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1.
Aging Cell ; 21(6): e13625, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35582959

RESUMO

Mutation in Werner (WRN) RECQL helicase is associated with premature aging syndrome (Werner syndrome, WS) and predisposition to multiple cancers. In patients with solid cancers, deficiency of the WRN RECQL helicase is paradoxically associated with enhanced overall survival in response to treatment with TOP1 inhibitors, which stabilize pathological TOP1-DNA-covalent-complexes (TOP1cc) on the genome. However, the underlying mechanism of WRN in development of chemoresistance to TOP1 inhibitors is not yet explored. Our whole-genome transcriptomic analysis for ~25,000 genes showed robust activation of NF-κB-dependent prosurvival genes in response to TOP1cc. CRISPR-Cas9 knockout, shRNA silencing, and under-expression of WRN confer high-sensitivity of multiple cancers to TOP1 inhibitor. We demonstrated that WRN orchestrates TOP1cc repair through proteasome-dependent and proteasome-independent process, unleashing robust ssDNA generation. This in turn ensues signal transduction for CHK1 mediated NF-κB-activation through IκBα-degradation and nuclear localization of p65 protein. Intriguingly, our site-directed mutagenesis and rescue experiments revealed that neither RECQL-helicase nor DNA-exonuclease enzyme activity of WRN (WRNE84A , WRNK577M , and WRNE84A-K577M ) were required for TOP1cc removal, ssDNA generation and signaling for NF-κB activation. In correlation with patient data and above results, the TOP1 inhibitor-based targeted therapy showed that WRN-deficient melanoma tumors were highly sensitive to TOP1 inhibition in preclinical in vivo mouse model. Collectively, our findings identify hitherto unknown non-enzymatic role of WRN RECQL helicase in pathological mechanisms underlying TOP1cc processing and subsequent NF-κB-activation, offering a potential targeted therapy for WRN-deficient cancer patients.


Assuntos
Neoplasias da Mama , Síndrome de Werner , Animais , DNA/metabolismo , DNA de Cadeia Simples , Exodesoxirribonucleases/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Camundongos , NF-kappa B/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , RecQ Helicases/genética , RecQ Helicases/metabolismo , Transdução de Sinais , Síndrome de Werner/genética , Helicase da Síndrome de Werner/genética
2.
Indian J Pharmacol ; 54(2): 90-96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35546459

RESUMO

OBJECTIVES: Sinonasal mucormycosis is a serious fungal infection. Early diagnosis and prompt antifungal therapy along with surgical intervention is the key to its management. Liposomal amphotericin B (LAmB) given intravenously is the antifungal agent of choice. However, the current literature is not clear on its optimum dosage. We did a retrospective study to find the optimum dose of LAmB in cases with sinonasal mucormycosis. MATERIALS AND METHODS: Thirty patients diagnosed with mucormycosis involving sinonasal, rhino-orbital, or rhino-orbito-cerebral regions and receiving only LAmB as pharmacotherapy were included in our retrospective study from 2017 to 2020. A multiple logistic regression model was developed to correlate the total dose of LAmB and other parameters with the final outcome which was defined clinico-radiologically as improved, worsened, or death. The dose of LAmB which led to the first significant change in urea, creatinine, and potassium levels was also determined. RESULTS: The model showed a good fit in goodness-to-fit analysis (Pearson = 0.999, deviance = 0.995), while the likelihood ratio was statistically significant (0.001). The overall model prediction was 83.3%. However, the correlation of outcome with any of the variables, including mean LAmB dose per kilogram (82.2 ± 13.02 mg/kg), was statistically not significant. CONCLUSION: Many patient-related factors (such as age, comorbidities, extent of the disease, and side effects from LAmB therapy), which vary on a case-to-case basis, contribute to the outcome in a mucormycosis patient. The optimum dose of LAmB for improved outcome still requires individualization guided by experience, till well-designed studies address the question.


