers i.e. Decision Tree, Random Forest, Support Vector Machine, Logistic Regression, and XGBoost were used to build efficient decision models. Results: XGBoost was the most effective in classifying antiprotozoal peptides from each negative dataset based on the features selected by the mRMR feature selection method. The proposed machine learning framework efficiently differentiate the antiprotozoal peptides from (i) non-antimicrobial (ii) antiviral (iii) antibacterial (iv) antifungal and (v) antimicrobial with accuracy of 97.27 %, 93.64 %, 86.36 %, 90.91 %, and 89.09 % respectively on the validation dataset. Conclusion: The models are incorporated in a user-friendly web server (www.soodlab.com/appred) to predict the antiprotozoal activity of given peptides.

13.
Clin Exp Optom ; : 1-2, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267232

RESUMO

We report an interesting case of superficial corneal vascularization along with haemorrhages and microcystic edema confined to the inferior cornea in a female patient that are clearly attributed to netarsudil eye drops which she had been instilling for the last 8 weeks . Complete regression of all these corneal changes was noted after 3 months of discontinuation of this Rho kinase inhibitor. This is a unique finding and to our knowledge ; has not been reported so far.

14.
JAMIA Open ; 7(3): ooae089, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39282084

RESUMO

Objective: During the 2-year maintenance treatment phase (MT) of acute lymphoblastic leukemia (ALL), personalized patient-specified titration of oral antimetabolite drug doses is required to ensure maximum tolerated systemic drug exposure. Drug titration is difficult to implement in practice and insufficient systemic drug exposure resulting from inadequate dose titration increases risk of ALL relapse. Materials and Methods: We developed an open-source R-based analytical toolkit, including the allMT R package and an interactive web-based R Shiny VIATAMIN application, to evaluate antimetabolite drug titration during MT. Results: Evaluation is initiated with basic visualization analysis of drug titration, in both individual patients and patient cohorts. Observations are supplemented with descriptive analyses of hematological toxicity frequency and prescriber compliance rates with protocol drug titration rules. In individual patients, visual and quantitative analyses indicate recurring potentially correctable suboptimal drug titration patterns. In patient cohorts, the toolkit enables evaluation of the impact of interventions to optimize MT drug titration. Discussion: Incorporation of the toolkit in a forthcoming clinical decision support system for MT would enable real-time examination and course correction of drug titration practice. Conclusion: Future versions will be enhanced to include other variables that influence drug titration practice, including clinical toxicity data and later, pharmacological markers of antimetabolite, adherence, and drug activity.

15.
bioRxiv ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39257775

RESUMO

The microbiome affects important aspects of mosquito biology and differences in microbial composition can affect the outcomes of laboratory studies. To determine how the biotic and abiotic conditions in an insectary affect the composition of the bacterial microbiome of mosquitoes we reared mosquitoes from a single cohort of eggs from one genetically homogeneous inbred Aedes aegypti colony, which were split into three batches, and transferred to each of three different insectaries located within the Liverpool School of Tropical Medicine. Using three replicate trays per insectary, we assessed and compared the bacterial microbiome composition as mosquitoes developed from these eggs. We also characterised the microbiome of the mosquitoes' food sources, measured environmental conditions over time in each climate-controlled insectary, and recorded development and survival of mosquitoes. While mosquito development was overall similar between all three insectaries, we saw differences in microbiome composition between mosquitoes from each insectary. Furthermore, bacterial input via food sources, potentially followed by selective pressure of temperature stability and range, did affect the microbiome composition. At both adult and larval stages, specific members of the mosquito microbiome were associated with particular insectaries; and the insectary with less stable and cooler conditions resulted in slower pupation rate and higher diversity of the larval microbiome. Tray and cage effects were also seen in all insectaries, with different bacterial taxa implicated between insectaries. These results highlight the necessity of considering the variability and effects of different microbiome composition even in experiments carried out in a laboratory environment starting with eggs from one batch; and highlights the impact of even minor inconsistencies in rearing conditions due to variation of temperature and humidity.

16.
bioRxiv ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39257816

RESUMO

Alpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson's disease and forms intraneuronal inclusions called Lewy Bodies. While the mechanism underlying the dysregulation of αSyn in Parkinson's disease is unclear, it is thought that prionoid cell-to-cell propagation of αSyn has an important role. Through a high throughput screen, we recently identified 38 genes whose knock down modulates αSyn propagation. Follow up experiments were undertaken for two of those genes, TAX1BP1 and ADAMTS19, to study the mechanism with which they regulate αSyn homeostasis. We used a recently developed M17D neuroblastoma cell line expressing triple mutant (E35K+E46K+E61K) "3K" αSyn under doxycycline induction. 3K αSyn spontaneously forms inclusions that show ultrastructural similarities to Lewy Bodies. Experiments using that cell line showed that TAX1BP1 and ADAMTS19 regulate how αSyn interacts with lipids and phase separates into inclusions, respectively, adding to the growing body of evidence implicating those processes in Parkinson's disease. Through RNA sequencing, we identified several genes that are differentially expressed after knock-down of TAX1BP1 or ADAMTS19. Burden analysis revealed that those differentially expressed genes (DEGs) carry an increased frequency of rare risk variants in Parkinson's disease patients versus healthy controls, an effect that was independently replicated across two separate cohorts (GP2 and AMP-PD). Weighted gene co-expression network analysis (WGCNA) showed that the DEGs cluster within modules in regions of the brain that develop high degrees of αSyn pathology (basal ganglia, cortex). We propose a novel model for the genetic architecture of sporadic Parkinson's disease: increased burden of risk variants across genetic networks dysregulates pathways underlying αSyn homeostasis, thereby leading to pathology and neurodegeneration.

