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1.
J Biochem Mol Toxicol ; 38(9): e23812, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39163126

RESUMO

Aging is a process of time-associated depletion in the physiological functions, essential for the survival and reproducibility of living beings. Some age-related disorders can be successfully controlled with some biomedical techniques or pharmaceutical approaches. There are some precise remedies that demonstrate conspicuous promise in the preclinical and clinical setup of extending lifespan or enhancing health by altering natural senescence. The sirtuin family of proteins is one of the most favorable targets for antiaging strategies. Sirtuins were initially identified as transcription repressors in yeast, but today they are known to exist in bacteria and eukaryotes, as well as humans. The SIRT (1-7) family of proteins in humans is made up of seven members, each of which has either mono-ADP ribosyl transferase or deacetylase activity. Researchers suggest that sirtuins are essential for cell metabolism and play a major role in how cells react to various stimuli, such as oxidative or genotoxic stress. A healthy lifestyle, which includes exercise and a balanced diet, has been demonstrated to impact health span by adjusting the levels of sirtuins, suggesting the involvement of sirtuins in extending human longevity. The hunt for sirtuin activators is among the most extensive and comprehensive research subjects in the present scenario. Some optimism has been generated to investigate antiaging therapies by natural compounds, such as curcumin and others. This review article highlights the role of sirtuins in native senescence and their primordial roles in the progression of several life-threatening diseases. Further, it also provides recent information on the sirtuin activators and inhibitors and their therapeutic benefits.


Assuntos
Envelhecimento , Sirtuínas , Humanos , Sirtuínas/metabolismo , Envelhecimento/metabolismo , Animais , Senescência Celular , Longevidade
2.
J Transl Med ; 22(1): 759, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138492

RESUMO

BACKGROUND: Oral cancer poses a significant health challenge due to limited treatment protocols and therapeutic targets. We aimed to investigate the invasive margins of gingivo-buccal oral squamous cell carcinoma (GB-OSCC) tumors in terms of the localization of genes and cell types within the margins at various distances that could lead to nodal metastasis. METHODS: We collected tumor tissues from 23 resected GB-OSCC samples for gene expression profiling using digital spatial transcriptomics. We monitored differential gene expression at varying distances between the tumor and its microenvironvent (TME), and performed a deconvulation study and immunohistochemistry to identify the cells and genes regulating the TME. RESULTS: We found that the tumor-stromal interface (a distance up to 200 µm between tumor and immune cells) is the most active region for disease progression in GB-OSCC. The most differentially expressed apex genes, such as FN1 and COL5A1, were located at the stromal ends of the margins, and together with enrichment of the extracellular matrix (ECM) and an immune-suppressed microenvironment, were associated with lymph node metastasis. Intermediate fibroblasts, myocytes, and neutrophils were enriched at the tumor ends, while cancer-associated fibroblasts (CAFs) were enriched at the stromal ends. The intermediate fibroblasts transformed into CAFs and relocated to the adjacent stromal ends where they participated in FN1-mediated ECM modulation. CONCLUSION: We have generated a functional organization of the tumor-stromal interface in GB-OSCC and identified spatially located genes that contribute to nodal metastasis and disease progression. Our dataset might now be mined to discover suitable molecular targets in oral cancer.


Assuntos
Fibroblastos , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , Neoplasias Bucais , Células Mieloides , Microambiente Tumoral , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Metástase Linfática/patologia , Fibroblastos/patologia , Fibroblastos/metabolismo , Células Mieloides/patologia , Células Mieloides/metabolismo , Fibroblastos Associados a Câncer/patologia , Fibroblastos Associados a Câncer/metabolismo , Perfilação da Expressão Gênica , Feminino , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética
3.
Blood Cell Ther ; 7(2): 33-36, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38854402

RESUMO

Melphalan-induced encephalopathy is a rare complication observed in patients undergoing autologous stem cell transplantation (ASCT) and is characterized by symptoms ranging from drowsiness to seizures. Previous reports have described similar cases, including a review of a large cohort of patients in whom melphalan-associated encephalopathy was identified in 2% of the patients undergoing ASCT. We describe the case of a 63-year-old male with Multiple Myeloma and underlying chronic kidney disease (CKD) who underwent ASCT with a reduced dose of melphalan due to renal dysfunction in complete remission following induction therapy and subsequent neurological deterioration, which necessitated an extensive evaluation of several neurological and infective etiologies. In this report, we highlight that melphalan-associated encephalopathy is a distinct entity complicating ASCT in patients with myeloma, especially in those with preexisting renal insufficiency, and consider its management.

