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1.
J Genet Couns ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956816

RESUMO

Although the presence of companion(s) in a genetic counseling session can positively influence session dynamics, research has found that some patients prefer to attend their appointments alone. To date, no studies have examined patient accompaniment preferences across different cultural groups in the context of genetic counseling. This quantitative study aimed to identify factors associated with individual preferences in accompaniment at cancer genetic counseling appointments in a sample (N = 130) of Hispanic/Latine (n = 29) and non-Hispanic/Latine White (n = 101) participants at a large academic medical institution. Variables examined included demographics, horizontal and vertical collectivism, and Hispanic and American acculturation. A link to an online questionnaire was emailed to patients who met four criteria: (1) identified as either Hispanic/Latine or non-Hispanic/Latine White; (2) had attended a cancer genetic counseling appointment at UCLA Health to discuss genetic testing options between October 2020 and December 2022; (3) were at least 18 years of age at the time of their appointment; and (4) indicated they were comfortable reading in Spanish or English; responses were anonymous. Logistic regression analyses identified four significant variables in the model associated with accompaniment preferences: individuals with at least one parent born outside of the US, those who attended their appointment in-person, and those with a higher horizontal collectivism score were less likely to want to attend their cancer genetic counseling appointment alone, while the converse was true among those with a higher American acculturation score. These findings highlight cultural and demographic factors that are associated with patient accompaniment preferences unrelated to ethnicity, indicating genetic counselors should not make assumptions regarding accompaniment preferences based solely on cultural or racial/ethnic background. Genetic counselors should incorporate this understanding when assessing patients' accompaniment preferences.

2.
Neurobiol Dis ; : 106595, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972360

RESUMO

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-syn pre-formed fibrils (PFFs) into the striatum induces robust α-syn aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6 J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-syn show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that asymmetric synapses in mice with PFF-induced α-syn aggregates have reduced synaptic vesicle intervesicular distances, similar to a recent study showing phospho-serine-129 α-syn increases synaptic vesicle clustering. Thus, pathologic α-syn causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.

3.
Ecol Lett ; 27(7): e14461, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953253

RESUMO

Under the recently adopted Kunming-Montreal Global Biodiversity Framework, 196 Parties committed to reporting the status of genetic diversity for all species. To facilitate reporting, three genetic diversity indicators were developed, two of which focus on processes contributing to genetic diversity conservation: maintaining genetically distinct populations and ensuring populations are large enough to maintain genetic diversity. The major advantage of these indicators is that they can be estimated with or without DNA-based data. However, demonstrating their feasibility requires addressing the methodological challenges of using data gathered from diverse sources, across diverse taxonomic groups, and for countries of varying socio-economic status and biodiversity levels. Here, we assess the genetic indicators for 919 taxa, representing 5271 populations across nine countries, including megadiverse countries and developing economies. Eighty-three percent of the taxa assessed had data available to calculate at least one indicator. Our results show that although the majority of species maintain most populations, 58% of species have populations too small to maintain genetic diversity. Moreover, genetic indicator values suggest that IUCN Red List status and other initiatives fail to assess genetic status, highlighting the critical importance of genetic indicators.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Variação Genética , Animais
4.
Pediatr Res ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914764

