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1.
Int J Mol Sci ; 25(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39273366

RESUMO

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Imagem Molecular , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Imagem Molecular/métodos , COVID-19/metabolismo , COVID-19/diagnóstico por imagem , SARS-CoV-2/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Animais , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
2.
J Agromedicine ; : 1-13, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283082

RESUMO

BACKGROUND AND OBJECTIVES: Rubber tapping is a physically demanding and skilled agricultural operation that can cause musculoskeletal disorders (MSDs). This research investigated the impact of using an ergonomically modified rubber tapping knife on the hand posture of rubber tappers. METHODS: Initially, a postural assessment was conducted using CATIA V6 modelling software followed by a non-randomized longitudinal study with 32 rubber tappers. In the second phase, the study used a custom-modified Standard Nordic Questionnaire, video recordings, and direct observations. The study compared the results of the ergonomically modified rubber tapping knife with the traditional tapping knife, evaluating hand grip strength, endurance time chip thickness, time required to complete 300 trees, and posture using the Rapid Upper Limb Assessment (RULA) tool. RESULTS: Compared to pre-tapping values, the mean reduction in grip strength after tapping was significantly less with the modified rubber tapping knife than with the traditional tapping knife (2.96 kg, SD 0.85 kg vs 7.31 kg SD 2.13 kg). Similarly, the reduction in hand endurance time was less with the modified knife than with the traditional knife (1.78 seconds, SD 0.47 seconds vs 3.34 seconds, SD 0.87 seconds). The study also indicated that the modified knife did not significantly affect chip thickness. Additionally, a slight increasing in tapping time was observed with the ergonomically modified knife, which may be attributed to a learning curve phenomenon. This suggests that as rubber tappers become more accustomed to the new tool, their efficiency may improve over time. CONCLUSION: The hand grip strength and endurance time was significantly lower with the ergonomically modified tapping knife. The study concluded that using an ergonomically modified tapping knife led to a significant improvement in hand posture among rubber tappers.

3.
Proc Natl Acad Sci U S A ; 121(32): e2319091121, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39074279

RESUMO

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD.


Assuntos
Proteína Huntingtina , Lisossomos , Mitocôndrias , Proteínas de Ligação a RNA , Ubiquitina , Proteína Huntingtina/metabolismo , Proteína Huntingtina/genética , Lisossomos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Humanos , Ubiquitina/metabolismo , Mitocôndrias/metabolismo , Autofagia , Animais , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Camundongos , Ligação Proteica , Doença de Huntington/metabolismo , Doença de Huntington/genética , Doença de Huntington/patologia , Peptídeos/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-38953771

RESUMO

OBJECTIVES: One stage functional jaw reconstruction is defined as the resection and reconstruction of segmental defects in conjunction with the placement of dental implants in an ideal prosthetic position and loaded with a provisional restoration, during one surgical procedure. The aim of the study is to describe clinical outcomes of patients who underwent one stage functional jaw reconstruction. METHODS: Patients who underwent one-stage functional jaw reconstruction, from January 2013 to March 2016 were recalled in 2022 and 2023. Planning and execution for the reconstruction utilized either analogue or digital techniques. Outcome parameters recorded were treatment-related outcomes at patient level, implant-related outcomes and patient-reported outcome measures. RESULTS: Eighteen patients underwent one-stage jaw reconstruction with a total of 57 implants. Four patients had maxillary and 14 had mandibular reconstructions. Ten patients underwent postoperative radiotherapy. Ten patients were planned using analogue and eight by digital planning. Three patients had partial flap necrosis, three patients had plate fractures, implant loss was seen in one patient and four patients died during the period. A functional prosthesis was provided in 16 out of the 18 patients. CONCLUSION: One-stage functional jaw reconstruction is a predictable method for providing rehabilitation with successful outcomes at 7-11 years. However, caution should be exercised when the treatment modality is carried out in patients with malignant pathologies who have undergone radiotherapy.

5.
J Maxillofac Oral Surg ; 23(3): 639-643, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911398

RESUMO

This 10-year follow-up report describes the interdisciplinary comprehensive management of a patient with aneurysmal bone cyst of the maxilla in a 24-year-old patient. The treatment included resection and primary reconstruction with vascularized deep circumflex iliac artery-based composite free flap, implant placement, and peri-implant soft tissue management using denture-guided epithelial regeneration with interim dentures. Definitive management was done using implant-supported cast partial dentures, and the patient followed up for 10 years.