4.
Sci Rep ; 14(1): 11609, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773214

RESUMO

No biomarker has yet been identified that allows accurate diagnosis and prognosis of oral cancers. In this study, we investigated the presence of key metabolites in oral cancer using proton nuclear magnetic resonance (NMR) spectroscopy to identify metabolic biomarkers of gingivobuccal oral squamous cell carcinoma (GB-OSCC). NMR spectroscopy revealed that uracil was expressed in 83.09% of tumor tissues and pyrimidine metabolism was active in GB-OSCC; these results correlated well with immunohistochemistry (IHC) and RNA sequencing data. Based on further gene and protein analyses, we proposed a pathway for the production of uracil in GB-OSCC tissues. Uridinetriphosphate (UTP) is hydrolyzed to uridine diphosphate (UDP) by CD39 in the tumor microenvironment (TME). We hypothesized that UDP enters the cell with the help of the UDP-specific P2Y6 receptor for further processing by ENTPD4/5 to produce uracil. As the ATP reserves diminish, the weakened immune cells in the TME utilize pyrimidine metabolism as fuel for antitumor activity, and the same mechanism is hijacked by the tumor cells to promote their survival. Correspondingly, the differential expression of ENTPD4 and ENTPD5 in immune and tumor cells, respectively, indicatedtheir involvement in disease progression. Furthermore, higher uracil levels were detected in patients with lymph node metastasis, indicating that metastatic potential is increased in the presence of uracil. The presence of uracil and/or expression patterns of intermediate molecules in purine and pyrimidine pathways, such asCD39, CD73, and P2Y6 receptors together with ENTPD4 and ENTPD5, hold promise as biomarker(s) for oral cancer diagnosis and prognosis.


Assuntos
Biomarcadores Tumorais , Neoplasias Bucais , Pirimidinas , Uracila , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Uracila/metabolismo , Biomarcadores Tumorais/metabolismo , Pirimidinas/metabolismo , Feminino , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral , Idoso , Apirase/metabolismo
5.
Carbohydr Res ; 541: 109164, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815342

RESUMO

Stereoselective synthesis is essential for propelling mainstream academia toward a relentless pursuit of novel and cutting-edge strategies for constructing molecules with unparalleled precision. Naturally derived benzopyrans, benzopyrones, and flavonoids are an essentially prominent group of oxa-heterocycles, highly significant targets in medicinal chemistry owing to their extensive abundance in biologically active natural products and pharmaceuticals. The molecular complexity and stereoselectivity induced by heterocycles embedded with C-glycosides have attracted considerable interest and emerged as a fascinating area of research for synthetic organic chemists. This present article emphasizes the existing growths in the strategies involving the diastereoselective synthesis of C-glycosylated benzopyrans, benzopyrones, and flavonoids using naturally acquired glycones as chiral synthons.


Assuntos
Benzopiranos , Produtos Biológicos , Flavonoides , Glicosídeos , Flavonoides/química , Flavonoides/síntese química , Estereoisomerismo , Benzopiranos/química , Benzopiranos/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Glicosídeos/química , Glicosídeos/síntese química , Pironas/química , Pironas/síntese química , Glicosilação , Estrutura Molecular
6.
Ther Adv Ophthalmol ; 16: 25158414241237906, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533487