RESUMO

The systematic review and meta-analysis of newborn animal models by Irene Lok et al. is the first to extensively summarize the literature regarding postnatal systemic corticosteroid use on lung development of newborn rodent models. The meta-analysis showed that the use of postnatal corticosteroids resulted in a reduction in body weight along with persistent alveolar simplification. The most frequently used corticosteroid was dexamethasone. Corticosteroids have been extensively used in clinical trials in preterm newborns. Trials using early systemic administration of corticosteroids reduced the rate of BPD or mortality with no increase in the rates of cerebral palsy. Use of late systemic corticosteroids (administered >7 days after birth) also reduced the rate of BPD, mortality, and combined outcome of mortality or BPD. Late systemic corticosteroids showed no impact on the rates of neurodevelopmental outcomes in later childhood. It is important to note that later stages of inflammation leading to a more severe form of BPD continues to be a problem with no clear therapy in sight. The authors made a critical point in their paper - the negative effects of steroids were greater in the normal lung control animals than in the injured. This conveys caution in using steroids in a prophylactic manner. IMPACT: Use of systemic corticosteroids in clinical trials have shown good response in preterm neonates evidenced by reduced rate of bronchopulmonary dysplasia. Rodent models have not shown a similar beneficial response. Use of systemic corticosteroids have caused greater arrest of lung development in rodent models with normal lungs compared to those with lung damage.

5.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892146

RESUMO

Advanced oxidation processes, including photocatalysis, have been proven effective at organic dye degradation. Tailored porous materials with regulated pore size, shape, and morphology offer a sustainable solution to the water pollution problem by acting as support materials to grafted photocatalytic nanoparticles (NPs). This research investigated the influence of pore and particle sizes of photocatalytic MICROSCAFS® on the degradation of methyl orange (MO) in aqueous solution (10 mg/L). Photocatalytic MICROSCAFS® are made of binder-less supported P25 TiO2 NPs within MICROSCAFS®, which are silica-titania microspheres with a controlled size and interconnected macroporosity, synthesized by an adapted sol-gel method that involves a polymerization-induced phase separation process. Photocatalytic experiments were performed both in batch and flow reactors, with this latter one targeting a proof of concept for continuous transformation processes and real-life conditions. Photocatalytic degradation of 87% in 2 h (batch) was achieved, using a calibrated solar light simulator (1 sun) and a photocatalyst/pollutant mass ratio of 23. This study introduces a novel flow kinetic model which provides the modeling and simulation of the photocatalytic MICROSCAFS® performance. A scavenger study was performed, enabling an in-depth mechanistic understanding. Finally, the transformation products resulting from the MO photocatalytic degradation were elucidated by high-resolution mass spectrometry experiments and subjected to an in silico toxicity assessment.


Assuntos
Compostos Azo , Luz Solar , Titânio , Poluentes Químicos da Água , Purificação da Água , Catálise , Purificação da Água/métodos , Titânio/química , Poluentes Químicos da Água/química , Porosidade , Compostos Azo/química , Microesferas , Dióxido de Silício/química , Fotólise , Cinética , Processos Fotoquímicos
6.
Sci Rep ; 14(1): 14720, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926415

RESUMO

Dental calculus is a microbial biofilm that contains biomolecules from oral commensals and pathogens, including those potentially related to cause of death (CoD). To assess the utility of calculus as a diagnostically informative substrate, in conjunction with paleopathological analysis, calculus samples from 39 individuals in the Smithsonian Institution's Robert J. Terry Collection with CoDs of either syphilis or tuberculosis were assessed via shotgun metagenomic sequencing for the presence of Treponema pallidum subsp. pallidum and Mycobacterium tuberculosis complex (MTBC) DNA. Paleopathological analysis revealed that frequencies of skeletal lesions associated with these diseases were partially inconsistent with diagnostic criteria. Although recovery of T. p. pallidum DNA from individuals with a syphilis CoD was elusive, MTBC DNA was identified in at least one individual with a tuberculosis CoD. The authenticity of MTBC DNA was confirmed using targeted quantitative PCR assays, MTBC genome enrichment, and in silico bioinformatic analyses; however, the lineage of the MTBC strain present could not be determined. Overall, our study highlights the utility of dental calculus for molecular detection of tuberculosis in the archaeological record and underscores the effect of museum preparation techniques and extensive handling on pathogen DNA preservation in skeletal collections.


