Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 266
Filtrar
1.
bioRxiv ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38746153

RESUMO

Noroviruses are the leading global cause of acute gastroenteritis, responsible for 685 million annual cases. While all age groups are susceptible to noroviruses, children are vulnerable to more severe infections than adults, underscored by 200 million pediatric cases and up to 200,000 deaths in children annually. Understanding the basis for the increased vulnerability of young hosts is critical to developing effective treatments. The pathogenic outcome of any enteric virus infection is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors. A central mediator in these complex relationships are host- and microbiota-derived metabolites. Noroviruses bind a specific class of metabolites, bile acids, which are produced by the host and then modified by commensal bacterial enzymes. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Considering these opposing effects, the microbiota-regulated balance of the bile acid pool may be a key determinant of the pathogenic outcome of a norovirus infection. The bile acid pool in newborns is unique due to immaturity of host metabolic pathways and developing gut microbiota, which could underlie the vulnerability of these hosts to severe norovirus infections. Supporting this concept, we demonstrate herein that microbiota and their bile acid metabolites protect from severe norovirus diarrhea whereas host-derived bile acids promote disease. Remarkably, we also report that maternal bile acid metabolism determines neonatal susceptibility to norovirus diarrhea during breastfeeding by delivering proviral bile acids to the newborn. Finally, directed targeting of maternal and neonatal bile acid metabolism can protect the neonatal host from norovirus disease. Altogether, these data support the conclusion that metabolic immaturity in newborns and ingestion of proviral maternal metabolites in breast milk are the central determinants of heightened neonatal vulnerability to norovirus disease.

2.
Oncol Lett ; 27(5): 230, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38586213

RESUMO

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. The standard of care consists of surgical resection and concurrent chemoradiation, followed by adjuvant temozolomide chemotherapy. This protocol is associated with a median survival of 12-15 months, and <5% of patients survive >3 years. Ketogenic metabolic therapy (KMT) targets cancer cell metabolism by restricting glucose availability and evoking differential stress resistance and sensitization, which may augment the standard treatments and lead to therapeutic benefit. The present study reports the case of a 64-year-old woman with isocitrate dehydrogenase (IDH)-wildtype GBM who pursued the standard treatment protocol in conjunction with an intensive, multimodal KMT program for 3 years. The KMT program consisted of a series of prolonged (7-day, fluid-only) fasts, which were specifically timed to maximize the tolerability and efficacy of the standard treatments, combined with a time-restricted ketogenic diet on all other days. During the first and second treatment years the patient sustained a glucose ketone index (GKI) of 1.65 and 2.02, respectively, which coincided with complete clinical improvement, a healthy body-mass index and a high quality of life, with no visible progressive tumour detected on imaging at the end of the second year. In the setting of the death of an immediate family member leading to increased life stress, slightly relaxed KMT adherence, and a higher GKI of 3.20, slow cancer progression occurred during the third year. The adverse effects attributed to KMT were mild. Despite the limitations of this case report, it highlights the feasibility of implementing the standard treatment protocol for GBM in conjunction with an intensive, long-term, multimodal and specifically timed KMT program, the potential therapeutic efficacy of which may depend upon achieving as low a GKI as possible.

3.
J Eat Disord ; 12(1): 45, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581055

RESUMO

BACKGROUND: The First Episode Rapid Early Intervention for Eating Disorders (FREED) service has been shown to reduce the wait for care and improve clinical outcomes in initial evaluations. These findings led to the national scaling of FREED in England. To support this scaling, we conducted a mixed method evaluation of the perceptions and experiences of clinicians in the early phases of scaling. The Normalisation Process Theory (NPT) was used as a conceptual lens to understand if and how FREED becomes embedded in routine practice. METHODS: The convergent mixed method evaluation included 21 semi-structured interviews with clinicians from early adopter sites and 211 surveys administered to clinicians before, immediately after and 3 months after the FREED training. The interview guide and survey included questions evaluating attitudes towards early intervention for eating disorders (EDs) and NPT mechanisms. Interview data were analysed using an inductive thematic analysis. The NPT was applied to the inductively derived themes to evaluate if and how NPT domains impacted the implementation. Survey data were analysed using multilevel growth models. RESULTS: Six themes and 15 subthemes captured barriers and facilitators to implementation at the patient, clinician, service, intervention, implementation and wider system levels. These interacted with the NPT mechanisms to facilitate or hinder the embedding of FREED. Overall, clinicians were enthusiastic and positive towards early intervention for EDs and FREED, largely because of the expectation of improved patient outcomes. This was a considerable driver in the uptake and implementation of FREED. Clinicians also had reservations about capacity and the potential impact on other patients, which, at times, was a barrier for its use. The FREED training led to significant improvements in positive attitudes and NPT mechanisms that were largely maintained at the 3-month follow-up. However, negative attitudes did not significantly improve following training. CONCLUSIONS: Positive attitudes towards early intervention for EDs increased enthusiasm and engagement with the model. Features of the model and its implementation were effective at developing adopter commitment and capabilities. However, there were aspects of the model and its implementation which require attention in the future (e.g., capacity and the potential impact on the wider service).

