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1.
J Transl Med ; 22(1): 370, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637842

RESUMO

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.


Assuntos
Desenvolvimento de Medicamentos , Cabelo , Camundongos , Animais , Humanos , Camundongos Nus , Descoberta de Drogas , Janus Quinase 3
2.
Cureus ; 16(2): e53747, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38465048

RESUMO

Background The prevalence of obesity and thyroid cancer (TC) is increasing worldwide, and obesity is a risk factor for TC. Objectives This study aimed to elucidate physicians' awareness of obesity as a risk factor for TC. Materials and methods A cross-sectional, self-report online questionnaire was distributed to physicians in all regions of Saudi Arabia. The questionnaire comprised sociodemographic data and questions concerning the risk factors for TC, including obesity. Results A total of 310 physicians participated in this study. Of the respondents, 35.8% (n = 111) were aged 30-40 years, 40.6% (n = 126) were board certified, and 52.3% (n = 162) had >10 years of experience. Only 36.8% (n = 114) of respondents were familiar with the relationship between obesity and TC risk (P < 0.001). In terms of knowledge of obesity as a risk factor for TC, a significant difference was observed for the following sociodemographic characteristics: sex, educational attainment, and years of experience. A significant difference was also observed with awareness of other risk factors for TC. Conclusions In light of the limited awareness of the correlation between obesity and TC, the most effective approach to address these misconceptions would be to implement diverse and ongoing medical education initiatives.

3.
J Pharm Bioallied Sci ; 15(Suppl 2): S1089-S1092, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37694054

RESUMO

Objective: The study aimed to assess staff nurses' knowledge of the health concerns connected with biomedical waste disposal. Materials and Methods: The descriptive study was performed with a sample of 50 staff nurses from a tertiary hospital. The semi-structured questionnaire was made to be used when interviewing participants. It has information about the person's age in years, religion, monthly family income, family type, marital status, previous biomedical waste management education exposure, and the source of information. Results: Participants were between the ages of 20 and 60. Only five 20-30-year olds are moderately knowledgeable. Out of 50 nurses, 41 (82%) had an adequate level of knowledge, 9 (18%) had a moderate level of knowledge on biomedical waste management, and none of them had too inadequate knowledge. Conclusions: The proper handling of biomedical waste necessitates that all hospital staff undergo extensive training on the collection, sorting, transportation, and storage of waste in color-coded bins before disposal and treatment.

4.
Open Heart ; 10(2)2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37419525

RESUMO

BACKGROUND: Chronic kidney disease (CKD) and atrial fibrillation (AF) are increasing in prevalence globally and share common risk factors.Our aim was to characterise real-world evidence on direct oral anticoagulant (DOAC) prescribing for people with AF and CKD, in terms of adherence, persistence and renal dose titration. METHODS: PubMed, EMBASE and CINAHL were searched from inception to June 2022. Our search terms included a combination of Medical Subject Headings (MeSH) terms and keywords including 'atrial fibrillation', 'chronic kidney disease', 'adherence', 'persistence', 'direct oral anticoagulants' and 'dosing'. Data extraction and quality assessment were undertaken by two reviewers independently. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Age, sex, diabetes, hypertension and heart failure were chosen as variables of interest. RESULTS: From 19 studies, a total of 252 117 patients were included with CKD and AF. Meta-analysis was only possible in seven studies with 128 406 patients, five on DOAC dose titration and two on adherence. There were insufficient studies on persistence. Our meta-analysis of dosing showed that 68% of patients with CKD and AF had correct dosing. There was no evidence to show any association between correct DOAC dosing and variables of interest. Overall, 67% of patients were DOAC adherent. CONCLUSION: Adherence and correct dosing of DOACs were suboptimal compared with other medications in the pooled studies with respect to CKD and AF. Thus, further research is required as the lack of generalisation of findings is a rate-limiting factor for improved DOAC management in AF and CKD. PROSPERO REGISTRATION NUMBER: CRD;42022344491.


