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1.
J Biol Chem ; 300(4): 107140, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447795

RESUMO

RNA modification, a posttranscriptional regulatory mechanism, significantly influences RNA biogenesis and function. The accurate identification of modification sites is paramount for investigating their biological implications. Methods for encoding RNA sequence into numerical data play a crucial role in developing robust models for predicting modification sites. However, existing techniques suffer from limitations, including inadequate information representation, challenges in effectively integrating positional and sequential information, and the generation of irrelevant or redundant features when combining multiple approaches. These deficiencies hinder the effectiveness of machine learning models in addressing the performance challenges associated with predicting RNA modification sites. Here, we introduce a novel RNA sequence feature representation method, named BiPSTP, which utilizes bidirectional trinucleotide position-specific propensities. We employ the parameter ξ to denote the interval between the current nucleotide and its adjacent forward or backward dinucleotide, enabling the extraction of positional and sequential information from RNA sequences. Leveraging the BiPSTP method, we have developed the prediction model mRNAPred using support vector machine classifier to identify multiple types of RNA modification sites. We evaluate the performance of our BiPSTP method and mRNAPred model across 12 distinct RNA modification types. Our experimental results demonstrate the superiority of the mRNAPred model compared to state-of-art models in the domain of RNA modification sites identification. Importantly, our BiPSTP method enhances the robustness and generalization performance of prediction models. Notably, it can be applied to feature extraction from DNA sequences to predict other biological modification sites.


Assuntos
Processamento Pós-Transcricional do RNA , RNA , Máquina de Vetores de Suporte , Biologia Computacional/métodos , RNA/química , RNA/genética , RNA/metabolismo , Análise de Sequência de RNA/métodos , Nucleotídeos/química , Nucleotídeos/metabolismo
2.
Am J Hum Genet ; 108(2): 324-336, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33508233

RESUMO

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320∗]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.


Assuntos
Azoospermia/genética , Mutação , Insuficiência Ovariana Primária/genética , Adulto , Azoospermia/fisiopatologia , Pareamento Cromossômico , Códon sem Sentido , Proteínas de Ligação a DNA/metabolismo , Feminino , Homozigoto , Humanos , Masculino , Meiose , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Linhagem , Insuficiência Ovariana Primária/fisiopatologia , Espermatócitos/metabolismo , Espermatócitos/fisiologia , Complexo Sinaptonêmico/genética , Complexo Sinaptonêmico/metabolismo , Sequenciamento Completo do Genoma
3.
Langmuir ; 40(19): 10070-10084, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38701115

RESUMO

Developing an improved synthesis method that controls the morphology and crystal phase remains a substantial challenge. Herein, we report phase and morphology-controlled hydrothermal synthesis of tungsten oxides by varying acid concentration and utilizing glutathione (GSH) as a structural directing agent, together with the exploration of their applications in supercapacitors, photoconductivity, and photocatalysis. Orthorhombic hydrated tungsten oxide (WO3·0.33H2O) with nonuniform block and plate-like morphology was obtained at 3 M hydrochloric acid (HCl). In contrast, nonhydrated monoclinic tungsten oxide (WO3) with smaller rectangular blocks was obtained at 6 M HCl. Further, the addition of GSH results in an increase in the surface area of the materials along with a narrowing of the band gap. Moreover, it plays a pivotal role in regulating the morphology through oriented attachments, Ostwald ripening, and the self-assembly of WO3 nuclei. GHTO and GTO polymorphs showed pseudocapacitive behavior with the highest specific capacitances of 450 and 300 F g-1 at 0.5 A g-1, maintaining 94 and 92% retention stability, respectively, over 1000 cycles at 2 A g-1. Also, the synthesized materials displayed favorable photoconductivity under light irradiation, implying potential utilization in photovoltaic applications. Moreover, these materials exhibited remarkable photocatalytic performance in the degradation of methylene blue (MB) dye, establishing themselves as highly effective photocatalysts. Therefore, nanostructured tungsten oxide showcases its versatility, rendering it an appealing candidate for energy storage, photovoltaic systems, and photocatalysis.