Assuntos
Infecções Oculares Fúngicas , Mucormicose , Doenças Orbitárias , Anfotericina B , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Doenças Orbitárias/tratamento farmacológico , Estudos Retrospectivos
3.
J Int Adv Otol ; 18(3): 269-275, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35608498

RESUMO

Antibiotic prophylaxis is commonly given to all patients undergoing cochlear implant surgery. However, currently, there is no consensus if pro- phylactic usage of antibiotics in cochlear implantation accords any benefit and if the duration of such use varies according to the surgeon's experience or institutional preference. A systematic review was conducted to gather evidence on ideal duration for antibiotic prophylaxis rec- ommended for patients undergoing cochlear implantation. We registered the protocol in the International Prospective Register of Systematic Reviews (CRD42021235079) and reported the systematic review following the Preferred Reporting Items for Systematic Reviews and Meta- Analysis statement. Of the 278 screened articles, 6 full-text original articles satisfied the inclusion criteria and were included. There were a total of 2081 participants in these 6 retrospective studies and all studies except 1 included both adult and pediatric populations. Antibiotic therapy was given as intervention, either as single dose or multiple doses, and compared with other group(s) receiving either no antibiotic prophylaxis or a different duration of prophylaxis. Three studies did not find any significant difference between infection rates when a different duration of antibiotic prophylaxis was given, while 2 studies found a single dose to be more efficacious, and yet another study concluded that a longer dura- tion of antibiotic prophylaxis was more beneficial. Based on the available data, the ideal duration of post-operative antibiotic therapy to be given after cochlear implant surgery could not be defined. However, administrating a single dose of intraoperative antibiotic seems to be the most consistent practice so far.


Assuntos
Antibioticoprofilaxia , Implante Coclear , Adulto , Antibacterianos/uso terapêutico , Criança , Humanos , Estudos Retrospectivos
4.
Artigo em Inglês | MEDLINE | ID: mdl-35611787

RESUMO

AIM: To establish the role of inflammation in bortezomib induced peripheral neuropathy (BIPN). BACKGROUND: Peripheral neuropathy is the dose-limiting toxicity of bortezomib which can lead to discontinuation of the treatment. There are multiple mechanisms involved in the disposition of BIPN. However, the role of inflammatory mediators is still under investigation. The complete understanding of inflammatory markers in relation to BIPN can lead to the development of effective therapy for prophylaxis and treatment of peripheral neuropathy. OBJECTIVE: Based on the available data, postulate the role of inflammatory mediators in the development of peripheral neuropathy due to bortezomib. METHOD: The "Pubmed" and "Google Scholar" were used as the search engines with terms like "peripheral neuropathy", "bortezomib induced peripheral neuropathy" and "inflammation". Original research, case reports and review articles were considered. RESULTS: Bortezomib use is associated with the development of peripheral neuropathy. This effect is due to the damage to Schwann cells and dorsal root ganglion neurons; mitochondrial damage; increased ion channel susceptibility; and higher infiltration of macrophages in the spinal cord. All these factors collectively increase the secretion of inflammatory mediators and lead to the development of neuropathic pain. CONCLUSION: Targeting inflammatory mediators may be helpful in the treatment of bortezomib-induced peripheral neuropathy.

5.
Am J Med Sci ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35452629

RESUMO

BACKGROUND: Host biomarkers are needed to monitor the response to anti-tubercular therapy (ATT) for ensuring effective therapy and preventing drug-resistant tuberculosis. We sought to find the correlation between the serum levels of SAA1 and IL-1beta in response to ATT in adult patients with pulmonary TB (PTB) or extra-pulmonary TB (EPTB). METHODS: Blood samples of 32 patients with PTB and 28 patients with EPTB were analyzed. The blood samples were collected at baseline, two months and six months following treatment initiation. SAA1 and IL-1beta levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: In the PTB group, the mean levels of SAA1 decreased significantly (p <0.001) after the intensive phase (two months) and continuous phase (six months) of ATT in comparison with the baseline value. IL-1beta values also decreased significantly (p = 0.005) after the intensive phase (two months) compared with the baseline values. In the EPTB group, there was a significant reduction in the mean serum level of SAA1 (p <0.001) and IL-1beta (p = 0.001) after the intensive phase (two months) in comparison with the baseline value, whereas the reduction at six months was not significant. CONCLUSIONS: SAA1 and IL-1beta may be useful potential treatment-monitoring biomarkers, especially in the intensive phase of therapy for both PTB and EPTB.

