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1.
medRxiv ; 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39484282

RESUMO

Background: The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unpredictable, with multiple genetic variants influencing IPF outcomes. Notably, rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in these patients. Here we assessed whether rare qualifying variants (QVs) in monogenic adult-onset pulmonary fibrosis (PF) genes are associated with IPF survival. Using polygenic risk scores (PRS), we also evaluated the influence of common IPF risk variants in individuals carrying these QVs. Methods: We identified QVs in telomere and non-telomere genes linked to monogenic PF forms using whole-genome sequences (WGS) from 888 Pulmonary Fibrosis Foundation Patient Registry (PFFPR) individuals. We also derived a PRS for IPF (PRS-IPF) from 19 previously published common sentinel IPF variants. Using regression models, we then examined the mutual relationships of QVs and PRS-IPF and their association with survival. Validation of results was sought in WGS from an independent IPF study (PROFILE, n=472), and results from the two cohorts were meta-analyzed. Results: Carriers of QVs in monogenic adult-onset PF genes, representing nearly 1 out of 6 IPF patients, were associated with lower PRS-IPF (Odds Ratio [OR]: 1.79; 95% Confidence Interval [CI]: 1.15-2.81; p=0.010) and shorter survival (Hazard Ratio [HR]: 1.53; 95% CI: 1.12-2.10; p=7.3×10 -3 ). Notably, carriers of pathogenic variants at telomere genes showed the strongest association with survival (HR: 1.76; 95% CI: 1.13-2.76; p=0.013). The meta-analysis of the results showed a consistent direction of effect across both cohorts. Conclusions: We revealed the opposite effects of QVs and PRS-IPF on IPF survival. Thus, a distinct IPF molecular subtype might be defined by QVs in monogenic adult-onset PF genes. Assessing the carrier status for QVs and modelling PRS-IPF promises to further contribute to predicting disease progression among IPF patients.

2.
J AAPOS ; : 104016, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366650

RESUMO

We describe the use of trypan blue stain to enhance visualization of the tract of the fistula during congenital lacrimal fistulectomy in a 9-year-old boy. This video demonstrates the surgical technique and the intraoperative finding of deep branching of the fistula in this case. We discuss alternative methods of improving delineation of the fistula's path during congenital lacrimal fistulectomy.

3.
Indian J Ophthalmol ; 72(10): 1453-1457, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39331436

RESUMO

PURPOSE: Removal of clinically benign eyelid margin lesions is frequently desired for cosmetic concerns. Although surgical excision remains the standard therapy for such lesions, it carries the risk of unfavorable outcomes. Hence, this study aimed to evaluate a more aesthetic technique entailing a posterior lamellar wedge resection of lower eyelid margin lesions through an infraciliary incision. METHODS: A retrospective review of patients who underwent posterior lamellar wedge resection for benign lower eyelid margin lesions between May 2017 and June 2022 was performed. Patient satisfaction using the visual analog score (VAS) and cosmetic outcomes using the Strasser score. RESULTS: Forty-two patients met the inclusion criteria (61.9% female, mean age: 46.8 years). Nevus was the most frequent histologic diagnosis (57.1%). Furthermore, 66.7% of lesions extended to the back of the lid margin. The mean defect size was 5.8 mm (range: 3.5-8 mm). The mean follow-up interval was 24.1 months (range: 6-60 months). Thirty-two (76.2%) eyelids had scores indicating an excellent result, and 10 (23.8%) patients had a good result. The mean patient satisfaction VAS score for the eyelid appearance was 96 (range: 70-100). There were no cases of recurrence of resected lesions. No further surgery was performed on the operated eyelid for any reason during the follow-up period. CONCLUSION: Posterior lamellar wedge resection for lower eyelid margin lesions was associated with excellent cosmetic outcomes, high patient satisfaction, and minimal adverse events.


