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1.
Data Brief ; 54: 110550, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38868383

RESUMEN

This article presents a dataset of activities associated with stress and boredom obtained through wearable sensors. Data was collected from 40 right-handed participants aged 20 to 25, evenly split between males and females. Each individual wore a smart device on their dominant arm's wrists to facilitate the capture of data. This dataset covers five activities associated with stress and boredom, namely, smoking, eating, nail biting, face touching, and staying still. These activities were selected for their potential psychological implications and captured in an uncontrolled environment to mimic real-life scenarios. The data provides a unique resource for developing machine learning models aimed at recognizing these behaviors, which could lead to real-time analysis and interventions for stress. A custom holder was used to hold the device on the wrists in order to ensure that all participants had consistent orientation and placement. This holder was situated just above the wrist joint, a location typically associated with the placement of smartwatches. The dataset provides a unique opportunity for developing machine learning models for stress & boredom associated activities recognition apart from real-time symptomatic analysis of stress and boredom.

2.
Brain Tumor Res Treat ; 12(2): 109-114, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742259

RESUMEN

Langerhans cell histiocytosis (LCH) is a rare condition in adults, especially when it is limited to a single area of the skull, known as solitary calvarial involvement. In this case report, we present a unique instance of LCH affecting the parietal bone with a pus-draining fistula. This is a rare and unusual presentation at this location, which has been scarcely reported in medical literature. A 30-year-old woman with no prior comorbidity presented with complaints of headache that persisted for a year. She also had swelling on her scalp and a yellowish discharge for 3 weeks, but no neurological problems were observed. Radiology revealed thinning of the calvaria, with ragged margins along the inner table, multiple focal erosions, and involvement of overlying soft tissue and bony sequestrum. The patient underwent biparietal craniotomy and excision of the lesion. The histopathology report showed LCH. After 8 months of follow-up, there was no recurrence. The management of solitary calvarial involvement by LCH with masquerading presentation as a scalp infection can be achieved through complete excision of the lesions, resulting in a favorable outcome.

3.
Int J Med Inform ; 185: 105401, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38493546

RESUMEN

BACKGROUND: Wrist-worn gadgets like smartphones are ideal for unobtrusively gathering user data, in various fields such as health and fitness monitoring, communication, and productivity enhancement. They seamlessly integrate into users' daily lives, providing valuable insights and features without the need for constant attention or disruption. In sensitive domains like mental health, these devices provide user-friendly, privacy-protected means of diagnosis and treatment, offering a secure and cost-effective avenue for seeking help. OBJECTIVES: This study addresses the limitations of traditional mental health assessment techniques, such as intrusive sensing and subjective self-reporting, by harnessing the unobtrusive data collection capabilities of smartphones. Equipped with accelerometers and other sensors, these devices offer a novel approach to mental health research. Our objective was to develop methods for real-time detection of stress and boredom behavior markers using smart devices and machine learning algorithms. METHODOLOGY: By leveraging data from accelerometers (A), gyroscopes (G), and magnetometers (M), we compiled a dataset indicative of stress-related behaviors and trained various machine-learning models for predictive accuracy. The methodology involved collecting data from motion sensors (A, G, and M) on the dominant arm's wrist-worn smartphone, followed by data preprocessing, transformation from time series format, and training a Deep Neural Network (DNN) model for activity recognition. FINDINGS: Remarkably, the DNN achieved an accuracy of 93.50% on test data, outperforming traditional and ensemble machine learning methods across different window sizes, and demonstrated real-time accuracy of 77.78%, validating its practical application. CONCLUSION: In conclusion, this research presents a novel dataset for detecting stress and boredom behaviors using smartphones, reducing reliance on costly devices and offering a more objective assessment. It also proposes a DNN-based method for wrist-worn devices to accurately identify complex activities associated with stress and boredom, with benefits in terms of privacy and user convenience. This advancement represents a significant contribution to the field of mental health research, providing a less intrusive and more user-friendly approach to monitoring mental well-being.


Asunto(s)
Salud Mental , Teléfono Inteligente , Humanos , Ejercicio Físico , Redes Neurales de la Computación , Algoritmos
4.
Acta Pharm Sin B ; 13(4): 1383-1399, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37139430

RESUMEN

Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.