6.
Pharmaceuticals (Basel) ; 17(6)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38931352

RESUMO

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [18F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan-kynurenine pathway as a therapeutic target for treating NF1.

7.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2706-2713, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883495

RESUMO

Background: The occurrence of life-threatening events in hospitalized patients with tracheostomies are often preventable. Nurses have a vital role in providing consistent tracheostomy care to patients, thereby avoiding complications. This study was conducted to assess the knowledge of nurses in high dependency areas at a tertiary care hospital with regards to tracheostomy care, to train them and to assess the impact of a tracheostomy care teaching module. Methods: Purposive sampling techniques were used to recruit 65 nurses from high dependency areas in Father Muller Medical College Hospital. With appropriate informed, a detailed evaluation was conducted with a pre-validated questionnaire that assesses the knowledge, attitude and practices with regards to tracheostomy care. The nurses then underwent a tracheostomy training programme with a teaching module that emphasizes on tracheostomy care, a demonstration and hands on experience in the simulation lab, followed by an OSCE and a post-test. Statistical analysis was done using SPSS version 28 for paired T test and crosstabulation. Results: There was a mean increase in test scores, from 7.74 in pretest to 10.66 in post-test which was statistically significant. The comfort and confidence level of nurses after the module, increased by 80% and the OSCE scores were averaged around 73% giving a satisfactory outcome. Conclusion: This module significantly increased the quality of tracheostomy tube care provided by nurses thereby improving patient outcome. Small modifications to existing training programs can have a significant impact on overall health care as demonstrated by our study. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04489-y.

8.
Adv Funct Mater ; 34(13)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38706986

RESUMO

Collagen fibers in the 3D tumor microenvironment (TME) exhibit complex alignment landscapes that are critical in directing cell migration through a process called contact guidance. Previous in vitro work studying this phenomenon has focused on quantifying cell responses in uniformly aligned environments. However, the TME also features short-range gradients in fiber alignment that result from cell-induced traction forces. Although the influence of graded biophysical taxis cues is well established, cell responses to physiological alignment gradients remain largely unexplored. In this work, fiber alignment gradients in biopsy samples are characterized and recreated using a new microfluidic biofabrication technique to achieve tunable sub-millimeter to millimeter scale gradients. This study represents the first successful engineering of continuous alignment gradients in soft, natural biomaterials. Migration experiments on graded alignment show that HUVECs exhibit increased directionality, persistence, and speed compared to uniform and unaligned fiber architectures. Similarly, patterned MDA-MB-231 aggregates exhibit biased migration toward increasing fiber alignment, suggesting a role for alignment gradients as a taxis cue. This user-friendly approach, requiring no specialized equipment, is anticipated to offer new insights into the biophysical cues that cells interpret as they traverse the extracellular matrix, with broad applicability in healthy and diseased tissue environments.

9.
Indian J Otolaryngol Head Neck Surg ; 76(1): 1310-1313, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440662

RESUMO

This article deals with a rare occurrence of Ganglioneuroma of the left cervical sympathetic chain in a 9-year-old girl, presenting with painless paracervical swelling noticed since 7 months. Imaging studies showed a left parapharyngeal mass extending from C1 to C6, displacing the posterior pharyngeal wall and anterolaterally displacing the contents of the carotid sheath, with no significant vascular feeders. A provisional diagnosis of? Neurogenic tumour was established and the patient underwent surgical excision. Histopathologically, the diagnosis of Ganglioneuroma was confirmed.

10.
J Vis Exp ; (204)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38436378

RESUMO

Microphysiological systems are miniaturized cell culture platforms used to mimic the structure and function of human tissues in a laboratory setting. However, these platforms have not gained widespread adoption in bioscience laboratories where open-well, membrane-based approaches serve as the gold standard for mimicking tissue barriers, despite lacking fluid flow capabilities. This issue can be primarily attributed to the incompatibility of existing microphysiological systems with standard protocols and tools developed for open-well systems. Here, we present a protocol for creating a reconfigurable membrane-based platform with an open-well structure, flow enhancement capability, and compatibility with conventional protocols. This system utilizes a magnetic assembly approach that enables reversible switching between open-well and microfluidic modes. With this approach, users have the flexibility to begin an experiment in the open-well format using standard protocols and add or remove flow capabilities as needed. To demonstrate the practical usage of this system and its compatibility with standard techniques, an endothelial cell monolayer was established in an open-well format. The system was reconfigured to introduce fluid flow and then switched to the open-well format to conduct immunostaining and RNA extraction. Due to its compatibility with conventional open-well protocols and flow enhancement capability, this reconfigurable design is expected to be adopted by both engineering and bioscience laboratories.