Assuntos
Cálculos Dentários , Metagenômica , Mycobacterium tuberculosis , Paleopatologia , Tuberculose , Cálculos Dentários/microbiologia , Cálculos Dentários/história , Humanos , Metagenômica/métodos , Paleopatologia/métodos , Tuberculose/diagnóstico , Tuberculose/microbiologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , DNA Bacteriano/genética , Masculino , Treponema pallidum/genética , Treponema pallidum/isolamento & purificação , Sífilis/diagnóstico , Sífilis/microbiologia , Sífilis/história , Feminino , Adulto , Metagenoma/genética , Pessoa de Meia-Idade
7.
J Perinatol ; 44(6): 892-896, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38773216

RESUMO

OBJECTIVE: To describe the population to which we administered recombinant erythropoietin and to determine the effectiveness of this treatment as quantified by the change in hematocrit. STUDY DESIGN: This retrospective chart review study included infants who received erythropoietin for the treatment of anemia of prematurity. RESULTS: There were 132 infants representing 162 unique treatment courses included in the study. The average duration of therapy was 9 days (±7) and 6 doses (±2). The average change in hematocrit (Hct) was 6.2% (SD 3.9%, p < 0.001). Rise in Hct was associated with a higher number of rEPO doses (p < 0.001) and higher postmenstrual age (p < 0.001). In our small cohort we did not find an association between the number of rEPO doses and retinopathy of prematurity (ROP) requiring treatment. CONCLUSION: Erythropoietin is safe and effective at treating anemia of prematurity as evidenced by a clinically and statistically significant increase in Hct from baseline.


Assuntos
Anemia Neonatal , Eritropoetina , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Proteínas Recombinantes , Humanos , Estudos Retrospectivos , Recém-Nascido , Eritropoetina/uso terapêutico , Eritropoetina/administração & dosagem , Feminino , Masculino , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Anemia Neonatal/tratamento farmacológico , Hematócrito , Retinopatia da Prematuridade/tratamento farmacológico , Resultado do Tratamento , Idade Gestacional , Anemia/tratamento farmacológico
8.
J Perinatol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714842

RESUMO

BACKGROUND: Failure to reach full oral feeding remains a significant barrier for premature infants to discharge home. Postmenstrual age (PMA) at first oral feeding is significantly associated with the length of hospital stay (LOS). METHODS: Single-center QI to introduce oral feeding to infants on high-flow nasal cannula (HFNC) by reducing the flow to 2 L during feeds. GLOBAL AIM: To reduce PMA at first oral feeding and reduce the LOS. SMART AIM: To introduce oral feeds in 40% of infants who are on ≤4 L HFNC by the end of 12 months. RESULTS: Over 12 months, SMART aim reached with 100% enrollment. PMA at first oral feeding decreased from a median of 42.4w ((IQR) (40,46.6) to 37.8w (35.8,43.2), PMA at discharge decreased from 47w (44.6,50.7) to 42.6w (41.3,48.8). CONCLUSION: Allowing oral feeding in infants while on HFNC is feasible. This approach can significantly reduce PMA at first and full oral feeding.

9.
J Perinatol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698211

RESUMO

We review the pathophysiology, epidemiology, diagnosis, treatment, and prevention of ventilator-associated pneumonia (VAP) in neonates. VAP has been studied primarily in adult ICU patients, although there has been more focus on pediatric and neonatal VAP (neo-VAP) in the last decade. The definition as well as diagnosis of VAP in neonates remains a challenge to date. The neonatal intensivist needs to be familiar with the current diagnostic tools and prevention strategies available to treat and reduce VAP to reduce neonatal morbidity and the emergence of antibiotic resistance. This review also highlights preventive strategies and old and emerging treatments available.