4.
Molecules ; 29(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611800

RESUMO

4-Chloroisocoumarin compounds have broad inhibitory properties against serine proteases. Here, we show that selected 3-alkoxy-4-chloroisocoumarins preferentially inhibit the activity of the conserved serine protease High-temperature requirement A of Chlamydia trachomatis. The synthesis of a new series of isocoumarin-based scaffolds has been developed, and their anti-chlamydial properties were investigated. The structure of the alkoxy substituent was found to influence the potency of the compounds against High-temperature requirement A, and modifications to the C-7 position of the 3-alkoxy-4-chloroisocoumarin structure attenuate anti-chlamydial properties.


Assuntos
Álcoois , Chlamydia trachomatis , Inibidores de Proteases , Inibidores de Proteases/farmacologia , Terapia Enzimática , Isocumarinas , Serina Endopeptidases , Serina Proteases
5.
J Bacteriol ; 206(4): e0037123, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38445896

RESUMO

Chlamydia trachomatis is an intracellular bacterial pathogen that undergoes a biphasic developmental cycle, consisting of intracellular reticulate bodies and extracellular infectious elementary bodies. A conserved bacterial protease, HtrA, was shown previously to be essential for Chlamydia during the reticulate body phase, using a novel inhibitor (JO146). In this study, isolates selected for the survival of JO146 treatment were found to have polymorphisms in the acyl-acyl carrier protein synthetase gene (aasC). AasC encodes the enzyme responsible for activating fatty acids from the host cell or synthesis to be incorporated into lipid bilayers. The isolates had distinct lipidomes with varied fatty acid compositions. A reduction in the lipid compositions that HtrA prefers to bind to was detected, yet HtrA and MOMP (a key outer membrane protein) were present at higher levels in the variants. Reduced progeny production and an earlier cellular exit were observed. Transcriptome analysis identified that multiple genes were downregulated in the variants especially stress and DNA processing factors. Here, we have shown that the fatty acid composition of chlamydial lipids, HtrA, and membrane proteins interplay and, when disrupted, impact chlamydial stress response that could trigger early cellular exit. IMPORTANCE: Chlamydia trachomatis is an important obligate intracellular pathogen that has a unique biphasic developmental cycle. HtrA is an essential stress or virulence protease in many bacteria, with many different functions. Previously, we demonstrated that HtrA is critical for Chlamydia using a novel inhibitor. In the present study, we characterized genetic variants of Chlamydia trachomatis with reduced susceptibility to the HtrA inhibitor. The variants were changed in membrane fatty acid composition, outer membrane proteins, and transcription of stress genes. Earlier and more synchronous cellular exit was observed. Combined, this links stress response to fatty acids, membrane proteins, and HtrA interplay with the outcome of disrupted timing of chlamydial cellular exit.


Assuntos
Chlamydia trachomatis , Ácidos Graxos , Chlamydia trachomatis/genética , Ácidos Graxos/metabolismo , Proteínas de Membrana/metabolismo , Linhagem Celular , Peptídeo Hidrolases/metabolismo , Proteínas de Bactérias/genética
6.
JAMA ; 331(15): 1318-1319, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38506835

RESUMO

This JAMA Insights in the Climate Change and Health series discusses the importance of clinicians having awareness of changes in the geographic range, seasonality, and intensity of transmission of infectious diseases to help them diagnose, treat, and prevent these diseases.