Assuntos
Técnicas de Cultura de Células , Sistemas Microfisiológicos , Humanos , Células Endoteliais , Laboratórios , Microfluídica
11.
Foot Ankle Orthop ; 9(1): 24730114231224725, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288288

RESUMO

Background: Currently, more than 150 surgical techniques have been described for the treatment of hallux valgus. The abundance of techniques indicates that there is no technique that has been designated as a gold standard. In recent years, a particular interest in the use of minimally invasive techniques has grown. The aim of this study was to prospectively compare clinical, radiologic, and postoperative outcomes between the MICA technique and open chevron technique over a 1-year follow-up period. Methods: Between January 2016 and August 2020, data were prospectively collected from consecutive patients preoperatively and at 6 weeks, 3 months, and 12 months following minimally invasive chevron and Akin (MICA) or open chevron osteotomies. Radiographic outcomes were measured using weightbearing radiographs preoperatively and at 3 and 12 months postoperatively. Clinical outcomes were measured using the American Orthopaedic Foot & Ankle Society (AOFAS), Manchester-Oxford Foot Questionnaire (MOXFQ), VAS (visual analog scale), Foot Function Index (FFI), Foot and Ankle Outcome Score (FAOS), and Euro-QoL-5D (EQ5D) questionnaires. Results: Of the 68 patients, 42 patients (62%) underwent a MICA surgery and 26 patients (38%) underwent open chevron osteotomy. Both groups showed significant improvement in HVA, IMA, and DMAA at the 1-year follow-up. Our findings show that both clinical and radiologic outcomes of the MICA technique are comparable to the conventional open technique. No significant differences were found in clinical outcomes (VAS, AOFAS, MOXFQ, FFI, and FAOS), complication rate, and operative times. Conclusion: These results show that MICA is a safe alternative for chevron osteotomy. The clinical and radiologic outcomes of these 2 techniques by 12 months are comparable. Level of Evidence: Level II, prospective cohort study.

12.
Int J Angiol ; 32(4): 253-257, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37927842

RESUMO

In this case report, we describe the clinical course of a complicated transplant renal artery (TRA) pseudoaneurysm, clinically featured by gross and massive hematuria one month after a kidney transplant was performed on a 50 year-old male patient. TRA pseudoaneurysm is a rare but potentially life-threatening complication that may result in bleeding, infection, graft dysfunction/loss, lower limb ischemia/loss, hemorrhagic shock, and death. TRA pseudoaneurysm treatment remains challenging as it needs to be tailored to the patient characteristics including hemodynamic stability, graft function, anatomy, presentation, and pseudoaneurysm features. This publication discusses the clinical scenario of massive gross hematuria that derived from a retroperitoneal hematoma which originated from an actively bleeding TRA pseudoaneurysm. This case highlights the combined approach of endovascular stent placement and subsequent transplant nephrectomy as a last resort in the management of intractable bleeding from a complicated TRA pseudoaneurysm. To the best of our knowledge, this is the first published case report of an actively bleeding TRA anastomotic pseudoaneurysm that caused a massive retroperitoneal bleed that in turn evacuated via the bladder after disrupting the ureter-to-bladder anastomosis. A temporizing hemostatic arterial stent placed percutaneously allowed for a safer and controlled emergency transplant nephrectomy.

13.
Int J Implant Dent ; 9(1): 28, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698775

RESUMO

OBJECTIVES: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. MATERIALS AND METHODS: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. RESULTS: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. CONCLUSIONS: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient's perspective.