10.
Foot Ankle Surg ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38692981

RESUMO

BACKGROUND: Insertional Achilles tendinopathy (IAT) is a common pathology with multiple surgical interventions available for treatment. The Zadek, dorsal closing wedge calcaneal osteotomy (ZO) has been demonstrated to be effective treatment of IAT. There have been various recommendations in the literature as to what measurement of wedge removal should be considered ideal to produce greatest postoperative range of motion (ROM), thus postoperative biomechanical potential. Accordingly, the purpose of this cadaveric study was to assess the range of motion achieved after various measurements of wedge removal by ZO. METHODS: The ZO was performed on six cadaveric specimens. A 7.5 mm and 15 mm wedge osteotomy was marked and sequentially completed on each specimen. Lateral fluoroscopic imaging was utilized to take preoperative and postoperative ROM measurements for each osteotomy. Dorsiflexion (DF) and plantarflexion (PF) ROM arcs were measured for each wedge size and compared by t-test. Effect sizes were calculated by Cohen's d analysis. RESULTS: Maximal DF was 110.87 ± 12.97 deg in the pre-osteotomy state. Removal of a 7.5 mm wedge improved DF by 8 deg to a mean 102.93 ± 13.81 deg (p = 0.08). Removal of a 15 mm wedge improved DF by 16 deg to a mean 95.96 ± 11.41 deg (p = 0.003). Cohen's d and effect size calculation demonstrated a 7.5 mm wedge to have a small effect on DF, while a 15 mm wedge had a medium effect (0.29, 0.52 respectively). Maximal PF did not change significantly amongst the pre-osteotomy, 7.5 mm wedge, or 15 mm wedge positions. ICC was 0.96. CONCLUSION: Based on the results presented in this study, removal of a 15 mm wedge with ZO yields significant and greater improvement in ROM than a 7.5 mm wedge. We hope the current study will better inform preoperative planning for ZO. STUDY TYPE: Prospective Cadaver Study. LEVEL OF EVIDENCE: V.

11.
J Perinatol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769337

RESUMO

OBJECTIVE: To determine whether random cortisol levels obtained in neonates to assess for secondary adrenal insufficiency (AI) after prolonged steroid exposure are predictive of central AI. STUDY DESIGN: Data were collected on neonates born 2017-2022 who received ≥10 consecutive days of systemic steroids and had cortisol measured thereafter. Data were then collected on whether those neonates developed signs of AI or had a failed adrenocorticotropic hormone (ACTH) stimulation test. RESULTS: Of the 71 cortisol levels (in 67 neonates) that were analyzed, there was no difference in cortisol levels between neonates who developed AI (median cortisol level of 6.5 mcg/dl) and those who did not (median of 9.2 mcg/dl), or between those who failed their ACTH stimulation test or passed it, using Wilcoxon ranked sum tests. CONCLUSION: These findings demonstrate that cortisol levels may not be helpful in identifying AI in neonates exposed to prolonged steroids.

12.
AJPM Focus ; 3(4): 100207, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38770235

RESUMO

The U.S. population has suffered worse health consequences owing to COVID-19 than comparable wealthy nations. COVID-19 had caused more than 1.1 million deaths in the U.S. as of May 2023 and contributed to a 3-year decline in life expectancy. A coalition of public health workers and community activists launched an external review of the Centers for Disease Control and Prevention's pandemic management from January 2021 to May 2023. The authors used a modified Delphi process to identify core pandemic management areas, which formed the basis for a survey and literature review. Their analysis yields 3 overarching shortcomings of the Centers for Disease Control and Prevention's pandemic management: (1) Centers for Disease Control and Prevention leadership downplays the serious impacts and aerosol transmission risks of COVID-19, (2) Centers for Disease Control and Prevention leadership has aligned public guidance with commercial and political interests over scientific evidence, and (3) Centers for Disease Control and Prevention guidance focuses on individual choice rather than emphasizing prevention and equity. Instead, the agency must partner with communities most impacted by the pandemic and encourage people to protect one another using layered protections to decrease COVID-19 transmission. Because emerging variants can already evade existing vaccines and treatments and Long COVID can be disabling and lacks definitive treatment, multifaceted, sustainable approaches to the COVID-19 pandemic are essential to protect people, the economy, and future generations.