4.
Eur Radiol ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811388

RESUMO

OBJECTIVES: Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. MATERIALS AND METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. RESULTS: Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. CONCLUSION: There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. CLINICAL RELEVANCE STATEMENT: The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. KEY POINTS: RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.

5.
BMC Pediatr ; 24(1): 169, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459469

RESUMO

BACKGROUND: Waterpipe tobacco smoking has increased tremendously at a global level among all age groups, particularly young people. Previous studies have examined the impact of waterpipe tobacco pictorial health warnings on adults but scarce studies were done on adolescents. The aim of this study was to assess the association of textual versus pictorial warnings on tumbac boxes and the motivation to quit waterpipe smoking among adolescents located in two Eastern Mediterranean countries Lebanon and Iraq. METHODS: A cross-sectional study was conducted between May and November 2022, involving 294 adolescents waterpipe smokers from Lebanon and Iraq. The questionnaire included the Lebanese Waterpipe Dependence Smoking-11, the Depression, Anxiety and Stress Scale, the Waterpipe Harm Perception Scale, Waterpipe Knowledge Scale, Waterpipe Attitude Scale, the Fagerstrom Test for Nicotine Dependence, and the Motivation to Stop Scale. RESULTS: When adjusting the results over confounding variables, the results showed that compared to finding the warnings to stop smoking not efficacious at all, adolescents who find the warnings moderately (aOR = 2.83) and very (aOR = 6.64) efficacious had higher motivation to quit. Compared to finding the warnings not increasing their curiosity for information about how to stop waterpipe smoking at all, participants who confessed that warnings increased their curiosity a little (aOR = 2.59), moderately (aOR = 3.34) and very (aOR = 3.58) had higher motivation to quit. Compared to not considering changing the tumbac brand if the company uses pictorial warnings, adolescents who would consider changing the tumbac brand (aOR = 2.15) had higher motivation to quit. CONCLUSION: Pictorial and textual warnings on waterpipe packs were associated with higher motivation to stop waterpipe smoking. Public health education programs for this purpose seem warranted.


Assuntos
Abandono do Hábito de Fumar , Produtos do Tabaco , Tabaco para Cachimbos de Água , Fumar Cachimbo de Água , Adulto , Humanos , Adolescente , Motivação , Abandono do Hábito de Fumar/métodos , Iraque , Estudos Transversais , Rotulagem de Produtos/métodos , Prevenção do Hábito de Fumar
6.
J Cardiovasc Electrophysiol ; 34(12): 2514-2526, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37787013

RESUMO

BACKGROUND: Obesity is associated with an increased risk of developing recurrent atrial fibrillation (AF) after catheter ablation (CA). However, the current data on weight loss interventions show inconsistent results in preventing the recurrence of AF after CA. METHODS: We conducted a systematic search in MEDLINE and EMBASE to identify studies that reported the outcome of recurrence of AF after CA in obese patients undergoing weight interventions. The subgroup analysis included: (1) Weight loss versus no weight loss, (2) >10% weight loss versus <10% weight loss, (3) <10% weight loss versus no weight loss, (4) Follow-up <12 months, and (5) Follow-up >12 months after CA. Mantel-Haenszel risk ratios with a 95% confidence interval (CI) were calculated using a random effects model and for heterogeneity, I2 statistics were reported. RESULTS: A total of 10 studies (one randomized controlled trial and nine observational studies) comprising 1851 patients were included. The recurrence of AF was numerically reduced in the weight loss group (34.5%) versus no weight loss group (58.2%), but no statistically significant difference was observed (risk ratio [RR] = 0.76; 95% CI: 0.49-1.18, p = .22). However, there was a statistically significant reduction in recurrence of AF with weight loss versus no weight loss at follow-up >12 months after CA (RR = 0.47; 95% CI: 0.32-0.68, p < .0001). At follow-up >12 months after CA, both >10% weight loss versus <10% weight loss (RR = 0.49; 95% CI: 0.31-0.80, p = .004) and <10% weight loss versus no weight loss (RR = 0.39; 95% CI: 0.31-0.49, p < .00001) were associated with a statistically significant reduction in recurrent AF. CONCLUSION: In patients with AF undergoing CA, weight loss is associated with reducing recurrent AF at > 12 months after ablation and these benefits are consistently seen with both >10% and <10% weight loss. The benefits of weight loss in preventing recurrent AF after CA should be examined in larger studies with extended follow-up duration.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Resultado do Tratamento , Recidiva , Obesidade/complicações , Obesidade/diagnóstico , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Invest New Drugs ; 41(4): 587-595, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37402008