Assuntos
Mudança Climática , Doenças Transmissíveis , Humanos , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Processos Climáticos , Clima Extremo , Incêndios Florestais , Gases de Efeito Estufa/efeitos adversos , Combustíveis Fósseis/efeitos adversos , Vetores de Doenças , Zoonoses/epidemiologia , Micoses/epidemiologia , Doenças Transmitidas pela Água/epidemiologia , Educação Médica , Política Pública
7.
Health Qual Life Outcomes ; 22(1): 19, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378572

RESUMO

BACKGROUND: Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ. METHODS: Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed. RESULTS: 111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory. CONCLUSIONS: RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.


Assuntos
Infecções por Vírus Respiratório Sincicial , Adulto , Humanos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Psicometria , Reprodutibilidade dos Testes , Qualidade de Vida , Inquéritos e Questionários
8.
Ecol Evol ; 14(2): e10895, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38333093

RESUMO

Habitat fragmentation can increase the chance of population bottlenecks and inbreeding, and may ultimately lead to reduced fitness and local extinction. Notelaea lloydii is a native olive species endemic to Australia and listed as vulnerable due to its restricted distribution. A recent molecular systematics study has revealed there might be some geographic structuring among N. lloydii populations. Therefore, we undertook a genome-wide single nucleotide polymorphism (SNP) analysis to determine levels and patterns of genetic diversity, inbreeding and gene flow within and among N. lloydii populations in south-eastern Queensland. Furthermore, as the reproductive phase of a plant's life history has a profound influence on genetic diversity, life history reproductive traits were also studied. Our SNP analysis revealed low genetic diversity, inbreeding and significant genetic structuring even among proximate populations. Results of a flower and fruit bagging experiment in two consecutive seasons revealed that N. lloydii produced many flowers but only a few fruits survived to maturity. There were no differences in bagged and un-bagged flowering and fruiting rates, and therefore, we conclude that the high fruit abortion rate was probably due to inbreeding depression and/or suboptimal conditions, rather than pollinator availability and insect attack. Overall, results of this study indicate that the populations of N. lloydii are small, inbred and genetically isolated and represent unique management units that require local conservation management due to ongoing threats associated with urbanisation.

9.
Behav Cogn Psychother ; 52(3): 211-225, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38263907

RESUMO

BACKGROUND: Timely intervention is beneficial to the effectiveness of eating disorder (ED) treatment, but limited capacity within ED services means that these disorders are often not treated with sufficient speed. This service evaluation extends previous research into guided self-help (GSH) for adults with bulimic spectrum EDs by assessing the feasibility, acceptability, and preliminary effectiveness of virtually delivered GSH using videoconferencing. METHOD: Patients with bulimia nervosa (BN), binge eating disorder (BED) and other specified feeding and eating disorders (OSFED) waiting for treatment in a large specialist adult ED out-patient service were offered virtually delivered GSH. The programme used an evidence-based cognitive behavioural self-help book. Individuals were supported by non-expert coaches, who delivered the eight-session programme via videoconferencing. RESULTS: One hundred and thirty patients were allocated to a GSH coach between 1 September 2020 and 30 September 2022; 106 (82%) started treatment and 78 (60%) completed treatment. Amongst completers, there were large reductions in ED behaviours and attitudinal symptoms, measured by the ED-15. The largest effect sizes for change between pre- and post-treatment were seen for binge eating episode frequency (d = -0.89) and concerns around eating (d = -1.72). Patients from minoritised ethnic groups were over-represented in the non-completer group. CONCLUSIONS: Virtually delivered GSH is feasible, acceptable and effective in reducing ED symptoms amongst those with bulimic spectrum disorders. Implementing virtually delivered GSH reduced waiting times, offering a potential solution for long waiting times for ED treatment. Further research is needed to compare GSH to other brief therapies and investigate barriers for patients from culturally diverse groups.