Assuntos
Implantes Dentários , Humanos , Implantes Dentários/efeitos adversos , Redação , Atrofia , Consenso , Resultado do Tratamento
14.
bioRxiv ; 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37502844

RESUMO

In the tumor microenvironment (TME), collagen fibers facilitate tumor cell migration through the extracellular matrix. Previous studies have focused on studying the responses of cells on uniformly aligned or randomly aligned collagen fibers. However, the in vivo environment also features spatial gradients in alignment, which arise from the local reorganization of the matrix architecture due to cell-induced traction forces. Although there has been extensive research on how cells respond to graded biophysical cues, such as stiffness, porosity, and ligand density, the cellular responses to physiological fiber alignment gradients have been largely unexplored. This is due, in part, to a lack of robust experimental techniques to create controlled alignment gradients in natural materials. In this study, we image tumor biopsy samples and characterize the alignment gradients present in the TME. To replicate physiological gradients, we introduce a first-of-its-kind biofabrication technique that utilizes a microfluidic channel with constricting and expanding geometry to engineer 3D collagen hydrogels with tunable fiber alignment gradients that range from sub-millimeter to millimeter length scales. Our modular approach allows easy access to the microengineered gradient gels, and we demonstrate that HUVECs migrate in response to the fiber architecture. We provide preliminary evidence suggesting that MDA-MB-231 cell aggregates, patterned onto a specific location on the alignment gradient, exhibit preferential migration towards increasing alignment. This finding suggests that alignment gradients could serve as an additional taxis cue in the ECM. Importantly, our study represents the first successful engineering of continuous gradients of fiber alignment in soft, natural materials. We anticipate that our user-friendly platform, which needs no specialized equipment, will offer new experimental capabilities to study the impact of fiber-based contact guidance on directed cell migration.

15.
bioRxiv ; 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37292675

RESUMO

Cells evoke the DNA damage checkpoint (DDC) to inhibit mitosis in the presence of DNA double-strand breaks (DSBs) to allow more time for DNA repair. In budding yeast, a single irreparable DSB is sufficient to activate the DDC and induce cell cycle arrest prior to anaphase for about 12 to 15 hours, after which cells "adapt" to the damage by extinguishing the DDC and resuming the cell cycle. While activation of the DNA damage-dependent cell cycle arrest is well-understood, how it is maintained remains unclear. To address this, we conditionally depleted key DDC proteins after the DDC was fully activated and monitored changes in the maintenance of cell cycle arrest. Degradation of Ddc2ATRIP, Rad9, Rad24, or Rad53CHK2 results in premature resumption of the cell cycle, indicating that these DDC factors are required both to establish and to maintain the arrest. Dun1 is required for establishment, but not maintenance of arrest, whereas Chk1 is required for prolonged maintenance but not for initial establishment of the mitotic arrest. When the cells are challenged with 2 persistent DSBs, they remain permanently arrested. This permanent arrest is initially dependent on the continuous presence of Ddc2 and Rad53; however, after 15 hours both proteins become dispensable. Instead, the continued mitotic arrest is sustained by spindle-assembly checkpoint (SAC) proteins Mad1, Mad2, and Bub2 but not by Bub2's binding partner Bfa1. These data suggest that prolonged cell cycle arrest in response to 2 DSBs is achieved by a handoff from the DDC to specific components of the SAC. Furthermore, the establishment and maintenance of DNA damage-induced cell cycle arrest requires overlapping but different sets of factors.

16.
Electrophoresis ; 44(11-12): 884-909, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37002779

RESUMO

The selective positioning and arrangement of distinct types of multiscale particles can be used in numerous applications in microfluidics, including integrated circuits, sensors and biochips. Electrokinetic (EK) techniques offer an extensive range of options for label-free manipulation and patterning of colloidal particles by exploiting the intrinsic electrical properties of the target of interest. EK-based techniques have been widely implemented in many recent studies, and various methodologies and microfluidic device designs have been developed to achieve patterning two- and three-dimensional (3D) patterned structures. This review provides an overview of the progress in electropatterning research during the last 5 years in the microfluidics arena. This article discusses the advances in the electropatterning of colloids, droplets, synthetic particles, cells, and gels. Each subsection analyzes the manipulation of the particles of interest via EK techniques such as electrophoresis and dielectrophoresis. The conclusions summarize recent advances and provide an outlook on the future of electropatterning in various fields of application, especially those with 3D arrangements as their end goal.


Assuntos
Coloides , Microfluídica , Eletroforese/métodos
17.
J Family Med Prim Care ; 12(1): 181-185, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37025237

RESUMO

Granulomatosis with polyangiitis (GPA) is an etiologically unknown systemic disease characterized by necrotizing granulomatous inflammation. Additionally, it is accompanied by vasculitis of small and medium-sized blood vessels. It manifests clinically as a triad involving the lungs, upper airways, and kidneys. It is estimated that 90% of patients will exhibit upper or lower airway symptoms and around 80% develops the renal disease. In this article, we describe three case scenarios with varying presentations. GPA should be considered among the possible etiologies of cavitary pulmonary lesions with ear manifestations including hearing loss with poor response to unusual treatment.