RESUMO

Pancreatic cancer (PC) is one of the deadliest malignancies; p53 is mutated in approximately 75% of PC patients. Hence, the protein derived from mutant/wild-type TP53 may represent a therapeutic target. Interestingly, a p53 reactivator (PRIMA-1MET) showed promise in clinical trials of haematological malignancies; therefore, it warrants an in vitro evaluation in PC cell lines. To evaluate the antiproliferative effects of PRIMA-1MET, either alone or combined with the common chemotherapy 5-fluorouracil (5-FU), against mutated and wild-type p53 PC cell lines. This study involved p53-mutant (AsPC-1) and p53-wild type (Capan-2) PC cell lines. The cytotoxicity of PRIMA-1MET alone or in combination with 5-FU was evaluated by MTT assay. Synergism was assessed by calculating the combination index (CI) via CalcuSyn software. Fluorescence microscopy was used to analyse apoptosis following acridine orange/ethidium bromide (AO/EB) staining. Morphological changes were investigated with an inverted microscope. Quantitative reverse transcription PCR (RT‒qPCR) was used to measure gene expression. Both PC cell lines were sensitive to PRIMA-1MET monotherapy. Furthermore, PRIMA-1MET and 5-FU had a synergistic effect (CI < 1), reflected by significant enhancement of apoptosis and morphological changes in the combination vs. monotherapy treatments. Moreover, the RT‒qPCR results indicated increased expression of the NOXA and TP73 genes in combination-treated cells. Our data suggested that PRIMA-1MET, whether alone or combined with 5-FU, has an antiproliferative effect on PC cell lines regardless of p53 mutational status. The synergism of the combination was associated with significant apoptosis induction through p53-dependent and p53-independent pathways. Preclinical confirmation of these data in in vivo models is highly recommended.


Assuntos
Neoplasias Pancreáticas , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Fluoruracila/farmacologia , Linhagem Celular Tumoral , Apoptose , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas
8.
Neurosurg Rev ; 46(1): 267, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37815634

RESUMO

Brain metastases are a relatively common occurrence in patients with primary malignancies, with an incidence ranging from 9 to 17%. Their prevalence has increased due to treatment advancements that have led to improved survival in cancer patients. Frailty has demonstrated the ability to outperform greater patient age in surgical decision-making by predicting postoperative adverse events that include mortality, extended length of hospital stay, non-routine discharge disposition, and postoperative complications. Although predictive models based on frailty have been increasingly utilized in literature, their generalizability remains questionable due to inadequacies in model development and validation. Our systematic review describes development and validation cohorts of frailty indices used in patients undergoing surgical resection of brain metastases and serves as a guide to their incorporation in the outpatient clinical setting. A systematic review of literature was performed using PubMed and Google Scholar. Articles that reported outcomes using frailty indices in patients undergoing surgical resection of brain metastases were included. The Newcastle Ottawa Scale (NOS) was used to assess for risk of bias across individual studies. Studies with NOS > 5 were considered high quality. We identified 238 articles through our search strategy. After a title and abstract screen, followed by a full text review, 9 articles met criteria for inclusion. The 5- and 11-factor modified frailty indices were most frequently utilized (n = 4). Five studies utilized single-hospital databases, and four utilized nationwide databases. Six studies were considered high-quality based on the NOS. Although frailty indices have demonstrated the ability to predict outcomes in patients undergoing surgical resection of brain metastases, further validation of these indices is necessary prior to their incorporation in clinical practice.


