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1.
ESMO Open ; 9(3): 102903, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452436

RESUMO

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Reprodutibilidade dos Testes , Recidiva Local de Neoplasia/genética , RNA/análise , RNA Mensageiro/genética
2.
J Phys Condens Matter ; 36(29)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38316037

RESUMO

This paper explores yttrium and copper co-doped cobalt ferrite [Co1-xCuxFe1.85Y0.15O4] synthesized via the sol-gel auto-combustion route (0.0 ⩽x⩽ 0.08). Investigating the impact of co-dopants on CoFe2O4, the study reveals altered cation distribution affecting the structure, multiferroic, and electrical properties. X-ray diffraction studies show nanocrystalline co-doped cobalt ferrites with lattice expansion and smaller grains due to Cu-Y co-doping. Fourier transform infrared spectroscopy confirms inverse spinel family classification with tetrahedral lattice shrinkage. Field emission scanning electron microscopy indicates a grain size of approximately 0.12µm. Ferroelectric analysis reveals a peak saturation polarization of 23.42µC cm-2for 8% copper doping, attributed to increased Fe3+ions at tetrahedral sites. Saturation magnetization peaks at 54.4706 emu g-1for 2% Cu2+ion substitution [Co0.98Cu0.02Fe1.85Y0.15O4] and decreases to 37.09 emu g-1for 4% Cu substitution due to irregular iron atom distribution at tetrahedral sites. Dielectric studies uncover Maxwell-Wagner polarization and high resistance in grain and grain boundaries using impedance spectroscopy. Fabricated hydroelectric cells exhibit improved ionic diffusion, suggesting their use in potential hydroelectric cell applications.

3.
Mol Biol Rep ; 51(1): 286, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329638

RESUMO

BACKGROUND: Cellular resistance to cisplatin has been one of the major obstacles in the success of combination therapy for many types of cancers. Emerging evidences suggest that exosomes released by drug resistant tumour cells play significant role in conferring resistance to drug sensitive cells by means of horizontal transfer of genetic materials such as miRNAs. Though exosomal miRNAs have been reported to confer drug resistance, the exact underlying mechanisms are still unclear. METHODS AND RESULTS: In the present study, mature miRNAs secreted differentially by cisplatin resistant and cisplatin sensitive HepG2 cells were profiled and the effect of most significantly lowered miRNA in conferring cisplatin resistance when horizontally transferred, was analysed. we report miR-383 to be present at the lowest levels among the differentially abundant miRNAs expressed in exosomes secreted by cisplatin resistant cells compared to that that of cisplatin sensitive cells. We therefore, checked the effect of ectopic expression of miR-383 in altering cisplatin sensitivity of Hela cells. Drug sensitivity assay and apoptotic assays revealed that miR-383 could sensitise cells to cisplatin by targeting VEGF and its downstream Akt mediated pathway. CONCLUSION: Results presented here provide evidence for the important role of miR-383 in regulating cisplatin sensitivity by modulating VEGF signalling loop upon horizontal transfer across different cell types.


Assuntos
Cisplatino , MicroRNAs , Humanos , Cisplatino/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Células HeLa , Fator A de Crescimento do Endotélio Vascular/genética , MicroRNAs/genética
4.
J Cancer Res Ther ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38261447

RESUMO

AIM: The aim of the study was to assess the prevalence of types of head and neck cancer in Madurai, Tamil Nadu. OBJECTIVES: The objectives of the study were to assess the prevalence of types of head and neck cancer in Madurai, Tamil Nadu using a questionnaire. MATERIALS AND METHODS: A descriptive cross-sectional study was carried out for two months among 300 head and neck cancer patients at a tertiary cancer center in Madurai. A convenience sampling technique was used. The data were collected using a pretested, self-structured questionnaire. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0 software. RESULTS: Of 300 head and neck cancer patients, the mean age of the patients was about 51.04 ± 16.49 years. The majority of the patients were male (80%), employed (85%), and literate (65%). Among the head and neck cancer patients, 65% were tobacco users and 42.4% were alcohol consumers. Squamous cell carcinoma was the most common type of head and neck cancer, and 79.7% were diagnosed at an advanced stage of said cancer, such as stages III and IV. CONCLUSION: Lack of knowledge and awareness is a major cause of increasing prevalence of head and neck cancer in our country. It is most important to increase the knowledge and awareness of early symptom recognition and its seriousness among the general population.