18.
Int J Mol Sci ; 24(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36901893

RESUMO

Abusive head trauma (AHT) is a serious traumatic brain injury and the leading cause of death in children younger than 2 years. The development of experimental animal models to simulate clinical AHT cases is challenging. Several animal models have been designed to mimic the pathophysiological and behavioral changes in pediatric AHT, ranging from lissencephalic rodents to gyrencephalic piglets, lambs, and non-human primates. These models can provide helpful information for AHT, but many studies utilizing them lack consistent and rigorous characterization of brain changes and have low reproducibility of the inflicted trauma. Clinical translatability of animal models is also limited due to significant structural differences between developing infant human brains and the brains of animals, and an insufficient ability to mimic the effects of long-term degenerative diseases and to model how secondary injuries impact the development of the brain in children. Nevertheless, animal models can provide clues on biochemical effectors that mediate secondary brain injury after AHT including neuroinflammation, excitotoxicity, reactive oxygen toxicity, axonal damage, and neuronal death. They also allow for investigation of the interdependency of injured neurons and analysis of the cell types involved in neuronal degeneration and malfunction. This review first focuses on the clinical challenges in diagnosing AHT and describes various biomarkers in clinical AHT cases. Then typical preclinical biomarkers such as microglia and astrocytes, reactive oxygen species, and activated N-methyl-D-aspartate receptors in AHT are described, and the value and limitations of animal models in preclinical drug discovery for AHT are discussed.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Maus-Tratos Infantis , Traumatismos Craniocerebrais , Criança , Humanos , Animais , Ovinos , Suínos , Lactente , Reprodutibilidade dos Testes , Maus-Tratos Infantis/diagnóstico , Traumatismos Craniocerebrais/diagnóstico
19.
Oman Med J ; 38(5): e547, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38204595

RESUMO

Objectives: Tracheoesophageal fistula (TEF) is a congenital disorder that presents as a surgical emergency in neonates. In regions where neonatal intensive care unit facilities and resources are inadequate and skilled personnel are scarce, not extubating neonates on table, contributes to mortality. Our aim was to assess and compare the on-table extubation rate, extubation time, and postoperative pain scores between opioid and opioid-free anesthesia techniques in neonates undergoing surgical repair of TEF. Methods: We conducted a prospective, single-blind, randomized trial over 18 months between January 2021 and June 2022 in Safdarjung Hospital, New Delhi on 60 full-term neonates scheduled for TEF surgeries randomly allocated to two groups according to the mode of analgesia administered. Group O were given fentanyl injection 1 µg/kg intravenous (IV) loading dose with IV injection. acetaminophen at 7.5 mg/kg and top-up of 0.25 µg/kg fentanyl IV si opus sit. Group NO were given pre-surgical local infiltration and intercostal block with 0.25% and 0.5% bupivacaine, respectively, with IV acetaminophen at 7.5 mg/kg. Results: Mean age in days, gender distribution, and weight in both groups were statistically comparable. The difference in the number of neonates extubated on table was statistically significant (p =0.002) in group NO compared to group O. Lower mean extubation time was seen in group NO (9.0 min 40.0 secs±3.0 min 3.0 secs) compared to group O (16.0 min 45.0 secs±8.0 min 5.0 secs) (p < 0.001). There was a statistically significant (p =0.010) lower Neonatal Infant Pain Scale score in group NO with mean and SD as 1.8±0.8 compared with group O, 2.5±1.1 at 90 min. Conclusions: In neonates undergoing TEF repair, opioid-free anesthesia is a safe and effective method, providing a better extubation rate, faster time to extubation, and better postoperative pain control.

20.
J Family Med Prim Care ; 11(8): 4844-4846, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36352932

RESUMO

Methotrexate (MTX) is the commonly preferred drug in the treatment of various chronic inflammatory conditions. An uncommon, life-threatening, and fatal event associated with methotrexate use is methotrexate-induced pneumonitis (M-pneu). M-pneu does not correlate with the dosage, duration, or method of administration. We present a case of M-pneu in a diagnosed rheumatoid arthritis patient after six years of initiation of MTX. Prompt recognition, withdrawal, and supportive therapy have a positive outcome. If untreated, M-pneu has a proven fatality of 17-30% in published cases.

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