RESUMO

Pediatric corneal transplant is a highly demanding and technically challenging procedure for the cornea surgeon in today's era. These cases pose unique challenges in clinical and surgical management. The indications of pediatric corneal transplant can be therapeutic, tectonic, optical, and cosmetic. Pediatric patients undergoing corneal transplants are at a high risk of graft infection, failure, rejection, dehiscence, and amblyopia due to young age, robust immune system, increased incidence of trauma, and compliance issues. The other factors contributing to graft failure can be allograft rejection, secondary glaucoma, corneal vascularization, multiple surgeries, vitreous prolapse, and lack of treatment compliance. A successful corneal transplant in children depends on meticulous preoperative evaluation, uneventful surgery, the expertise of a corneal surgeon, and regular and timely postoperative follow-up. Therapeutic and optical penetrating keratoplasty are the most commonly performed transplants in children. However, with the advancements in surgical technique and management protocol, the current focus has shifted toward lamellar keratoplasty. Lamellar keratoplasty offers early visual recovery and potentially fewer complications. Visual rehabilitation through corneal transplant in otherwise blind eyes can be a boon for the children. Recently, keratoprostheses have been promising in children with multiple graft failures. The current review gives insights into epidemiology, etiology, indications, clinical characteristics, investigations, management options, recent advances, and the future of pediatric corneal transplants. As surgical techniques continue to grow and comprehension of pediatric corneal transplants is improving, we can safeguard these eyes with the best possible anatomical and functional outcomes.

7.
Neuro Oncol ; 26(2): 226-235, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-37713135

RESUMO

Brain tumors are the most common solid tumor in children and the leading cause of cancer-related deaths. Over the last few years, improvements have been made in the diagnosis and treatment of children with Central Nervous System tumors. Unfortunately, for many patients with high-grade tumors, the overall prognosis remains poor. Lower survival rates are partly attributed to the lack of efficacious therapies. The advent and success of immune checkpoint inhibitors (ICIs) in adults have sparked interest in investigating the utility of these therapies alone or in combination with other drug treatments in pediatric patients. However, to achieve improved clinical outcomes, the establishment and selection of relevant and robust preclinical pediatric high-grade brain tumor models is imperative. Here, we review the information that influenced our model selection as we embarked on an international collaborative study to test ICIs in combination with epigenetic modifying agents to enhance adaptive immunity to treat pediatric brain tumors. We also share challenges that we faced and potential solutions.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Humanos , Criança , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Imunoterapia , Neoplasias do Sistema Nervoso Central/terapia
8.
Ann Med Surg (Lond) ; 85(8): 4134-4136, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554865

RESUMO

Giant mastauxe is an uncomplicated physiological enlargement of the breasts in newborns, characterized by a breast bud diameter greater than 3 cm. While most newborns have some degree of breast enlargement, giant mastauxe is rare, which may be unnecessarily intervened upon. Case presentation: A 13-day-term male neonate presented with bilateral breast enlargement and milky nipple discharge, which worsened upon breast massage. The mother had an uneventful pregnancy, and neither the mother nor the baby had a history of drug intake. The examination revealed soft, non-tender, non-erythematous bilateral breast swellings measuring 3.6×3.8 cm on the right side and 3.2×3.4 cm on the left side. Ultrasonography confirmed their hypoechoic nature with minimum vascularization. The white blood cell count, C-reactive protein levels, and culture of nipple discharge yielded normal results. The baby was discharged, and upon follow-up after 2 weeks, it was observed that breast swellings had spontaneously reduced in size. Discussion: Neonatal breast enlargement can occur as a result of either the transplacental transfer of maternal estrogens or declining levels of estrogens toward the end of pregnancy, leading to hyperprolactinemia. However, the exact reasons behind the occurrence of giant mastauxe in some newborns remain incompletely understood. It may be due to increased sensitivity of the breast tissue to estrogens. Conclusion: Proper clinical examination, along with the use of ultrasonography and/or laboratory investigations if required, is essential to differentiate giant mastauxe from neonatal mastitis or breast abscess. Treatment primarily involves observation and providing reassurance to parents.