Assuntos
Fibrilação Atrial , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Anticoagulantes , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Fatores de Risco
5.
Cureus ; 15(4): e37713, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37206509

RESUMO

Cadaveric dissection, as a learning tool, has been a part of Indian medical education. Worldwide, with reforms in medical education and the introduction of new learning modalities, cadaveric dissection has been complemented with other modalities such as living anatomy and virtual anatomy. This study aims to collect the feedback of faculty members regarding the role of dissection in the present context of medical education. The method of the study involved a 32-item questionnaire to collect responses; they were collected using the 5-point Likert scale along with two open-ended questions. In general, the closed questions covered these sections: learning styles, interpersonal skills, teaching and learning, dissection, and other learning modes. The principal component analysis was used to explore the multivariate relationships among the items' perceptions. The multivariate regression analysis was conducted between the construct and the latent variable to develop the structural equation model. Four themes, PC1 (learning ability with structural orientation), PC2 (interpersonal skill), PC3 (multimedia-virtual tool), and PC5 (associated factors) had positive relation and were treated as a latent variable motivation for dissection, and theme 4 (PC4, safety) had a negative correlation and was treated as a latent variable repulsion for dissection. It was found that the dissection room is an important place for learning clinical and personal skills, along with empathy, in anatomy education. Safety issues and implementation of stress-coping activities during the induction phase are required. There is also a need to use mixed-method approaches that integrate technology-enhanced learning such as virtual anatomy, living anatomy, and radiological anatomy with cadaveric dissection.

7.
Br J Nutr ; 129(10): 1732-1739, 2023 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35983775

RESUMO

Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 µg/d (Group A), 1000 µg/d (Group B), 2000 µg/d (Group C) and 60 000 µg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration (P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks (P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks (P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) (P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 µg or monthly 60 000 µg of oral cholecalciferol among adults seems optimal and safe.


Assuntos
Colecalciferol , Deficiência de Vitamina D , Adulto , Humanos , Colecalciferol/efeitos adversos , Cálcio , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico , Hormônio Paratireóideo , Fosfatase Alcalina , Suplementos Nutricionais
8.
Arrhythm Electrophysiol Rev ; 11: e12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35846422

RESUMO

The burden of AF is increasing in prevalence and healthcare resource usage in the UK and worldwide. It can result in impaired quality of life for affected patients, as well as increased risk of stroke, heart failure and mortality. A holistic, integrated approach to AF management is recommended, which may include a focus on reducing risk factors and on medical management with anticoagulation and anti-arrhythmic drugs. There are also various ablation strategies that may be considered when anti-arrhythmic drugs fail to alleviate symptoms and reduce AF burden. These ablation techniques range from standalone percutaneous endocardial catheter ablation to open surgical ablation procedures concomitant with cardiac surgery. More recently, hybrid ablation that combines aspects of both surgical and electrophysiologically targeted ablation has been described. This article reviews the evolution of ablation strategies, beginning with the origin of the Cox maze IV procedure and continuing to the recent hybrid convergent approach, and provides a summary of the associated outcomes.

9.
Expert Opin Pharmacother ; 23(8): 947-958, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35575484

RESUMO

INTRODUCTION: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder associated with an increased incidence and prevalence of cardiovascular disease (CVD), including myocardial infarction and heart failure. In addition to traditional risk factors, evidence suggests inflammation is critical to the pathophysiology of both conditions. Despite the association being well-recognised, challenges remain in managing cardiovascular risk in RA. AREAS COVERED: This manuscript analyses the association between CVD and RA and explores the limitations in evaluating cardiovascular risk in RA with available risk assessment tools. The authors review the optimal management of traditional risk factors such as hypertension and dyslipidaemia and contemporary risk factors such as inflammation and analyse the cardiovascular impact of RA medications. EXPERT OPINION: Analysis points to the critical role of inflammation in the pathogenesis of RA and CVD. It is well established that conventional disease-modifying anti-rheumatic drugs (DMARDs) improve cardiovascular outcomes; however, underlying risk often remains underappreciated. The authors suggest there remains an opportunity to improve mortality and morbidity with the early recognition and of at-risk populations and the timely initiation of appropriate cardiovascular and anti-inflammatory medications. More research is necessary into the role that imaging may play in stratifying risk and in the longer-term cardiovascular impact of biological DMARDs.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Cardiovasculares , Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Inflamação/tratamento farmacológico , Fatores de Risco
10.
Indian Pediatr ; 59(2): 114-116, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35193989

