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Nowadays, ß-lactam antibiotics are one of the most consumed OTC (over-the-counter) medicines in the world. Its frequent use against several infectious diseases leads to the development of antibiotic resistance. Another unavoidable risk factor of ß-lactam antibiotics is environmental toxicity. Numerous terrestrial as well as aquatic species have suffered due to the excessive use of these pharmaceuticals. In this present study, we have performed a toxicity assessment employing a novel in silico technique like quantitative structure-toxicity relationships (QSTRs) to explore toxicity against zebrafish (Danio rerio). We have developed single as well as inter-endpoint QSTR models for the ß-lactam compounds to explore important structural attributes responsible for their toxicity, employing median lethal (LC50) and median teratogenic concentration (TC50) as the endpoints. We have shown how an inter-endpoint model can extrapolate unavailable endpoint values with the help of other available endpoint values. To verify the models' robustness, predictivity, and goodness-of-fit, several universally popular metrics for both internal and external validation were extensively employed in model validation (single endpoint models: r2 = 0.631 - 0.75, Q2F1 = 0.607 - 0.684; inter-endpoint models: r2 = 0.768 - 0.84, Q2F1 = 0.678 - 0.76). Again, these models were engaged in the prediction of these two responses for a true external set of ß-lactam molecules without response values to prove the reproducibility of these models.
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Background Salpingectomy is a common surgical procedure in gynecology performed for various indications. Given its proximity to the ovaries and shared vascular supply, concerns have arisen regarding compromised ovarian reserve post-salpingectomy. Objective We aim to study the effect of two different energy sources (group 1: salpingectomy using bipolar electrocautery followed by division with scissors versus group 2: salpingectomy with ultrasonic shears) on residual ovarian reserve. The effect on ovarian reserve was assessed using serum levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), antral follicle count (AFC), and ovarian size pre- and postoperatively. Materials and methods According to the inclusion criteria, 68 women were included in the study and randomized into the bipolar electrocautery group and the ultrasonic shear group. The final analysis included 34 women in the bipolar electrocautery group and 32 in the ultrasonic shear group. Preoperatively, the ovarian reserve of all women was assessed using FSH, AMH, AFC, and ovarian size. These parameters were then reassessed at three months postoperatively, and the percentage change was analyzed. Results The mean baseline serum AMH and serum FSH values in the bipolar electrocautery group were 3.9 ± 2.9 ng/ml and 6.6 ± 2.1 IU/L, respectively, comparable with the values in the ultrasonic shear group, where serum AMH was 3.2 ± 2.9 ng/ml and serum FSH was 7.3 ± 3.9 IU/L. AFC and ovarian size were comparable between the two groups preoperatively (bipolar electrocautery group AFC was 8 ± 2.2, ovarian size on the right side was 3.3 ± 0.7 cm and on the left was 3.2 ± 0.6 cm; ultrasonic shear group AFC was 5.7 ± 2.3, ovarian size on the right side was 3.4 ± 0.8 cm and on the left was 3.2 ± 0.8 cm). After three months of postoperative analysis, AFC showed a significant fall from the preoperative value in the bipolar electrocautery group compared to the ultrasonic shear group (AFC reduced from 8 ± 2.2 to 5.5 ± 2.3 vs. 8.6 ± 0.5 to 7.9 ± 2.3; p=0.002). The other parameters showed no statistically significant change. Conclusion Our study suggests that ultrasonic shear is safer than bipolar electrocautery for preserving ovarian reserve after salpingectomy. However, further research is needed to confirm these findings.