Assuntos
Neoplasias Palpebrais , Pálpebras , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Masculino , Adulto , Pálpebras/cirurgia , Pálpebras/patologia , Neoplasias Palpebrais/cirurgia , Neoplasias Palpebrais/patologia , Seguimentos , Idoso , Satisfação do Paciente , Adulto Jovem , Blefaroplastia/métodos , Adolescente
4.
Q J Exp Psychol (Hove) ; : 17470218241290909, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340360

RESUMO

We provide a broad overview of our original investigation of working memory, how the multicomponent model followed from our use of a dissociative methodology and our intention that it should be simple, robust, and applicable. We describe how subsequent development of the model has increased its scope, depth, and applications while at the same time retaining its core features. Comparisons with the growing number of alternative models suggest agreement on the basic phenomena to be explained and more similarities than differences. While differences between models attract interest, we caution that they do not necessarily reflect the most important issues for future research, which we suggest relate principally to the nature of executive control. The longevity of the multicomponent model reflects not only the importance of working memory in cognition but the usefulness of a simple, robust framework for further theoretical development and applications.

5.
Q J Exp Psychol (Hove) ; : 17470218241282426, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39225162

RESUMO

Visuospatial bootstrapping refers to the well-replicated phenomena in which serial recall in a purely verbal task is boosted by presenting digits within the familiar spatial layout of a typical telephone keypad. The visuospatial bootstrapping phenomena indicates that additional support comes from long-term knowledge of a fixed spatial pattern, and prior experimentation supports the idea that access to this benefit depends on the availability of the visuospatial motor system. We investigate this by tracking participants' eye movements during encoding and retention of verbal lists to learn whether gaze patterns support verbal memory differently when verbal information is presented in the familiar visual layout. Participants' gaze was recorded during attempts to recall lists of seven digits in three formats: centre of the screen, typical telephone keypad, or a spatially identical layout with randomised number placement. Performance was better with the typical than with the novel layout. Our data show that eye movements differ when encoding and retaining verbal information that has a familiar layout compared with the same verbal information presented in a novel layout, suggesting recruitment of different spatial rehearsal strategies. However, no clear link between gaze pattern and recall accuracy was observed, which suggests that gazes play a limited role in retention, at best.

6.
Orbit ; : 1-9, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222381

RESUMO

PURPOSE: To identify and evaluate the risk factors for ptosis repair failure. METHODS: Retrospective, case-controlled study evaluating adult patients with ptosis who underwent ptosis surgery by external levator advancement/resection (ELR) or Müller muscle conjunctival resection (MMCR) with at least 3 months postoperative follow-up. Regression analyses were performed of ptosis repair outcomes comparing preoperative and perioperative risk factors for failure. RESULTS: A total of 240 patients (404 eyelids) met the inclusion criteria for the study. Surgical outcomes were measured categorically by success rate and measured quantitively over time using Kaplan-Meier survival analysis. Success was categorically achieved in 101/112 (90%) eyelids after MMCR and 231/292 (79%) eyelids after ELR (p = .0088). Success as measured over 5 years of follow-up was significantly better in eyelids following MMCR compared to ELR (p = .0469). In terms of surgical failure, the following variables were found to be predictive in order of decreasing risk: chronic topical prostaglandin use, chronic topical corticosteroid use, surgical approach, lower preoperative margin reflex distance 1, prior intraocular surgery, age, lower preoperative levator function, concomitant blepharoplasty, presence of a glaucoma filtering bleb, and female gender. CONCLUSIONS: Ptosis repair surgery is a complex and challenging procedure. This study provides the largest comparative analysis of ELR versus MMCR to date with findings suggesting MMCR to be more a successful surgery than ELR. Topical prostaglandin analogue use appears to be the highest known risk factor for MMCR and ELR ptosis repair failure.

7.
Cortex ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39261234

RESUMO

People with epilepsy often report experiencing memory problems though these are not always detectable using standard neuropsychological measures. One form of difficulty that may be relatively prevalent in epilepsy is termed accelerated long-term forgetting (ALF), typically described as relatively greater loss of memory over days or weeks following initial encoding. The current study used remote assessment to examine memory and forgetting over one week in a broad community sample of people with epilepsy and healthy control participants, using two recently developed tests, one verbal (the Crimes test) and one visual (the Four Doors test). These were administered as part of a short battery of cognitive measures, run remotely with participants over Zoom. Across this community-derived sample, people with epilepsy reported more memory complaints and demonstrated significantly faster forgetting on both the verbal and visual tests. This difference was not attributable to level of initial learning performance and was not detectable through delayed recall on a standard existing test. Our results suggests that ALF may be more common than suspected in people with epilepsy, leading to a potentially important source of memory problems that are currently undetected by standard memory tests.