5.
bioRxiv ; 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37214825

RESUMEN

Tumor angiogenesis is a cancer hallmark, and its therapeutic inhibition has provided meaningful, albeit limited, clinical benefit. While anti-angiogenesis inhibitors deprive the tumor of oxygen and essential nutrients, cancer cells activate metabolic adaptations to diminish therapeutic response. Despite these adaptations, angiogenesis inhibition incurs extensive metabolic stress, prompting us to consider such metabolic stress as an induced vulnerability to therapies targeting cancer metabolism. Metabolomic profiling of angiogenesis-inhibited intracranial xenografts showed universal decrease in tricarboxylic acid cycle intermediates, corroborating a state of anaplerotic nutrient deficit or stress. Accordingly, we show strong synergy between angiogenesis inhibitors (Avastin, Tivozanib) and inhibitors of glycolysis or oxidative phosphorylation through exacerbation of anaplerotic nutrient stress in intracranial orthotopic xenografted gliomas. Our findings were recapitulated in GBM xenografts that do not have genetically predisposed metabolic vulnerabilities at baseline. Thus, our findings cement the central importance of the tricarboxylic acid cycle as the nexus of metabolic vulnerabilities and suggest clinical path hypothesis combining angiogenesis inhibitors with pharmacological cancer interventions targeting tumor metabolism for GBM tumors.

6.
Am J Pathol ; 193(11): 1789-1808, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36965774

RESUMEN

This study investigated retinal changes in a Western diet (WD)-induced nonhuman primate model of type 2 diabetes. Rhesus nonhuman primates, aged 15 to 17 years, were fed a high-fat diet (n = 7) for >5 years reflective of the traditional WD. Age-matched controls (n = 6) were fed a standard laboratory primate diet. Retinal fundus photography, optical coherence tomography, autofluorescence imaging, and fluorescein angiography were performed before euthanasia. To assess diabetic retinopathy (DR), eyes were examined using trypsin digests, lipofuscin autofluorescence, and multimarker immunofluorescence on cross-sections and whole mounts. Retinal imaging showed venous engorgement and tortuosity, aneurysms, macular exudates, dot and blot hemorrhages, and a marked increase in fundus autofluorescence. Post-mortem changes included the following: decreased CD31 blood vessel density (P < 0.05); increased acellular capillaries (P < 0.05); increased density of ionized calcium-binding adaptor molecule expressing amoeboid microglia/macrophage; loss of regular distribution in stratum and spacing typical of ramified microglia; and increased immunoreactivity of aquaporin 4 and glial fibrillary acidic protein (P < 0.05). However, rhodopsin immunoreactivity (P < 0.05) in rods and neuronal nuclei antibody-positive neuronal density of 50% (P < 0.05) were decreased. This is the first report of a primate model of DR solely induced by a WD that replicates key features of human DR.


Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Animales , Humanos , Retinopatía Diabética/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Dieta Occidental , Vasos Retinianos/metabolismo , Primates , Tomografía de Coherencia Óptica/métodos
7.
Proc Natl Acad Sci U S A ; 120(3): e2212075120, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36634137

RESUMEN

Liquid methanol has the potential to be the hydrogen energy carrier and storage medium for the future green economy. However, there are still many challenges before zero-emission, affordable molecular H2 can be extracted from methanol with high performance. Here, we present noble-metal-free Cu-WC/W plasmonic nanohybrids which exhibit unsurpassed solar H2 extraction efficiency from pure methanol of 2,176.7 µmol g-1 h-1 at room temperature and normal pressure. Macro-to-micro experiments and simulations unveil that local reaction microenvironments are generated by the coperturbation of WC/W's lattice strain and infrared-plasmonic electric field. It enables spontaneous but selective zero-emission reaction pathways. Such microenvironments are found to be highly cooperative with solar-broadband-plasmon-excited charge carriers flowing from Cu to WC surfaces for efficient stable CH3OH plasmonic reforming with C3-dominated liquid products and 100% selective gaseous H2. Such high efficiency, without any COx emission, can be sustained for over a thousand-hour operation without obvious degradation.