Assuntos
Neoplasias Encefálicas , Fragilidade , Humanos , Neoplasias Encefálicas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Bases de Dados Factuais , Tempo de Internação
9.
Curr Cardiol Rep ; 25(7): 761-779, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37222916

RESUMO

PURPOSE OF REVIEW: This study aims to evaluate the sensitivity and specificity of wearable devices for AF detection in older adults, as well as examine the incidence of AF across various studies, contextual factors impacting AF detection, and safety and adverse events associated with wearable use. RECENT FINDINGS: A systematic search of three databases identified 30 studies on wearables for AF detection in older adults, encompassing 111,798 participants. Both PPG-based and single-lead electrocardiography-based wearables show scalable potential for screening and managing AF. The results of this systematic review demonstrate that wearable devices, such as smartwatches, can effectively identify arrhythmias like AF in older adults, with scalable potential in PPG-based and single-lead electrocardiography-based wearables. As wearable technologies continue to gain prominence in healthcare, it is crucial to understand their challenges and incorporate them as preventative and monitoring tools for AF detection in elderly populations to improve patient care and prevention techniques.


Assuntos
Fibrilação Atrial , Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Sensibilidade e Especificidade , Eletrocardiografia , Incidência
10.
Environ Geochem Health ; 45(12): 8929-8942, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35948700

RESUMO

The risk assessment of trace elements has received substantial attention for the achievement of UN Sustainable Developmental Goals (UN-SDGs). The present study aimed to evaluate health and ecological risks associated with trace element accumulation in Brassica oleracea under wastewater irrigations from three different areas. This study, for the first time, compared the pros and cons of mixed water crop irrigation (wastewater with fresh/groundwater). A pot experiment was conducted to evaluate the buildup of eight trace elements (As, Cu, Cd, Mn, Fe, Pb, Ni and Zn) in soil and B. oleracea plants irrigated with wastewater alone and mixed with fresh/groundwater. Specific ecological [degree of contamination (Cd), potential ecological risk index (PERI), pollution load index (PLI), geo-accumulation index (Igeo)], phytoaccumulation [bioconcentration factor (BCF) and transfer factor (TF)] and health risk models [chronic daily intake (CDI), hazard quotient (HQ), cancer risk (CR)] were applied to assess the overall contamination of trace elements in the soil-plant-human system. Moreover, these indices were compared with the literature data. The concentration of Cd, Fe and Mn exceeded the threshold limits of 10, 500 and 200 mg kg-1, respectively, for agricultural soil. Overall, all the irrigation waters caused significant pollution load in soil indicating high ecological risk (Cd > 24, PERI > 380, Igeo > 5, PLI > 2). Not all the mixing treatments caused a reduction in trace element buildup in soil. The mixing of wastewater-1 with either groundwater or freshwater increased trace element levels in the soil as well as risk indices compared to wastewater alone. The BCF and TF values were > 1, respectively, for 66% and 7% treatments. Trace element concentration in plants and associated health risk were minimized in mixed wastewater treatments. There were 22% and 32% reduction in HQ and CR when wastewater was mixed with freshwater and 29% and 8% when mixed with groundwater. Despite total reduction, a great variation in % change in risk indices was observed with respect to the area of wastewater collection. Therefore, mixed water irrigation may be a good management strategy, but its recommendation depends on soil properties and composition of waters used for mixing. Moreover, it is recommended that the freshwater and wastewater of the particular area may be continuously monitored to avoid potential associated health hazards.


Assuntos
Brassica , Metais Pesados , Poluentes do Solo , Oligoelementos , Humanos , Águas Residuárias , Solo , Monitoramento Ambiental/métodos , Oligoelementos/análise , Cádmio , Metais Pesados/análise , Poluentes do Solo/análise , Medição de Risco , Água
11.
Mol Genet Genomics ; 297(3): 719-730, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35305148

