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1.
J Pharm Bioallied Sci ; 16(Suppl 1): S877-S879, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595486

RESUMO

This study is the first study to incorporate a novel approach to single-implant-retained mandibular overdenture with a bar attachment on a single implant in the symphysis region. The use of a single-implant-retained bar overdenture significantly improved patients' chewing efficiency, indicating enhanced overdenture retention and stability. Materials and Methods: Ten maxillary and mandibular completely edentulous patients were enrolled in the study. A complete denture was fabricated for them. On completion, bite force, retention force, and bone change were recorded. Bite force was recorded with the strain gauge, retention force with the force measurement gauge, and bone changes with radiographs. Conclusion: Single-implant-supported bar mandibular overdenture (SISBOD) can be a suitable standard economic option for edentulous mandible and can greatly improve the quality of life of patients.

2.
J Pharm Bioallied Sci ; 16(Suppl 1): S838-S840, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595525

RESUMO

Background: Despite a huge number of advancements in the medical field, periodontitis still remains one of the most prevalent oral diseases worldwide. Aim: Thus, the primary aim of our study was to evaluate the prevalence of periodontal diseases in patients reporting to the tertiary healthcare setup in Ranchi. Materials and Methods: Based on inclusion criteria, subjects aged 18-60 years were selected and a per forma was filled by the observer. The prevalence of periodontal disease was measured using the community periodontal index, simplified oral hygiene index, and stage of periodontitis. Results: Descriptive variables were assessed using frequency, percentage, mean, and standard deviations, while the categorical analysis was performed using the Chi-square tests. Conclusion: General awareness about periodontal health and regular dental visits should be given utmost importance among the rural populations of every developing country.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38625464

RESUMO

Comprehensive and proper management of fecal sludge (FS) is an ongoing concern in many nations. Decentralized fecal sludge treatment plants (FSTPs) are effective in this regard; however, many have experienced strong public opposition based partly on suspicion of malodor. Fecal sludge and freshly generated fecal matter (FM) samples from various FSTPs were collected, characterized, and investigated for biomethane potential. The homogenized samples were anaerobically digested for 28 days. Digestion successfully reduced total suspended solids, biochemical oxygen demand, and threshold odor number values of 97,350-97,420 mg/l, 43,230-43,260 mg/l, and 130-150 for FM, to 49,500-49,650 mg/l, 23,760-23,850 mg/l, and 3338, respectively, for FS samples. The comprehensive gas yield from Bhongir, Boduppal, and Shadnagar FS samples was 40, 55, and 31 ml, respectively. In contrast, cumulative gas generation from the FM was 26,361 ml. Digestion of FS samples also reduced concentrations of volatile solids and coliforms by 66-72% and 99%, respectively. Characterization of gas samples revealed methane and carbon dioxide concentrations as 56% and 22% for FM, and 0.4% and 61% for FS samples, respectively. Hydrogen sulfide and ammonia gas were absent in FS samples, dispelling common societal misconceptions of FSTPs being associated with malodor.

4.
Mov Disord ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38586905

RESUMO

BACKGROUND: Midbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), observed in PSP-Richardson's syndrome (PSP-RS) and to a lesser extent PSP-parkinsonism (PSP-P). OBJECTIVE: Our aim was to critically evaluate the utility of manual magnetic resonance imaging measurements of the midbrain tectal plate as a diagnostic biomarker in PSP. METHODS: Length of the tectal plate and width of the superior and inferior colliculi were measured in 40 PSP (20 PSP-RS and 20 PSP-P) patients and compared with 20 Parkinson's disease and 20 healthy control subjects. RESULTS: Tectal plate length was reduced in both PSP groups compared with Parkinson's disease and control subjects and was most abnormal in PSP-RS followed by PSP-P. Reduced tectal plate length was associated with worse PSP Rating Scale scores. CONCLUSIONS: Simple manual measurements of tectal plate length show utility as a diagnostic biomarker in PSP, particularly for PSP-RS. © 2024 International Parkinson and Movement Disorder Society.