6.
Singapore Med J ; 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37675674

RESUMO

Introduction: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. Methods: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. Results: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS (P = 0.026) and OS (P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. Conclusion: Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.

7.
Phys Chem Chem Phys ; 25(32): 21280-21296, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37551414

RESUMO

Substitution with rare earth (RE3+) and transition (X = Cu, Ni, Mn, Zn, etc.) metals can distort the spinel ferrite structure and create defects, which can be exploited in multifarious applications. In this study, yttrium and nickel co-substituted cobalt ferrites [Co1-xNixFe1.85Y0.15O4], (0.0 ≤ x ≤ 0.15) were synthesized by a modified sol-gel reaction route. The X-ray diffraction (XRD) patterns confirmed the single phase and highly crystalline nature of the prepared samples. Field emission scanning electron microscopy with energy dispersive X-ray (FESEM-EDX) spectroscopy confirmed the morphology of the prepared samples sintered at 800 °C and showed the grain sizes of the particles decreased with the addition of nickel ions. The simultaneous co-existence of saturation magnetization and ferroelectricity at room temperature confirmed the multiferroic nature of the co-substituted cobalt ferrites. The dielectric and impedance studies confirmed the Maxwell-Wagner polarization phenomenon and the enhanced values with Y-Ni co-substitution. The maximum saturation ferroelectric polarization was attained around 6.142 µC cm-2 for yttrium-substituted cobalt ferrite and then decreased with the increase in the substitution % of nickel. The maximum value of saturation magnetization (Ms = 99.50 emu g-1) was obtained with the highest substitution % of nickel of x = 0.15 in yttrium-substituted cobalt ferrite (YCFO) nanoferrites, which was also confirmed from the vibrating sample magnitude (VSM) studies at room temperature. The improvements in the structural, morphological, electrical, and multiferroic properties in the co-substituted cobalt ferrites were found to correlated to the substitution of the bigger cationic Y3+ ions compared to the Fe3+ ions, while the small substitution of Ni2+ ions lead to changes in the lattice parameters, porosity, and conduction behavior. These significant enhancements in co-substituted cobalt ferrites can be exploited for hydroelectric cell applications.

8.
J Biomol Struct Dyn ; : 1-15, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37288801

RESUMO

Meteorin (Metrn) and Meteorin-like (Metrnl) are homologous secreted proteins involved in neural development and metabolic regulation. In this study, we have performed de novo structure prediction and analysis of both Metrn and Metrnl using Alphafold2 (AF2) and RoseTTAfold (RF). Based on the domain and structural homology analysis of the predicted structures, we have identified that these proteins are composed of two functional domains, a CUB domain and an NTR domain, connected by a hinge/loop region. We have identified the receptor binding regions of Metrn and Metrnl using the machine-learning tools ScanNet and Masif. These were further validated by docking Metrnl with its reported KIT receptor, thus establishing the role of each domain in the receptor interaction. Also, we have studied the effect of non-synonymous SNPs on the structure and function of these proteins using an array of bioinformatics tools and selected 16 missense variants in Metrn and 10 in Metrnl that can affect the protein stability. This is the first study to comprehensively characterize the functional domains of Metrn and Metrnl at their structural level and identify the functional domains, and protein binding regions. This study also highlights the interaction mechanism of the KIT receptor and Metrnl. The predicted deleterious SNPs will allow further understanding of the role of these variants in modulating the plasma levels of these proteins in disease conditions such as diabetes.Communicated by Ramaswamy H. Sarma.