8.
Conserv Biol ; 37(2): e13997, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36047697

RESUMEN

Illegal wildlife trade (IWT) is one of the leading causes of the decline in high-value species. Crime-reduction strategies to counter IWT can have unintended effects, with crime displacement occurring when offenders react to such interventions. Despite the value of understanding how and why displacement occurs for informing conservation strategies, few examples are published. We explored a case of perpetrator replacement following an intervention and drew lessons for conservation strategies for high-value species. Poaching and subsequent trade threaten the Sundarbans tiger (Panthera tigris). Pirate gangs were the dominant poachers from 1980 to 2017, but following an extensive campaign, the Sundarbans was declared pirate free in 2018. We interviewed 280 individuals, including 100 tiger poachers, from 26 administrative unions bordering the Sundarbans and used interviewee responses to compare the poaching situation during and after the pirate era. We analyzed the spatial distribution of tiger poachers among the unions and used crime script analysis of the dominant poacher type to identify intervention. Because pirates opportunistically poached tigers, the government's successful counter-pirate campaign inadvertently removed the dominant tiger poaching type. However, a temporary reduction in poaching was rapidly cancelled out by the emergence of at least 32 specialist tiger-poaching teams. With the risk of extortion and robbery from pirates gone, other groups increased the frequency of opportunistic and targeted tiger poaching. Based on expert interviews, we estimated that 341 tiger poachers of all types are active throughout the unions, with 79% of specialists concentrated in 27% of unions. The highly focused counter-pirate campaign reduced motivations and opportunities for piracy but left intact the opportunity structure and trade connections for tiger poaching, and with insufficient enforcement officers trading has flourished. Interventions targeting opportunities for poaching by specialist tiger poachers include heightened surveillance and reporting mechanisms and alternative livelihood provision to disincentivize poaching.


Aprendizaje a partir de la sustitución del infractor para eliminar las oportunidades de crimen y prevenir la caza furtiva del tigre de Sundarbans Resumen El mercado ilegal de fauna (MIF) es una de las principales causas de la declinación de especies importantes. Las estrategias de reducción de crímenes para contrarrestar el MIF pueden tener efectos no deseados, como el desplazamiento del crimen que ocurre cuando los infractores reaccionan a dichas intervenciones. A pesar de lo valioso que es para las estrategias de conservación entender cómo y por qué ocurre este desplazamiento, se publican pocos ejemplos. Exploramos un caso de sustitución del infractor después de una intervención sacamos lecciones para las estrategias de conservación de especies importantes. La caza furtiva y el mercado subsecuente son una amenaza para el tigre de Sundarbans (Panthera tigris). Los piratas fueron los cazadores dominantes entre 1980 y 2017, pero después de una campaña exhaustiva, el Sundarbans fue declarado libre de piratas en 2018. Entrevistamos a 280 individuos, incluidos 100 cazadores furtivos, de 26 uniones administrativas que rodean al Sundarbans y usamos sus respuestas para comparar la situación de la caza furtiva durante y después de los piratas. Analizamos la distribución espacial de los cazadores furtivos entre las uniones y usamos el análisis de escritura criminal del tipo dominante de cazador para identificar las intervenciones. Ya que los piratas eran cazadores furtivos oportunistas, la campaña exitosa del gobierno para contrarrestarlos eliminó sin saberlo el tipo dominante de caza furtiva. Sin embargo, una reducción temporal de la caza se canceló rápidamente con la emergencia de al menos 32 equipos especialistas en la cacería furtiva de los tigres. Sin el riesgo de la extorsión o robo por parte de los piratas, otros grupos incrementaron la frecuencia de la cacería oportunista y focalizada. Con base en las entrevistas a expertos, estimamos que 341 cazadores de tigres de todos los tipos están activos en las uniones, con 79% de los especialistas concentrados en 27% de las uniones. La campaña focalizada anti-piratas redujo las motivaciones y oportunidades de piratería, pero no afectó la estructura de oportunidades y conexiones mercantiles de la cacería furtiva de tigres, lo cual, sumado a la falta de suficientes agentes policiales, ha aumentado el mercado. Las intervenciones enfocadas en las oportunidades de cacería de los cazadores especialistas incluyen una mayor vigilancia y mecanismos de reporte y el suministro de sustentos alternativos para desalentar la cacería furtiva.