5.
Semin Arthritis Rheum ; 66: 152444, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604118

RESUMO

OBJECTIVE: Avascular necrosis (AVN) is a devastating complication often necessitating arthroplasty, particularly common in systemic lupus erythematosus (SLE). Limited research exists on arthroplasty trends since new steroid-sparing agents. We analyzed trends and characteristics associated with AVN and AVN-related arthroplasties among SLE and RA hospitalizations using two decades of data from the U.S. National Inpatient Sample (NIS). METHODS: This cross-sectional study used NIS (2000-2019) to identify hospitalized adults with SLE and RA, with or without AVN, using ICD codes. AVN was further grouped by arthroplasty status. Primary outcomes were AVN and AVN-related arthroplasty rates and time trends in SLE and RA. Baseline sociodemographics and comorbidities were compared. Analyses used STATA and Joinpoint regression to calculate annual percent change (APC). RESULTS: Overall, 42,728 (1.3 %) SLE and 43,600 (0.5 %) RA hospitalizations had concomitant AVN (SLE-AVN and RA-AVN). Of these, 16,724 (39 %) and 25,210 (58 %) underwent arthroplasties, respectively. RA-AVN increased (APC: 0.98*), with a decrease in arthroplasties (APC: -0.82*). In contrast, SLE-AVN initially increased with a breakpoint in 2011 (APC 2000-2011: 1.94* APC 2011-2019 -2.03), with declining arthroplasties (APC -2.03*). AVN hospitalizations consisted of individuals who were younger and of Black race; while arthroplasties were less likely in individuals of Black race or Medicaid coverage. CONCLUSION: We report a breakpoint in rising SLE-AVN after 2011, which may relate to newer steroid-sparing therapies (i.e., belimumab). AVN-associated arthroplasties decreased in SLE and RA. Fewer AVN-associated arthroplasties were noted for Black patients and those with Medicaid, indicating potential disparities. Further research should examine treatment differences impacting AVN and arthroplasty rates.

6.
Alzheimers Dement ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528318

RESUMO

INTRODUCTION: Glial fibrillary acidic protein (GFAP) in plasma is a proxy for astrocytic activity and is elevated in amyloid-ß (Aß)-positive individuals, making GFAP a potential blood-based biomarker for Alzheimer's disease (AD). METHODS: We assessed plasma GFAP in 72 Aß-positive participants diagnosed with the visual or language variant of AD who underwent Aß- and tau-PET. Fifty-nine participants had follow-up imaging. Linear regression was applied on GFAP and imaging quantities. RESULTS: GFAP did not correlate with Aß- or tau-PET cross-sectionally. There was a limited positive correlation between GFAP and rates of tau accumulation, particularly in the language variant of AD, although associations were weaker after removing one outlier patient with the highest GFAP level. DISCUSSION: Among Aß-positive AD participants with atypical presentations, plasma GFAP did not correlate with levels of AD pathology on PET, suggesting that the associations between GFAP and AD pathology might plateau during the advanced phase of the disease.

7.
J Neurol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551740

RESUMO

Overlap between language and visual variants of atypical Alzheimer's disease (AD) has been reported. However, the extent, frequency of overlap, and its neuroanatomical underpinnings remain unclear. Eighty-two biomarker-confirmed AD patients who presented with either predominant language (n = 34) or visuospatial/perceptual (n = 48) deficits underwent detailed clinical examinations, MRI, and [18F]flortaucipir-PET. Subgroups were defined based on language/visual testing and patterns of volume loss and tau uptake were assessed. 28% of the language group had visual dysfunction (marked in 8%), and 47% of the visual group had language impairment (marked in 26%). Progressive involvement of the parieto-occipital and frontal lobes was noted with greater visual impairment in the language group, and greater left parieto-temporal and frontal involvement with worsening language impairment in the visual group. Only 25% of our cohort showed a pure language or visual presentation, highlighting the high frequency of syndromic overlap in atypical AD and the diagnostic challenge of categorical phenotyping.

8.
Autops Case Rep ; 14: e2024478, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487035

RESUMO

Ovarian steroid cell tumors are rare, representing less than 0.1% of all ovarian neoplasms. Among the myriad causes of hirsutism, ovarian tumors account for 1% of the reported cases. We present the case of a 49-year-old parous postmenopausal woman who sought medical attention for hirsutism for 2 years. This case illustrates the unusual and interesting connection between rare ovarian pathology and the clinical manifestation of hirsutism in a postmenopausal patient. Her ultrasonography and MRI showed a right adnexal mass of solid-cystic consistency with thin septations. Her laboratory workup revealed high levels of total testosterone of 256 ng/ml (8.4-48.1ng/ml) and free testosterone of 7.36 pg/ml (0.2-4.1 pg/ml), while DHEAS - 234 µg/dl (35.4-256 µg/dl) and CA125 - 15.8U/L (0.0-35 U/L) were in the normal range. She underwent exploratory laparotomy with a total abdominal hysterectomy and oophorectomy. Histopathological examination and immunohistochemistry conclusively established the presence of a steroid cell tumor, specifically classified as "Not Otherwise Specified"(NOS), in the right ovary.