17.
Int J Surg Case Rep ; 123: 110207, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39288482

RESUMO

INTRODUCTION: Penetrating carotid artery injury is rare and particularly uncommon in zone 3 of the vessel. Due to anatomical challenges to open operative management in zone 3, there are minimal treatment recommendations for this highly morbid condition. The urgency associated with understanding proper management of this traumatic injury is further supported by the nearly 100 % rate of fatality in untreated penetrating carotid artery injuries. PRESENTATION OF CASE: A 17-year-old male presented with a bullet wound to the right temple. He was intubated for airway protection given left-sided tracheal deviation secondary to a right neck hematoma. His Glasgow Coma Scale (GCS) was 11 on initial presentation, E3V2M6. The patient remained hemodynamically stable and underwent a CT angiogram of the head and neck. Imaging revealed a complete transection of the cervical (zone III) right internal carotid artery (RICA), a large pseudoaneurysm of the RICA distal to carotid bifurcation, and comminuted mandibular fracture. Collateral blood flow was preserved to the right hemisphere. Multi-disciplinary discussions deemed risks of operative intervention outweighed the benefits in the immediate peri-trauma period as the increased risk of hemispheric stroke, exsanguination, and death was thought to be prohibitive. Therefore, treatment of delayed intervascular stenting of the RICA was performed as opposed to emergent open RICA ligation or repair. DISCUSSION: Treatment decisions for zone 3 CAI rely on the patient's hemodynamic stability, with surgical ligation favored for immediate hemorrhage control in unstable cases, while stable patients may undergo observation or delayed endovascular intervention. Balancing the need for hemostasis to prevent further blood loss with the potential benefits of anticoagulation to maintain cerebral perfusion underscores the decision-making required in managing such cases. CONCLUSION: The rarity and challenge of ICA injury at this anatomical location presents unique challenges. Our description of observation and delayed revascularization outlines the precarious, yet validated, treatment method for hemodynamically stable patients.

19.
Cureus ; 16(8): e66858, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39280402

RESUMO

Introduction Retention is essential to prevent unwanted tooth movement due to growth changes, to allow the gingival and periodontal tissues affected by orthodontic treatment to realign, and to stabilize teeth that have been moved to potentially unstable positions, thus reducing the risk of relapse. This study aimed to evaluate the distortion of Essix retainers over time to enhance their retention and stability. Methods Patients who visited the Department of Orthodontics and Dentofacial Orthopedics at Ranjeet Deshmukh Dental College & Research Centre, Nagpur, India, after completing their orthodontic treatment were included in the study, according to the established inclusion and exclusion criteria. A total of 26 patients participated. Each patient received an Essix retainer fabricated from a Duran+ Biostar round sheet (1 mm thickness) using a Biostar machine based on their post-debonded maxillary cast. The patients were instructed on the correct insertion and removal of the Essix retainer. The inner surface of the retainers was scanned at one month, three months, and six months using an intraoral digital scanner. These scans were analyzed and compared for distortion at different time intervals using Medit software. Results The Essix retainers exhibited varying degrees of distortion at different time intervals. Notably, distortion was more significant in the posterior region compared to the anterior region. Additionally, distortion increased over time, with the least amount observed at one month and progressively worsening by the sixth month. Specifically, the average distortion in the posterior region ranged from 0.133 mm after the first month to 0.304 mm after six months. In contrast, the average distortion in the anterior region was lower, ranging from 0.057 mm at one month to 0.068 mm at six months. Conclusions Distortion was more pronounced on the posterior surface of the Essix retainer compared to the anterior region.

20.
RSC Adv ; 14(40): 29675-29682, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39297050

RESUMO

The recognition of specific genomic arrangements by rationally designed small molecules is fundamental for the expansion of targeted gene expression. Here, we report the first X-ray crystal structures that demonstrate single G (guanine) recognition by a highly selective diamidine (DB2447) in a mixed DNA sequence. The study presents detailed structural information on the mechanism of single G recognition by D2447 and its various interactions in the DNA minor groove. Molecular dynamics and binding studies were used to evaluate the details of our reported structures. The study provides structural insight and resources necessary for understanding single G selection in genomic sequences.

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