RESUMO

OBJECTIVES: To study the efficacy and adverse effects of opioids in management of pain in children. METHODS: A descriptive study was conducted in children aged below 15 years with moderate to severe pain, and response to opioids and adverse effects were assessed at 24, 48 and 72 hours after administration. RESULTS: 100 children (68% males) with median (IQR) age of 6.5 (3.5,10) years were studied. 81% (n=81) children with moderate pain and 78.9% (n=15) with severe pain responded to opioids in 72 hours. Among children with severe pain of non-malignant origin, 80% (n=8) responded in 48 hours compared to 11.1% (n=1) with malignancy and this difference was statistically significant at 24 hours (P=0.005). Of children with severe pain 73.7% (n=14) developed adverse reactions compared to 30.9% (n=25) with moderate pain. CONCLUSIONS: Children with moderate-severe pain, either of malignant or non-malignant origin could be managed effectively with opioids without severe adverse effects.


Assuntos
Analgésicos Opioides , Manejo da Dor , Adolescente , Analgésicos Opioides/efeitos adversos , Criança , Feminino , Humanos , Masculino , Dor/tratamento farmacológico
11.
Pathobiology ; 89(3): 146-156, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35078195

RESUMO

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma (NHL) accounting for 30% of adult NHL worldwide and 50% in developing countries like India. DNA damage and Myc-induced transformation are well-known contributing factors towards development of DLBCL. A recently identified HSP90 co-chaperone complex R2TP has been shown to contribute towards DNA damage and Myc-induced transformation. This study aimed to analyse the immunohistochemical (IHC) expression of R2TP complex components RUVBL1, PIH1D1, and RPAP3 in DLBCL patients and correlate with prognosis. METHODS: DLBCL (n = 54) histological slides were retrieved from archives, and detailed histomorphological and clinical features were noted. IHC staining of R2TP complex components RUVBL1, PIH1D1, and RPAP3 was performed on 54 cases (FFPE) of DLBCL. Expression data were correlated with survival and clinical features. RESULTS: Out of the 54 DLBCL cases, 59.26% (n = 32) stained positive for RUVBL1. The RUVBL1 expression was associated with poor prognosis in both progression-free survival (PFS) (p = 0.0146) and overall survival (OS) (p = 0.0328). The expression was positively correlated with bone marrow involvement (p = 0.0525). The expression of PIH1D1 was observed in 68.51% (n = 32) of DLBCL cases, and positive correlation was observed with international prognostic index score (p = 0.0246); however, no correlation was observed with PFS or OS. Finally, RPAP3 was found immunopositive in only 1 case of DLBCL. CONCLUSIONS: Immunopositivity for RUVBL1 is associated with poor prognosis along with a higher relapse rate amongst the DLBCL patients. PIH1D1 immunopositivity correlated with a higher IPI score.


Assuntos
Linfoma Difuso de Grandes Células B , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Adulto , Proteínas de Transporte/genética , DNA Helicases/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética
12.
Arrhythm Electrophysiol Rev ; 10(3): 198-204, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34777825

RESUMO

Recent advances have been made in AF treatment, including the role of early rhythm control and landmark clinical trials using ablation therapy. However, some treatment gaps remain, including the creation of durable lesions outside the pulmonary veins and effective treatment of longstanding persistent AF. A novel epicardial-endocardial ablation approach - the hybrid convergent procedure - was developed to combine surgical and catheter ablation techniques into a collaborative, multidisciplinary approach to managing AF. In this review, the authors discuss recently published data on hybrid convergent ablation, including results of the CONVERGE clinical trial, in the context of current challenges to treatment of persistent and long-standing persistent AF. The review also aims to provide perspective on outstanding questions and future directions in this area.

13.
Materials (Basel) ; 14(21)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34772234

RESUMO

Current discoveries as well as research findings on various types of carbon nanostructures have inspired research into their utilization in a number of fields. These carbon nanostructures offer uses in pharmacy, medicine and different therapies. One such unique carbon nanostructure includes carbon nanotubes (CNTs), which are one-dimensional allotropes of carbon nanostructure that can have a length-to-diameter ratio greater than 1,000,000. After their discovery, CNTs have drawn extensive research attention due to their excellent material properties. Their physical, chemical and electronic properties are excellent and their composites provide great possibilities for enormous nanometer applications. The current study provides a systematic review based on prior literature review and data gathered from various sources. The various research studies from many research labs and organizations were systematically retrieved, collected, compiled and written. The entire collection and compilation of this review concluded the use of CNT approaches and their efficacy and safety for the treatment of various diseases such as brain tumors or cancer via nanotechnology-based drug delivery, phototherapy, gene therapy, antiviral therapy, antifungal therapy, antibacterial therapy and other biomedical applications. The current review covers diverse applications of CNTs in designing a range of targeted drug delivery systems and application for various therapies. It concludes with a discussion on how CNTs based medicines can expand in the future.