Assuntos
Transtorno da Compulsão Alimentar , Bulimia Nervosa , Bulimia , Terapia Cognitivo-Comportamental , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , Humanos , Transtorno da Compulsão Alimentar/terapia , Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/terapia , Bulimia Nervosa/psicologia , Bulimia/terapia
10.
Psychol Trauma ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38227445

RESUMO

BACKGROUND: Evidence suggests that adverse childhood experiences (ACEs) predict cognitive dysfunction, possibly through direct (e.g., brain structure/function changes) and indirect (e.g., increased psychopathology risk) pathways. However, extant studies have focused on young and older adults, with limited understanding of how ACEs affect cognitive health in midadulthood. OBJECTIVE: This study compared psychiatric and cognitive differences between adults at high- and low-risk of adverse health outcomes based on the ACE risk classification scheme. PARTICIPANTS AND SETTING: Adult patients (N = 211; 46.9% female; Mage = 44.1, SD = 17.1; Meducation = 13.8, SD = 3.0) consecutively referred for outpatient neuropsychological evaluation within a large, Midwestern academic medical center. METHOD: Patients were divided into high and low ACE groups based on the number of ACEs endorsed. Subsequently, a series of one-way analyses of variances were conducted to compare high versus low ACE groups on the Test of Premorbid Functioning, Wechsler Adult Intelligence Scale-Fourth Edition Digit Span Test, Trail Making Test-Parts A and B, Rey Auditory Verbal Learning Test, Beck Depression Inventory-II, and Beck Anxiety Inventory scores. RESULTS: Significant group differences were detected for anxiety and depression with the high ACE group endorsing significantly greater depression and anxiety symptoms relative to the low ACE group. High and low ACE groups did not significantly differ on any cognitive measures. CONCLUSIONS: Results indicate that an individual's psychological health, but not cognitive functioning, is impacted by the level of ACE exposure. Study findings highlight the importance of including ACE measures in neuropsychological evaluations, as it will aid in case conceptualization and tailoring treatment recommendations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

11.
Eur Eat Disord Rev ; 32(3): 476-489, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38109218

RESUMO

OBJECTIVE: The relative merits of inpatient or day-treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non-inferiority of a stepped-care day patient treatment (DPT) approach versus inpatient treatment as usual (IP-TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure. METHOD: Fifteen patients with AN (of 53 approached) participated and were followed-up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis. RESULTS: At baseline, participants in both trial arms rated stepped-care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38). CONCLUSIONS: No conclusions can be drawn concerning the effectiveness of IP-TAU and stepped-care DPT, but the latter was perceived more positively. Patient-related, service-related and systemic factors (COVID-19) contributed to the trial's failure. Lessons learnt can inform future studies.


Assuntos
Anorexia Nervosa , Adulto , Humanos , Anorexia Nervosa/terapia , Hospitalização , Índice de Massa Corporal , Aprendizagem , Autopsia
12.
Pain Manag ; 13(12): 723-728, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059379

RESUMO

Although the pathogenesis of migraine is not fully understood, accumulating evidence indicates migraine may be driven by impaired brain energy metabolism in the context of pathologically high levels of adenosine. Considerable evidence indicates that aminophylline, an adenosine receptor antagonist, can provide strong therapeutic relief in pain, particularly post-dural headache. Moreover, direct observations from a previously published observational case series have demonstrated a strong therapeutic impact of low-dose aminophylline in patients with severe, unremitting migraine attacks. Although higher doses of aminophylline are associated with an unfavourable adverse effect profile, low doses of aminophylline are associated with minimal adverse effects. Despite this promise, double-blinded randomized trials will be needed to determine the true therapeutic efficacy of low-dose aminophylline in migraine.


Assuntos
Aminofilina , Transtornos de Enxaqueca , Dor , Humanos , Aminofilina/administração & dosagem , Aminofilina/efeitos adversos , Transtornos de Enxaqueca/tratamento farmacológico , Dor/tratamento farmacológico
13.
Ecol Evol ; 13(12): e10783, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38053788

