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1.
Nature ; 627(8003): 295-300, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38383784

RESUMO

The ability to detect single photons has led to the advancement of numerous research fields1-11. Although various types of single-photon detector have been developed12, because of two main factors-that is, (1) the need for operating at cryogenic temperature13,14 and (2) the incompatibility with complementary metal-oxide-semiconductor (CMOS) fabrication processes15,16-so far, to our knowledge, only Si-based single-photon avalanche diode (SPAD)17,18 has gained mainstream success and has been used in consumer electronics. With the growing demand to shift the operation wavelength from near-infrared to short-wavelength infrared (SWIR) for better safety and performance19-21, an alternative solution is required because Si has negligible optical absorption for wavelengths beyond 1 µm. Here we report a CMOS-compatible, high-performing germanium-silicon SPAD operated at room temperature, featuring a noise-equivalent power improvement over the previous Ge-based SPADs22-28 by 2-3.5 orders of magnitude. Key parameters such as dark count rate, single-photon detection probability at 1,310 nm, timing jitter, after-pulsing characteristic time and after-pulsing probability are, respectively, measured as 19 kHz µm-2, 12%, 188 ps, ~90 ns and <1%, with a low breakdown voltage of 10.26 V and a small excess bias of 0.75 V. Three-dimensional point-cloud images are captured with direct time-of-flight technique as proof of concept. This work paves the way towards using single-photon-sensitive SWIR sensors, imagers and photonic integrated circuits in everyday life.

2.
Trends Genet ; 39(3): 217-232, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36642680

RESUMO

Topologically associating domains (TADs) are integral to spatial genome organization, instructing gene expression, and cell fate. Recently, several advances have uncovered roles for noncoding RNAs (ncRNAs) in the regulation of the form and function of mammalian TADs. Phase separation has also emerged as a potential arbiter of ncRNAs in the regulation of TADs. In this review we discuss the implications of these novel findings in relation to how ncRNAs might structurally and functionally regulate TADs from two perspectives: moderating loop extrusion through interactions with architectural proteins, and facilitating TAD phase separation. Additionally, we propose future studies and directions to investigate these phenomena.


Assuntos
Montagem e Desmontagem da Cromatina , Genoma , Animais , Diferenciação Celular , Cromatina , Mamíferos/genética
3.
Bioorg Med Chem Lett ; 104: 129711, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38521175

RESUMO

WRN helicase is a critical protein involved in maintaining genomic stability, utilizing ATP hydrolysis to dissolve DNA secondary structures. It has been identified as a promising synthetic lethal target for microsatellite instable (MSI) cancers. However, few WRN helicase inhibitors have been discovered, and their potential binding sites remain unexplored. In this study, we analyzed potential binding sites for WRN inhibitors and focused on the ATP-binding site for screening new inhibitors. Through molecular dynamics-enhanced virtual screening, we identified two compounds, h6 and h15, which effectively inhibited WRN's helicase and ATPase activity in vitro. Importantly, these compounds selectively targeted WRN's ATPase activity, setting them apart from other non-homologous proteins with ATPase activity. In comparison to the homologous protein BLM, h6 exhibits some degree of selectivity towards WRN. We also investigated the binding mode of these compounds to WRN's ATP-binding sites. These findings offer a promising strategy for discovering new WRN inhibitors and present two novel scaffolds, which might be potential for the development of MSI cancer treatment.


Assuntos
Trifosfato de Adenosina , Antineoplásicos , Inibidores Enzimáticos , Simulação de Dinâmica Molecular , Helicase da Síndrome de Werner , Trifosfato de Adenosina/química , Sítios de Ligação , Helicase da Síndrome de Werner/antagonistas & inibidores , Helicase da Síndrome de Werner/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/química , Antineoplásicos/farmacologia , Instabilidade de Microssatélites/efeitos dos fármacos , Neoplasias/genética , Humanos
4.
Cardiology ; : 1-12, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39342934