13.
Sci Total Environ ; 931: 172939, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38701928

RESUMO

Southern hemisphere humpback whale (Megaptera novaeangliae, SHHW) breeding populations follow a high-fidelity Antarctic krill (Euphausia superba) diet while feeding in distinct sectors of the Southern Ocean. Their capital breeding life history requires predictable ecosystem productivity to fuel migration and migration-related behaviours. It is therefore postulated that populations feeding in areas subject to the strongest climate change impacts are more likely to show the first signs of a departure from a high-fidelity krill diet. We tested this hypothesis by investigating blubber fatty acid profiles and skin stable isotopes obtained from five SHHW populations in 2019, and comparing them to Antarctic krill stable isotopes sampled in three SHHW feeding areas in the Southern Ocean in 2019. Fatty acid profiles and δ13C and δ15N varied significantly among all five populations, however, calculated trophic positions did not (2.7 to 3.1). Similarly, fatty acid ratios, 16:1ω7c/16:0 and 20:5ω3/22:6ω3 were above 1, showing that whales from all five populations are secondary heterotrophs following an omnivorous diet with a diatom-origin. Thus, evidence for a potential departure from a high-fidelity Antarctic krill diet was not seen in any population. δ13C of all populations were similar to δ13C of krill sampled in productive upwelling areas or the marginal sea-ice zone. Consistency in trophic position and diet origin but significant fatty acid and stable isotope differences demonstrate that the observed variability arises at lower trophic levels. Our results indicate that, at present, there is no evidence of a divergence from a high-fidelity krill diet. Nevertheless, the characteristic isotopic signal of whales feeding in productive upwelling areas, or in the marginal sea-ice zone, implies that future cryosphere reductions could impact their feeding ecology.


Assuntos
Dieta , Euphausiacea , Jubarte , Animais , Isótopos de Carbono/análise , Isótopos de Nitrogênio/análise , Regiões Antárticas , Ácidos Graxos/análise , Mudança Climática
14.
bioRxiv ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38798467

RESUMO

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-synuclein pre-formed fibrils (PFFs) into the striatum induces robust α-synuclein aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-synuclein show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that PFF-injected mice showed reduced intervesicular distances similar to a recent study showing phospho-serine-129 α-synuclein increases synaptic vesicle clustering. Thus, pathologic α-synuclein causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.

15.
J Neurosci ; 44(26)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38664012

RESUMO

l-DOPA-induced dyskinesia (LID) is a debilitating motor side effect arising from chronic dopamine (DA) replacement therapy with l-DOPA for the treatment of Parkinson's disease. LID is associated with supersensitivity of striatal dopaminergic signaling and fluctuations in synaptic DA following each l-DOPA dose, shrinking the therapeutic window. The heterogeneous composition of the striatum, including subpopulations of medium spiny output neurons (MSNs), interneurons, and supporting cells, complicates the identification of cell(s) underlying LID. We used single-nucleus RNA sequencing (snRNA-seq) to establish a comprehensive striatal transcriptional profile during LID development. Male hemiparkinsonian mice were treated with vehicle or l-DOPA for 1, 5, or 10 d, and striatal nuclei were processed for snRNA-seq. Analyses indicated a limited population of DA D1 receptor-expressing MSNs (D1-MSNs) formed three subclusters in response to l-DOPA treatment and expressed cellular markers of activation. These activated D1-MSNs display similar transcriptional changes previously associated with LID; however, their prevalence and transcriptional behavior were differentially influenced by l-DOPA experience. Differentially expressed genes indicated acute upregulation of plasticity-related transcription factors and mitogen-activated protein kinase signaling, while repeated l-DOPA-induced synaptic remodeling, learning and memory, and transforming growth factor-ß (TGF-ß) signaling genes. Notably, repeated l-DOPA sensitized Inhba, an activin subunit of the TGF-ß superfamily, in activated D1-MSNs, and its pharmacological inhibition impaired LID development, suggesting that activin signaling may play an essential role in LID. These data suggest distinct subsets of D1-MSNs become differentially l-DOPA-responsive due to aberrant induction of molecular mechanisms necessary for neuronal entrainment, similar to processes underlying hippocampal learning and memory.