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Introduction: Human milk is the preferred source of enteral nutrition for very low birthweight (VLBW) infants, and it possibly decreases dependence on parenteral nutrition (PN) and reduces incidence of late-onset sepsis (LOS). No systematic review to date has specifically addressed the value of early versus late introduction of human milk diet (HMD) on duration of PN and incidence of LOS among VLBW infants. Objective: To review the evidence for an early versus late introduction of HMD on duration of PN and incidence of LOS in VLBW infants. Method: Preferred reporting items for systematic reviews and meta-analysis-guided search of EMBASE and PubMed/Medline databases was conducted for this systematic review using phrases addressing population, intervention, comparator, and outcome framework to identify articles published over the past two decades without language restrictions. Full-text articles (both observational and randomized) that studied an early versus late initiation of HMD were included. Mean difference (MD) and relative risk (RR) with 95% confidence intervals (CIs) were calculated for PN and LOS. Quality of evidence was analyzed using UK National Service Framework and the risk-of-bias was assessed using Robvis®. Results: One randomized controlled trial (RCT) and two observational studies (two English and one Chinese) recruited 474 VLBW infants (455 analyzed). Among an intrauterine growth-restricted cohort enrolled in the RCT (n = 72), early HMD resulted in statistically significant reduction in PN dependence. However, no statistically significant difference was found in LOS. Two observational studies found similar reductions in PN duration and LOS incidence among the early HMD cohort. One observational study reported significant PN reduction; however, the incidence of LOS did not reach statistical significance in either case. Conclusion: An early HMD may reduce the duration of PN for a growth-restricted VLBW cohort. Observational studies suggesting reduced PN and LOS from early HMD endorse the need for bioactivity-focused human milk research. Variations in feeding guidelines among VLBW infants have the potential to influence neonatal outcomes significantly.
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Recém-Nascido de muito Baixo Peso , Leite Humano , Nutrição Parenteral , Humanos , Recém-Nascido , Incidência , Sepse/epidemiologia , Sepse/prevenção & controle , Fenômenos Fisiológicos da Nutrição do Lactente , Fatores de Tempo , Recém-Nascido Prematuro , Aleitamento Materno/estatística & dados numéricosRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is the world's leading cause of viral acute lower respiratory infections (ALRI) in infants. WHO has identified maternal RSV vaccination a priority and candidate vaccines are in development; however, vaccine hesitancy remains an impediment to successful implementation of maternal immunization. This study, the largest antenatal survey conducted to-date, aimed to examine maternal RSV awareness, likely acceptance of RSV vaccination in pregnancy, and attitudes to maternal vaccination. METHODS: Pregnant women of all gestations attending antenatal clinic of a university maternity hospital in Ireland were invited to participate. An information leaflet provided, consent obtained, and survey administered examining RSV awareness, willingness to avail of antenatal RSV vaccination, factors influencing acceptability and preferred sources of assistance. Research Ethics Committee (REC) approval obtained, and general data protection regulation (GDPR) guidelines followed. RESULTS: 528 women completed the survey. A large proportion (75.6%) had never heard of RSV, yet 48.5% would still avail of a vaccine, 45.8% were undecided and only 5.3% would not. The main factor making vaccination acceptable to women (76.4%) was that it protects their infant from illness (p < .001, CV 0.336 for association with acceptance) and general practitioner (GP) was the preferred guidance source in decision-making (57.7%). CONCLUSIONS: Despite low levels of maternal awareness of RSV, pregnant women in Ireland are open to availing of antenatal vaccination. Maternal immunization strategies need to focus on infant's protection from RSV-associated ALRI along with vaccine safety, and build on an interdisciplinary collaboration of maternal, neonatal, primary care and public health services.