RESUMO

INTRODUCTION: The aim of this study was to evaluate the utility of 2D-STI and real-time three-dimensional echocardiography (RT-3DE) in assessing changes in left atrial (LA) structure and function in patients with paroxysmal atrial fibrillation (PAF) post-radiofrequency catheter ablation (RFCA). METHODS: A retrospective analysis was conducted on 44 PAF patients who underwent RFCA at BA Hospital from March 2022 to March 2023. An age- and gender-matched control group of 32 healthy individuals was also included. Comprehensive echocardiographic parameters including LA dimensions (LAAPD, LALRD), volumes (LAVmin, LAVmax), ejection fraction (LAEF), and tissue velocities (a', Ar) were compared between groups. Post-RFCA changes in these parameters were also assessed at 1, 3, and 6 months. RESULTS: Pre-RFCA, PAF patients demonstrated larger LA dimensions and volumes with reduced LAEF and tissue velocities compared to controls. Post-RFCA, there was a significant improvement in LAEF and left ventricular ejection fraction at 1, 3, and 6 months, with the most pronounced changes observed at 6 months. LA dimensions increased initially but then decreased from 1 to 6 months post-RFCA. Notably, strain rate (SRS, SRE, SRA) measurements in various LA segments improved progressively, with the most significant enhancements at 6 months, suggesting improved atrial mechanics. CONCLUSION: The application of 2D-STI and RT-3DE provides a quantitative means to evaluate the structural and functional changes in the LA of PAF patients following RFCA. The progressive improvements in LA dimensions, volumes, and strain measurements up to 6-month post-RFCA indicate the potential of these techniques in monitoring treatment efficacy and patient recovery.

5.
Neurol Sci ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090356

RESUMO

BACKGROUND: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. METHODS: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. RESULTS: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. CONCLUSIONS: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra.

6.
Arch Phys Med Rehabil ; 105(4): 631-638, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38092231

RESUMO

OBJECTIVE: To compare the efficacy of combination therapy (hydrodilatation and subdeltoid bursa injection with corticosteroid, mobilization, and physical therapy [PT]) with that of PT alone for treating frozen shoulder. DESIGN: A prospective, 2-arm parallel, single-blinded, randomized controlled trial. SETTING: Rehabilitation clinic of a private academic hospital. PARTICIPANTS: Patients (n=70) with frozen shoulder (freezing stage). INTERVENTIONS: Participants (n=35) in the combination group underwent hydrodilatation and subdeltoid bursa injection with corticosteroid twice, mobilization, and usual-care PT for 8 weeks; participants (n=35) in the PT group received only the usual-care PT for 8 weeks. MAIN OUTCOME MEASURES: The Shoulder Pain and Disability Index (SPADI) was the primary outcome measure. The secondary outcome measures were pain scores on a visual analog scale, range of motion (ROM), the Shoulder Disability Questionnaire (SDQ), quality of life (evaluated using the 36-item Short-Form Health Survey [SF-36]), and self-assessment of the treatment effect. RESULTS: Compared with the PT group, the combination group had significantly better pain (during activity), SPADI, SDQ, active and passive ROM, and self-assessment scores (all P<.001) as well as scores on some parts of the SF-36 (physical function and bodily pain, P<.05). Between-group differences were significant at the 1-, 2-, 4-, and 6-month follow-ups. CONCLUSIONS: A combination of hydrodilatation (with corticosteroid), bursal corticosteroid injection, and joint mobilization with PT was superior to PT alone for treating frozen shoulder, and the effects persisted for at least 6 months.


Assuntos
Bursite , Articulação do Ombro , Humanos , Ombro , Estudos Prospectivos , Método Simples-Cego , Qualidade de Vida , Injeções Intra-Articulares , Corticosteroides/uso terapêutico , Modalidades de Fisioterapia , Bursite/tratamento farmacológico , Dor de Ombro , Amplitude de Movimento Articular , Resultado do Tratamento
7.
Perception ; 53(1): 44-60, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37899595

RESUMO

One of key mechanisms implicated in multisensory processing is neural oscillations in distinct frequency band. Many studies explored the modulation of attention by recording the electroencephalography signals when subjects attended one modality, and ignored the other modality input. However, when attention is directed toward one modality, it may be not always possible to shut out completely inputs from a different modality. Since many situations require division of attention between audition and vision, it is imperative to investigate the neural mechanisms underlying processing of concurrent auditory and visual sensory streams. In the present study, we designed a task of audiovisual semantic discrimination, in which the subjects were asked to share attention to both auditory and visual stimuli. We explored the contribution of neural oscillations in lower-frequency to the modulation of divided attention on audiovisual integration. Our results implied that theta-band activity contributes to the early modulation of divided attention, and delta-band activity contributes to the late modulation of divided attention to audiovisual integration. Moreover, the fronto-central delta- and theta-bands activity is likely a marker of divided attention in audiovisual integration, and the neural oscillation on delta- and theta-bands is conducive to allocating attention resources to dual-tasking involving task-coordinating abilities.