Assuntos
Corpo Estriado , Discinesia Induzida por Medicamentos , Levodopa , Camundongos Endogâmicos C57BL , Animais , Levodopa/efeitos adversos , Levodopa/toxicidade , Discinesia Induzida por Medicamentos/metabolismo , Masculino , Camundongos , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/genética , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
16.
Cell Rep ; 43(4): 114076, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38607917

RESUMO

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/fisiologia , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/transmissão , Replicação Viral , Mutação/genética , Mucosa Respiratória/virologia , Aptidão Genética , Animais , Células Epiteliais/virologia , Chlorocebus aethiops , Adaptação Fisiológica/genética , Células Vero
17.
Sci Rep ; 14(1): 9862, 2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684707

RESUMO

The process of creating a series of 3-amino-1-aryl-8-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-q) involved reacting 6-methoxynaphthalen-2-ol (1), the appropriate aromatic aldehydes (2a-q), and malononitrile (3) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1H-benzo[f]chromene-2,8-dicarbonitrile (6a, d, e) was unsuccessful when 6-cyanonaphthalen-2-ol (5) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives (4 m, i, k) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br (4c, e) and a double bromine at 3,5-positions with a single methoxy group at 2-position (4n), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated (4a, b, d, f), dihalogenated (4 g, h, j, l) or trisubstituent phenyl ring (4o, p, q). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives (4a-f, g-q) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g, revealing bactericidal effects. Lastly, SAR and molecular docking were studied.


Assuntos
Antineoplásicos , Testes de Sensibilidade Microbiana , Piranos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Piranos/farmacologia , Piranos/química , Piranos/síntese química , Linhagem Celular Tumoral , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Simulação de Acoplamento Molecular , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Relação Estrutura-Atividade , Escherichia coli/efeitos dos fármacos
18.
Int J Equity Health ; 23(1): 83, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678232

RESUMO

BACKGROUND: People living with HIV (PLWH) are at increased risk of cardiometabolic disorders (CMD). Adequate access to care for both HIV and CMD is crucial to improving health outcomes; however, there is limited research that have examined couples' experiences accessing such care in resource-constrained settings. We aimed to identify barriers to accessing CMD care among PLWH in Malawi and the role of partners in mitigating these barriers. METHODS: We conducted a qualitative investigation of barriers to CMD care among 25 couples in Malawi. Couples were eligible if at least one partner was living with HIV and had hypertension or diabetes (i.e., the index patient). Index patients were recruited from HIV care clinics in the Zomba district, and their partners were enrolled thereafter. Interviews were conducted separately with both partners to determine barriers to CMD care access and how partners were involved in care. RESULTS: Participants framed their experiences with CMD care by making comparisons to HIV treatment, which was free and consistently available. The main barriers to accessing CMD care included shortage of medications, cost of tests and treatments, high cost of transportation to health facilities, lengthy wait times at health facilities, faulty or unavailable medical equipment and supplies, inadequate monitoring of patients' health conditions, some cultural beliefs about causes of illness, use of herbal therapies as an alternative to prescribed medicine, and inadequate knowledge about CMD treatments. Partners provided support through decision-making on accessing medical care, assisting partners in navigating the healthcare system, and providing financial assistance with transportation and treatment expenses. Partners also helped manage care for CMD, including communicating health information to their partners, providing appointment reminders, supporting medication adherence, and supporting recommended lifestyle behaviors. CONCLUSIONS: Couples identified many barriers to CMD care access, which were perceived as greater challenges than HIV care. Partners provided critical forms of support in navigating these barriers. With the rise of CMD among PLWH, improving access to CMD care should be prioritized, using lessons learned from HIV and integrated care approaches. Partner involvement in CMD care may help mitigate most barriers to CMD care.