14.
J Clin Med ; 10(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34300301

RESUMO

Atrial fibrillation (AF) is a global disease with rapidly rising incidence and prevalence. It is associated with a higher risk of stroke, dementia, cognitive decline, sudden and cardiovascular death, heart failure and impairment in quality of life. The disease is a major burden on the healthcare system. Paroxysmal AF is typically managed with medications or endocardial catheter ablation to good effect. However, a large proportion of patients with AF have persistent or long-standing persistent AF, which are more complex forms of the condition and thus more difficult to treat. This is in part due to the progressive electro-anatomical changes that occur with AF persistence and the spread of arrhythmogenic triggers and substrates outside of the pulmonary veins. The posterior wall of the left atrium is a common site for these changes and has become a target of ablation strategies to treat these more resistant forms of AF. In this review, we discuss the role of the posterior left atrial wall in persistent and long-standing persistent AF, the limitations of current endocardial-focused treatment strategies, and future perspectives on hybrid epicardial-endocardial approaches to posterior wall isolation or ablation.

15.
J Periodontol ; 92(9): 1329-1338, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33107036

RESUMO

BACKGROUND: Metallothionein (MT), a cysteine rich protein is involved as a radical scavenger in several pathological conditions associated with oxidative stress; however, its role in periodontal disease still remains elusive. The aim of this cross-sectional study is to determine the serum, saliva and gingival crevicular fluid (GCF) levels of MT in smokers (S) and non-smokers (NS) with chronic periodontitis (CP), and compare them with those of periodontally healthy (PH) individuals. METHODS: A total of 85 participants were enrolled: 45 patients with CP (23 S [CP+S] and 22 NS [CP+NS]) and 40 PH individuals (20 S [PH+S] and 20 NS [PH+NS]). In all the study participants, clinical periodontal parameters (plaque index, gingival index, sulcus bleeding index, probing depth, and clinical attachment level) were recorded and samples of serum, saliva and GCF were collected. Enzyme-linked immunosorbent assay was used to determine the levels of MT in the samples. RESULTS: All periodontal clinical parameters were significantly higher in the CP groups as compared to PH groups (P < 0.05). MT levels in CP+S group were significantly raised in comparison to other three groups. There was no statistically significant difference in MT levels among CP+NS and PH+S groups (P > 0.05); however, relatively higher levels were observed in GCF and saliva in CP+NS group. When all the study groups were observed together, MT levels were positively correlated with clinical parameters. CONCLUSIONS: Results of present study suggest that smoking and CP can induce the synthesis of MT owing to increased oxidative stress and heavy metals intoxication. Further longitudinal studies with large sample size and an interventional arm are needed to substantiate the role of MT as a potential biomarker in periodontitis.


Assuntos
Periodontite Crônica , Metalotioneína , Estudos Transversais , Líquido do Sulco Gengival , Humanos , não Fumantes , Saliva , Fumantes
16.
Europace ; 23(2): 205-215, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33205201

RESUMO

AIMS: Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury. METHODS AND RESULTS: A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively). CONCLUSION: Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Esôfago/cirurgia , Humanos , Estudos Prospectivos , Temperatura , Resultado do Tratamento
17.
Heart Rhythm ; 18(2): 303-312, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33045430

RESUMO

The absence of strategies to consistently and effectively address nonparoxysmal atrial fibrillation by nonpharmacological interventions has represented a long-standing treatment gap. A combined epicardial/endocardial ablation strategy, the hybrid Convergent procedure, was developed in response to this clinical need. A subxiphoid incision is used to access the pericardial space facilitating an epicardial ablation directed at isolation of the posterior wall of the left atrium. This is followed by an endocardial ablation to complete isolation of the pulmonary veins and for additional ablation as needed. Experience gained with the hybrid Convergent procedure during the last decade has led to the development and adoption of strategies to optimize the technique and mitigate risks. Additionally, a surgical and electrophysiology "team" approach including comprehensive training is believed critical to successfully develop the hybrid Convergent program. A recently completed randomized clinical trial indicated that this ablation strategy is superior to an endocardial-only approach for patients with persistent atrial fibrillation. In this review, we propose and describe best practice guidelines for hybrid Convergent ablation on the basis of a combination of published data, author consensus, and expert opinion. A summary of clinical outcomes, emerging evidence, and future perspectives is also given.