RESUMO

Infertility is a multifactorial disorder that affects approximately 12% of couples of childbearing ages worldwide. Few studies have been conducted to understand the genetic causes of infertility in depth. The synaptonemal complex (SC), which is essential for the progression of meiosis, is a conserved tripartite structure that binds homologous chromosomes together and is thus required for fertility. This study investigated genetic causes of infertility in a Pakistani consanguineous family containing two patients suffering from non-obstructive azoospermia (NOA). We performed whole-exome sequencing, followed by Sanger sequencing, and identified a novel pathogenic variant (c.7G > A [p.D3N]) in the SC coding gene C14orf39, which was recessively co-segregated with NOA. In silico analysis revealed that charges on wild-type residues were lost, which may result in loss of interactions with other molecules and residues, and a reduction in protein stability occurred, which was caused by the p.D3N mutation. The novel variant generated the mutant protein C14ORF39D3N, and homozygous mutations in C14orf39 resulted in NOA. The transcriptome profile of C14ORF39 shows that it is specifically expressed in early brain development, which suggests that research in this area is required to study other functions of C14ORF39 in addition to its role in the germline. This research highlights the conserved role of C14orf39/SIX6OS1 in assembly of the SC and its indispensable role in facilitating genetic diagnosis in patients with infertility, which may enable the development of future treatments.


Assuntos
Azoospermia , Azoospermia/diagnóstico , Azoospermia/genética , Azoospermia/patologia , Homozigoto , Humanos , Masculino , Mutação , Paquistão , Sequenciamento do Exoma
12.
Geophys Res Lett ; 49(12): e2022GL099138, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35860424

RESUMO

Short-duration precipitation extremes (PE) increase at a rate of around 7%/K explained by the Clausius-Clapeyron relationship. Previous studies show uncertainty in the extreme precipitation-temperature relationship (scaling) due to various thermodynamic/dynamic factors. Here, we show that uncertainty may arise from the choice of data and methods. Using hourly precipitation (PPT) and daily dewpoint temperature (DPT) across 2,905 locations over the United States, we found higher scaling for quality-controlled data, all locations showing positive (median 6.2%/K) scaling, as compared to raw data showing positive (median 5.3%/K) scaling over 97.5% of locations. We found higher scaling for higher measurement precision of PPT (0.25 mm: median 7.8%/K; 2.54 mm: median 6.6%/K). The method that removes seasonality in PPT and DPT gives higher (with seasonality: median 6.2%/K; without seasonality: median 7.2%/K) scaling. Our results demonstrate the importance of quality-controlled, high-precision observations and robust methods in estimating accurate scaling for a better understanding of PE change with warming.

13.
Mol Biol Rep ; 49(7): 6261-6268, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35449315

RESUMO

BACKGROUND: Fascins belong to a family of actin-bundling proteins that are involved in a wide range of biological functions. FSCN3, a newly identified testis-specific actin-bundling protein, is specifically expressed in elongated spermatids. However, its in vivo function in mouse spermiogenesis remains unknown. METHODS AND RESULTS: We generated Fscn3 knockout mice through CRISPR/Cas9 gene-editing technology. Fscn3-/- mice displayed normal testis morphology and testis to bodyweight ratio, and sperm concentrations did not differ significantly between Fscn3+/+ and Fscn3-/- mice. Fertility assays consistently revealed that Fscn3-/- mice are completely fertile and their reproductive status does not differ from that of wild-type. Moreover, hematoxylin and eosin staining of the testis sections of Fscn3-/- mice detected various germ cells, ranging from spermatogonia to mature spermatozoa. Furthermore, the swimming velocity of the sperm of Fscn3-/- mice was comparable to that of their wild-type littermates. Both Fscn3+/+ and Fscn3-/-mice had normal sperm morphology, indicating that the disruption of Fscn3 does not affect sperm morphology. The analysis of meiotic prophase I progression demonstrated normal prophase-I phases (leptonema to diplonema) in both Fscn3+/+ and Fscn3-/- mice, suggesting that Fscn3 is not essential for meiosis I. CONCLUSION: Our study provides the first evidence that FSCN3 is a testis-specific actin-bundling protein that is not required for mouse spermatogenesis. Our results will help reproductive biologists focus their efforts on genes that are crucial for fertility and avoid research duplication.