Assuntos
Percepção Auditiva , Percepção Visual , Humanos , Estimulação Acústica/métodos , Eletroencefalografia/métodos , Semântica , Estimulação Luminosa
8.
Int Rev Psychiatry ; 36(4-5): 350-360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39470074

RESUMO

East Asian countries are known to take a more permissive attitude towards suicide. However, the nuanced beliefs fostering these attitudes remain unexplored. This study aimed to examine socio-demographic and clinical factors associated with the three normative beliefs on suicide in Taiwan - suicide as human rights, suicide as an individual choice, and that suicide is irrational - and the association of these beliefs with supportive attitudes towards governmental suicide prevention measures. A nationally representative survey, based on calls to landlines and mobile phones, was conducted in 2020 with a sample size of 1,087. Logistic regression analyses were employed to examine the associations between socio-demographic variables, mental health status, normative suicide beliefs, and attitudes towards suicide prevention. We found that the prevalence rates for the three normative beliefs were 55.3% for human rights, 26.7% for individual choice, and 73.7% for irrationality, respectively. Human rights belief was more prevalent among younger, unmarried, and highly educated individuals. Individual choice belief was more common among the younger, those in the 'other' marital group, less educated individuals, and those without mental conditions. The irrationality belief was more likely to be endorsed by the unemployed group. Regardless of participants' normative suicide beliefs, a significant majority (89.0%) supported governmental investment in suicide prevention. However, human rights and individual choice beliefs were associated with diminished support for governmental suicide prevention measures (aOR = 0.6, p = 0.003, and aOR = 0.6, p = 0.005, respectively). Taiwanese society overwhelmingly supports governmental suicide prevention measures, suggesting a leaning towards hard paternalism. However, those who believed that suicide is a human right and individual choice were less likely to support governmental suicide prevention efforts. Our findings suggest that health education addressing these two normative beliefs, particularly among the youth and unmarried individuals, could be potential strategies in future suicide prevention measures.


Assuntos
Direitos Humanos , Prevenção do Suicídio , Humanos , Taiwan , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Suicídio/psicologia , Idoso , Conhecimentos, Atitudes e Prática em Saúde
9.
Chem Biodivers ; 21(3): e202400118, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38349284

RESUMO

Five new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H-K (1-4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine-derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR-ESI-MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti-inflammatory activities of compounds 1-12 were tested. Unfortunately, all of isolated compounds were inactivity.


Assuntos
Fungos , Fusarium , Antibacterianos/química , Fungos/química , Fusarium/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
10.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38610533

RESUMO

In this paper, we introduce a novel artificial intelligence technique with an attention mechanism for half-space electromagnetic imaging. A dielectric object in half-space is illuminated by TM (transverse magnetic) waves. Since measurements can only be made in the upper space, the measurement angle will be limited. As a result, we apply a back-propagation scheme (BPS) to generate an initial guessed image from the measured scattered fields for scatterer buried in the lower half-space. This process can effectively reduce the high nonlinearity of the inverse scattering problem. We further input the guessed images into the generative adversarial network (GAN) and the self-attention generative adversarial network (SAGAN), respectively, to compare the reconstruction performance. Numerical results prove that both SAGAN and GAN can reconstruct dielectric objects and the MNIST dataset under same measurement conditions. Our analysis also reveals that SAGAN is able to reconstruct electromagnetic images more accurately and efficiently than GAN.

11.
Anal Chem ; 95(6): 3317-3324, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36724516

RESUMO

Mass spectrometry imaging (MSI) is a powerful tool that can be used to simultaneously investigate the spatial distribution of different molecules in samples. However, it is difficult to comprehensively analyze complex biological systems with only a single analytical technique due to different analytical properties and application limitations. Therefore, many analytical methods have been combined to extend data interpretation, evaluate data credibility, and facilitate data mining to explore important temporal and spatial relationships in biological systems. Image registration is an initial and critical step for multimodal imaging data fusion. However, the image registration of multimodal images is not a simple task. The property difference between each data modality may include spatial resolution, image characteristics, or both. The image registrations between MSI and different imaging techniques are often achieved indirectly through histology. Many methods exist for image registration between MSI data and histological images. However, most of them are manual or semiautomatic and have their prerequisites. Here, we built MSI Registrar (MSIr), a web service for automatic registration between MSI and histology. It can help to reduce subjectivity and processing time efficiently. MSIr provides an interface for manually selecting region of interests from histological images; the user selects regions of interest to extract the corresponding spectrum indices in MSI data. In the performance evaluation, MSIr can quickly map MSI data to histological images and help pinpoint molecular components at specific locations in tissues. Most registrations were adequate and were without excessive shifts. MSIr is freely available at https://msir.cmdm.tw and https://github.com/CMDM-Lab/MSIr.