9.
Indian J Ophthalmol ; 71(9): 3235-3241, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37602614

RESUMO

Purpose: To assess the current trends in use of perioperative antibiotic prophylaxis, especially intracameral antibiotics (ICAB), for cataract surgery in India. Methods: This was an E-survey using a previously validated questionnaire carried out by the All India Ophthalmological Society (AIOS) in August 2022. An E-mail invitation to complete an online 40-point survey was sent to all members of the AIOS using a digital E-mail service (Survey Monkey) and social media platforms. Results: Out of 1804 total respondents, 58% (n = 1022) reported using routine ICAB prophylaxis. Of those using ICAB, 89% (n = 909) reported using it for all cases, whereas the rest used it for specific indications such as post-PC rent (n = 43), one eyed patient (n = 19), and high-risk cases (n = 50). Commercially available moxifloxacin was by far the commonest agent used for ICAB (n = 686, 67%). Eighty respondents (8%) reported noticing occasional toxic reactions and nontoxic corneal edema (n = 64, 6%) with ICAB. Surgeons with >10 years' experience especially practicing in medical colleges used fewer ICAB (OR = 0.52, 95%CI = 0.38 - 0.72, P < 0,001) compared to younger surgeons (<5-year experience) in solo clinics. The commonest reason for nonadoption of IC antibiotics was "unconvinced of the need to use it in my setting" (n = 296, 52% of those who answered this question). Conclusion: IC antibiotic prophylaxis for cataract surgery has significantly increased in India from 40% in 2017 to 58% in 2022. Commercially available moxifloxacin was preferred by the majority users. Intraocular inflammation may occur occasionally and needs safer formulations to avoid this.


Assuntos
Catarata , Oftalmologistas , Humanos , Antibioticoprofilaxia , Moxifloxacina , Antibacterianos/uso terapêutico
10.
Fetal Pediatr Pathol ; 42(6): 972-978, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37584237

RESUMO

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is characterized by its large size and potential for transformation into melanoma. It can be associated with other neural cristopathies, including neurofibroma, however, it has not previously been described with a congenital neurofibroma. CASE REPORT: A newborn girl presented with a large congenital neurofibroma arising in a bathing trunk type of giant congenital melanocytic nevus. CONCLUSION: Congenital neurofibromas can be associated with (or a component of) a GCMN.


Assuntos
Melanoma , Neurofibroma , Nevo Pigmentado , Neoplasias Cutâneas , Recém-Nascido , Feminino , Humanos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/congênito , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/congênito
11.
Int Immunopharmacol ; 121: 110521, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37385122

RESUMO

Immunity refers to the body's defense mechanism to protect itself against illness or to produce antibodies against pathogens. Senescence is a cellular phenomenon that integrates a sustainable growth restriction, other phenotypic abnormalities and including a pro-inflammatory secretome. It is highly involved in regulating developmental stages, tissue homeostasis, and tumor proliferation monitoring. Contemporary experimental reports imply that abolition of senescent cells employing evolved genetic and therapeutic approaches augment the chances of survival and boosts the health span of an individual. Immunosenescence is considered as a process in which dysfunction of the immune system occurs with aging and greatly includes remodeling of lymphoid organs. This in turn causes fluctuations in the immune function of the elderly that has strict relation with the expansion of autoimmune diseases, infections, malignant tumors and neurodegenerative disorders. The interaction of the nervous and immune systems during aging is marked by bi-directional influence and mutual correlation of variations. The enhanced systemic inflammatory condition in the elderly, and the neuronal immune cell activity can be modulated by inflamm-aging and peripheral immunosenescence resulting in chronic low-grade inflammatory processes in the central Nervous system known as neuro-inflammaging. For example, glia excitation by cytokines and glia pro-inflammatory productions contribute significantly to memory injury as well as in acute systemic inflammation, which is associated with high levels of Tumor necrosis factor -α and a rise in cognitive decline. In recent years its role in the pathology of Alzheimer's disease has caught research interest to a large extent. This article reviews the connection concerning the immune and nervous systems and highlights how immunosenescence and inflamm-aging can affect neurodegenerative disorders.


Assuntos
Imunossenescência , Doenças Neurodegenerativas , Humanos , Idoso , Imunossenescência/fisiologia , Envelhecimento , Inflamação , Sistema Imunitário
12.
Indian J Ophthalmol ; 71(6): 2526-2530, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37322674