Assuntos
Proteínas de Transporte/metabolismo , Meiose , Proteínas dos Microfilamentos/metabolismo , Testículo , Actinas/genética , Actinas/metabolismo , Animais , Fertilidade/genética , Masculino , Camundongos , Camundongos Knockout , Sêmen , Espermátides , Espermatogênese/genética , Espermatozoides/metabolismo , Testículo/metabolismo
14.
BMC Health Serv Res ; 22(1): 929, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854383

RESUMO

BACKGROUND: Previous qualitative studies exploring the experiences of community pharmacists (CP) in implementing weight management services (WMS) often lack a theoretical underpinning. This study applied the capability, opportunity, motivation, behaviour (COM-B) model to factors associated with WMS implementation among CPs to develop and recommend better intervention strategies. METHODS: A qualitative study design was used by conducting in-depth, semi-structured interviews with CPs. All the interviews were audio-recorded and duly transcribed. The thematic analysis approach was used to analyse the data, and the themes generated were mapped onto COM-B model components. RESULTS: The themes that emerged were (1) motivation of pharmacists and (2) knowledge and skills, which were identified as both barriers and facilitators, and (3) the barriers to implementation in aspects of social norms and resources. Factors were subsequently categorised into the subcomponents of the model: physical capability (e.g., training), psychological capability (e.g., lack of knowledge), physical opportunity (e.g., product range), social opportunity (e.g., stigma), automatic motivation (e.g., remuneration) and reflective motivation (e.g., CPs extended roles). CONCLUSIONS: In conclusion, programs or training For Cps should develop their psychological capability to change their behaviour by being more proactive in promoting and providing weight management services, with a vital educational component. This behavioural change will improve the promotion of this service and will help many customers who were unaware of this service. Learning opportunities will leave CPs to feel more empowered and overcome barriers to implementing and maintaining WMS in primary care. The study findings provided essential insights into the factors that affect this provided service in Malaysia. The results will help to encourage the embedding of nutrition counselling in academic curricula.


Assuntos
Motivação , Farmacêuticos , Humanos , Malásia , Farmacêuticos/psicologia , Pesquisa Qualitativa , Estigma Social
15.
Parasitol Res ; 121(2): 675-689, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34984543

RESUMO

Eimeria maxima (E. maxima) are an intracellular apicomplexan protozoan that causes intestinal coccidiosis in chickens. The purpose of this research was to develop a novel delivery approach for recombinant E. maxima (rEm) 14-3-3 antigen to elicit enhanced immunogenic protection using poly (D, L-lactide-co-glycolide) (PLGA) and chitosan (CS) nanoparticles (NPs) against E. maxima challenge. The morphologies of prepared antigen-loaded NPs (PLGA/CS-rEm14-3-3 NPs) were visualized by a scanning electron microscope. The rEm14-3-3 and PLGA/CS-rEm14-3-3 NPs-immunized chicken-induced changes of serum cytokines, IgY-antibody level, and T-lymphocyte subsets and protective efficacies against E. maxima challenge were evaluated. The results revealed that encapsulated rEm14-3-3 in PLGA and CS NPs presented spherical morphology with a smooth surface. The chickens immunized with only rEm14-3-3 and PLGA/CS-rEm14-3-3 NPs elicited a significant (p<0.05) higher level of IFN-γ cytokine, stimulated the proportions of CD4+/CD3+, CD8+/CD3+ T-cells, and provoked sera IgY-antibody immune response compared to control groups (PBS, pET-32a, PLGA, and CS). Whereas, PLGA-rEm14-3-3 NP-immunized chicken provoked a higher level of IFN- γ production and IgY-antibody response rather than CS-rEm14-3-3 and bare antigen, relatively. The animal experiment results ratified that PLGA-rEm14-3-3 NP-immunized chicken significantly alleviated the relative body weight gain (%), decreased lesion score, and enhanced oocyst decrease ratio compared to CS-rEm14-3-3 NPs and only rEm14-3-3. The anti-coccidial index of the chicken vaccinated with the PLGA-rEm14-3-3 NPs was (180.1) higher than that of the Cs-rEm14-3-3 NPs (167.4) and bare antigen (165.9). Collectively, our statistics approved that PLGA NPs might be an efficient antigen carrier system (Em14-3-3) to act as a nanosubunit vaccine that can improve protective efficacies in chicken against E. maxima challenge.