9.
ACS Appl Mater Interfaces ; 15(10): 13405-13414, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36857615

RESUMO

Herein, simple acceptor-donor-acceptor (A-D-A)-type small molecules denoted as DICTF and DRCTF with modification in terminal units were synthesized and used as electron acceptors. With the tuning of the electron-withdrawing units in electron acceptors, their photovoltaic properties were investigated when combined with low-band-gap BODIPY-thiophene-backboned donor material, named P(BdP-HT). The P(BdP-HT):DICTF-based organic solar cells (OSCs) displayed excellent efficiency of around 11.94%, which is superior to the P(BdP-HT):DRCTF counterpart (8.78%). Although the open-circuit voltage (VOC) of the P(BdP-HT):DRCTF-based OSC is greater than that for the P(BdP-HT):DICTF counterpart, the rise in the short-circuit current density (JSC) may be attributed to the fact that the P(BdP-HT):DICTF blend displayed impressive panchromatic absorption compared to P(BdP-HT):DRCTF. The improved fill factor (FF) is responsible for the balanced transport of charges in the P(BdP-HT):DICTF-based device. Moreover, the P(BdP-HT):DRCTF- and P(BdP-HT):DICTF-based OSCs showed 17.68 and 21.84%, respectively, under indoor illumination (1000 lx). To the best of our observation, this might be the first report on BODIPY-based donors with power conversion efficiency (PCE) of 21.84% under indoor illumination conditions.

10.
J Biomol Struct Dyn ; 41(8): 3265-3280, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35257637

RESUMO

Being highly transmissible, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected millions of people causing devastating global impact and has also not slowed down even after vaccination. The emerges of new strains has made more concerns than the original one. We need a new therapeutic approach against the disease. Our comprehensive in silico study investigates dual herbal combinatorial methanolic extracts of W. somnifera (W) alone and with P. emblica (P) (W:P/1:4) , T. sinensis (T) (W:T/1:4), B. monnieri (B) (W:B/1:1), O. basilicum (O) (W:O/1:4), A. racemosus (A) (W:A/4:1) for potential four phytochemicals as ligands docked with eight COVID-19 Nonstructural proteins (nsp)-main protease (PDB ID:6LU7), papain-like protease (6WUU), helicase ADP (2XZL), N7-methyltransferase (5C8S), endoribonuclease (6WLC), 2'O-methyltransferase (6WVN), RNA dependent RNA polymerase (6M71), and 3Cprotease (6YNQ) along with Remdesivir and Hydroxychloroquine. Ligands from W:P/1:4 showed remarkable docking score (-9.01 kcal/mol) 6M71-(8E,11E,14E)-eicosa-8,11,14-trienoicacidmethylester (EIS) and (-9.99 kcal/mol) 6YNQ-N-[(E)-[4-[(2-methoxydibenzofuran-3-yl)amino]-4-oxobutan-2-ylidene]amino] 4nitrobenzamide (MET). Further, MD simulations were studied for 100 ns and showed the complexes were flexible, stable in the binding pockets of the receptors, and MM-PBSA analysis determined high binding energy of -129.673 ± 15.284 and -134.594 ± 7.085 for 6M71-EIS (Asn496, Lys577, Arg569) and 6YNQ-MET (Cys145, His41). Finally, in vitro JURKAT E6.1 cell lines treated with W:P/1:4 and W:O/1:4 methanolic extracts yielded 44.06 and 31.53 ng/mL levels for interferon alpha to counteract an external stimulus by establishing an antiviral state. Thus, nsp is targeted to design effective antiviral drugs for developing an effective therapeutic approach to combat viral RNA synthesis, processing, and suppression of host immunity.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , Withania , Humanos , SARS-CoV-2 , Antivirais/farmacologia , Metanol , Metiltransferases , Papaína , Peptídeo Hidrolases
11.
Biochim Biophys Acta Gen Subj ; 1867(3): 130290, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36529243