RESUMO

Purpose: To study the corelation between outer retinal layer thickness (ORL), outer photoreceptor segment thickness (PROS), and central macular thickness (CMT) with best-corrected visual acuity (BCVA) in patients having clinically significant macular edema (CSME) and compare these parameters with normal patients. Methods: This was a prospective, nonrandomized, observational, comparative study done during the period of January to May 2019. The study included 60 eyes of 36 patients. The patient population was segregated into two Groups: Group I (30 normal eyes of 15 normal patients) and Group II (30 eyes of 21 diabetic patients) with CSME. The comparison between ORL, PROS, and CMT was made between both the groups, and the correlation between ORL thickness, PROS thickness, and CMT with BCVA in Group II was studied. Results: The mean age in Group I was 52.6+10.66 years, and 53.42+8.15 years in Group II. The male/female ratio was 1.1:1 in Group I and 4:3 in Group II. The mean CMT was greater in Group II (330.13 ± 37.01) than in Group I (222.20 ± 12.30). The mean ORL thickness was greater in Group I (97.73 ± 6.92) than in Group II (80.63 ± 9.03). The PROS thickness was statistically significant in Group I (35.05 ± 3.4) than in Group II (28.57 ± 3.53). There was a strong correlation between BCVA and ORL thickness (r = -0.580, P < 0.001) and more strong correlation between BCVA and PROS thickness in Group II (r = -0.611, P < 0.000). There was a moderate correlation between BCVA and CMT (r = 0.410, P < 0.025), and all results were statistically significant. Conclusion: Both ORL and PROS thickness were greater in healthy normal eyes than in eyes with CSME. BCVA was strongly correlated with PROS and ORL thickness and moderately associated with CMT.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Edema Macular/etiologia , Edema Macular/complicações , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Estudos Prospectivos , Retina/diagnóstico por imagem , Acuidade Visual
13.
Indian J Ophthalmol ; 71(5): 1706-1717, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37203022

RESUMO

Corneal cross-linking (CXL), a corneal strengthening procedure, is known to alter anterior stroma swelling behavior and is one of the treatment modalities of bullous keratopathy (BK). There are multiple studies published on the role of CXL in the treatment of BK. These articles had heterogeneous study population, different protocols used, and variable conclusions. This systematic review aimed to determine the role of CXL in the treatment of BK. The primary outcomes considered were changes in central corneal thickness (CCT) after 1, 3, and 6 months of CXL. The secondary outcome measures were changes in visual acuity, corneal clarity, subjective symptoms, and complications after CXL. We included randomized control trials (RCTs), observational and interventional studies, and case series with reports of more than 10 cases in this review. In RCTs, the mean pre-CXL CCT (794.0 ± 178.5 µm) in the intervention group (n = 37), decreased at 1 month (750.9 ± 154.3 µm) followed by a subsequent increase, but this difference was not significant during the 6-month follow-up (P- value 0.28, 0.82, and 0.82 at 1, 3, and 6 months, respectively). In noncomparative clinical studies (n = 188), the mean pre-CXL CCT (794.0 ± 178.5 µm) decreased at 1 month (710.9 ± 127.2 µm, P < 0.0001). Seven of the 11 articles included in the review reported no significant improvement in vision with CXL. The initial improvement in corneal clarity and clinical symptoms was not sustained. Current evidence suggests that CXL has short-term efficacy in the treatment of BK. More RCTs with high-quality evidence are needed.


Assuntos
Crosslinking Corneano , Ceratocone , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Raios Ultravioleta , Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Substância Própria , Ceratocone/tratamento farmacológico , Topografia da Córnea
14.
Indian J Ophthalmol ; 71(3): 743-749, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36872669

RESUMO

Purpose: To assess the quantum of cataract surgical training opportunities for trainees enrolled in ophthalmology residency programs in India. Methods: An anonymous online survey was sent across to resident ophthalmologists across India through various social media platforms. The results were tabulated and analyzed. Results: A total of 740 resident ophthalmologists participated in the survey. In all, 40.1% (297/740) were independently performing cataract surgeries. Of those who were not performing independent cataract surgeries, 62.5% (277/443) were in the third year of residency. A significantly higher proportion of trainees who were not operating independent cataract surgeries were enrolled in MD/MS programs as compared with DNB courses (65.6% vs. 43.7%; P < 0.0001). Of those who were operating independent cases; 97.1% had exposure to manual small incision cataract surgery (MSICS), whereas only 14.1% performed phacoemulsification. It was noted that 31.3% of residents reported that on an average a trainee in their training program performed less than 100 independent cataract surgeries throughout the residency. Apart from cataract surgery, the most performed surgeries by residents were pterygium excision (85.3%), followed by enucleation/evisceration (68.1%). When it came to training aids, 47.2% (349/740) of the respondents reported no access to wet lab, animal/cadaver eyes, or surgical simulators for training. Conclusion: The amount of surgical exposure in terms of cataract surgery across residency programs in India is low with most of the ophthalmology residents who participated in this survey not operating cataracts independently; even in their final year of residency. Exposure to phacoemulsification in residency programs is very limited across the country. Although some programs do provide well-rounded surgical exposure to trainees, such centers are scarce; the stark variations in infrastructure, training opportunities, and surgical numbers warrant an overhaul in the structure and curriculum of residency programs in India.