Assuntos
Quitosana , Coccidiose , Eimeria , Nanopartículas , Doenças das Aves Domésticas , Vacinas Protozoárias , Animais , Galinhas , Coccidiose/prevenção & controle , Coccidiose/veterinária , Doenças das Aves Domésticas/prevenção & controle
16.
BMC Med Inform Decis Mak ; 22(1): 90, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379228

RESUMO

BACKGROUND: The digital pathology images obtain the essential information about the patient's disease, and the automated nuclei segmentation results can help doctors make better decisions about diagnosing the disease. With the speedy advancement of convolutional neural networks in image processing, deep learning has been shown to play a significant role in the various analysis of medical images, such as nuclei segmentation, mitosis detection and segmentation etc. Recently, several U-net based methods have been developed to solve the automated nuclei segmentation problems. However, these methods fail to deal with the weak features representation from the initial layers and introduce the noise into the decoder path. In this paper, we propose a multiscale attention learning network (MSAL-Net), where the dense dilated convolutions block captures more comprehensive nuclei context information, and a newly modified decoder part is introduced, which integrates with efficient channel attention and boundary refinement modules to effectively learn spatial information for better prediction and further refine the nuclei cell of boundaries. RESULTS: Both qualitative and quantitative results are obtained on the publicly available MoNuseg dataset. Extensive experiment results verify that our proposed method significantly outperforms state-of-the-art methods as well as the vanilla Unet method in the segmentation task. Furthermore, we visually demonstrate the effect of our modified decoder part. CONCLUSION: The MSAL-Net shows superiority with a novel decoder to segment the touching and blurred background nuclei cells obtained from histopathology images with better performance for accurate decoding.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Atenção , Humanos , Processamento de Imagem Assistida por Computador/métodos
17.
Trop Anim Health Prod ; 54(6): 369, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323906

RESUMO

Castration is frequently used to reduce aggressive behavior and improve the meat quality of animals. Traditionally, surgical and mechanical castration are used to sterilize the animals, but these approaches are associated with a high level of pain, stress, long recovery periods, and post-operative infections. Immunocastration is a new animal-friendly, painless alternative castration technique that is used to prevent undesired sexual behavior, reduce aggressive behavior, prevent unwanted pregnancy, control wildlife populations and wandering species, enhance growth performance, improve meat quality, and treat various sex hormone-dependent disorders. The mechanism of immunocastration includes the immunological block of the hypothalamic-pituitary-gonadal axis (HPG axis) which inhibits gonadotropin secretions, causes atrophy of gonadal tissues, and inhibits gametogenesis, resulting in infertility in both female and male mammals. By the mid-1990s, various immunocastration vaccines have been tested in different animal models to achieve successful castration effects. Recently, genetic immunocastration especially DNA vaccine has gained increasing attention due to its safety, being animal-friendly, and being easy to use. This review aims to evaluate the potential of traditional castration methods, as well as the current status of immunocastration vaccines, their effects, and future prospective.


Assuntos
Bem-Estar do Animal , Vacinas , Masculino , Feminino , Animais , Orquiectomia/veterinária , Carne , Hormônio Liberador de Gonadotropina , Mamíferos
18.
Curr Psychol ; : 1-9, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35136327

RESUMO

Governments worldwide have imposed lockdowns in their countries to restrict unnecessary movement and curb the spread and transmission of the Covid-19 as a mitigation measure. The education sector has also implemented rapid changes, and this has transformed the operational procedures for both students and lecturers. As the pandemic has progressed, its emotional and psychological toll is equally bearing on students, leading to lockdown fatigue. This study aimed to investigate the level of lockdown-induced fatigue and its correlation with personal resilience and coping skills among university students in Iraq. This study used quantitative methods of research using a cross-sectional study design. A questionnaire survey was distributed electronically among 819 university students in Iraq. The study used three standardised scales: the lockdown fatigue scale, brief resilience scale, and coping behaviours questionnaire for data collection. Descriptive and inferential statistical analysis were done using SPSS. Overall, students indicated a high level of lockdown fatigue with a mean score of 33.48out of 50. Fear of personal safety and the wellbeing of the family was the most fear expressed by the students. The ability to go through stressful times and unpleasant events was the most common worry among the students. Female, urbanised, and science field students were the most students who suffered from lockdown-induced fatigue. However, positive coping behaviours and personal resilience were significantly correlated with decreasing fatigue levels during the lockdown period. Level of lockdown fatigue accelerated in an alarming stage among university students in Iraq. Hence, students need to build their emotional resilience and learn how to navigate surviving hard times and bounce back after a loss. This could be facilitated by counselling services being availed to educational and social institutions to benefit university students.