8.
Memory ; : 1-15, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116079

RESUMO

Selectively remembering more valuable information can improve memory efficiency. Such value effects have been observed on long-term memory for item-colour binding, but the possible contributory factors are unclear. The current study explored contributions from attention (Experiment 1) and verbal rehearsal (Experiment 2). Across two experiments, memory was superior for item-colour bindings that were associated with high (relative to low) point values at encoding, both in an immediate test and a delayed re-test. When availability of attentional resources was reduced during encoding, value only influenced immediate and not delayed memory (Experiment 1). This indicates that a transient value effect can be obtained with little attentional resources, but attentional resources are involved in creating a longer lasting effect. When articulatory suppression was implemented during encoding (Experiment 2), value effects were somewhat reduced in the immediate test and abolished in the delayed re-test, suggesting a role for verbal rehearsal in value effects on item-colour binding memory. These patterns of value effects did not interact with encoding presentation format (i.e., sequential vs. simultaneous presentation of objects). Together, these results suggest that attentional resources and verbal rehearsal both contribute to value effects on item-colour binding memory, with varying impacts on the durability of these effects.

9.
J Immunother Cancer ; 12(7)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39060021

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival. ADT is known to stimulate the accumulation of immunosuppressive cells like protumoral tumor-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T cells in prostate tumors, as well as hypofunctional T cells. Protumoral TAMs have been shown to accumulate around tumor blood vessels during chemotherapy and radiotherapy in other forms of cancer, where they drive tumor relapse. Our aim was to see whether such perivascular (PV) TAMs also accumulate in ADT-treated prostate tumors prior to CRPC, and, if so, whether selectively inducing them to express a potent immunostimulant, interferon beta (IFNß), would stimulate antitumor immunity and delay CRPC. METHODS: We used multiplex immunofluorescence to assess the effects of ADT on the distribution and activation status of TAMs, CD8+T cells, CD4+T cells and NK cells in mouse and/or human prostate tumors. We then used antibody-coated, lipid nanoparticles (LNPs) to selectively target a STING agonist, 2'3'-cGAMP (cGAMP), to PV TAMs in mouse prostate tumors during ADT. RESULTS: TAMs accumulated at high density around blood vessels in response to ADT and expressed markers of a protumoral phenotype including folate receptor-beta (FR-ß), MRC1 (CD206), CD169 and VISTA. Additionally, higher numbers of inactive (PD-1-) CD8+T cells and reduced numbers of active (CD69+) NK cells were present in these PV tumor areas. LNPs coated with an antibody to FR-ß selectively delivered cGAMP to PV TAMs in ADT-treated tumors, where they activated STING and upregulated the expression of IFNß. This resulted in a marked increase in the density of active CD8+T cells (along with CD4+T cells and NK cells) in PV tumor areas, and significantly delayed the onset of CRPC. Antibody depletion of CD8+T cells during LNP administration demonstrated the essential role of these cells in delay in CRPC induced by LNPs. CONCLUSION: Together, our data indicate that targeting a STING agonist to PV TAMs could be used to extend the treatment window for ADT in prostate cancer.


Assuntos
Macrófagos , Proteínas de Membrana , Masculino , Animais , Camundongos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/agonistas , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/farmacologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Resistencia a Medicamentos Antineoplásicos
10.
Clin Epidemiol ; 16: 433-443, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952572