RESUMO

Anserine and carnosine represent histidine-containing dipeptides that exert a pluripotent protective effect on human physiology. Anserine is known to protect against oxidative stress in diabetes and cardiovascular diseases. Human carnosinases (CN1 and CN2) are dipeptidases involved in the homeostasis of carnosine. In poikilothermic vertebrates, the anserinase enzyme is responsible for hydrolyzing anserine. However, there is no specific anserine hydrolyzing enzyme present in humans. In this study, we have systematically investigated the anserine hydrolyzing activity of human CN1 and CN2. A targeted multiple reaction monitoring (MRM) based approach was employed for studying the enzyme kinetics of CN1 and CN2 using carnosine and anserine as substrates. Surprisingly, both CN1 and CN2 can hydrolyze anserine effectively. The observed catalytic turnover rate (Vmax/[E]t) was 21.6 s-1 and 2.8 s-1 for CN1 and CN2, respectively. CN1 is almost eight-fold more efficient in hydrolyzing anserine compared to CN2, which is comparable to the efficiency of the carnosine hydrolyzing activity of CN2. The Michaelis constant (Km) value for CN1 (1.96 mM) is almost three-fold lower compared to CN2 (6.33 mM), representing higher substrate affinity for anserine-CN1 interactions. Molecular docking studies showed that anserine binds at the catalytic site of the carnosinases with an affinity similar to carnosine. Overall, the present study elucidated the inherent promiscuity of human carnosinases in hydrolyzing anserine using a sensitive LC-MS/MS approach.


Assuntos
Carnosina , Dipeptidases , Animais , Humanos , Anserina/metabolismo , Carnosina/metabolismo , Dipeptidases/química , Dipeptidases/metabolismo , Cromatografia Líquida , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem
12.
J Family Med Prim Care ; 11(9): 5077-5081, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36505612

RESUMO

Background: Frontline health care workers (FLHCW) like doctors and nurses are bound to treat COVID patients being themselves not immune to disease are at a greater risk of COVID infection than the general population. The study was started with objectives to find out the vaccine hesitancy towards the COVID vaccine and to find out the factors associated with vaccine hesitancy among FLHCW working in a designated COVID care center. Materials and Methods: The present study was a cross-sectional study carried out for a period of 6 months from Jan 2021 to June 2021 at a designated COVID care center. FLHCWs who were part of treating COVID patients were our study participants. Among them, FLHCWs who had not received even one dose of COVID vaccine (Covishield) were included in the study. FLHCWs who had been part of the COVID vaccine trial were excluded from the study. The sample size calculated based on a previous study found to be 240. The data collected were entered into a Microsoft office excel sheet, analyzed using SPSS v 22(IBM Corp). Descriptive statistics were applied, and parametric tests were used to compare among the groups with statistically significant P value lesser than 0.05. Results: A total of 121 (52.6%) of FLHCWs were aged more than 30 years, 118 (51.5%) were male participants, 100 (43.5%) were paramedics by occupation, 51 (22.1%) had contracted COVID infection, 202 (87.8%) had received information, education, and communication (IEC) regarding COVID vaccine. FLHCWs more than 30 years, male participants, currently not working in COVIDward, FLHCWs who had not received IEC about COVIDvaccination and paramedics had higher scores of Vaccine hesitancy, and the difference was statistically significant indicating vaccine hesitancy. Conclusion: Vaccine hesitancy remains a persistent global threat. Awareness campaigns can be tailored to specific locales to address identified concerns regarding vaccines.