19.
Retrovirology ; 18(1): 27, 2021 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538278

RESUMO

BACKGROUND: We observe the emergence of several promoter-variant viral strains in India during recent years. The variant viral promoters contain additional copies of transcription factor binding sites present in the viral modulatory region or enhancer, including RBEIII, LEF-1, Ap-1 and/or NF-κB. These sites are crucial for governing viral gene expression and latency. Here, we infer that one variant viral promoter R2N3-LTR containing two copies of RBF-2 binding sites (an RBEIII site duplication) and three copies of NF-κB motifs may demonstrate low levels of gene expression noise as compared to the canonical RN3-LTR or a different variant R2N4-LTR (a duplication of an RBEIII site and an NF-κB motif). To demonstrate this, we constructed a panel of sub-genomic viral vectors of promoter-variant LTRs co-expressing two reporter proteins (mScarlet and Gaussia luciferase) under the dual-control of Tat and Rev. We established stable pools of CEM.NKR-CCR5 cells (CEM-CCR5RL reporter cells) and evaluated reporter gene expression under different conditions of cell activation. RESULTS: The R2N3-LTR established stringent latency that was highly resistant to reversal by potent cell activators such as TNF-α or PMA, or even to a cocktail of activators, compared to the canonical RN3- or the variant R2N4-LTR. The R2N3-LTR exhibited low-level basal gene expression in the absence of cell activation that enhanced marginally but significantly when activated. In the presence of Tat and Rev, trans-complemented in the form of an infectious virus, the R2N3-LTR demonstrated gene expression at levels comparable to the wild-type viral promoter. The R2N3-LTR is responsive to Tat and Rev factors derived from viral strains representing diverse genetic subtypes. CONCLUSION: With extremely low-level transcriptional noise, the R2N3-LTR can serve as an excellent model to examine the establishment, maintenance, and reversal of HIV-1 latency. The R2N3-LTR would also be an ideal viral promoter to develop high-throughput screening assays to identify potent latency-reversing agents since the LTR is not affected by the usual background noise of the cell.


Assuntos
Repetição Terminal Longa de HIV , HIV-1/genética , Regiões Promotoras Genéticas , Sítios de Ligação , Regulação Viral da Expressão Gênica , Genes Reporter , Variação Genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , NF-kappa B , Transcrição Gênica , Replicação Viral , Produtos do Gene rev do Vírus da Imunodeficiência Humana/genética , Produtos do Gene rev do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
20.
Langmuir ; 37(14): 4355-4369, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33789039

RESUMO

Water droplet impacting on a slanted dusty hydrophobic surface is examined in relation to dust mitigation from surfaces. Impacting droplet characteristics including droplet spreading/retraction rates, slipping length, and rebound heights are analyzed via high-speed recording and a tracker program. The environmental dust characteristics in terms of size, shape, elemental composition, and surface free energy are evaluated by adopting the analytical methods. The findings reveal that the dynamic characteristics of the impacting droplet on the slanted hydrophobic surface are significantly influenced by the dust particles. The maximum droplet spreading over the dusty surface becomes smaller than that of the nondusty surface. The presence of the dust particles on the slanted hydrophobic surface increases energy dissipation, and the water droplet slipping length over the surface becomes less than that corresponding to the nondusty surface. Impacting droplet fluid infuses over the dust particle surface, which enables mitigation of dust from the surface to the droplet fluid. A dust-mitigated area on the slanted surface is larger than that corresponding to the horizontal surface; in which case, the area ratio becomes almost six-fold, which slightly reduces with increasing Weber number. The optical transmittance of the dust-mitigated surface by the impacting droplet remains high.

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