RESUMO

Background: Electronic healthcare records (EHRs) are used to document diagnoses, symptoms, tests, and prescriptions. Though not primarily collected for research purposes, owing to the size of the data as well as the depth of information collected, they have been used extensively to conduct epidemiological research. The Clinical Practice Research Datalink (CPRD) is an EHR database containing representative data of the UK population with regard to age, sex, race, and social deprivation measures. Fibrotic conditions are characterised by excessive scarring, contributing towards organ dysfunction and eventual organ failure. Fibrosis is associated with ageing as well as many other factors, it is hypothesised that fibrotic conditions are caused by the same underlying pathological mechanism. We calculated the prevalence of fibrotic conditions (as defined in a previous Delphi survey of clinicians) as well as the prevalence of fibrotic multimorbidity (the proportion of people with multiple fibrotic conditions). Methods: We included a random sample of 993,370 UK adults, alive, and enrolled at a UK general practice, providing data to the CPRD Aurum database as of 1st of January 2015. Individuals had to be eligible for linkage to hospital episode statistics (HES) and ONS death registration. We calculated the point prevalence of fibrotic conditions and multi-morbid fibrosis on the 1st of January 2015. Using death records of those who died in 2015, we investigated the prevalence of fibrosis associated death. We explored the most commonly co-occurring fibrotic conditions and determined the settings in which diagnoses were commonly made (primary care, secondary care or after death). Results: The point prevalence of any fibrotic condition was 21.46%. In total, 6.00% of people had fibrotic multimorbidity. Of the people who died in 2015, 34.82% had a recording of a fibrotic condition listed on their death certificate. Conclusion: The key finding was that fibrotic multimorbidity affects approximately 1 in 16 people.


Fibrotic conditions are scarring conditions which impact the way an organ functions and eventually lead to organ failure. We studied routinely collected health data from GPs, hospitals, and death certificates to estimate the percentage of UK adults who had fibrotic diseases. We found that 1 in 5 people had at least one fibrotic disease, and we also found that 1 in 16 people had more than one fibrotic disease.

11.
Orbit ; : 1-6, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861504

RESUMO

PURPOSE: Periocular lesions in pediatric patients usually require general anesthesia for surgical intervention. The US Food and Drug Administration (FDA) warns against multiple exposures to anesthesia in children younger than 3 years due to the increased risk of learning disabilities in this population. This study aimed to evaluate risk factors associated with chalazion recurrence after surgery. METHODS: A retrospective chart review over a five-year period identified 649 patients at our institution undergoing surgical intervention for chalazion. The primary outcomes examined were as follows: (1) return to the operating room for additional surgical intervention and (2) recurrence of chalazion during convalescence from surgery and follow-up. RESULTS: Fewer than one-third of patients suffered a recurrence after surgery. Multivariate logistic regression found younger age (p = 0.01), female sex (p = 0.01), and a greater number of chalazia drained (p < 0.001) were significantly correlated with recurrence of chalazia after surgery. CONCLUSIONS: Patients presenting at a younger age and with a greater number of chalazion were statistically more likely to have a recurrence of chalazion after surgery. Given recurrence is more likely in younger children, reconciling this with the risk-benefit ratio with regard to FDA guidelines on anesthesia in children under three years is a critical consideration for ophthalmologists.

12.
Nat Commun ; 15(1): 5390, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918370

RESUMO

The central San Andreas Fault (CSAF) exhibits a simple linear large-scale fault geometry, yet seismic and aseismic deformation features vary in a complex way along the fault. Here we investigate fault zone behaviors using geodetic observation, seismicity and microearthquake focal mechanisms. We employ an improved focal-mechanism characterization method using relative earthquake radiation patterns on 75,164 Ml ≥ 1 earthquakes along a 2-km-wide, 190-km-long segment of the CSAF, from 1984 to 2015. The data reveal the 3D fine-scale structure and interseismic kinematics of the CSAF. Our findings indicate that the first-order spatial variations in interseismic fault creep rate, creep direction, and the fault zone stress field can be explained by a simple fault coupling model. The inferred 3D mechanical properties of a mechanically weak and poorly coupled fault zone provide a unified understanding of the complex fine-scale kinematics, indicating distributed slip deficits facilitating small-to-moderate earthquakes, localized stress heterogeneities, and complex multi-scale ruptures along the fault. Through this detailed mapping, we aim to relate the fine-scale fault architecture to potential future faulting behavior along the CSAF.