13.
Med J Armed Forces India ; 78(Suppl 1): S273-S276, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36147388

RESUMO

Shulman's disease (eosinophilic fasciitis) is a very rare autoimmune disorder with an unknown etiopathogenesis. During the initial period of disease, it usually causes limb and trunk edema followed by collagenous thickening of the subcutaneous fascia. Eosinophilia is a predominant laboratory finding during the initial phase of the disease and less prominent in the later phases. Patients may also present with arthritis, myositis, peripheral neuropathy, and rarely pleuropericarditis. Here, we are reporting a case of eosinophilic fasciitis presenting with vague constitutional symptoms, fever, and peripheral blood eosinophilia followed by rapidly evolving skin tightening with joint contractures and muscle stiffness, which misled the treating team toward Scleroderma and its overlap syndromes. The diagnosis was finally clinched by a full-thickness skin biopsy along with underlying fascia and muscle tissue from an effected area, with a gratifying treatment response to standard immune suppression.

14.
J Pharm Bioallied Sci ; 14(Suppl 1): S698-S701, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36110685

RESUMO

Introduction: The novel COVID-19 which spread's primarily through oral and nasal passage poses a major threat of spread during dental treatments. It is important for dental practitioners to use minimal aerosol techniques. The aim of this study is to compare the time taken, efficiency and aerosol generated between modified and conventional technique (CT) of bracket bonding. Methods: This study includes 40 patients who required complete orthodontic treatment. In all 40 patients, one of the arches was bonded with modified technique (MT) and the opposing with CT. The time taken to prepare tooth in both the techniques were accessed. The efficiency of bond was seen over a period of 6 months. The amount of aerosol particulate matter generated during CT and MT was observed using a laser air quality monitor. Conclusion: There is no significant difference in the bond failure and time taken between both the techniques. The aerosol generated in MT was minimal or almost negligible when compared to the use of CT.

15.
Nat Commun ; 13(1): 4651, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085141

RESUMO

X-ray imaging has been boosted by the introduction of phase-based methods. Detail visibility is enhanced in phase contrast images, and dark-field images are sensitive to inhomogeneities on a length scale below the system's spatial resolution. Here we show that dark-field creates a texture which is characteristic of the imaged material, and that its combination with conventional attenuation leads to an improved discrimination of threat materials. We show that remaining ambiguities can be resolved by exploiting the different energy dependence of the dark-field and attenuation signals. Furthermore, we demonstrate that the dark-field texture is well-suited for identification through machine learning approaches through two proof-of-concept studies. In both cases, application of the same approaches to datasets from which the dark-field images were removed led to a clear degradation in performance. While the small scale of these studies means further research is required, results indicate potential for a combined use of dark-field and deep neural networks in security applications and beyond.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Microscopia de Contraste de Fase , Radiografia , Raios X
16.
J Neurosci Rural Pract ; 13(3): 495-509, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35946008

RESUMO

Background The cavernous sinus is a complex space composed of extradural venous plexus within dural folds. Several important structures like the carotid artery, cranial nerves, and sympathetic nerve fibers traverse through this space. Radiological diagnosis may not be definitive and in the context of discordance between clinical and neuroimaging diagnosis, histopathological evaluation becomes essential for diagnosis and management. Literature on the pathological spectrum of lesions is scarce as, with a shift in the treatment paradigm, most small lesions of cavernous sinus are treated with radiosurgery. However, surgical management still plays a role for larger lesions and in radiologically ambiguous cases for planning the definitive management. Materials and Methods We retrospectively reviewed all surgically resected lesions of the cavernous sinus over the last two decades (1998-2019). The clinical presentation, neuroimaging features, and histopathological findings were reviewed. Lesions extending from sella and other adjacent areas were excluded. Results Thirty-eight cases of isolated cavernous sinus mass lesions were diagnosed over the last two decades (1998-2019). Cavernous hemangiomas (19 cases, 50%) constituted the most frequent pathology, followed by aspergilloma, meningioma, schwannoma, metastatic adenocarcinoma, chondrosarcoma, and chordoma. Overall, 29.4% (10/34) could not be accurately diagnosed on neuroimaging. Of these, four cases of cavernous hemangiomas were mistaken for either meningioma (three cases) or schwannoma (one case). Neither chordoma nor chondrosarcoma was suspected. Conclusion This is the first study in literature, enumerating the pathological and imaging spectrum of surgically resected cavernous sinus lesions. Cavernous hemangiomas, metastases and chordomas, and chondrosarcoma posed the greatest difficulty in diagnosis on neuroimaging and the reasons for the same are analyzed. In the context of clinical and neuroimaging discordance in diagnosis, pathological characterization becomes essential for appropriate and timely management.