Asunto(s)
Conservación de los Recursos Naturales , Tigres , Humanos , Animales , Tigres/fisiología , Crimen/prevención & control , Comercio de Vida Silvestre
9.
Int J Mol Sci ; 23(17)2022 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-36077535

RESUMEN

Clearance of ocular fluid and metabolic waste is a critical function of the eye in health and disease. The eye has distinct fluid outflow pathways in both the anterior and posterior segments. Although the anterior outflow pathway is well characterized, little is known about posterior outflow routes. Recent studies suggest that lymphatic and glymphatic systems play an important role in the clearance of fluid and waste products from the posterior segment of the eye. The lymphatic system is a vascular network that runs parallel to the blood circulatory system. It plays an essential role in maintenance of fluid homeostasis and immune surveillance in the body. Recent studies have reported lymphatics in the cornea (under pathological conditions), ciliary body, choroid, and optic nerve meninges. The evidence of lymphatics in optic nerve meninges is, however, limited. An alternative lymphatic system termed the glymphatic system was recently discovered in the rodent eye and brain. This system is a glial cell-based perivascular network responsible for the clearance of interstitial fluid and metabolic waste. In this review, we will discuss our current knowledge of ocular lymphatic and glymphatic systems and their role in retinal degenerative diseases.


Asunto(s)
Sistema Glinfático , Vasos Linfáticos , Encéfalo/fisiología , Sistema Nervioso Central , Sistema Linfático , Vasos Linfáticos/metabolismo , Retina
10.
Eur J Appl Physiol ; 122(8): 1797-1810, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35362800

RESUMEN

Heat-induced hypo-hydration (hyperosmotic hypovolemia) can reduce prolonged skeletal muscle performance; however, the mechanisms are less well understood and the reported effects on all aspects of neuromuscular function and brief maximal contractions are inconsistent. Historically, a 4-6% reduction of body mass has not been considered to impair muscle function in humans, as determined by muscle torque, membrane excitability and peak power production. With the development of magnetic resonance imaging and neurophysiological techniques, such as electromyography, peripheral nerve, and transcranial magnetic stimulation (TMS), the integrity of the brain-to-muscle pathway can be further investigated. The findings of this review demonstrate that heat-induced hypo-hydration impairs neuromuscular function, particularly during repeated and sustained contractions. Additionally, the mechanisms are separate to those of hyperthermia-induced fatigue and are likely a result of modulations to corticospinal inhibition, increased fibre conduction velocity, pain perception and impaired contractile function. This review also sheds light on the view that hypo-hydration has 'no effect' on neuromuscular function during brief maximal voluntary contractions. It is hypothesised that irrespective of unchanged force, compensatory reductions in cortical inhibition are likely to occur, in the attempt of achieving adequate force production. Studies using single-pulse TMS have shown that hypo-hydration can reduce maximal isometric and eccentric force, despite a reduction in cortical inhibition, but the cause of this is currently unclear. Future work should investigate the intracortical inhibitory and excitatory pathways within the brain, to elucidate the role of the central nervous system in force output, following heat-induced hypo-hydration.


Asunto(s)
Potenciales Evocados Motores , Contracción Isométrica , Estimulación Eléctrica/métodos , Electromiografía/métodos , Potenciales Evocados Motores/fisiología , Calor , Humanos , Contracción Isométrica/fisiología , Contracción Muscular/fisiología , Fatiga Muscular/fisiología , Músculo Esquelético/fisiología , Estimulación Magnética Transcraneal
11.
J Pak Med Assoc ; 72(3): 424-429, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35320218

RESUMEN

OBJECTIVE: To determine the immunophenotypic pattern and aberrant expression of myeloid antigens in newly diagnosed patients of acute lymphoblastic leukaemia(ALL). METHODS: This descriptive cross-sectional study was carried out in Haematology / Pathology department, Army Medical College, National University of Medical Sciences (NUMS) in collaboration with Immunology and Haematology departments of Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January, 2019 to 31st December, 2019. Seventy-three (73) recently diagnosed patients of Acute Lymphoblastic leukaemia of all age groups and both genders were included in the study. A proforma was used to note demographic data. CBC, cytochemical stains and bone marrow examinations were carried out and assessed for morphology and percentage of blasts using a microscope. Flow cytometry was used to perform immunophenotyping on samples of peripheral blood and bone marrow, using a standard panel. RESULTS: The most commonly expressed markers were weak CD45, TdT, CD19, CD10 and HLA-DR. Weak CD45 was present in almost all blast cells and there was no remarkable difference in its positivity among various subtypes of ALL. Myeloid expression was observed in 13 (17.8%) cases. CD13 and CD33 were aberrantly expressed in 11 and 12.3 of all cases of ALL respectively. CONCLUSIONS: Expression of aberrant myeloid CD markers in acute lymphocytic leukaemia has prognostic significance and should be documented during lineage assignment of acute leukaemias while performing immunophenotyping.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Enfermedad Aguda , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología
12.
J Coll Physicians Surg Pak ; 32(4): 528-530, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35330531