6.
Appl Opt ; 61(8): 1958-1964, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35297887

RESUMO

This work demonstrates an interferometric technique to measure the refractive index (RI) of microliter volume of biosample solutions with the help of an optical fiber negative axicon and Bessel beam with the micrometer-size central spot. The RI measuring device consists of a broadband superluminescent diode (SLD) source along with an optical circulator and spectrometer. The axicon optical fiber probe packaged with a glass slide is connected to a broadband SLD source through an optical circulator, and a drop of microliter bioliquid sample is placed on the packaged probe's head. The reflected light from the glass-liquid interface couples back to the axicon probe and interferes with the reference beam generated at the air-glass interface of the axicon. The interference spectrum is further analyzed by applying the fast Fourier transform to calculate power from the respective interface and solve the Fresnel equation for the RI measurement. The RI of small sample volume ∼2µl of glucose solutions and bovine serum albumin protein solutions are reported as an application of the proposed method. This sensing platform shows promising applications in biomedicine for monitoring small volume various biosample concentrations. We also demonstrate RI measurement of flowing liquid sample using the developed setup in case the design can be considered for microfluidic channel research.


Assuntos
Interferometria , Refratometria , Microfluídica , Fibras Ópticas
7.
Opt Lett ; 47(3): 497-500, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103658

RESUMO

We demonstrate an all-fiber negative axicon probe with a Bessel beam for low coherence phase microscopy including refractive index measurement of a cellular level sample in reflection mode. The negative axicon chemically incised at the distal end of the optical fiber spawns the Bessel beam. The system provides a phase sensitivity of ∼0.28 mrad and optical path length sensitivity of ∼23 pm in air. The lateral resolution and working distance are found to be ∼3.91 µm and 650 µm to exhibit the performance of the system experimentally. The three-dimensional (3D) phase map of the cheek cell along with the refractive index is obtained from the reflected power spectrum. The combined low coherence phase microscopy and refractive index measurement provides the system with a potential for biological application. Also, the all-fiber probe can be easily integrated as an endoscopic probe.


Assuntos
Microscopia , Refratometria , Endoscopia , Fibras Ópticas
8.
Br Dent J ; 232(4): 269-272, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35217748

RESUMO

Cultural competence of healthcare professionals requires a combination of awareness, knowledge and skills to provide healthcare services to culturally and lingually diverse populations. The aim of this paper is to raise awareness regarding animal-based constituents in dental products which may not be acceptable to patients from different cultural, spiritual, or religious backgrounds. Animal-based products are used widely in medicine and dentistry. However, patients and sometimes even dental professionals may not be aware of this. This paper identifies some common products used in clinical dentistry which are derived from animal-based sources and discusses the implications of their use in a multicultural society.


Assuntos
Competência Cultural , Diversidade Cultural , Animais , Odontologia , Pessoal de Saúde , Humanos , Assistência Centrada no Paciente
9.
JAMA Netw Open ; 5(1): e2142210, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34994793

RESUMO

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.


Assuntos
COVID-19/epidemiologia , Pessoal de Saúde , Reinfecção , SARS-CoV-2 , Adulto , COVID-19/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Imunogenicidade da Vacina , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Atenção Terciária , Vacinas de Produtos Inativados/administração & dosagem , Vírion/imunologia , Adulto Jovem
10.
Pacing Clin Electrophysiol ; 45(3): 302-313, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34856638