17.
Int J Tuberc Lung Dis ; 26(8): 733-740, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35898145

RESUMO

BACKGROUND: TB is commonly categorised as pulmonary (PTB) or extrapulmonary TB (EPTB). Knowledge of TB disease patterns (PTB and/or EPTB) and determining risk factors remains limited.METHODS: This was a prospective cohort study using point-of-care ultrasound (POCUS) in Indian patients with presumed TB. Clinical and imaging data were used to develop refined case definitions for PTB, concurrent PTB and EPTB (PTB + EPTB) and EPTB without PTB (EPTB). These groups were analysed by HIV (HIV+/-) and diabetes mellitus (DM+/-) status.RESULTS: Of 172 HIV-/DM- patients with TB, 48% had PTB, 23% PTB + EPTB and 29% had EPTB, totalling 52% with any EPTB (PTB + EPTB or EPTB). In HIV+/DM- patients with TB (n = 35), 6% had PTB, 40% had PTB + EPTB and 54% had EPTB, accounting for 94% with EPTB. In HIV-/DM+ patients with TB (n = 61), 61% had PTB, 28% had PTB + EPTB and 11% had EPTB, representing 39% with EPTB.CONCLUSION: Refined case definitions revealed high proportions of EPTB even without HIV or DM. HIV further altered the TB disease pattern towards EPTB and DM towards PTB. Therefore, the dichotomy between PTB or EPTB does not represent the actual spectrum of TB disease. EPTB should receive higher priority in research and clinical practice.


Assuntos
Diabetes Mellitus , Infecções por HIV , Tuberculose , Diabetes Mellitus/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Estudos Prospectivos , Fatores de Risco , Tuberculose/epidemiologia
18.
Nat Commun ; 13(1): 3121, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35660734

RESUMO

Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10+ Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19+ B cells drives >900-fold expansion of IL-10+ B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19+CD73-CD25+CD71+TIM-1+CD154+ Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1+ and pSTAT3+ B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.


Assuntos
Linfócitos B Reguladores , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Animais , Antígenos CD19/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Interleucina-10/metabolismo , Ativação Linfocitária , Camundongos , Fator de Transcrição STAT3/metabolismo , Neoplasias Cutâneas/metabolismo
19.
Cureus ; 14(5): e24953, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35706752

RESUMO

Tailgut cysts or retrorectal cystic hamartomas are rare, congenital, development lesions arising from the remnants of the hindgut during embryogenesis. It is most often misdiagnosed due to its rarity, variable clinical presentation, and malignant potential. The following report describes an unusual case of a tailgut cyst in a 60-year-old male with a history of a perianal mass for 12 years. Surgical resection was done, and histopathological examination revealed a multiloculated cyst filled with brownish fluid, grossly, and a cyst lined by various epithelia such as stratified squamous epithelium, pseudostratified columnar epithelium, and flattened to cuboidal and mucin-secreting columnar epithelium along with cyst wall made up of bundles of smooth muscles, microscopically. Several lesions mimic a tailgut cyst and need to be excluded from the differentials. Although no malignancy was documented in this case, these cysts have been known to undergo malignant transformation into adenocarcinoma and neuroendocrine carcinoma, to name a few. This warrants a thorough and accurate histopathological assessment and mandatory follow-up.

20.
Cureus ; 14(4): e24485, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35651397

RESUMO

Craniofacial involvement in fibrous dysplasia is a rare occurrence and complications of it are even rarer. Involvement of the sinonasal region can pose a challenge in both diagnosis and management. We hereby present a case of craniofacial fibrous dysplasia complicated with secondary aneurysmal bone cyst formation in a 15-year-old male patient.

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