RESUMEN

Solitary fibrous tumour (SFT) is a ubiquitous benign mesenchymal tumour of fibroblastic origin, which occurs most often in middle-aged adults. It usually presents as lung mass originating from pleura, but extrapleural occurrence is also common. Tumour is characterised by hypo- and hyper-cellular areas of spindle-shaped cells, arranged in haphazard manner with dispersed staghorn-shaped vessels. Surgical excision is the curative treatment. SFTs of the primary testicular or paratesticular region are extremely rare, but they exhibit histologic findings similar to SFTs originating at other body sites. Here, we report the case of a paratesticular SFT in a 37-year male, who presented with a non-tender, firm, mobile, left-sided retrotesticular swelling with unique histological features closely mimicking cellular angiofibroma, a common tumour of paratesticular location. Key Words: Solitary fibrous tumour, Paratesticular, benign, angiofibroma.


Asunto(s)
Angiofibroma , Tumores Fibrosos Solitarios , Adulto , Angiofibroma/diagnóstico , Angiofibroma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/cirugía , Testículo/patología
13.
Clin J Sport Med ; 32(6): 580-587, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35325898

RESUMEN

OBJECTIVE: There is a high incidence of concussion and frequent utilization of rapid weight loss (RWL) methods among combat sport athletes, yet the apparent similarity in symptoms experienced as a result of a concussion or RWL has not been investigated. This study surveyed combat sports athletes to investigate the differences in symptom onset and recovery between combat sports and evaluated the relationships between concussion and RWL symptoms. DESIGN: Cross-sectional study. SETTING: Data were collected through an online survey. PARTICIPANTS: One hundred thirty-two (115 male athletes and 17 female athletes) combat sport athletes. INTERVENTIONS: Modified Sport Concussion Assessment Tool (SCAT) symptom checklist and weight-cutting questionnaire. MAIN OUTCOME MEASURES: Survey items included combat sport discipline, weight loss, medical history, weight-cutting questionnaire, and concussion and weight-cutting symptom checklists. RESULTS: Strong associations ( rs = 0.6-0.7, P < 0.05) were observed between concussion and RWL symptoms. The most frequently reported symptom resolution times were 24 to 48 hours for a weight cut (WC; 59%) and 3 to 5 days for a concussion (43%), with 60% to 70% of athletes reporting a deterioration and lengthening of concussion symptoms when undergoing a WC. Most of the athletes (65%) also reported at least one WC in their career to " not go according to plan ," resulting in a lack of energy (83%) and strength/power (70%). CONCLUSIONS: Rapid weight loss and concussion symptoms are strongly associated, with most of the athletes reporting a deterioration of concussion symptoms during a WC. The results indicate that concussion symptoms should be monitored alongside hydration status to avoid any compound effects of prior RWL on the interpretation of concussion assessments and to avoid potential misdiagnoses among combat athletes.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Masculino , Femenino , Humanos , Estudios Transversales , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/etiología , Atletas , Pérdida de Peso , Encuestas y Cuestionarios , Traumatismos en Atletas/diagnóstico , Traumatismos en Atletas/complicaciones
14.
J Pak Med Assoc ; 71(Suppl 5)(8): S83-S86, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34634023