RESUMO

OBJECTIVES: To evaluate any association between non-sustained ventricular tachycardia (NSVT) detected by intra-cardiac device and clinical outcomes in repaired adult congenital heart disease (ACHD) without tetralogy of Fallot (TOF). BACKGROUND: NSVT portends a higher risk of serious ventricular tachyarrhythmia in TOF. However its clinical significance when incidentally detected by implantable cardiac device is not well elucidated in non-TOF ACHD cohort. METHODS: We performed a single center, retrospective, longitudinal follow-up study in repaired ACHD (≥18 years) patients without TOF who hosted a pacemaker or automatic implantable cardiac defibrillator (AICD). The cohort was divided based on presence/absence of device detected NSVT. The primary end-point was a composite of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death (SCD). RESULTS: One hundred fifty eight patients (male 56.3%, median [IQR] age of 35 [28-43] years at last follow-up] with longitudinal post-implant follow-up duration of 8 (5-12) years were included. NSVT was detected in 52 (33%) patients. The primary composite end-point was more frequent in NSVT group [11.5% vs. 2.8%; p = .04]. Patients with NSVT were (i) older at the time of initial implant (age 25 vs. 18 years, p = .011) and more frequently demonstrated (ii) systemic ventricular dysfunction (44% vs. 26%; p = .015), as well as (iii) history of ventriculotomy (38% vs. 21%; p = .017). CONCLUSIONS: In our repaired ACHD cohort, we noted a significant association between device-detected-NSVT and the primary composite end-point of sustained VT/VF or SCD. Systemic ventricular dysfunction and history of ventriculotomy were more frequent in the NSVT group and likely constituted the clinical milieu.


Assuntos
Desfibriladores Implantáveis , Cardiopatias Congênitas , Taquicardia Ventricular , Tetralogia de Fallot , Disfunção Ventricular , Adulto , Morte Súbita Cardíaca , Seguimentos , Cardiopatias Congênitas/complicações , Humanos , Masculino , Estudos Retrospectivos , Tetralogia de Fallot/complicações , Tetralogia de Fallot/cirurgia , Fibrilação Ventricular
11.
J Cosmet Dermatol ; 21(3): 1154-1162, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33894101

RESUMO

BACKGROUND: Oxidative stress parameters have been reported to be significantly higher than controls in diverse disorders of pigmentation but no such data seem to be extant for IGH. OBJECTIVES: To verify whether heightened oxidative stress levels are seen in patients with IGH (compared with matched controls) and quantify the same in blood using appropriate biochemical markers. Further, an attempt to determine if there might be any correlation between the amount of oxidative stress and the severity of the disease. METHODOLOGY: This prospective case-control study was conducted in Northern India. Thirty Indian patients (Fitzpatrick skin phototype (SPT) IV-V) were included. The diagnosis of IGH lesions was confirmed based on characteristic clinical, and dermoscopic characteristics and confirmed on histopathological examination (H & E) of one of the lesions. RESULTS: The oxidative stress enzyme level was significantly higher among the cases compared to controls which were statistically significant (p < 0.05). A positive correlation was also observed between the levels of these markers and number of lesions, but this finding was statistically not significant [p > 0.05]. Assessment of melanin level by Dopa staining method in the IGH lesions revealed irregularly distributed melanin with areas of high and low melanin content and greater accumulation in the basement layer. CONCLUSION: The results of this probably the first study evaluating oxidative stress in IGH show that the oxidative stress is increased in patients with IGH. Level of oxidative stress seems to be correlated with both age of the patient (more in the elderly) and number of lesions.


Assuntos
Hipopigmentação , Transtornos da Pigmentação , Idoso , Estudos de Casos e Controles , Humanos , Hipopigmentação/etiologia , Melaninas , Estresse Oxidativo
12.
Cardiol Young ; 32(3): 497-499, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34350823

RESUMO

We report a neonate with dilated cardiomyopathy and have echocardiographic findings consistent with "functional" tricuspid atresia. There was an echo-bright, plate-like tissue at the tricuspid valve position with no forward flow across it. This report underscores the role of right ventricle intracavitary haemodynamic influence on the tricuspid valve leaflet excursion and demonstrates a phenomenon of "pseudo or functional tricuspid atresia" mimicking tricuspid atresia in a patient with acute presentation of cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada , Atresia Pulmonar , Atresia Tricúspide , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Recém-Nascido , Atresia Tricúspide/diagnóstico por imagem , Valva Tricúspide/anormalidades , Valva Tricúspide/diagnóstico por imagem
13.
J Indian Soc Pedod Prev Dent ; 39(3): 303-309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34810349