Assuntos
Diagnóstico por Imagem , Técnicas Histológicas , Espectrometria de Massas/métodos , Mineração de Dados
12.
Genet Med ; 25(3): 100348, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36571464

RESUMO

PURPOSE: RAS genes (HRAS, KRAS, and NRAS) are commonly found to be mutated in cancers, and activating RAS variants are also found in disorders of somatic mosaicism (DoSM). A survey of the mutational spectrum of RAS variants in DoSM has not been performed. METHODS: A total of 938 individuals with suspected DoSM underwent high-sensitivity clinical next-generation sequencing-based testing. We investigated the mutational spectrum and genotype-phenotype associations of mosaic RAS variants. RESULTS: In this article, we present a series of individuals with DoSM with RAS variants. Classic hotspots, including Gly12, Gly13, and Gln61 constituted the majority of RAS variants observed in DoSM. Furthermore, we present 12 individuals with HRAS and KRAS in-frame duplication/insertion (dup/ins) variants in the switch II domain. Among the 18.3% individuals with RAS in-frame dup/ins variants, clinical findings were mainly associated with vascular malformations. Hotspots were associated with a broad phenotypic spectrum, including vascular tumors, vascular malformations, nevoid proliferations, segmental overgrowth, digital anomalies, and combinations of these. The median age at testing was higher and the variant allelic fraction was lower in individuals with in-frame dup/ins variants than those in individuals with mosaic RAS hotspots. CONCLUSION: Our work provides insight into the allelic and clinical heterogeneity of mosaic RAS variants in nonmalignant conditions.


Assuntos
Mosaicismo , Malformações Vasculares , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Mutação , Alelos , Malformações Vasculares/genética
13.
Alzheimer Dis Assoc Disord ; 37(3): 215-221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37615486

RESUMO

OBJECTIVE: To examine international variations in national diagnosis and certification habits prefer recording dementia (D) versus Alzhiemer disease (AD) as the underlying cause of death (UCOD) and their associations with mortality rates of dementia and AD. METHODS: We calculated proportions of D/D+AD and AD/D+AD deaths as proxies of national diagnosis and certification habits. Pearson correlation coefficients (r) were estimated to assess the associations of proportions with the mortality rates of dementia or AD among adults aged 75 to 84 years across 38 countries. RESULTS: The countries with a high preference for recording dementia as the UCOD were Taiwan and Latvia with proportion of D/D+AD deaths of 92% and 88%, respectively, and those with a high preference for recording AD as the UCOD were Slovenia, Turkey, and Poland with proportion of AD/D+AD deaths of 100%, 99%, and 89%, respectively. The r values for the proportions and mortality rate for dementia and AD were 0.67 (95% CI: 0.44-0.81) and 0.46 (95% CI: 0.16-0.68), respectively. CONCLUSION: We identified a small number of countries with obvious natonal diagnosis and certification habits preferring dementia or AD and had moderate effects on international variations in the mortality rates of dementia and AD.


Assuntos
Doença de Alzheimer , Adulto , Humanos , Doença de Alzheimer/diagnóstico , Estudos Transversais , Causas de Morte , Taiwan/epidemiologia , Turquia
14.
Analyst ; 148(10): 2343-2351, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37185609

RESUMO

Helicases are crucial enzymes in DNA and RNA metabolism and function by unwinding particular nucleic acid structures. However, most convenient and high-throughput helicase assays are limited to the typical duplex DNA. Herein, we developed an immunosorbent assay to monitor the Werner syndrome (WRN) helicase unwinding a wide range of DNA structures, such as a replication fork, a bubble, Holliday junction, G-quadruplex and hairpin. This assay could sensitively detect the unwinding of DNA structures with detection limits around 0.1 nM, and accurately monitor the substrate-specificity of WRN with a comparatively less time-consuming and high throughput process. Remarkably, we have established that this new assay was compatible in evaluating helicase inhibitors and revealed that the inhibitory effect was substrate-dependent, suggesting that diverse substrate structures other than duplex structures should be considered in discovering new inhibitors. Our study provided a foundational example for using this new assay as a powerful tool to study helicase functions and discover potent inhibitors.