13.
Orbit ; : 1-6, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743616

RESUMO

PURPOSE: To describe a novel transconjunctival technique for excision of well-defined masses of the orbital lobe of the lacrimal gland. METHODS: Case series of three patients undergoing excision of a well-defined mass of the orbital lobe of lacrimal gland using a swinging upper eyelid flap. This technique entails a supratarsal conjunctival incision combined with lateral canthotomy and superior cantholysis. RESULTS: Complete removal of the mass without visible scars was achieved in all cases. There were no complications related to this approach. CONCLUSION: The swinging upper eyelid approach produces a wide exposure of the superolateral orbit. It allows safe removal of large lacrimal gland masses without the need for bone removal, while affording acceptable cosmesis.

14.
Q J Exp Psychol (Hove) ; : 17470218241258102, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38769883

RESUMO

Working memory is an active system responsible for the temporary maintenance and processing of information in the support of cognition and action. In keeping with this, a growing body of research has explored the close links between working memory and attention, and how these might be harnessed to impact performance and possibly improve working memory efficiency. This is theoretically and practically important, given that working memory is a central hub in complex cognition yet is extremely capacity- and resource-limited. We review work carried out over the last 10 years or so looking at how high "value" items in working memory can be strategically prioritised through selective attention, drawing principally from visual working memory paradigms with young adult participants, while also discussing how the core effects extend to different task domains and populations. A consistent set of core findings emerges, with improved memory for items that are allocated higher value but no change in overall task performance, and a recency advantage regardless of point allocation when items are encountered sequentially. Value-directed prioritisation is effortful, under top-down strategic control, and appears to vary with perceptual distraction and executive load. It is driven by processes operating during encoding, maintenance, and retrieval, though the extent to which these are influenced by different features of the task context remains to be mapped out. We discuss implications for working memory, attention, and strategic control, and note some possible future directions of travel for this promising line of research.

15.
BMC Ophthalmol ; 24(1): 164, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622551

RESUMO

PURPOSE: To analyze the clinicopathological characteristics and surgical outcomes of patients with Wolfring gland ductal cysts (WGDCs). METHODS: A retrospective, consecutive, interventional comparative case series was performed over a period of 7 years. Data on demographic and clinical characteristics, pathological findings and outcomes of surgically excised cysts were collected. A comparison between the transconjunctival and transcutaneous approaches was also assessed. RESULTS: Forty-eight patients (48 eyelids) were included in the final analysis. The most common presenting symptom was painless eyelid swelling (81.3%). The median symptom duration was 11.5 months (IQR, 18.25). The upper eyelid was involved in 31 (64.6%) patients, 29/31 of whom had cysts in a medial or centromedial location. Forty-five (93.8%) cysts were bluish gray and transilluminable with clear contents on lid eversion and a median largest dimension of 22 mm (IQR, 8). A transverse conjunctival fibrotic band was observed along the proximal tarsal border in the cyst area in all patients. Signs of chronic trachoma were noted in 38 (79.2%) patients. Preoperative significant ptosis was present in 28/31 (90.3%) of the upper eyelid cysts. Thirty cysts (62.5%) were excised through the skin, and 18 cysts (37.5%) were excised transconjunctivally. Intraoperative cyst rupture, the need for conjunctival grafting and postoperative residual upper lid ptosis were significantly greater in the transconjunctival group (p = 0.009, p < 0.001, and p = 0.016, respectively). CONCLUSION: The present study highlights the clinicopathological characteristics of a relatively large series of surgically excised WGDCs. Transcutaneous excision of WGDCs has proven to be an effective treatment with fewer adverse sequelae than the transconjunctival approach.


Assuntos
Blefaroptose , Cistos , Humanos , Estudos Retrospectivos , Pálpebras/cirurgia , Pálpebras/patologia , Resultado do Tratamento , Cistos/cirurgia , Cistos/patologia
16.
Open Heart ; 11(1)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626934