RESUMO

BACKGROUND: Pulpotomy is a vital pulp therapy performed in carious pulp exposures in teeth in which the inflamed coronal pulp is removed and medicament is placed to conserve the vital root pulps. Recently, simvastatin which is a cholesterol-lowering drug has been found to be associated with the pulp regenerative potential. AIM: The aim of this parallel two-arm randomized control trial was to evaluate and compare the clinical and radiographic efficacy of diode laser (DL) and simvastatin gel (SG) in pulpotomy of carious primary molars. METHODS: Hundred primary molars (in 98 children, 65 males, 33 females with age 4-8 years) requiring pulpotomy were randomized into the DL or SG group. Pulpotomy was performed as per the standardized protocol; thereafter, all teeth were restored with resin modified glass ionomer cement followed by stainless steel crowns. Follow-up evaluations were done at 3 and 12 months using clinical and radiographic criteria. Statistical analysis was done using Chi-square test at a significance level of 0.05. RESULTS: At 12 months, out of 92 teeth available for clinical and radiographic evaluation by blinded evaluators, DL group showed clinical and radiographic success rates of 76.1% and 52.1%, while SG group showed 80.4% and 65.2% success rates, respectively. There was no statistically significant difference between the efficacy of two techniques clinically (P = 0.49) or radiographically (P = 0.30). CONCLUSIONS: Both SG and DL had similar efficacy for primary tooth pulpotomy, clinically and radiographically after 12 months. Considering its ease of application and low-cost, SG can be recommended as a potential pulpotomy medicament in primary molars.


Assuntos
Cárie Dentária , Pulpotomia , Compostos de Alumínio , Compostos de Cálcio , Criança , Pré-Escolar , Cárie Dentária/tratamento farmacológico , Combinação de Medicamentos , Feminino , Humanos , Lasers Semicondutores/uso terapêutico , Masculino , Dente Molar/diagnóstico por imagem , Dente Molar/cirurgia , Óxidos , Silicatos , Sinvastatina , Dente Decíduo , Resultado do Tratamento
14.
Wiley Interdiscip Rev RNA ; : e1695, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825502

RESUMO

Non-coding RNAs (ncRNAs) work as crucial posttranscriptional modulators of gene expression regulating a wide array of biological processes that impact normal physiology, including reproductive health. The health of women, especially reproductive health, is now a prime focus of society that ensures the females' overall physical, social, and mental well-being. Furthermore, there has been a growing cognizance of ncRNAs' possible applications in diagnostics and therapeutics of dreaded diseases. Hence, understanding the functions and mode of actions of ncRNAs in the context of women's health will allow us to develop effective prognostic and therapeutic strategies that will enhance the quality of life of women. Herein, we summarize recent progress on ncRNAs, such as microRNAs (miRNAs) and long ncRNAs (lncRNAs), and their implications in reproductive health by tying the knot with lifestyle factors that affect fertility complications, pregnancy outcomes, and so forth. We also discourse the interplay among the RNA species, especially miRNAs, lncRNAs, and protein-coding RNAs, through the competing endogenous RNA regulations in diseases of women associated with maternal and fetal health. This review provides new perspectives correlating ncRNAs, lifestyle, and reproductive health of women, which will attract future studies to improve women's lives. This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

15.
Microbiol Resour Announc ; 10(46): e0101321, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792384

RESUMO

Bacillus paralicheniformis bcasdu2018/01 was isolated from the indoor environment of a chemistry laboratory. As part of the extracellular matrix, this isolate produces copious amounts of poly-γ-glutamic acid (γ-PGA). Here, we report the 4.25-Mbp draft genome assembly of the organism with an average G+C content of 45.92%.