Assuntos
Infecções por HIV , Acessibilidade aos Serviços de Saúde , Pesquisa Qualitativa , Humanos , Malaui , Infecções por HIV/psicologia , Infecções por HIV/terapia , Infecções por HIV/complicações , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resiliência Psicológica , Doenças Cardiovasculares/terapia , Hipertensão/terapia , Hipertensão/psicologia
19.
J Perinatol ; 44(4): 478-487, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38459371

RESUMO

Surfactant replacement therapy is currently approved by the United States Food and Drug Administration (FDA) for premature infants with respiratory distress syndrome (RDS) caused by surfactant deficiency due to immaturity. There is strong evidence that surfactant decreases mortality and air leak syndromes in premature infants with RDS. However, surfactant is also used "off-label" for respiratory failure beyond classic RDS. This review discusses current evidence for the use of off-label surfactant therapy for (1) term infants with lung disease such as meconium aspiration syndrome (MAS), pneumonia/sepsis, and congenital diaphragmatic hernia (2) premature infants after 72 h for acute respiratory failure, and (3) the use of surfactant lavage. At last, we briefly describe the use of surfactants for drug delivery and the current evidence on evaluating infants for surfactant deficiency.


Assuntos
Síndrome de Aspiração de Mecônio , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Feminino , Tensoativos/uso terapêutico , Síndrome de Aspiração de Mecônio/tratamento farmacológico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Surfactantes Pulmonares/uso terapêutico , Recém-Nascido Prematuro
20.
World J Microbiol Biotechnol ; 40(4): 133, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480610

RESUMO

Campylobacter and Salmonella are the two most prominent foodborne zoonotic pathogens reported in the European Union. As poultry is one of the major sources of these pathogens, it is imperative to mitigate the colonization of these pathogens in poultry. Many strains of lactic acid bacteria (LAB) have demonstrated anti-Salmonella and anti-Campylobacter characteristics to varying degrees and spectrums which are attributed to the production of various metabolites. However, the production of these compounds and consequent antimicrobial properties are highly strain dependent. Therefore, the current study was performed to select a potent LAB and determine its causal attribute in inhibiting Salmonella enterica and Campylobacter jejuni, in-vitro. Six LAB (Lactiplantibacillus plantarum (LP), Lacticaseibacillus casei (LC), Limosilactobacillus reuteri (LR), Lacticaseibacillus rhamnosus (LRh), Leuconostoc mesenteroides (LM) and Pediococcus pentosaceus (PP)) and three serovars of Salmonella enterica (Typhimurium, Enterica and Braenderup) and Campylobacter jejuni were used in the current study. Spot overlays, well diffusion, co-culture and co-aggregation assays against Salmonella and well diffusion assays against Campylobacter jejuni were performed. Organic acid profiling of culture supernatants was performed using HPLC. The results indicated that LRh, LM and PP had the most significant anti-Salmonella effects while LP, LC, LM and PP displayed the most significant anti-Campylobacter effects. Lactic acid and formic acid detected in the culture supernatants seem the most likely source of the anti-Salmonella and anti-Campylobacter effects exhibited by these LAB. In conclusion, Leuconostoc mesenteroides displayed the most significant overall anti-pathogenic effects when compared to the other LAB strains studied, indicating its potential application in-vivo.


Assuntos
Infecções por Campylobacter , Campylobacter jejuni , Campylobacter , Lactobacillales , Lactobacillus plantarum , Doenças das Aves Domésticas , Salmonella enterica , Animais , Galinhas/microbiologia , Salmonella , Infecções por Campylobacter/microbiologia , Doenças das Aves Domésticas/microbiologia
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