Assuntos
Fibrilação Atrial/cirurgia , Endocárdio/cirurgia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Pericárdio/cirurgia , Guias de Prática Clínica como Assunto , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/métodos , Humanos , Recidiva
18.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-418806

RESUMO

Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile. ImportanceIn the current ongoing COVID-19 pandemic, neutralizing antibodies have been shown to be a critical feature of recovered patients. HIV-1 bnAbs recognize extensively diverse cross-reactive epitopes and tolerate diversity within their core epitope. Given the unique nature of HIV-1 bnAbs and their ability to recognize and/or accommodate viral glycans, we reasoned that the glycan shield of SARS-CoV-2 spike protein can be targeted by HIV-1 specific bnAbs. Herein, we showed that HIV-1 specific antibodies cross-react and neutralize SARS-CoV-2. Understanding cross-reactive neutralization epitopes of antibodies generated in divergent viral infections will provide key evidence for engineering so called super-antibodies (antibodies that can potently neutralize diverse pathogens with similar antigenic features). Such cross-reactive antibodies can provide a blueprint upon which synthetic variants can be generated in the face of future pandemics.

19.
Vet Anim Sci ; 9: 100112, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32734113

RESUMO

Three adult Corriedale cryptorchid sheep were subjected to laparoscope-assisted orchiectomy of the retained testicles. One (n = 2) or both (n = 1) the testicles were missing in their scrotal sac and inguinal regions. Ultrasonography was used to locate the retained testicles and their distance from the abdominal surface. The animals were restrained in dorsal recumbency and Trendlenburg posture under lumbosacral epidural anaesthesia using 2% lignocaine hydrochloride. Two laparoscopic ports were created in the caudal abdomen adjacent to the retained testicles. They were identified by their ovoid shape, white glistening surface (Tunica albuginea) and typical vasculature. Laparoscope-assisted exteriorization of the testicles after enlarging the ports, ligation of their blood supply and resection of the spermatic cord was performed successfully. The scrotal testes in two rams were then subjected to routine Burdizzoo castration. The laparoscopic port sites healed without complications and all the animals continued to do well subsequently. From this case report, it is concluded that in sheep the laparoscopy; a minimally invasive procedure can confirm abdominal retention of testicle/s and may also be used for their retrieval in a single sitting. Although total laparoscopic procedure is expected to reduce the incision size further but requires advanced laparoscopic instruments and expertise.

20.
Sci Rep ; 9(1): 18346, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797967

RESUMO

Recently, the field of Metal-Insulator-Transition (MIT) materials has emerged as an unconventional solution for novel energy efficient electronic functions, such as steep slope subthermionic switches, neuromorphic hardware, reconfigurable radiofrequency functions, new types of sensors, terahertz and optoelectronic devices. Employing radiofrequency (RF) electronic circuits with a MIT material like vanadium Dioxide, VO2, requires appropriate characterization tools and fabrication processes. In this work, we develop and use 3D Smith charts for devices and circuits having complex frequency dependences, like the ones resulting using MIT materials. The novel foundation of a 3D Smith chart involves here the geometrical fundamental notions of oriented curvature and variable homothety in order to clarify first theoretical inconsistencies in Foster and Non Foster circuits, where the driving point impedances exhibit mixed clockwise and counter-clockwise frequency dependent (oriented) paths on the Smith chart as frequency increases. We show here the unique visualization capability of a 3D Smith chart, which allows to quantify orientation over variable frequency. The new 3D Smith chart is applied as a joint complex-scalar 3D multi-parameter modelling and characterization environment for reconfigurable RF design exploiting Metal-Insulator-Transition (MIT) materials. We report fabricated inductors with record quality factors using VO2 phase transition to program multiple tuning states, operating in the range 4 GHz to 10 GHz.

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