9.
Brain Commun ; 6(2): fcae005, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444909

RESUMO

Disruption of the default mode network is a hallmark of Alzheimer's disease, which has not been extensively examined in atypical phenotypes. We investigated cross-sectional and 1-year longitudinal changes in default mode network sub-systems in the visual and language variants of Alzheimer's disease, in relation to age and tau. Sixty-one amyloid-positive Alzheimer's disease participants diagnosed with posterior cortical atrophy (n = 33) or logopenic progressive aphasia (n = 28) underwent structural MRI, resting-state functional MRI and [18F]flortaucipir PET. One-hundred and twenty-two amyloid-negative cognitively unimpaired individuals and 60 amyloid-positive individuals diagnosed with amnestic Alzheimer's disease were included as controls and as a comparison group, respectively, and had structural and resting-state functional MRI. Forty-one atypical Alzheimer's disease participants, 26 amnestic Alzheimer's disease participants and 40 cognitively unimpaired individuals had one follow-up functional MRI ∼1-2 years after the baseline scan. Default mode network connectivity was calculated using the dual regression method for posterior, ventral, anterior ventral and anterior dorsal sub-systems derived from independent component analysis. A global measure of default mode network connectivity, the network failure quotient, was also calculated. Linear mixed-effects models and voxel-based analyses were computed for each connectivity measure. Both atypical and amnestic Alzheimer's disease participants had lower cross-sectional posterior and ventral and higher anterior dorsal connectivity and network failure quotient relative to cognitively unimpaired individuals. Age had opposite effects on connectivity in Alzheimer's disease participants and cognitively unimpaired individuals. While connectivity declined with age in cognitively unimpaired individuals, younger Alzheimer's disease participants had lower connectivity than the older ones, particularly in the ventral default mode network. Greater baseline tau-PET uptake was associated with lower ventral and anterior ventral default mode network connectivity in atypical Alzheimer's disease. Connectivity in the ventral default mode network declined over time in atypical Alzheimer's disease, particularly in older participants, with lower tau burden. Voxel-based analyses validated the findings of higher anterior dorsal default mode network connectivity, lower posterior and ventral default mode network connectivity and decline in ventral default mode network connectivity over time in atypical Alzheimer's disease. Visuospatial symptoms were associated with default mode network connectivity disruption. In summary, default mode connectivity disruption was similar between atypical and amnestic Alzheimer's disease variants, and discriminated Alzheimer's disease from cognitively unimpaired individuals, with decreased posterior and increased anterior connectivity and with disruption more pronounced in younger participants. The ventral default mode network declined over time in atypical Alzheimer's disease, suggesting a shift in default mode network connectivity likely related to tau pathology.

10.
Neuroimage ; 290: 120564, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38442778

RESUMO

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Imagem de Tensor de Difusão , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Atrofia , Doença de Alzheimer/metabolismo
11.
BMJ Glob Health ; 9(3)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553049

RESUMO

INTRODUCTION: Progress related to sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH) has stalled. COVID-19, conflict and climate change threaten to reverse decades of progress and to ensure the health and well-being of vulnerable populations in humanitarian and fragile settings (HFS) going forward, there is a need for tailored guidance for women, children and adolescents (WCA). This review seeks to map and appraise current resources on SRMNCAH in HFS. METHODS: In line with the updated Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews framework, a manual literature review was conducted of global and regional guidance published between January 2008 and May 2023 from members of the Global Health Cluster, the Global Nutrition Cluster and the Inter-Agency Working Group on Reproductive Health in Crises. A content analysis was conducted. Scores were then calculated according to the Appraisal of Guidelines for Research and Evaluation II scoring tool and subsequently categorised as high quality or low quality. RESULTS: A total of 730 documents were identified. Of these, 141 met the selection criteria and were analysed. Available guidance for delivering SRMNCH services exists, which can inform policy and programming for the general population and WCA. Important gaps related to beneficiaries, health services and health system strengthening strategies were identified. CONCLUSION: The review revealed there is evidence-based guidance available to support interventions targeting WCA in HFS, including: pregnant and lactating women, women of reproductive age, adolescents, newborns, small vulnerable newborns, stillbirths, refugees and internally displaced persons and WCA with disabilities. However, gaps related to beneficiaries, health services and health system strengthening strategies must be addressed in updated guidance that is created, disseminated and monitored in a standardised way that is mindful of the need to respond rapidly in HFS.