18.
J Cancer Res Ther ; 17(4): 912-916, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34528541

RESUMO

INTRODUCTION: Dysembryoplastic neuroepithelial tumor (DNT) is a rare benign brain tumor predominantly involving children and young adults. Histologically, it corresponds to WHO Grade I tumors; however, it may masquerade aggressive neural tumors such as oligodendroglioma, oligoastrocytoma, pilocytic astrocytoma, and ganglioglioma. The literature on clinical, radiological, and pathological spectrum of DNT is described mostly in the form of case reports, with only a few case series reported till date. METHODS: A retrospective review of files with diagnosis of DNT (2016 to 2018) was made in the Department of Pathology, National Institute of Pathology, New Delhi. A total of ten cases were retrieved, and their clinical, radiological, and histopathological features were reviewed and studied. Special stains and immunohistochemistry were done, wherever required. RESULTS: The mean age was 14.8 (±7.9) years, with a male-to-female ratio of 1.5:1. The most common mode of presentation was recurrent, intractable seizures. The most common site of lesion was parietal lobe followed by temporal and frontal lobes of the brain. On histology, mucoid matrix admixed with floating neurons and oligodendrocyte-like cells was a consistent feature; however, the presence of specific glioneuronal elements was observed in only a few cases. CONCLUSIONS: DNT is a benign, low-grade, nonrecurrent neuroepithelial neoplasm. It is important to differentiate this rare entity from other mimickers, as it is surgically curable and carries an excellent prognosis without the need for adjuvant chemotherapy and radiotherapy. The study helps to enrich the clinicopathological aspects of this rare but important entity.


Assuntos
Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Neuroepiteliomatosas/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Adolescente , Adulto , Neoplasias Encefálicas/cirurgia , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Neuroepiteliomatosas/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
19.
Drug Discov Ther ; 15(4): 218-221, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34456195

RESUMO

Nivolumab is a programmed death receptor-1 blocking monoclonal antibody which has been approved by United States Food and Drug Administration for patients with metastatic non-squamous non-small cell lung cancer. Endocrinopathies like thyroid dysfunction and adrenal insufficiency are its known immune related adverse effects. Hypophysitis is very rare and usually presents with minimal symptoms. We report development of hypophysitis in an 84-year-old female patient who developed a range of symptoms (fatigue, headache, nausea) as well as laboratory confirmation of both central hypothyroidism and central adrenal deficiency which is unusual in cases of nivolumab induced hypophysitis. The patient had well differentiated adenocarcinoma of the left upper lobe of the lung. She underwent wedge resection followed by chemotherapy and was started on nivolumab due to recurrence. After 14 cycles of nivolumab, she started complaining of intense fatigue. She was found to have central thyroid deficiency and was started on levothyroxine. But her symptoms did not improve. Then she underwent adrenocorticotropic hormone stimulation test which showed central adrenal deficiency, but her brain magnetic resonance imaging did not reveal any pituitary or sellar changes. A diagnosis of nivolumab induced hypophysitis was made, based on clinical grounds and hormonal profile and she was started on oral steroids. She responded dramatically to this steroidal therapy within four weeks of its initiation and her immunotherapy with nivolumab was restarted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Hipofisite , Neoplasias Pulmonares , Hormônio Adrenocorticotrópico , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Humanos , Hipofisite/induzido quimicamente , Hipofisite/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Estados Unidos
20.
Comput Struct Biotechnol J ; 19: 3491-3506, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194673

RESUMO

The L-arginine biosynthesis pathway consists of eight enzymes that catalyse the conversion of L-glutamate to L-arginine. Arginine auxotrophs (argB/argF deletion mutants) of Mycobacterium tuberculosis are rapidly sterilised in mice, while inhibition of ArgJ with Pranlukast was found to clear chronic M. tuberculosis infection in a mouse model. Enzymes in the arginine biosynthetic pathway have therefore emerged as promising targets for anti-tuberculosis drug discovery. In this work, the ligandability of four enzymes of the pathway ArgB, ArgC, ArgD and ArgF is assessed using a fragment-based approach. We identify several hits against these enzymes validated with biochemical and biophysical assays, as well as X-ray crystallographic data, which in the case of ArgB were further confirmed to have on-target activity against M. tuberculosis. These results demonstrate the potential for more enzymes in this pathway to be targeted with dedicated drug discovery programmes.

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