Assuntos
RecQ Helicases , Síndrome de Werner , Humanos , RecQ Helicases/genética , RecQ Helicases/metabolismo , Imunoadsorventes , Replicação do DNA , Helicase da Síndrome de Werner/genética , Helicase da Síndrome de Werner/metabolismo , Exodesoxirribonucleases/metabolismo , DNA/química , Síndrome de Werner/genética
15.
Inorg Chem ; 62(19): 7212-7219, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37139601

RESUMO

Developing a photosensitizer with high efficiency and long-term stability for photocatalytic hydrogen evolution is highly desirable yet remains a challenge. Herein, a novel Ir(III) complex-based photosensitizer (Ir3) bearing coumarin and triphenylamine groups is designed. Ir3 exhibits record activity and durability among reported transition metal complexes for photocatalytic hydrogen evolution, with a TON of 198,363 and a duration of 214 h. The excellent photocatalytic performance of Ir3 can be attributed to the synergistic effect of coumarin and triphenylamine, which improves the visible light absorption, charge separation, and electron transfer capacity of photosensitizers. This is an efficient and long-lived Ir(III) photosensitizer constructed on the basis of a synergistic approach, which could provide a new insight for the development of high-performance Ir(III) photosensitizers at the molecular level.

16.
Inorg Chem ; 62(45): 18331-18337, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37910803

RESUMO

Here, two isomeric ionic zero-dimensional indium bromide crystals of α (1)/ß (2)-[OPy][InBr4(Phen)] (OPy = N-octylpyridinium; Phen = 1,10-phenanthroline) have been isolated simply by changing the cooling conditions in solvothermal syntheses. Structural comparisons indicate their different supramolecular interactions, which can be confirmed by Hirshfeld surface analyses. The crystal 2 has additional hydrogen bonds and π-π interactions; as a result, the more compact stacking of 2 could result in a 10-fold higher photoluminescence (PL) quantum yield (PLQY) than that of 1. Density functional theory calculations confirm the electron transition from the inorganic moiety to the organic ligand, which provides a further understanding of the optical process. This work provides a new idea for designing PL indium-based halides by understanding the structure-PL relationship.

17.
Clin Rehabil ; 37(9): 1189-1200, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37021475

RESUMO

OBJECTIVE: To investigate whether combination of corticosteroid subdeltoid injections and physiotherapy was more effective than either treatment alone in chronic subacromial bursitis. DESIGN: Prospective, three-arm randomised controlled trial. SETTING: Rehabilitation department of an academic hospital. SUBJECTS: Patients with chronic subacromial bursitis. INTERVENTIONS: Patients were divided into corticosteroid injection (N = 36), physiotherapy (N = 40) and combined (N = 35) groups. Two corticosteroid subdeltoid injections in corticosteroid group, 8-week physical therapy emphasising on therapeutic exercise in physiotherapy group, and combined both treatments in combined group. MAIN OUTCOME MEASURES: The primary outcome measures were pain visual analogue scale and Shoulder Pain and Disability Index at 8 weeks after finishing treatment. The secondary outcome measures were active range of motion, Shoulder Disability Questionnaire, Western Ontario Rotator Cuff Index, patient's evaluation of treatment effect, and symptom recurrence. RESULTS: Group comparison showed significant statistical difference in shoulder flexion (P < 0.003) and patient's evaluation of treatment effect (P < 0.001). The time and group interactions comparison revealed significant statistical differences in pain score (P < 0.024), external rotation (P < 0.044) and patient's evaluation of treatment effect (P < 0.001). The above statistics were in favour of the corticosteroid and combined groups rather than physiotherapy group. The percentage of recurrence was 36.1, 7.5 and 17.1 in the corticosteroid, physiotherapy and combined groups, respectively (P < 0.001). CONCLUSION: Corticosteroid subdeltoid injection, or combined with physiotherapy, was superior to physiotherapy alone, but the recurrence rate was least in the physiotherapy group.


Assuntos
Bursite , Síndrome de Colisão do Ombro , Humanos , Estudos Prospectivos , Injeções Intra-Articulares , Corticosteroides/uso terapêutico , Modalidades de Fisioterapia , Doença Crônica , Bursite/diagnóstico , Bursite/terapia , Dor , Resultado do Tratamento , Dor de Ombro/diagnóstico , Dor de Ombro/tratamento farmacológico , Dor de Ombro/etiologia , Síndrome de Colisão do Ombro/terapia
18.
Proc Natl Acad Sci U S A ; 117(6): 3053-3062, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31980526

RESUMO

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (n = 24), cardiomyopathy, arrhythmia, and other cardiac diseases (n = 42), and diabetes and endocrine diseases (n = 17). A lack of genotype and phenotype associations, a potential burden for patient care, was observed in 69 (5.8%) individuals with P/LP variants. Genomics and metabolomics associations identified 61 (5.1%) heterozygotes with phenotype manifestations affecting serum metabolite levels in amino acid, lipid and cofactor, and vitamin pathways. Our descriptive analysis provides results on the integration of whole-genome sequencing and deep phenotyping for clinical assessments in adults.


Assuntos
Diagnóstico por Imagem , Metabolômica , Medicina de Precisão/métodos , Sequenciamento Completo do Genoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Predisposição Genética para Doença/genética , Genótipo , Cardiopatias/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
19.
J Orthop Sci ; 28(5): 1004-1010, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35945122

RESUMO

BACKGROUND: Shoulder disorders, including frozen shoulder, bursitis, and rotator cuff lesions, are common musculoskeletal problems in patients with Parkinson disease (PD). Because musculoskeletal ultrasound (US) can clearly image shoulder joints, we aimed to evaluate shoulder joints using US in patients with PD and healthy participants and correlation between US and PD severity. METHODS: This is a prospective case-control study. 50 patients with PD and 50 healthy subjects from the outpatient department were administered US for bilateral shoulders. For data analysis, we chose the more severely affected side in the PD group for matching with the corresponding shoulder in the control group according to age, sex, and body mass index. Pain and disability were measured using the Visual Analogue Scale (VAS) for pain, Shoulder Pain and Disability Index (SPADI), and the Shoulder Disability Questionnaire (SDQ). RESULTS: The PD group had higher VAS pain scores during activity (p = 0.003) and rest (p < 0.001), as well as the SPADI and SDQ scores (p < 0.001). In US findings, biceps long head tendon sheath effusion (p = 0.001), humeral head cortical irregularity (p = 0.012), and abnormality in the supraspinatus tendon (p = 0.003) were significantly greater in the PD group. Intra-group analysis in the PD group demonstrated a significant difference in passive flexion (p = 0.019) and supraspinatus tendinopathy (p = 0.033) on US examination during different disease stages. CONCLUSIONS: Patients with PD had more supraspinatus tendinopathy on US findings than control subjects. The lesion was significantly associated with disease severity. CLINICAL TRIAL NUMBER: NCT02702232.


Assuntos
Bursite , Doença de Parkinson , Lesões do Manguito Rotador , Articulação do Ombro , Tendinopatia , Humanos , Bursite/diagnóstico por imagem , Estudos de Casos e Controles , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/patologia , Ombro , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Dor de Ombro/etiologia , Dor de Ombro/complicações , Tendinopatia/complicações , Ultrassonografia , Masculino , Feminino
20.
Molecules ; 28(4)2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36838966

RESUMO

Recently zero-dimensional (0-D) inorganic-organic metal halides (IOMHs) have become a promising class of optoelectronic materials. Herein, we report a new photoluminescent (PL) 0-D antimony(III)-based IOMH single crystal, namely [H2BPZ][SbCl5]·H2O (BPZ = benzylpiperazine). Photophysical characterizations indicate that [H2BPZ][SbCl5]·H2O exhibits singlet/triplet dual-band emission. Density functional theory (DFT) calculations suggest that [H2BPZ][SbCl5]·H2O has the large energy difference between singlet and triplet states, which might induce the dual emission in this compound. Temperature-dependent PL spectra analyses suggest the soft lattice and strong electron-phonon coupling in this compound. Thermogravimetric analysis shows that the water molecules in the lattice of the title crystal could be removed by thermal treatment, giving rise to a dehydrated phase of [H2BPZ][SbCl5]. Interestingly, such structural transformation is accompanied by a reversible PL emission transition between red light (630 nm, dehydrated phase) and yellow light (595 nm, water-containing phase). When being exposed to an environment with 77% relative humidity, the emission color of the dehydrated phase was able to change from red to yellow within 20 s, and the red emission could be restored after reheating. The red to yellow emission switching could be achieved in acetone with water concentration as low as 0.2 vol%. The reversible PL transition phenomenon makes [H2BPZ][SbCl5]·H2O a potential material for luminescent water-sensing.


Assuntos
Temperatura Alta , Hipertermia Induzida , Antimônio , Cloretos , Luminescência , Halogênios
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