Assuntos
Saúde do Adolescente , Lactação , Gravidez , Criança , Adolescente , Humanos , Recém-Nascido , Feminino , Serviços de Saúde , Comportamento Sexual , Saúde Reprodutiva
12.
Arch Oral Biol ; 162: 105944, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492547

RESUMO

OBJECTIVE: Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation. MATERIAL AND METHODS: Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis. RESULTS: Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001). CONCLUSION: The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis.


Assuntos
Fibrose Oral Submucosa , Humanos , Fibrose Oral Submucosa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Transformação Celular Neoplásica , Fibrose , Hipóxia
13.
Acta Neurochir (Wien) ; 166(1): 122, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446271

RESUMO

BACKGROUND: One of the major challenges in operating on the spine lies in taking an anterior approach for the high cervical spine. In patients with a short neck, Klippel-Fiel syndrome or when the C3 vertebra is high in relation to the hyoid bone, it will be difficult to access the C3 body. The transoral route is a highly contaminated zone, and therefore, no instrumentation or grafts can be placed through it. METHOD: The anterior retropharyngeal approach (ARPA) for the high cervical spine. CONCLUSION: The anterior retropharyngeal approach is an excellent approach for the high cervical spine where instrumentation is needed. This route provides wide exposure of the C1-C3 region, avoiding the contaminated of the oral cavity.


Assuntos
Vértebras Cervicais , Fraturas Ósseas , Humanos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Pescoço , Boca , Procedimentos Neurocirúrgicos
14.
J Mol Cell Cardiol ; 188: 61-64, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301803

RESUMO

The mammalian heart has a limited regenerative capacity. Previous work suggested the heart can regenerate during development and immediately after birth by inducing cardiomyocyte (CM) proliferation; however, this capacity is lost seven days after birth. modRNA gene delivery, the same technology used successfully in the two mRNA vaccines against SARS-CoV-2, can prompt cardiac regeneration, cardiovascular regeneration and cardiac protection. We recently established a novel CM-specific modRNA translational system (SMRTs) that allows modRNA translation only in CMs. We demonstrated that this system delivers potent intracellular genes (e.g., cell cyclepromoting Pkm2), which are beneficial when expressed in one cell type (i.e., CMs) but not others (non-CMs). Here, we identify Lin28a as an important regulator of the CM cell cycle. We show that Lin28a is expressed in CMs during development and immediately after birth, but not during adulthood. We describe that specific delivery of Lin28a into CM, using CM SMRTs, enables CM cell division and proliferation. Further, we determine that this proliferation leads to cardiac repair and better outcome post MI. Moreover, we identify the molecular pathway of Lin28a in CMs. We also demonstrate that Lin28a suppress Let-7 which is vital for CM proliferation, partially due to its suppressive role on cMYC, HMGA2 and K-RAS.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Miócitos Cardíacos , Animais , Humanos , Adulto , Vacinas contra COVID-19 , Divisão Celular , Biossíntese de Proteínas , Mamíferos
15.
Vaccines (Basel) ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38400137

RESUMO

Somalia is one of 20 countries in the world with the highest numbers of zero-dose children. This study aims to identify who and where zero-dose and under-vaccinated children are and what the existing vaccine delivery strategies to reach zero-dose children in Somalia are. This qualitative study was conducted in three geographically diverse regions of Somalia (rural/remote, nomadic/pastoralists, IDPs, and urban poor population), with government officials and NGO staff (n = 17), and with vaccinators and community members (n = 52). The data were analyzed using the GAVI Vaccine Alliance IRMMA framework. Nomadic populations, internally displaced persons, and populations living in remote and Al-shabaab-controlled areas are three vulnerable and neglected populations with a high proportion of zero-dose children. Despite the contextual heterogeneity of these population groups, the lack of targeted, population-specific strategies and meaningful engagement of local communities in the planning and implementation of immunization services is problematic in effectively reaching zero-dose children. This is, to our knowledge, the first study that examines vaccination strategies for zero-dose and under-vaccinated populations in the fragile context of Somalia. Evidence on populations at risk of vaccine-preventable diseases and barriers to vital vaccination services remain critical and urgent, especially in a country like Somalia with complex health system challenges.