RESUMO

Medium to large rainforest mammals are key conservation flagship groups that offer non-redundant ecosystem functions, but anthropic pressures, such as illegal hunting, may strongly affect their occupancy in Amazonia. We combined camera traps and occupancy models to assess the influence of distance from human settlements, the number of families per settlement and the synergetic effect of the average weight of 27 species on the occupancy probability of mammals. Specifically, we classified mammal species according to the game preferences of hunters (i.e. a group of species depleted for bushmeat, a group of species hunted for retaliation and a group of non-hunted species). We also accounted for the influence on the detection probability of each group of both the number of days each camera operated and the body weight of mammals. The occupancy probability of the bushmeat group (i.e. deer, peccaries, agoutis, pacas and armadillos) was lower at locations closer to human settlements. Still, the number of families correlated positively with occupancy, with the occupancy probability of the group being slightly higher at sites with more families. This difference was probably due to larger and more abundant crops and fruiting trees attracting wildlife at such sites. Conversely, the occupancy probability of the retaliation group (i.e. carnivores) and the non-hunted group (i.e. opossums, spiny rats, squirrels and anteaters) were indifferent to anthropogenic stressors. The detection probability of the non-hunted and particularly the most depleted species correlated negatively with body weight. This may suggest that larger species, especially those from the bushmeat group, are rarer or less abundant in the system, possibly because they are the preferable target of hunters. In the long term, locals will likely need to travel long distances to find harvest meat. Poaching also threatens food security since game bushmeat is an essential source of protein for isolated rural Amazonians.

14.
Viruses ; 15(12)2023 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-38140684

RESUMO

Norovirus infection is influenced by the presence of commensal bacteria, and both human and murine norovirus (MNV) bind to these bacteria. These virus-bacterial interactions, as well as MNV infection, promote the increased production of bacterial extracellular vesicles (bEVs). However, no correlation has been made between specific bacterial groups, their vesicles, and their impact on norovirus infection. The current study evaluated the impact of select bacterial compositions of murine microbiomes using antibiotic (ABX) cocktails on MNV infection and bEV production. The goal of this research was to determine if increases in bEVs following MNV infection in mice were associated with changes in specific bacterial populations. Bacterial taxa were found to be differentially abundant in both ABX-treated and untreated mice, with the greatest change in bacterial taxa seen in mice treated with a broad-spectrum ABX cocktail. Specifically, Lachnospiraeae were found to be differentially abundant between a variety of treatment factors, including MNV infection. Overall, these results demonstrate that MNV infection can alter the abundance of bacterial taxa within the microbiota, as well as their production of extracellular vesicles, and that the use of selective antibiotic treatments can allow the detection of viral impacts on the microbiome that might otherwise be masked.


Assuntos
Infecções por Caliciviridae , Microbiota , Animais , Humanos , Camundongos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
15.
BMJ Open ; 13(11): e077377, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993158

RESUMO

INTRODUCTION: Clinical staging models in psychiatry assert that there are earlier, less severe or more malleable forms of illness that are distinguishable from later, more chronic forms of illness, and that these stages may have different prognostic and treatment implications. Previous reviews on clinical staging in eating disorders (EDs) suggest a staging heuristic could be useful for anorexia nervosa, but less research is available on how this applies to other EDs. An up-to-date review is required to synthesise new and heterogenous avenues of research. This scoping review aims to explore the extent and types of evidence in relation to illness staging for EDs and how these concepts are associated with treatment response and outcomes. METHODS AND ANALYSIS: This protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension for Scoping Reviews checklist and the Joanna Briggs Institute Reviewer's Manual. We will consider any documents providing evidence for clinical staging such as those which describe full or partial staging models, for all EDs, across various domains of assessment and functioning. Participants will include clinical or non-clinical population samples with full-syndrome EDs or disordered eating behaviour. PubMed, PsycINFO, MEDLINE and Web of Science databases will be systematically searched for relevant literature. Two authors will export documents and screen titles, abstracts and full texts. Data will be extracted into a charting form drafted by the authors. A narrative summary of the documents will be conducted in line with the study aims. Finally, clinical and research recommendations will be outlined. ETHICS AND DISSEMINATION: Ethical approval will not be required to synthesise published and unpublished literature. The study will be published in a peer-reviewed journal and shared at conferences, via social media, and in other communications.