RESUMO

BACKGROUND AND AIMS: Hypertension is a leading risk factor for cardiovascular disease. Electronic health records (EHRs) are routinely collected throughout a person's care, recording all aspects of health status, including current and past conditions, prescriptions and test results. EHRs can be used for epidemiological research. However, there are nuances in the way conditions are recorded using clinical coding; it is important to understand the methods which have been applied to define exposures, covariates and outcomes to enable interpretation of study findings. This study aimed to identify codelists used to define hypertension in studies that use EHRs and generate recommended codelists to support reproducibility and consistency. ELIGIBILITY CRITERIA: Studies included populations with hypertension defined within an EHR between January 2010 and August 2023 and were systematically identified using MEDLINE and Embase. A summary of the most frequently used sources and codes is described. Due to an absence of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) codelists in the literature, a recommended SNOMED CT codelist was developed to aid consistency and standardisation of hypertension research using EHRs. FINDINGS: 375 manuscripts met the study criteria and were eligible for inclusion, and 112 (29.9%) reported codelists. The International Classification of Diseases (ICD) was the most frequently used clinical terminology, 59 manuscripts provided ICD 9 codelists (53%) and 58 included ICD 10 codelists (52%). Informed by commonly used ICD and Read codes, usage recommendations were made. We derived SNOMED CT codelists informed by National Institute for Health and Care Excellence guidelines for hypertension management. It is recommended that these codelists be used to identify hypertension in EHRs using SNOMED CT codes. CONCLUSIONS: Less than one-third of hypertension studies using EHRs included their codelists. Transparent methodology for codelist creation is essential for replication and will aid interpretation of study findings. We created SNOMED CT codelists to support and standardise hypertension definitions in EHR studies.


Assuntos
Registros Eletrônicos de Saúde , Hipertensão , Humanos , Reprodutibilidade dos Testes , Systematized Nomenclature of Medicine , Classificação Internacional de Doenças , Hipertensão/diagnóstico , Hipertensão/terapia
18.
Am J Hematol ; 99(6): 1077-1083, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38476079

RESUMO

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.


Assuntos
Administração Intravenosa , Anemia Ferropriva , Compostos Ferrosos , Síndrome das Pernas Inquietas , Humanos , Síndrome das Pernas Inquietas/tratamento farmacológico , Anemia Ferropriva/tratamento farmacológico , Administração Oral , Método Duplo-Cego , Masculino , Feminino , Projetos Piloto , Pessoa de Meia-Idade , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/uso terapêutico , Compostos Ferrosos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Óxido Ferroso-Férrico/administração & dosagem , Óxido Ferroso-Férrico/uso terapêutico , Óxido Ferroso-Férrico/efeitos adversos , Ferro/administração & dosagem , Ferro/uso terapêutico
19.
ERJ Open Res ; 10(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375425

RESUMO

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. Methods: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. Results: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Conclusion: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

20.
Q J Exp Psychol (Hove) ; 77(11): 2354-2363, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38282209

RESUMO

There is a growing body of evidence that higher-value information can be prioritised for both visual and auditory working memory. The present study examines whether valuable items can similarly be prioritised for the tactile domain. Employing an immediate serial recall procedure (ISR), participants reconstructed a 6-item tactile sequence by moving their fingers in the order of original stimulation. Participants were informed either that one serial position was worth notionally more points (prioritisation condition) or that all items were of equal value (control condition). For Experiment 1 (N = 48), significant boosts in correct recall were evident when serial positions 4 or 5 were more valuable (i.e., prioritisation effects). Experiment 2 (N = 24) demonstrated that the prioritisation effect persisted with concurrent articulation, suggesting that task performance was not a function of verbal recoding and rehearsal of the tactile information. Importantly, a significant recall cost for low-value (non-prioritised) items within the sequence was evident for both experiments. Taken together, these findings demonstrate that (1) prioritisation effects transfer to the tactile domain and (2) finite attentional resources can be deliberately and strategically redistributed to specific items within a sequence, dependent upon the prevailing task demands.


Assuntos
Atenção , Memória de Curto Prazo , Rememoração Mental , Aprendizagem Seriada , Percepção do Tato , Humanos , Feminino , Memória de Curto Prazo/fisiologia , Masculino , Rememoração Mental/fisiologia , Adulto Jovem , Aprendizagem Seriada/fisiologia , Adulto , Atenção/fisiologia , Percepção do Tato/fisiologia , Tato/fisiologia , Adolescente , Análise de Variância
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