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Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinação , Humanos , Feminino , Irlanda/epidemiologia , Gravidez , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/psicologia , Infecções por Vírus Respiratório Sincicial/imunologia , Adulto , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinação/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/psicologia , Complicações Infecciosas na Gravidez/imunologia , Inquéritos e Questionários , Adulto Jovem , Hesitação Vacinal/psicologia , Hesitação Vacinal/estatística & dados numéricos , Gestantes/psicologia , Vírus Sincicial Respiratório Humano/imunologia , AdolescenteRESUMO
Osteoarthritis (OA) is now considered as a multifaceted disease affecting various articular tissues, including cartilage, bone, synovium, and surrounding ligaments. The pathophysiology strongly implicates intricate chemical communication, primarily through cytokines, leading to the production of degradative enzymes in cartilage, inflammatory peptides in synovium, and structural changes in bone, resulting in characteristic clinical features such as joint deformities and loss of cartilage space seen on X-rays. Recent studies highlight the previously underestimated role of subchondral bone in OA, revealing its permeability to cytokines and raising questions about the influence of abnormal perfusion on OA pathophysiology, suggesting a vascular component in the disease's etiology. In essence, alterations in bone perfusion, including reduced venous outflow and intraosseous hypertension, play a crucial role in influencing the physicochemical environment of subchondral bone, impacting osteoblast cytokine expression and contributing to trabecular remodeling, changes in chondrocyte phenotype, and ultimately cartilage matrix degeneration in OA. Dynamic contrast (gadolinium) enhanced magnetic resonance imaging (DCE-MRI) was used to quantify perfusion kinetics in normal and osteoarthritic subchondral bone, demonstrating that decreased perfusion temporally precedes and spatially correlates with cartilage lesions in both young Dunkin-Hartley (D-H) guinea pigs and humans with osteoarthritis. Pharmacokinetic analysis of DCE-MRI generated data reveals decreased tracer clearance and outflow obstruction in the medial tibial plateau of osteoarthritic guinea pigs, coinciding with progressive cartilage degradation, loss of Safranin O staining, and increased expression of matrix metalloproteinases and interleukin-1. Positron emission tomographic (PET) scanning using 18F-Fluoride reveals a relationship among bone blood flow, cartilage lesions, and 18F-Fluoride influx rate in OA, highlighting the intricate relationships between decreased perfusion, altered bone metabolism, and the progression of osteoarthritis. These findings, supported by 18F-Fluoride PET data, suggest the presence of venous stasis associated with outflow obstruction, emphasizing the role of decreased subchondral bone perfusion in the pathophysiology of OA and its association with reduced osteoblast activity and advanced cartilage degeneration.
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Cartilagem Articular , Osteoartrite , Doenças Vasculares , Humanos , Animais , Cobaias , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Fluoretos , Osteoartrite/diagnóstico por imagem , CitocinasRESUMO
OBJECTIVES: The COVID-19 pandemic changed the adult vaccination landscape, possibly permanently. This review attempts to quantitate the magnitude of those changes. METHODS: PubMed was searched for studies on adult / life-course vaccination between 1 January 2020 until 8 November 2022. RESULTS: Twenty-one articles were identified and observations summarised as positive developments/impediments to life-course immunisation, and areas needing policy and structural reform. Unprecedented funding, international co-operation and technical advances led to COVID-19 vaccines authorised in record time. Investments in infrastructure and an expanded healthcare workforce streamlined vaccine delivery to adults. Constant media coverage and targeted messaging have improved health literacy. Conversely, the speed of vaccine development was perceived as a safety risk, and an 'infodemic' of misinformation propagated through social media negatively influenced vaccine uptake. Vaccine access and affordability remains inequitable among older adults and minority groups. CONCLUSIONS: The COVID pandemic led to an opportunity to permanently change policies, attitudes, and systems for vaccine delivery to adults to establish a global life-course approach to immunisation. This is a call for action to sustain the momentum triggered by the COVID-19 pandemic. Addressing inequalities, improving health literacy and optimally using social media are critical to sustain adult vaccinations in post-COVID-19 era.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Idoso , Pandemias/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , ImunizaçãoRESUMO
Excessive use of chemicals is the outcome of the industrialization of agricultural sectors which leads to disturbance of ecological balance. Various agrochemicals are widely used in agricultural fields, urban green areas, and to protect from various pest-associated diseases. Due to their long-term health and environmental hazards, chronic toxicity assessment is crucial. Since in vivo and in vitro toxicity assessments are costly, lengthy, and require a large number of animal experiments, in silico toxicity approaches are better alternatives to save time, cost, and animal experimentation. We have developed the first regression-based 2D-QSAR models using different sub-chronic and chronic toxicity data of pesticides against dogs employing 2D descriptors. From the statistical results (ntrain=53-62, r2 = 0.614 to 0.754, QLOO2 = 0.501 to 0.703 and QF12 = 0.531 to 0.718, QF22=0.523-0.713), it was concluded that the models are robust, reliable, interpretable, and predictive. Similarity-based read-across algorithm was also used to improve the predictivity (QF12=0.595-0.813,QF22=0.573-0.809) of the models. 5132 chemicals obtained from the CPDat and 1694 pesticides obtained from the PPDB database were also screened using the developed models, and their predictivity and reliability were checked. Thus, these models will be helpful for eco-toxicological data-gap filling, toxicity prediction of untested pesticides, and development of novel, safer & eco-friendly pesticides.
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Praguicidas , Cães , Animais , Praguicidas/toxicidade , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes , Bases de Dados FactuaisRESUMO
This review compares internal fixation versus arthroplasty in the treatment of nondisplaced femoral neck fractures (FNFs) calling attention to evolving areas of consensus that influence clinical decision-making. The Garden classification system, typically dichotomized into nondisplaced (types I and II) and displaced (types III and IV) fractures, has been used as a guide for surgical decision-making. Conventionally, treatment of nondisplaced FNF in the elderly has been with internal fixation, and treatment of a displaced FNF has been hemi-, or more recently total hip, arthroplasty. Studies over the last decade have raised concern over the appropriate treatment of nondisplaced FNFs due to high rates of reoperation of nondisplaced FNFs treated with internal fixation. Avascular necrosis (AVN), failure of internal fixation, secondary malunion, and pin/nail penetration through the femoral head have all been observed. Several studies have attributed fixation failure to a degree of femoral neck tilt ≥20°, either posteriorly or anteriorly as seen on the lateral X-ray. Because of these observations of fixation failures, the suggestion has been made that arthroplasty be used when the degree of posterior tilt exceeds a threshold of ≥20° tilt with the expectation of diminishing failure of fixation, decreasing the risk of reoperation and preserving function without increasing mortality rate. Frustrating additional analyses are uncertainties over the mechanisms of failure of internal fixation with ≥20° tilt and the persistently substantial 1-year mortality rate after FNF, which has not been influenced by fixation or replacement type. Due to the lack of consensus regarding the determination of the appropriate surgical intervention for nondisplaced FNFs, an improved algorithm for surgical decision-making for these fractures may prove useful.
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INTRODUCTION: Greater than half of in-hospital maternal deaths are caused by sepsis, a condition that occurs when infection exceeds local tissue containment and results in organ dysfunction. Determining the source of infection can be challenging. Microbiological cultures of the uterine cavity are often difficult to obtain, so antimicrobial susceptibility results may not be available to guide treatment. The aim of this retrospective study was to assess the potential clinical value of microbiology samples used in the maternal "septic screen" of patients in an Irish maternity hospital. METHODS: A review was completed of all maternal "septic screen" (i.e., high vaginal swabs, placenta swabs, blood cultures, throat swabs and urine samples) microbiology results from July 2016 to December 2021. RESULTS: In the relevant period, 845 patients were subject to a "septic screen", of whom 430 also had a placental swab collected. These 430 patients comprise our study population. 2% of blood cultures yielded potential pathogens, compared with 37%, 33%, 9% and 7% respectively for placental swabs, high vaginal swabs, throat swabs and urine specimens. 95% of blood cultures were sterile, compared with 52%, 0%, 0% and 53% respectively for placental swabs, high vaginal swabs, throat swabs and urine specimens. CONCLUSION: Of the five microbiological specimen types examined, placental swabs yielded the highest number of potential pathogens. Our results suggest that placental swabs are useful specimens for detecting potential pathogens from the uterine cavity, the most common source of perinatal infections.
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Placenta , Sepse , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Sepse/microbiologiaRESUMO
The fast-increasing number of commercially produced chemicals challenges the experimental ecotoxicity assessment methods, which are costly, time-consuming, and dependent on the sacrifice of animals. In this regard, Quantitative Structure-Property/Activity Relationships (QSPR/QSAR) have led the way in developing ecotoxicity assessment models. In this study, QSAR models have been developed using the pEC50 values of 82 diverse agrochemicals or agro-molecules against a planktonic crustacean Daphnia magna with easily interpretable 2D descriptors. Moreover, a link among octanol-water partition coefficient (KOW), bio-concentration factor (BCF), and critical body residue (CBR) has been addressed, and their imputation for the prediction of the toxicity endpoint (EC50) has been done with an objective of the advanced exploration of several ecotoxicological parameters for toxic chemicals. The developed partial least squares (PLS) models were validated rigorously and proved to be robust, sound, and immensely well-predictive. The final Daphnia toxicity model derived from experimental derived properties along with computed descriptors emerged better in statistical quality and predictivity than those obtained solely from computed descriptors. Additionally, the pEC50 and other important properties (log KOW, log BCF, and log CBR) for a set of external agro-molecules, not employed in model development, were predicted to show the predictive ability of the models.