Assuntos
Anorexia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Academias e Institutos , Lista de Checagem , Comunicação , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Literatura de Revisão como Assunto
16.
Front Neurol ; 14: 1235909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780723

RESUMO

Fahr's disease, or primary familial brain calcification (PFBC), is a rare genetic neurologic disease characterized by abnormal calcification of the basal ganglia, subcortical white matter and cerebellum. Common clinical features include parkinsonism, neuropsychiatric symptoms, and cognitive decline. Genes implicated in Fahr's disease include PDGFB, PDGFRB, SLC20A2, XPR1, MYORG, and JAM2. We present the case of a 51-year-old woman who developed subacute cognitive and behavioral changes primarily affecting frontal-subcortical pathways and parkinsonism in association with extensive bilateral calcifications within the basal ganglia, subcortical white matter, and cerebellum on neuroimaging. Relevant family history included a paternal aunt with parkinsonism at age 50. Normal parathyroid hormone and calcium levels in the patient's serum ruled out hypoparathyroidism or pseudohypoparathyroidism as causes for the intracranial calcifications. Genetic panel sequencing revealed a variant of unknown significance in the PDGFRB gene resulting in a p.Arg919Gln substitution in the tyrosine kinase domain of PDGFRB protein. To our knowledge this is the first report of a p.Arg919Gln variant in the PDGFRB gene associated with PFBC. Although co-segregation studies were not possible in this family, the location of the variant is within the tyrosine kinase domain of PDGFRB and pathogenicity calculators predict it is likely to be pathogenic. This report adds to the list of genetic variants that warrant functional analysis and could underlie the development of PFBC, which may help to further our understanding of its pathogenesis and the development of targeted therapies for this disorder.

17.
Metab Brain Dis ; 38(8): 2583-2589, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37747630

RESUMO

Metabolic dysfunction is an important factor in the pathogenesis of motor neuron disease, but its prevalence and association with survival in this disorder is unknown. We hypothesized that patients with motor neuron disease would show a higher prevalence of metabolic syndrome compared to the general New Zealand population, and that metabolic syndrome would be associated with worsened survival. We undertook a retrospective analysis in 109 motor neuron disease patients diagnosed and treated at Waikato Hospital from 2013 to 2020. Demographic, clinical, and laboratory data were collected. Survival was defined as the date of initial symptom onset to the date of death. Of 104 eligible patients, 34 patients (33%) had metabolic syndrome (33% of Europeans, 46% of Maori). Mean survival in motor neuron disease patients with metabolic syndrome was significantly reduced compared to patients without metabolic syndrome (38 vs. 61 months, P = 0.044), with a 5-year survival rate of 21% for the former and 38% for the latter (P = 0.012). Compared with the general New Zealand population, metabolic syndrome is highly prevalent amongst motor neuron disease patients in the Waikato region and it is associated with worsened survival. Metabolic dysfunction may be a key factor underlying the pathogenesis of motor neuron disease.


Assuntos
Esclerose Lateral Amiotrófica , Síndrome Metabólica , Doença dos Neurônios Motores , Humanos , Povo Maori , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Doença dos Neurônios Motores/epidemiologia , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/diagnóstico , Prevalência , Estudos Retrospectivos
18.
JFMS Open Rep ; 9(2): 20551169231191076, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37614780

RESUMO

Case summary: A 5-year-old female neutered Siberian Forest Cat presented with a 7-day history of lethargy, hyporexia and weight loss. Abdominal ultrasonography revealed bilateral renal changes suggestive of neoplasia. Thoracic radiography documented diffuse pulmonary nodules. The cat was euthanased during diagnostic investigations. Histopathological assessment and immunohistochemical staining of post-mortem renal biopsies were consistent with a histiocytic lesion, most likely histiocytic sarcoma (HS). The lung lesions were suspected of representing disseminated disease. Relevance and novel information: HS is considered a rare neoplastic process in cats. This report describes a case of feline bilateral renal HS with suspected concomitant pulmonary involvement. A primary renal origin was suspected, with the lung lesions being a result of disseminated disease. Renal HS should be included as a differential diagnosis when renal ultrasonography reveals changes suggestive of neoplasia.

19.
J Prosthet Dent ; 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37640608

RESUMO

Bacterial recontamination of the empty space is of concern in the time between the post space preparation and cementation of a cast post-and-core. This dental technique describes a novel treatment approach with sterilized polytetrafluoroethylene tape and a reinforced zinc-oxide eugenol restorative material to maintaining asepsis of the root canal space while awaiting fabrication and delivery of a cast post-and-core. On delivery of the cast post-and-core, the material can be removed with minimal time and effort.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA