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1.
Nature ; 612(7939): 246-251, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36385532

RESUMO

A step towards the next generation of high-capacity, noise-resilient communication and computing technologies is a substantial increase in the dimensionality of information space and the synthesis of superposition states on an N-dimensional (N > 2) Hilbert space featuring exotic group symmetries. Despite the rapid development of photonic devices and systems, on-chip information technologies are mostly limited to two-level systems owing to the lack of sufficient reconfigurability to satisfy the stringent requirement for 2(N - 1) degrees of freedom, intrinsically associated with the increase of synthetic dimensionalities. Even with extensive efforts dedicated to recently emerged vector lasers and microcavities for the expansion of dimensionalities1-10, it still remains a challenge to actively tune the diversified, high-dimensional superposition states of light on demand. Here we demonstrate a hyperdimensional, spin-orbit microlaser for chip-scale flexible generation and manipulation of arbitrary four-level states. Two microcavities coupled through a non-Hermitian synthetic gauge field are designed to emit spin-orbit-coupled states of light with six degrees of freedom. The vectorial state of the emitted laser beam in free space can be mapped on a Bloch hypersphere defining an SU(4) symmetry, demonstrating dynamical generation and reconfiguration of high-dimensional superposition states with high fidelity.


Assuntos
Comunicação , Tecnologia da Informação , Fótons , Tecnologia
2.
Nano Lett ; 24(19): 5799-5807, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701332

RESUMO

Controlled growth of semiconductor nanowires with atomic precision offers the potential to tune the material properties for integration into scalable functional devices. Despite significant progress in understanding the nanowire growth mechanism, definitive control over atomic positions of its constituents, structure, and morphology via self-assembly remains challenging. Here, we demonstrate an exquisite control over synthesis of cation-ordered nanoscale superstructures in Ge-Sb-Te nanowires with the ability to deterministically vary the nanowire growth direction, crystal facets, and periodicity of cation ordering by tuning the relative precursor flux during synthesis. Furthermore, the role of anisotropy on material properties in cation-ordered nanowire superstructures is illustrated by fabricating phase-change memory (PCM) devices, which show significantly different growth direction dependent amorphization current density. This level of control in synthesizing chemically ordered nanoscale superstructures holds potential to precisely modulate fundamental material properties such as the electronic and thermal transport, which may have implications for PCM, thermoelectrics, and other nanoelectronic devices.

3.
Nano Lett ; 24(18): 5436-5443, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38656103

RESUMO

The ultrahigh surface area of two-dimensional materials can drive multimodal coupling between optical, electrical, and mechanical properties that leads to emergent dynamical responses not possible in three-dimensional systems. We observed that optical excitation of the WS2 monolayer above the exciton energy creates symmetrically patterned mechanical protrusions which can be controlled by laser intensity and wavelength. This observed photostrictive behavior is attributed to lattice expansion due to the formation of polarons, which are charge carriers dressed by lattice vibrations. Scanning Kelvin probe force microscopy measurements and density functional theory calculations reveal unconventional charge transport properties such as the spatially and optical intensity-dependent conversion in the WS2 monolayer from apparent n- to p-type and the subsequent formation of effective p-n junctions at the boundaries between regions with different defect densities. The strong opto-electrical-mechanical coupling in the WS2 monolayer reveals previously unexplored properties, which can lead to new applications in optically driven ultrathin microactuators.

4.
Eur Respir J ; 63(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423624

RESUMO

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.


Assuntos
Aspergilose Broncopulmonar Alérgica , Aspergilose Pulmonar Invasiva , Adulto , Criança , Humanos , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Imunoglobulina E , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Itraconazol/uso terapêutico , Micologia , Prednisolona
5.
Curr Opin Pulm Med ; 30(2): 156-166, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902135

RESUMO

PURPOSE OF REVIEW: Post-tuberculosis lung disease (PTLD) is an increasingly recognized and debilitating consequence of pulmonary tuberculosis (PTB). In this review, we provide a comprehensive overview of PTLD with airflow obstruction (PTLD-AFO), focusing on its burden, pathophysiology, clinical manifestations, diagnostic methods, and management strategies. RECENT FINDINGS: The relationship between PTLD and airflow obstruction is complex and multifactorial. Approximately 60% of the patients with PTLD have some spirometric abnormality. Obstruction is documented in 18-22% of PTLD patients. The host susceptibility and host response to mycobacterium drive the pathogenic mechanism of PTLD. A balance between inflammatory, anti-inflammatory, and fibrotic pathways decides whether an individual with PTB would have PTLD after microbiological cure. An obstructive abnormality in PTLD-AFO is primarily due to destruction of bronchial walls, aberrant healing, and reduction of mucosal glands. The most common finding on computed tomography (CT) of thorax in patients with PTLD-AFO is bronchiectasis and cavitation. Therefore, the 'Cole's vicious vortex' described in bronchiectasis applies to PTLD. A multidisciplinary approach is required for diagnosis and treatment. The disability-adjusted life-years (DALYs) attributed to PTLD represent about 50% of the total estimated burden of DALYs due to tuberculosis (TB). Patients with PTLD require comprehensive care that includes psychosocial support, pulmonary rehabilitation, and vaccination against respiratory pathogens. In the absence of trials evaluating different treatments for PTLD-AFO, therapy is primarily symptomatic. SUMMARY: PTLD with airflow obstruction has considerable burden and causes a significant morbidity and mortality. However, many aspects of PTLD-AFO still need to be answered. Studies are required to evaluate different phenotypes, especially concerning Aspergillus -related complications. The treatment should be personalized based on the predominant phenotype of airflow obstruction. Extensive studies to understand the exact burden, pathogenesis, and treatment of PTBLD-AFO are needed.


Assuntos
Bronquiectasia , Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Tuberculose Pulmonar , Humanos , Pulmão , Pneumopatias/complicações , Bronquiectasia/complicações
6.
J Asthma ; : 1-6, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38520686

RESUMO

BACKGROUND: The utility of two disease-severity indices, namely bronchiectasis severity index (BSI) and FACED score in allergic bronchopulmonary aspergillosis (ABPA) remains unknown. OBJECTIVE: To correlate the BSI and FACED scores with immunological parameters (serum IgE [total and A. fumigatus-specific], A. fumigatus-specific IgG, blood eosinophil count), and high-attenuation mucus on chest computed tomography in ABPA. The secondary objectives were to evaluate the correlation between BSI and FACED scores and correlate the BSI/FACED scores with the bronchiectasis health questionnaire (BHQ) and Saint George's Respiratory Questionnaire (SGRQ). METHODS: We included treatment-naïve ABPA subjects with bronchiectasis in a prospective observational study. We computed the BSI and FACED scores for each subject before initiating treatment. The subjects also completed two quality-of-life questionnaires (BHQ and SGRQ). RESULTS: We included 91 subjects. The mean (standard deviation) BSI and FACED scores were 3.43 (3.39) and 1.43 (1.27). We found no correlation between BSI or FACED with any immunological parameter or high-attenuation mucus. There was a strong correlation between BSI and FACED scores (r = 0.76, p < 0.001). We found a weak correlation between BSI and BHQ/SGRQ and FACED and SGRQ. CONCLUSION: We found no correlation between BSI and FACED with immunological parameters in ABPA. However, we found a significant correlation between BSI and FACED and a weak correlation between SGRQ and BHQ. ABPA likely requires a separate disease-severity scoring system.

7.
Semin Respir Crit Care Med ; 45(1): 114-127, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154470

RESUMO

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by Aspergillus fumigatus in patients with asthma and cystic fibrosis. The pathophysiology of ABPA involves a complex interplay between the fungus and the host immune response, which causes persistent inflammation and tissue damage. Patients present with chronic cough, wheezing, and dyspnea due to uncontrolled asthma. Characteristic symptoms include the expectoration of brownish mucus plugs. Radiographic findings often reveal fleeting pulmonary infiltrates, bronchiectasis, and mucus impaction. However, the definitive diagnosis of ABPA requires a combination of clinical, radiological, and immunological findings. The management of ABPA aims to reduce symptoms, prevent disease progression, and minimize the future risk of exacerbations. The treatment approach involves systemic glucocorticoids or antifungal agents to suppress the inflammatory response or fungal growth and prevent exacerbations. Biological agents may be used in patients with severe disease or glucocorticoid dependence. This review provides an overview of the clinical manifestations and current treatment options for ABPA.


Assuntos
Aspergilose Broncopulmonar Alérgica , Asma , Bronquiectasia , Fibrose Cística , Humanos , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Asma/tratamento farmacológico , Aspergillus fumigatus , Fibrose Cística/complicações , Bronquiectasia/tratamento farmacológico , Glucocorticoides/uso terapêutico
8.
Semin Respir Crit Care Med ; 45(1): 102-113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38196060

RESUMO

Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.


Assuntos
Pneumopatias , Aspergilose Pulmonar , Tuberculose , Humanos , Doença Crônica , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/terapia , Pulmão , Pneumopatias/complicações , Tuberculose/complicações , Infecção Persistente
9.
Respiration ; 103(6): 336-343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38531335

RESUMO

INTRODUCTION: Observational data suggest that the 19-gauge (G) needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) offers a higher diagnostic yield than the 22-G needle in sarcoidosis. No randomized trial has compared the yield of the two needles. METHODS: We randomized consecutive subjects with suspected sarcoidosis and enlarged thoracic lymph nodes to undergo EBUS-TBNA with either the 19-G or the 22-G needle. We compared the study groups for diagnostic sensitivity (primary outcome) assessed by the yield of granulomas in subjects finally diagnosed with sarcoidosis. We also compared the sample adequacy, difficulty performing the needle puncture assessed on a visual analog scale (VAS), the subject's cough intensity on an operator-rated VAS, and procedure-related complications (secondary outcomes). RESULTS: We randomized 150 (mean age, 43.0 years; 55% women) subjects and diagnosed sarcoidosis in 116 subjects. The diagnostic sensitivity of the 19-G needle (45/60, 75.0%) was not higher (p = 0.52) than the 22-G needle (39/56, 69.6%). We obtained adequate aspirates in 90.0% and 85.7% of subjects in the respective groups (p = 0.48). The operators had greater difficulty puncturing lymph nodes with the 19-G needle (p = 0.03), while the operator-assessed cough intensity was similar in the groups (p = 0.41). Transient hypoxemia was the only complication encountered during EBUS-TBNA (two subjects in either group). CONCLUSION: We did not find the 19-G needle superior to the 22-G in diagnostic sensitivity, specimen adequacy, or safety of EBUS-TBNA in sarcoidosis. Puncturing the lymph nodes was more difficult with the 19-G needle.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfonodos , Sarcoidose Pulmonar , Humanos , Feminino , Masculino , Adulto , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Linfonodos/patologia , Agulhas , Broncoscopia/métodos , Sensibilidade e Especificidade , Sarcoidose/diagnóstico , Sarcoidose/patologia
10.
Mycoses ; 67(1): e13679, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38214399

RESUMO

BACKGROUND AND OBJECTIVES: The mechanisms underlying COVID-19-associated pulmonary mucormycosis (CAPM) remain unclear. We use a transcriptomic analysis of the innate immune cells to investigate the host immune and metabolic response pathways in patients with CAPM. PATIENTS AND METHODS: We enrolled subjects with CAPM (n = 5), pulmonary mucormycosis (PM) without COVID-19 (n = 5), COVID-19 (without mucormycosis, n = 5), healthy controls (n = 5) without comorbid illness and negative for SARS-CoV-2. Peripheral blood samples from cases were collected before initiating antifungal therapy, and neutrophils and monocytes were isolated. RNA sequencing was performed using Illumina HiSeqX from monocytes and neutrophils. Raw reads were aligned with HISAT-2 pipeline and DESeq2 was used for differential gene expression. Gene ontology (GO) and metabolic pathway analysis were performed using Shiny GO application and R packages (ggplot2, Pathview). RESULTS: The derangement of core immune and metabolic responses in CAPM patients was noted. Pattern recognition receptors, dectin-2, MCL, FcRγ receptors and CLEC-2, were upregulated, but signalling pathways such as JAK-STAT, IL-17 and CARD-9 were downregulated; mTOR and MAP-kinase signalling were elevated in monocytes from CAPM patients. The complement receptors, NETosis, and pro-inflammatory responses, such as S100A8/A9, lipocalin and MMP9, were elevated. The major metabolic pathways of glucose metabolism-glycolysis/gluconeogenesis, pentose phosphate pathway, HIF signalling and iron metabolism-ferroptosis were also upregulated in CAPM. CONCLUSIONS: We identified significant alterations in the metabolic pathways possibly leading to cellular iron overload and a hyperglycaemic state. Immune responses revealed altered recognition, signalling, effector functions and a pro-inflammatory state in monocytes and neutrophils from CAPM patients.


Assuntos
COVID-19 , Mucormicose , Humanos , Mucormicose/microbiologia , SARS-CoV-2 , Perfilação da Expressão Gênica , Imunidade Inata
11.
Mycoses ; 67(2): e13700, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38369615

RESUMO

BACKGROUND: Aspergillus fumigatus-specific IgG estimation is crucial for diagnosing allergic bronchopulmonary aspergillosis (ABPA). A point-of-care LDBio immunochromatographic lateral flow assay (LFA) had 0%-90% sensitivity to detect IgG/IgM antibodies against A. fumigatus. OBJECTIVE: To assess the accuracy of LDBio-LFA in diagnosing ABPA, using the modified ISHAM-ABPA working group criteria as the reference standard. The secondary objective was to compare the diagnostic performance between LDBio-LFA and A. fumigatus-specific IgG (cut-offs, 27 and 40 mgA/L), using a multidisciplinary team (blinded to A. fumigatus-IgG and LDBio-LFA results) diagnosis of ABPA as the reference standard. METHODS: We prospectively enrolled adult subjects with asthma and ABPA. We performed the LDBio-LFA per the manufacturer's recommendations. We used the commercially available automated fluorescent enzyme immunoassay for measuring serum A. fumigatus-specific IgG. We used the same serum sample to perform both index tests. The tests were performed by technicians blinded to the results of other tests and clinical diagnoses. RESULTS: We included 123 asthmatic and 166 ABPA subjects, with a mean ± SD age of 37.4 ± 14.4 years. Bronchiectasis and high-attenuation mucus were seen in 93.6% (146/156) and 24.3% (38/156) of the ABPA subjects. The sensitivity and specificity of LDBio-LFA in diagnosing ABPA were 84.9% and 82.9%, respectively. The sensitivity of serum A. fumigatus-specific IgG ≥27 mgA/L was 13% better than LDBio-LFA, with no difference in specificity. There was no significant difference in sensitivity and specificity between LDBio-LFA and serum A. fumigatus-IgG ≥40 mgA/L. CONCLUSION: LDBio-LFA is a valuable test for diagnosing ABPA. However, a negative test should be confirmed using an enzyme immunoassay.


Assuntos
Aspergilose Broncopulmonar Alérgica , Asma , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Aspergillus fumigatus , Imunoglobulina E , Anticorpos Antifúngicos , Aspergillus , Asma/complicações , Asma/diagnóstico , Imunoglobulina G
12.
Mycoses ; 67(5): e13746, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767275

RESUMO

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Aspergilose Pulmonar , Tuberculose Pulmonar , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/complicações , Estudos Prospectivos , Aspergilose Pulmonar/imunologia , Aspergilose Pulmonar/complicações , Neutrófilos/imunologia , Pulmão/imunologia , Explosão Respiratória , Adulto Jovem
13.
Mycoses ; 67(3): e13711, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38414309

RESUMO

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for developing chronic pulmonary aspergillosis (CPA). However, the prevalence and incidence of CPA in PTLA patients in India remain unknown. OBJECTIVES: We aimed to ascertain the incidence and prevalence of CPA in subjects with PTLA. METHODS: We identified a cohort of pulmonary tuberculosis who completed anti-tuberculosis therapy (ATT) before November 2019 from the records of the 12 tuberculosis treatment centers attached to the national program. We recorded the clinical and demographic details. We performed computed tomography (CT) of the chest and estimated serum A. fumigatus-specific IgG. We categorised subjects as PTLA with or without CPA using a composite of clinical, radiological, and microbiological features. We resurveyed the subjects at 6 months (or earlier) for the presence of new symptoms. We calculated the prevalence and the incidence rate (per 100-person years) of CPA. RESULTS: We included 117 subjects with PTLA, with a median of 3 years after ATT completion. Eleven subjects had CPA in the initial survey, and one additional case developed CPA during the second survey. The prevalence of CPA in PTLA subjects was 10.3% (12/117). The total observation period was 286.7 person-years. The median (interquartile range) time to develop CPA after ATT completion was 12.5 (5-36.7) months. We found the CPA incidence rate (95% confidence interval) of 4.2 (1.8-6.5) per 100-person years. CONCLUSION: Chronic pulmonary aspergillosis complicates 10% of PTLA subjects after successful outcomes with ATT. Four new CPA cases may develop per 100-persons years of observation after ATT completion. We suggest screening patients with PTLA who develop new symptoms for CPA.


Assuntos
Pneumopatias , Aspergilose Pulmonar , Tuberculose Pulmonar , Humanos , Incidência , Prevalência , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/diagnóstico , Pneumopatias/complicações , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Inquéritos e Questionários , Doença Crônica
14.
Mycoses ; 67(5): e13730, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38712824

RESUMO

BACKGROUND: Due to a delay in diagnosis by conventional techniques and high mortality, the development of a standardised and rapid non-culture-based technique is an unmet need in pulmonary, gastrointestinal, and disseminated forms of mucormycosis. Though limited studies have been conducted for molecular diagnosis, there are no established serologic tests for this highly fatal infection. OBJECTIVE: To develop and evaluate an indirect in-house enzyme-linked immunosorbent assay (ELISA) utilising antigens of Rhizopus arrhizus for detecting anti-Rhizopus antibodies (IgG and IgM) in sera of patients with mucormycosis. METHODS: We extracted both secretory and mycelial Rhizopus antigens using standardised protocols. Bradford assay was used for protein quantification. We then standardised an indirect ELISA using R. arrhizus mycelial and secretory antigens (10.0 µg/mL in bicarbonate buffer pH 9.2) for detecting anti-Rhizopus IgG and IgM antibodies in patient sera. We included patients with mucormycosis, other fungal infections, and healthy controls. Antibody index value (E-value) was calculated for each patient sample. RESULTS: Asparagine broth culture filtrate utilising 85% ammonium sulphate salt fractionation and mycelial homogenate grown in yeast extract peptone dextrose (YPD) broth precipitated with trichloroacetic acid (TCA) yielded a large amount of good-quality protein for the assay. We included 55 patients with mucormycosis (rhino-orbito-cerebral mucormycosis [ROCM, n = 39], pulmonary [n = 15], gastrointestinal [n = 1]), 24 with other fungal infections (probable aspergillosis [n = 14], candidiasis [n = 10]), and healthy controls (n = 16). The sensitivity of the antibody test for diagnosing mucormycosis ranged from 83.6-92.7% for IgG and 72.7-87.3% for IgM, with a specificity of 91.7-92.5% for IgG and 80-82.5% for IgM. The sera from patients with other fungal infections and healthy individuals did not show significant cross-reactivity. CONCLUSION: The detection of anti-Rhizopus IgG antibody performed significantly better in comparison to IgM-based ELISA for diagnosing both ROCM (sensitivity of 84.6% vs. 69.2%) and pulmonary cases (86.6% vs. 80.0%). More extensive studies are required to confirm our findings.


Assuntos
Anticorpos Antifúngicos , Antígenos de Fungos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Imunoglobulina M , Mucormicose , Rhizopus , Sensibilidade e Especificidade , Testes Sorológicos , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/imunologia , Humanos , Rhizopus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos de Fungos/imunologia , Antígenos de Fungos/análise , Testes Sorológicos/métodos , Anticorpos Antifúngicos/sangue , Imunoglobulina M/sangue , Imunoglobulina G/sangue , Feminino , Masculino , Pessoa de Meia-Idade
15.
Mycoses ; 67(5): e13745, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767273

RESUMO

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.


Assuntos
COVID-19 , Coinfecção , Mucormicose , Humanos , COVID-19/complicações , COVID-19/mortalidade , Mucormicose/mortalidade , Mucormicose/epidemiologia , Mucormicose/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prevalência , Coinfecção/mortalidade , Coinfecção/epidemiologia , Coinfecção/microbiologia , Índia/epidemiologia , Adulto , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/mortalidade , Aspergilose Pulmonar/epidemiologia , SARS-CoV-2 , Idoso , Estudos de Casos e Controles , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/epidemiologia
16.
Mycopathologia ; 189(2): 23, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407762

RESUMO

Innate and adaptive immunity play a crucial role in allergic bronchopulmonary aspergillosis (ABPA) pathogenesis. We performed next-generation sequencing using the Illumina TruSight One panel (4,811 human disease-associated genes, at least 20 × coverage) and selected 22 known immune genes (toll-like receptors (TLRs), C-type lectin, interleukin-4 receptor, and others). We included ABPA (n = 18), asthma without ABPA (n = 12), and healthy controls (n = 8). We analyzed 3011 SNPs from 22 genes and identified 145 SNPs (13 genes) that were present only in the disease groups and absent in controls. The SNP frequency overall was significantly higher in ABPA than in asthmatics (89/145 [61.4%] vs. 56/145 [38.6%], p = 0.0001). The SNP frequency in the TLR10 gene was also significantly higher in ABPA than in asthma (p = 0.017). Association analysis further revealed three genes having significant associations. Of these, NOS3 and HLA-DQB1 are associated with antimicrobial activity and adaptive immunity. More extensive studies are required to confirm our findings.


Assuntos
Aspergilose Broncopulmonar Alérgica , Asma , Humanos , Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/genética , Polimorfismo de Nucleotídeo Único , Asma/complicações , Asma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Lectinas Tipo C
17.
Nano Lett ; 23(20): 9634-9640, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37812066

RESUMO

The strongly correlated charge density wave (CDW) phase of 1T-TiSe2 is of interest to verify the claims of a chiral order parameter. Characterization of the symmetries of 1T-TiSe2 is critical to understand the origin of its intriguing properties. Here we use very low-power, continuous wave laser excitation to probe the symmetries of 1T-TiSe2 by using the circular photogalvanic effect. We observe that the ground state of the CDW phase (D3d) is achiral. However, laser excitation above a threshold intensity transforms 1T-TiSe2 into a nonequilibrium chiral phase (C3), which changes the electronic correlations in the material. The inherent sensitivity of the photogalvanic technique to structural symmetries provides evidence of the different optically driven phase of 1T-TiSe2, which allows us to assign symmetry groups to these states. Our work demonstrates that optically induced phase change can occur at extremely low optical intensities in strongly correlated materials, providing a pathway to engineer new phases using light.

18.
Emerg Infect Dis ; 29(7): 1313-1322, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347535

RESUMO

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02-0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03-16], itraconazole [0.03-16], posaconazole [0.03-8], and isavuconazole [0.03-16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.


Assuntos
Mucorales , Mucormicose , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Mucorales/genética , Estudos Retrospectivos , Rhizopus/genética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico
19.
Eur Respir J ; 62(3)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37690784

RESUMO

BACKGROUND: Current guidelines recommend 20-40 mg·day-1 of oral prednisolone for treating pulmonary sarcoidosis. Whether the higher dose (40 mg·day-1) can improve outcomes remains unknown. METHODS: We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised controlled trial (ClinicalTrials.gov identifier NCT03265405). Consecutive subjects with pulmonary sarcoidosis were randomised (1:1) to receive either high-dose (40 mg·day-1 initial dose) or low-dose (20 mg·day-1 initial dose) oral prednisolone, tapered over 6 months. The primary outcome was the frequency of relapse or treatment failure at 18 months from randomisation. Key secondary outcomes included the time to relapse or treatment failure, overall response, change in forced vital capacity (FVC, in litres) at 6 and 18 months, treatment-related adverse effects and health-related quality of life (HRQoL) scores using the Sarcoidosis Health Questionnaire and Fatigue Assessment Scale. FINDINGS: We included 86 subjects (43 in each group). 42 and 43 subjects completed treatment in the high-dose and low-dose groups, respectively, while 37 (86.0%) and 41 (95.3%), respectively, completed the 18-month follow-up. 20 (46.5%) subjects had relapse or treatment failure in the high-dose group and 19 (44.2%) in the low-dose group (p=0.75). The mean time to relapse/treatment failure was similar between the groups (high-dose 307 days versus low-dose 269 days, p=0.27). The overall response, the changes in FVC at 6 and 18 months and the incidence of adverse effects were also similar. Changes in HRQoL scores did not differ between the study groups. INTERPRETATION: High-dose prednisolone was not superior to a lower dose in improving outcomes or the HRQoL in sarcoidosis and was associated with similar adverse effects.


Assuntos
Prednisolona , Sarcoidose Pulmonar , Humanos , Prednisolona/administração & dosagem , Qualidade de Vida , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/psicologia , Adulto Jovem , Adulto
20.
Clin Exp Allergy ; 53(7): 751-764, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37062874

RESUMO

Allergic bronchopulmonary aspergillosis (ABPA) is a lung disorder caused by immune-mediated reactions mounted against Aspergillus fumigatus. The disorder most commonly complicates the course of patients with asthma and cystic fibrosis. From its first description in 1952, significant advances have been made in understanding the pathogenesis and the diagnosis and treatment of ABPA. In the last two decades, most research on ABPA has been published from India. The prevalence and clinical presentation may differ in India from that reported elsewhere. Herein, we review the epidemiology, clinical and radiological characteristics, and distinctive features of ABPA in the Indian subcontinent. To support the review, we surveyed pulmonologists nationwide to understand the challenges in diagnosing and managing ABPA. The survey has yielded valuable insights into the practices associated with the diagnosis and management of ABPA in India.


Assuntos
Aspergilose Broncopulmonar Alérgica , Asma , Fibrose Cística , Humanos , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/epidemiologia , Asma/epidemiologia , Aspergillus fumigatus , Índia/epidemiologia
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