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Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that turns black upon standing. Though rarely fatal, joint degradation is a common sequela, and many patients require multiple large joint arthroplasties throughout their lifetime. Though many aspects of the pathophysiological mechanisms of the disease have been described, questions remain, such as how the initiation of ochronotic pigmentation is prompted and the specific circumstances that make some tissues more resistant to pigmentation-related damage than others. In this report, we present the case of an 83-year-old female previously diagnosed with alkaptonuria including high-quality arthroscopic images displaying the fraying of articular cartilage. We also offer a summary of the latest literature on the pathophysiological mechanisms of the disease, including cellular-level changes observed in ochronotic chondrocytes, biochemical and mechanical alterations to the cartilaginous extracellular matrix, and patterns of pigmentation and joint degradation observed in humans and mice models. With these, we present an overview of the mechanisms of ochronotic chondropathy and joint degradation as the processes are currently understood. While alkaptonuria itself is rare, it has been termed a "fundamental disease," implying that its study and greater understanding have the potential to lead to insights in skeletal biology in general, as well as more common pathologies such as osteoarthritis and their potential treatment mechanisms.
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The formation and maintenance of the gross structure and microarchitecture of the human skeleton require the concerted functioning of a plethora of morphogenic signaling processes. Through recent discoveries in the field of genetics, numerous genotypic variants have been implicated in pathologic skeletal phenotypes and disorders arising from the disturbance of one or more of these processes. For example, total loss-of-function variants of LRP5 were found to be the cause of osteoporosis-pseudoglioma syndrome (OPPG). LRP5 encodes for the low-density lipoprotein receptor-related protein 5, a co-receptor in the canonical WNT-ß-catenin signaling pathway and a crucial protein involved in the formation and maintenance of homeostasis of the human skeleton. Beyond OPPG, other partial loss-of-function variants of LRP5 have been found to be associated with other low bone mass phenotypes and disorders, while LRP5 gain-of-function variants have been implicated in high bone mass phenotypes. This review introduces the roles that LRP5 plays in skeletal morphogenesis and discusses some of the structural consequences that result from abnormalities in LRP5. A greater understanding of how the LRP5 receptor functions in bone and other body tissues could provide insights into a variety of pathologies and their potential treatments, from osteoporosis and a variety of skeletal abnormalities to congenital disorders that can lead to lifelong disabilities.
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Osteogênese Imperfeita , Osteoporose , Humanos , Densidade Óssea/genética , Osteoporose/genética , Osteoporose/complicações , Osteogênese Imperfeita/genética , Osso e Ossos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genéticaAssuntos
Distrofias Musculares , Distrofia Muscular de Duchenne , Adulto , Humanos , Adolescente , Estudos Transversais , EmpregoRESUMO
Background Animal models of distributive hypotension and resuscitation allow the assessment of hemodynamic monitoring modalities and resuscitation strategies. The fluid-first paradigm for resuscitation is currently being challenged with clinical trials. In this investigation, venous return and perfusion are assessed, and full hemodynamics are characterized, in a porcine model of endotoxemic hypotension with and without fluid pre-loading. Methods Two groups of six pigs had the induction of standardized endotoxemic hypotension ("critical hypotension"). Group 1 underwent four 10 cc/kg crystalloid boluses, and Group 2 was not fluid pre-resuscitated. Both groups underwent progressive norepinephrine (NE) up-titration to 0.25 mcg/kg/minute over 30 minutes. Vital signs, central parameters, and laboratory values were obtained at baseline, "critical hypotension," after each bolus and during NE administration. Results Endotoxemia decreased the systemic vascular resistance (SVR) in Group 1 (1031±106 dyn/s/cm-5 versus 738±258 dyn/s/cm-5; P=0.03) and Group 2 (1121±196 dyn/s/cm-5 versus 759±342 dyn/s/cm-5; P=0.003). In Group 1, the four fluid boluses decreased heart rate (HR), pulmonary capillary wedge pressure (PCWP), and central venous pressure (CVP) (P<0.05). No changes were observed in blood pressure, cardiac output (CO), or lactate. NE up-titration increased HR in Group 1 and decreased CVP in both groups. Higher final CVP (11 {3} versus 4 {4} mmHg; P=0.01) and PCWP (5 {1} versus 2 {2} mmHg; P=0.005) values were observed in Group 1 relative to Group 2, reflecting increased venous return. Conclusions Porcine endotoxemic hypotension and resuscitation were robustly characterized. In this model, fluid loading improved venous return with NE, though perfusion (CO) was preserved by increased NE-induced chronotropy.