16.
ACS Chem Neurosci ; 15(4): 745-771, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38327209

RESUMO

An efficient and promising method of treating complex neurodegenerative diseases like Alzheimer's disease (AD) is the multitarget-directed approach. Here in this work, a series of quinazoline derivatives (AV-1 to AV-21) were rationally designed, synthesized, and biologically evaluated as multitargeted directed ligands against human cholinesterase (hChE) and human ß-secretase (hBACE-1) that exhibit moderate to good inhibitory effects. Compounds AV-1, AV-2, and AV-3 from the series demonstrated balanced and significant inhibition against these targets. These compounds also displayed excellent blood-brain barrier permeability via the PAMPA-BBB assay. Compound AV-2 significantly displaced propidium iodide (PI) from the acetylcholinesterase-peripheral anionic site (AChE-PAS) and was found to be non-neurotoxic at the maximum tested concentration (80 µM) against differentiated SH-SY5Y cell lines. Compound AV-2 also prevented AChE- and self-induced Aß aggregation in the thioflavin T assay. Additionally, compound AV-2 significantly ameliorated scopolamine and Aß-induced cognitive impairments in the in vivo behavioral Y-maze and Morris water maze studies, respectively. The ex vivo and biochemical analysis further revealed good hippocampal AChE inhibition and the antioxidant potential of the compound AV-2. Western blot and immunohistochemical (IHC) analysis of hippocampal brain revealed reduced Aß, BACE-1, APP/Aß, and Tau molecular protein expressions levels. The pharmacokinetic analysis of compound AV-2 demonstrated significant oral absorption with good bioavailability. The in silico molecular modeling studies of lead compound AV-2 moreover demonstrated a reasonable binding profile with AChE and BACE-1 enzymes and stable ligand-protein complexes throughout the 100 ns run. Compound AV-2 can be regarded as the lead candidate and could be explored more for AD therapy.


Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Doença de Alzheimer/metabolismo , Acetilcolinesterase/metabolismo , Relação Estrutura-Atividade , Inibidores da Colinesterase/química , Desenho de Fármacos , Peptídeos beta-Amiloides/metabolismo , Simulação de Acoplamento Molecular
18.
J Mol Graph Model ; 128: 108702, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38219505

RESUMO

In recent years, Onco-immunotherapies (OIMTs) have been shown to be a potential therapy option for cancer. Several immunotherapies have received regulatory approval, while many others are now undergoing clinical testing or are in the early stages of development. Despite this progress, a large number of challenges to the broad use of immunotherapies to treat cancer persists. To make immunotherapy more useful as a treatment while reducing its potentially harmful side effects, we need to know more about how to improve response rates to different types of immunotherapies. Nanocarriers (NCs) have the potential to harness immunotherapies efficiently, enhance the efficiency of these treatments, and reduce the severe adverse reactions that are associated with them. This article discusses the necessity to incorporate nanomedicines in OIMTs and the challenges we confront with current anti-OIMT approaches. In addition, it examines the most important considerations for building nanomedicines for OIMT, which may improve upon current immunotherapy methods. Finally, it highlights the applications and future scenarios of using nanotechnology.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Imunoterapia , Nanomedicina
20.
Mol Biol Rep ; 51(1): 178, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252231

RESUMO

BACKGROUND: Porcine Sapelovirus (PSV) infection has been confirmed in pigs worldwide, mostly asymptomatic, but in some cases, it can lead to significant issues in the gastrointestinal, respiratory, neurological, or reproductive systems. PSV is considered an emerging pathogen of porcine species. Recombinase polymerase amplification (RPA) is a simple and fast isothermal technique that uses three enzymes for amplification without the use of any sophisticated equipment. METHODS AND RESULTS: The reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed and optimized for field based detection of PSV. The assay was developed by targeting 5´UTR region of PSV genome and optimized for reaction time, temperature, primer and MgOAc concentration. The analytical sensitivity and specificity of assay was determined. The assay was evaluated on 85 porcine faecal samples collected from field. In addition to conventional format, this assay was also optimized for visual dye-based detection format and lateral flow strips based detection (in combination with probe). The developed assay works at constant temperature of 35 °C for 20 min with forward primer concentration 20pm, reverse primer concentration 10pm and MgOAc concentration of 14mM. This assay is highly sensitive and detects up to 28 copies of viral nucleic acid both in the conventional as well as in fluorescent dye based detection format. Using the newly developed assay 21 samples out of 85 samples were found positive, showing positivity rate of 24.7%. The positivity rate of RT-RPA assay corroborated with the gold standard RT-PCR test. CONCLUSIONS: This study presented the development of an RT-RPA isothermal assay for rapid and accurate detection of PSV. The assay is highly sensitive, specific, works at a low and constant temperature, does not require any high-end instrument and can be a potential diagnostics tool for pen-side testing of PSV in the field conditions. The newly developed RT-RPA assay could successfully detect PSV circulating in swine population of Haryana, India. This is a first report of this kind from the region.


Assuntos
Picornaviridae , Recombinases , Animais , Suínos , Recombinases/genética , Transcrição Reversa/genética , Regiões 5' não Traduzidas , Bioensaio
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