RESUMEN

OBJECTIVE: To determine the experience at the Aga Khan University Hospital in diagnosing and treating adult patients with primary lymphoma of bone. METHODOLOGY: All patients with Primary lymphoma of bone (PLB) that were diagnosed and/or treated at Aga Khan University Hospital, Karachi from 2005 to 2019 were included as part of this study. RESULTS: There were 17 patients with PLB including 13 (76.5%) males and 4 (23.5%) females with a mean age of 44 ± 16.5 years. Nine patients were between 30-59 years of age at diagnosis. The mean follow-up time of patients was 80±46.7 months. Six patients had tumours of pelvic bone followed by tibia (5) and femur (4). Four patients had a pathological fracture at the time of presentation whereas 2 (11.8%) required surgical fixation of the pathological fracture. The stage of the tumour was based on Ann Arbor classification. Nine (52.9%) cases had Stage 1 disease, 7 (41.2%) had stage IV disease with metastasis in extra nodal tissues. As for treatment, every patient received chemotherapy whereas 5 (29.4%) received adjuvant radiotherapy. Complete remission in the size of the tumour was seen in 11 (64.7%) patients while 6 (35.3%) had partial remission. Post-treatment, 4 (23.5%) patients expired. The mean Overall Survival (OS) time was 80.18 ± 46.71months with a survival rate of 76.5. CONCLUSIONS: Primary lymphoma of the bone can be treated with medical regime and good prophylactic surgeries to avoid pathological fracture such as intramedullary nailing.


Asunto(s)
Linfoma , Adulto , Estudios Transversales , Femenino , Hospitales Universitarios , Humanos , Linfoma/epidemiología , Linfoma/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria
15.
Mol Pharm ; 18(9): 3452-3463, 2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34387498

RESUMEN

Gene therapy aims to treat patients by altering or controlling gene expression. The field of gene therapy has had increasing success in recent years primarily using viral-based approaches; however, there is still significant interest toward the use of polymeric materials due to their potential as flexible, low-cost scaffolds for gene delivery that do not suffer the mutagenesis and immunogenicity concerns of viral vectors. To address the challenges of efficiency and biocompatibility, a series of zwitterion-like polyethylenimine derivatives (zPEIs) were produced via the succinylation of 2-11.5% of polyethylenimine (PEI) amines. With increasing modification, zPEI polyplexes exhibited decreased serum-protein aggregation and dissociated more easily in the presence of a competitor polyanion when compared to unmodified PEI. Surprisingly, the gene delivery mediated in the presence of serum showed that succinylation of as few as 2% of PEI amines resulted in transgene expression 260- to 480-fold higher than that of unmodified PEI and 50- to 65-fold higher than that of commercial PEI-PEG2k in HEK293 and HeLa cells, respectively. Remarkably, the same zPEIs also produced 16-fold greater efficiency of CRISPR/Cas9 gene knock-in compared to unmodified PEI in the presence of serum. In addition, we show that 2% succinylation does not significantly decrease polymer/DNA binding ability or serum protein interaction to a significant extent, yet this small modification is still sufficient to provide a remarkable increase in transgene expression and gene knock-in in the presence of serum.


Asunto(s)
Sistemas CRISPR-Cas/genética , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Polietileneimina/química , Técnicas de Sustitución del Gen , Células HEK293 , Células HeLa , Humanos , Polietileneimina/análogos & derivados , Reparación del ADN por Recombinación
16.
Biol Rev Camb Philos Soc ; 96(6): 2694-2715, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34231315

RESUMEN

The crisis generated by the emergence and pandemic spread of COVID-19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local communities across the world, and might be unachievable at scale. There is thus a need for a more complex package of policy and practical responses. We undertook a solution scan to identify and collate 161 possible options for reducing the risks of further epidemic disease transmission from animals to humans, including potential further SARS-CoV-2 transmission (original or variants). We include all categories of animals in our responses (i.e. wildlife, captive, unmanaged/feral and domestic livestock and pets) and focus on pathogens (especially viruses) that, once transmitted from animals to humans, could acquire epidemic potential through high rates of human-to-human transmission. This excludes measures to prevent well-known zoonotic diseases, such as rabies, that cannot readily transmit between humans. We focused solutions on societal measures, excluding the development of vaccines and other preventive therapeutic medicine and veterinary medicine options that are discussed elsewhere. We derived our solutions through reading the scientific literature, NGO position papers, and industry guidelines, collating our own experiences, and consulting experts in different fields. Herein, we review the major zoonotic transmission pathways and present an extensive list of options. The potential solutions are organised according to the key stages of the trade chain and encompass solutions that can be applied at the local, regional and international scales. This is a set of options targeted at practitioners and policy makers to encourage careful examination of possible courses of action, validating their impact and documenting outcomes.