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BACKGROUND: The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. OBJECTIVE: The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. METHODS: KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. RESULTS: KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. CONCLUSIONS: KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49933.
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BACKGROUND: The relationship between operative times and patient outcomes in total hip arthroplasty (THA) has not been well defined. METHODS: From January 2016 to December 2019, data were prospectively collected for THA patients in the FORCE-TJR registry and hospital EMR of an academic total-joint center. RESULTS: 1,123 patients were included. Operative times ranged from 36 to 366 minutes, with a mean operative time of 111.26+/-31.37 minutes. Unadjusted GLM showed HOOS pain, ADL, and QoL scores differed across operative times, with patients who had operative times between 106 and 120 minutes having significantly lower pain, higher function, and better quality of life at 12 months, especially compared to patients with operative times < 90 minutes. Patients who had operative times between 106 and 120 minutes had significantly better VR-12 PCS and MCS at 12 months. Although statistically significant, differences were small and did not persist after controlling for within-surgeon effects, patient socio-demographics and baseline patient-reported outcomes, suggesting that patient characteristics or within-surgeon effects may play a more significant role in these patient-reported outcomes than operative time. CONCLUSION: This study showed that among THA patients, operative times were significantly associated with patient-reported outcomes at 12 months post-operatively, but is one of many surgeon and patient-related factors with effect on THA outcome.
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Artroplastia de Quadril , Cirurgiões , Humanos , Artroplastia de Quadril/efeitos adversos , Qualidade de Vida , Dados de Saúde Coletados Rotineiramente , Atenção Terciária à Saúde , Medidas de Resultados Relatados pelo Paciente , Dor , Resultado do TratamentoRESUMO
Background: There is a lack of consensus on the management of thrombocytopenia in preterm infants, and the threshold for prophylactic platelet transfusion varies widely among clinicians and institutions. Reports in animal models suggested that platelets may play a relevant role in lung alveolarization and regeneration. Bronchopulmonary dysplasia (BPD) is a severe respiratory condition with a multifactorial origin that affects infants born at the early stages of lung development. Recent randomized controlled trials on the platelets count threshold for prophylactic transfusions in preterm infants with thrombocytopenia suggest that a higher exposition to platelet transfusion may increase the risk of BPD. Here, we report a protocol for a systematic review, which aims to assist evidence-based clinical practice and clarify if the administration of platelet products may be associated with the incidence of BPD and/or death in preterm infants. Methods: MEDLINE, Embase, Cochrane databases, and sources of gray literature for conference abstracts and trial registrations will be searched with no time or language restrictions. Case-control studies, cohort studies, and nonrandomized or randomized trials that evaluated the risk for BPD and/or death in preterm infants exposed to platelet transfusion will be included. Data from studies that are sufficiently similar will be pooled as appropriate. Data extraction forms will be developed a priori. Observational studies and nonrandomized and randomized clinical trials will be analyzed separately. Odds ratio with 95% confidence interval (CI) for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes will be combined. The expected heterogeneity will be accounted for using a random-effects model. Subgroup analysis will be performed based on a priori-determined covariate of interest. In case of sufficient homogeneity of interventions and outcomes evaluated, results from subgroups of studies will be pooled together in a meta-analysis. Discussion: This systematic review will investigate the association of BPD/death with platelet components administration in preterm infants, and, consequently, it will provide reliable indications for the evidence-based management of premature patients with thrombocytopenia.