Assuntos
Extração de Catarata , Catarata , Animais , Currículo , Olho , Índia
16.
Indian J Med Microbiol ; 41: 104-110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36244851

RESUMO

PURPOSE: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections. METHODS & OBJECTIVES: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. RESULTS: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median â€‹= â€‹44) was 1.8 times than wave-1 sample (median â€‹= â€‹24). Spike protein in wave-2 samples had 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q-vaccine escape mutant was detected in five samples of wave-2; T478K - highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p. Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n â€‹= â€‹39) samples. CONCLUSION: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).


Assuntos
COVID-19 , Doenças Transmissíveis , Neoplasias , Humanos , Institutos de Câncer , Epidemiologia Molecular , SARS-CoV-2 , ChAdOx1 nCoV-19 , Glicoproteína da Espícula de Coronavírus , Infecções Irruptivas , Genômica , Pessoal de Saúde , Índia , Complicações Pós-Operatórias
17.
Indian J Cancer ; 60(4): 486-492, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38258869

RESUMO

INTRODUCTION: High-dose chemotherapy with melphalan, followed by autologous hematopoietic stem cell transplantation (AHCT) remains the standard of care for consolidation therapy of fit patients with newly diagnosed multiple myeloma (NDMM), for more than 20 years now. MATERIAL AND METHODS: This is a retrospective study of NDMM patients who underwent AHCT at our center from 2011 to 2018. Data was undertaken using the hospital electronic medical records (EMR). RESULTS: Among transplant eligible patients (which were 764), 78 patients (10.2%) underwent AHCT. The predominant stage in the study cohort was International Scoring System (ISS)-III (55%), and IgG-kappa (44%) was the commonest subtype of multiple myeloma (MM). Light chain myeloma was found in 23.5% of patients. Pretransplant, 42%, 48%, and 10% patients were in more than very good partial response (>VGPR), very good partial response (VGPR), and partial response (PR), respectively. The median duration of follow-up was 57.2 months (range: 12.1-120.2 months). The entire cohort's 5-year overall survival (OS) and progression-free survival (PFS) were 89.1% and 41.8%, respectively. CONCLUSION: Bortezomib based triplet induction regimens were effective and well tolerated in this retrospective analysis of Indian patients. We observed that AHCT effectively achieves deep and durable remission in MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Bortezomib/uso terapêutico , Quimioterapia de Indução , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
18.
Indian J Ophthalmol ; 70(11): 3791-3796, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36308098

RESUMO

Cataract causes bilateral blindness in 20 million people globally, the vast majority of whom live in developing countries. Manual small-incision cataract surgery (MSICS) has emerged as an efficient and economical alternative to phacoemulsification, giving comparable results in terms of final visual gain. One of the important determinants of postoperative visual gain is the status of the corneal endothelium. Multiple factors such as corneal distortion, irrigation solution turbulence, mechanical trauma by instruments, nuclear fragments, intraocular lens contact, and free oxygen radicals, all have been implicated in causing corneal damage during cataract surgery. MSICS with posterior chamber intraocular lens implantation has been reported to cause an endothelial cell loss of 15.83%, which is comparable with other modes of cataract surgery like extracapsular cataract extraction and phacoemulsification. Thorough preoperative assessment of endothelial status and taking necessary steps for endothelial protection during surgery can decrease the endothelial cell loss and overall burden of pseudophakic bullous keratopathy. In addition to surgical techniques, the type of irrigating solutions, ocular viscoelastic devices, intracameral dyes, and drugs all affect the endothelial cell status. This review presents a summary of available literature on the protection of endothelial cells during different steps of MSICS. This is especially relevant for developing countries where large-scale MSICS cataract surgeries are performed to decrease the cataract blindness burden.


Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares , Facoemulsificação , Ferida Cirúrgica , Humanos , Endotélio Corneano , Células Endoteliais , Extração de Catarata/efeitos adversos , Extração de Catarata/métodos , Facoemulsificação/métodos , Cegueira
19.
Indian J Ophthalmol ; 70(11): 3773-3778, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36308095

RESUMO

Cataract is the most common cause of reversible blindness worldwide, accounting for approximately 50% of blindness worldwide. Cataract surgery is the most common surgical procedure performed in routine ophthalmic practice. It has undergone tremendous evolution, and the incision size has progressively reduced from 10-12 mm in extracapsular cataract surgery (ECCE) to 6-8 mm for manual small-incision cataract surgery (MSICS) and 2.2-2.8 mm in phacoemulsification. In a developing country like India, with a massive backlog of cataract, everyone cannot afford private surgery like phacoemulsification. Moreover, annual maintenance of the machine, cost of foldable IOLs, need for greater skill, learning curve, and difficulty in performing the surgery in mature and brown cataracts are other barriers. Due to these factors, MSICS is the surgery of choice in the developing world, with profound societal and economic benefits and similar visual recovery compared to phacoemulsification. During the last two decades, MSICS gained popularity in developing countries and has undergone tremendous advances. This article aims to review the various techniques of MSICS and how the surgery has evolved over the years, particularly focusing on the current technique of 2-mm MSICS.


Assuntos
Extração de Catarata , Catarata , Facoemulsificação , Humanos , Extração de Catarata/métodos , Facoemulsificação/métodos , Implante de Lente Intraocular/métodos , Cegueira
20.
Indian J Ophthalmol ; 70(11): 3960-3966, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36308135

RESUMO

Purpose: The purpose of this study was to compare and analyze the endothelial cell loss during manual small-incision cataract surgery (MSICS) using the viscoelastic-assisted nucleus removal versus basal salt solution plus technique. Methods: This was a prospective randomized trial of 204 patients who underwent MSICS using viscoelastic-assisted nucleus removal (Group 1- OVD) versus basal salt solution plus technique (Group 2- BSS) at a tertiary eye care hospital in North India from January 2018 to 2021. Of these 204 patients, 103 (50.5%) and 101 (49.5%) were allocated to Group 1 and 2, respectively. The parameters assessed were detailed history, demographics, and anterior and posterior segment details. Visual acuity, intraocular pressure (IOP), keratometry, pachymetry, and endothelial cell density were evaluated preoperatively and postoperatively on day 1 and 30. Results: The mean age of the patients was 64.5 ± 8.2 years (range 48-82 years). There were 129 (63.2%) males and 75 (36.8%) females. The mean LogMAR visual acuity for both groups on day 1 (Group 1- 0.3 ± 0.1, Group 2- 0.5 ± 0.2) and day 30 (Group 1- 0.1 ± 0.2, Group 2- 0.1 ± 0.1) was statistically significant (P < 0.001), and the mean IOP value showed a statistically significant value (P < 0.009) on day 1 in Group 2 (15.0 ± 2.4 mmHg) and on day 30 (P < 0.001) in both the groups (Group 1- 13.6 ± 1.8 mmHg, Group 2- 13.5 ± 2 mmHg). The horizontal and vertical k values also showed a statistically significant difference on day 1 and day 30 (P < 0.001). The mean percentage change of central corneal thickness (CCT) in Group 1 was 17.7% and in Group 2 was 17.4% on day 1, and it was 1.1% on day 30 in both the groups, which was statistically significant (P < 0.001) compared to preoperative values. The percentage change in endothelial cell density on day 1 was 9% in Group 1 and 4.6% in Group 2, which was statistically significant (P < 0.001). On day 30, it was 9.7% and 4.8%, respectively, which was statistically significant (P < 0.001). Conclusion: Our study highlights statistically significant endothelial cell loss with viscoelastic-assisted nuclear delivery compared to BSS-assisted nuclear delivery during MSICS in a short follow-up of 1 month. The CCT values showed a slight increase, and the keratometry and IOP were unaffected compared to the preoperative parameters in both the groups.


Assuntos
Extração de Catarata , Catarata , Facoemulsificação , Ferida Cirúrgica , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Perda de Células Endoteliais da Córnea/diagnóstico , Perda de Células Endoteliais da Córnea/etiologia , Estudos Prospectivos , Extração de Catarata/métodos , Implante de Lente Intraocular/métodos , Cloreto de Sódio , Facoemulsificação/métodos , Contagem de Células
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