Asunto(s)
COVID-19 , Animales , Animales Salvajes , Humanos , Pandemias , SARS-CoV-2 , Zoonosis/epidemiología
17.
J Coll Physicians Surg Pak ; 30(6): 722-724, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34102789

RESUMEN

Spermatocytic tumor is a rare germ cell tumor not related to germ cell neoplasia in situ, and derived from postpubertal-type germ cells. It was previously called "Spermatocytic Seminoma" due to false belief of its origin from germ cell neoplasia in situ. The tumor usually occurs in an older age group and orchidectomy is curative. We present a case of spermatocytic tumor in a 25-year male who presented with right-sided testicular swelling and right-sided varicocele. Radiology revealed a 9.8 × 9 cm testicular mass and the patient underwent right-sided orchidectomy. Microscopic examination showed classic morphology with three characteristic cell types and diagnosis of spermatocytic tumor was made. Key Words: Spermatocytic tumor, testis, young.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Anciano , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/cirugía , Orquiectomía , Seminoma/cirugía , Neoplasias Testiculares/cirugía , Testículo/cirugía
18.
J Adv Vet Anim Res ; 7(3): 414-420, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33005666

RESUMEN

OBJECTIVES: Knowledge, attitude, and practice (KAP) of rabies in the community are essential for developing post-exposure behavioral treatment and for understanding current prevention and control policy on rabies. This was a cross-sectional study in Gaibandha Sadar, a northern district of Bangladesh, investigating the level of KAP about rabies. MATERIALS AND METHODS: A total of 368 interviewed respondents, of whom 280 (76.09%) were male, and 88 (23.91%) were female. A structured questionnaire was used for the data collection from respondents on socio-demographic information and KAP regarding rabies. The data analyzed with STATA-IC-11.0 and the association of independent variables with rabies KAP scores were calculated using Pearson's Chi-square. RESULTS: Most respondents had adequate KAP levels and positive thoughts on rabies prevention. The KAP scores were strongly associated with education and employment status (p < 0.05). Most respondents said that stray dogs are a headache in the area and believed that control of the dog population in Gaibandha is essential. CONCLUSION: These outcomes also revealed that there is an information gap about rabies that might improve by developing an education program for awareness.

19.
AIMS Microbiol ; 6(3): 350-360, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33029570

RESUMEN

Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational attributes of the molecular complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike protein. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provides structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.

20.
J Strength Cond Res ; 34(11): 3232-3240, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33105375

RESUMEN

Uddin, N, Jeffries, O, Read, P, Howe, L, Patterson, S, and Waldron, M. Physiological responses to linear and nonlinear soccer-specific match simulations and their effects on lower-limb muscle fatigue. J Strength Cond Res 34(11): 3232-3240, 2020-The aims of this study were to: (a) investigate the effects of linear and nonlinear soccer simulations on lower-limb muscle function and physiological responses and (b) evaluate the relationship between match-running demands and changes in lower-limb muscle function. In a repeated-measures cross-over design, 8 participants completed either a linear or nonlinear adapted Loughborough Intermittent Shuttle Test (LIST) on 2 occasions. The movement of players was tracked with a global positioning system, while lower-limb muscle function tests and physiological measurements were performed before and every 15 minutes during the simulation. There were no differences in distance covered, yet high-speed running (p = 0.007), accelerations (p = 0.008), and decelerations (p = 0.015) were higher in the linear LIST. Mean heart rate (p = 0.001) and ratings of perceived exertion (p = 0.013) were higher in the nonlinear LIST. Peak landing forces (p = 0.017) and jump height (p = 0.001) were reduced between baseline and 90 minutes but were not different between conditions. Changes in peak landing forces from baseline to half-time (r = -0.57, n = 16, p = 0.022) and full-time (r = -0.58, n = 16, p = 0.019) were related to high-speed running. Hamstring force was unaffected by time (p = 0.448) but was reduced in the linear LIST (p = 0.044). Protocols posing different external and internal demands elicited similar levels of fatigue across simulations. Hamstring function was not an effective indicator of fatigue, but our results highlight the greater demands placed on this muscle group when higher-speed running is performed.


Asunto(s)
Prueba de Esfuerzo/métodos , Músculos Isquiosurales/fisiología , Fatiga Muscular/fisiología , Carrera/fisiología , Fútbol/fisiología , Aceleración , Adaptación Fisiológica , Adolescente , Adulto , Rendimiento Atlético/fisiología , Desaceleración , Sistemas de Información Geográfica , Frecuencia Cardíaca , Humanos , Extremidad Inferior , Masculino , Adulto Joven
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