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Metal oxide nanoparticles (MeOxNPs) can be made safer by understanding the interaction between the immune system and nanoparticles. A nano-quantitative structure-activity relationship (nano-QSAR) model can be used to evaluate nanoparticle risk quickly and conveniently. The present work attempts to develop nano-QSAR models to determine the inflammatory potential of MeOxNPs based on the THP-1 cell line. A comprehensive dataset comprising 32 MeOxNPs was used to develop a regression model with fold change (FC) of pro-inflammatory cytokine interleukin (IL)-1beta (IL-1b) release in the THP-1 cell line as the endpoint. Further, the same number of MeOx NPs with varying doses was modelled for the cell viability [-ln(p/(1-p))] endpoint. The results obtained from regression models were statistically significant. The descriptors obtained from the developed predictive models inferred that dose, electronegativity and the presence of metal ions and oxygen can be responsible for IL-1ß leakage from the THP-1 cell line. Based on our results, we can conclude that periodic table-based descriptors, incorporated into the QSAR models, are reliable for modelling pro-inflammatory potential. Researchers can use these comprehensive results to design metal oxide nanoparticles with lower toxicity and determine the cause of pro-inflammatory conditions induced by MeOxNPs.
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Nanopartículas Metálicas , Nanopartículas , Humanos , Óxidos/toxicidade , Relação Quantitativa Estrutura-Atividade , Nanopartículas Metálicas/toxicidade , Nanopartículas/toxicidade , Metais/toxicidade , Células THP-1RESUMO
Soil invertebrates serve as great biological indicators of soil quality. However, there are very few in silico models developed so far on the soil toxicity of chemicals against soil invertebrates due to paucity of data. In this study, three available soil ecotoxicity data (pLC50, pLOEL and pNOEL) against the soil invertebrate Folsomia candida were collected from the ECOTOX database (cfpub.epa.gov/ecotox) and subjected to quantitative structure-activity relationship (QSAR) analysis using 2D descriptors. The collected data for each endpoint were initially curated and used to develop a partial least squares (PLS) regression model based on the features selected through a genetic algorithm followed by the best subset selection. Both internal and external validation metrics of the models' predictions are well-balanced and within the acceptable range as per the Organization for the Economic Cooperation and Development (OECD) criteria. From the developed models, it has been found that molecular weight and presence of phosphate group, electron donor groups, and polyhalogen substitution have a significant impact on the soil ecotoxicity. The soil ecotoxicological risk assessment of organic chemicals can therefore be prioritized by these features. With the availability of additional data in the future, the models may be further refined for more precise predictions.
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Artrópodes , Solo , Animais , Relação Quantitativa Estrutura-Atividade , Análise dos Mínimos Quadrados , Compostos OrgânicosRESUMO
Background: Human milk (HM) fortification has been recommended for the nutritional optimization of very low-birthweight infants. This study analyzed the bioactive components of HM and evaluated fortification choices that could accentuate or attenuate the concentration of such components, with special reference to human milk-derived fortifier (HMDF) offered to extremely premature infants as an exclusive human milk diet. Materials and Methods: An observational feasibility study analyzed the biochemical and immunochemical characteristics of mothers' own milk (MOM), both fresh and frozen, and pasteurized banked donor human milk (DHM), each supplemented with either HMDF or cow's milk-derived fortifier (CMDF). Gestation-specific specimens were analyzed for macronutrients, pH, total solids, antioxidant activity (AA), α-lactalbumin, lactoferrin, lysozyme, and α- and ß-caseins. Data were analyzed for variance applying general linear model and Tukey's test for pairwise comparison. Results: DHM exhibited significantly lower (p < 0.05) lactoferrin and α-lactalbumin concentrations than fresh and frozen MOM. HMDF reinstated lactoferrin and α-lactalbumin and exhibited higher protein, fat, and total solids (p < 0.05) in comparison to unfortified and CMDF-supplemented specimens. HMDF had the highest (p < 0.05) AA, suggesting the potential capability of HMDF to enhance oxidative scavenging. Conclusion: DHM, compared with MOM, has reduced bioactive properties, and CMDF conferred the least additional bioactive components. Reinstatement and further enhancement of bioactivity, which has been attenuated through pasteurization of DHM, is demonstrated through HMDF supplementation. Freshly expressed MOM fortified with HMDF and given early, enterally, and exclusively (3E) appears an optimal nutritional choice for extremely premature infants.