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1.
Mol Cell ; 65(3): 432-446.e5, 2017 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-28157505

RESUMO

Master regulatory genes require stable silencing by the polycomb group (PcG) to prevent misexpression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in ESCs and neural progenitors using 5C and super-resolution microscopy. The genomic loci of repressed PcG targets formed discrete, small (20-140 Kb) domains of tight interaction that corresponded to locations bound by canonical polycomb repressive complex 1 (PRC1). These domains changed during differentiation as PRC1 binding changed. Their formation depended upon the Polyhomeotic component of canonical PRC1 and occurred independently of PRC1-catalyzed ubiquitylation. PRC1 domains differ from topologically associating domains in size and boundary characteristics. These domains have the potential to play a key role in transmitting epigenetic silencing of PcG targets by linking PRC1 to formation of a repressive higher-order structure.


Assuntos
DNA/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Neurais/citologia , Complexo Repressor Polycomb 1/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , DNA/química , DNA/genética , Células-Tronco Embrionárias/metabolismo , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , Células-Tronco Neurais/metabolismo , Complexo Repressor Polycomb 1/química , Domínios Proteicos , Ubiquitinação
2.
Blood ; 139(8): 1184-1197, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33908607

RESUMO

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired antimetabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is reprogramming gene expression in a metabolism-dependent manner. MondoA (also known as Myc-associated factor X-like protein X-interacting protein [MLXIP]), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets, we found that MondoA overexpression is associated with worse survival in pediatric common acute lymphoblastic leukemia (ALL; B-precursor ALL [B-ALL]). Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and RNA-interference approaches, we observed that MondoA depletion reduces the transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced pyruvate dehydrogenase activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Estresse Fisiológico , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
3.
Nature ; 556(7701): 332-338, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29643512

RESUMO

Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral ß-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.


Assuntos
Encéfalo/imunologia , Encéfalo/patologia , Imunidade Inata , Memória Imunológica , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/patologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Amiloidose/imunologia , Amiloidose/patologia , Animais , Modelos Animais de Doenças , Epigênese Genética , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Tolerância Imunológica , Inflamação/genética , Inflamação/imunologia , Masculino , Camundongos , Microglia/imunologia , Microglia/metabolismo , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia
4.
Pediatr Cardiol ; 45(3): 648-659, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36995405

RESUMO

Surgical myectomy is recommended for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) after optimal pharmacological therapy. Percutaneous transluminal septal myocardial ablation (PTSMA) is reserved for high-risk adults. Symptomatic patients below 25 years underwent either surgery or PTSMA after heart-team discussion and informed consent. Echocardiography assessed gradients in surgical group. PTSMA group underwent invasive transseptal hemodynamic assessment, selective coronary angiography and super-selective cannulation of septal perforators using microcatheters. Contrast echocardiography through the microcatheter identified the myocardial target for PTSMA. Hemodynamic and electrocardiographic monitoring guided alcohol injection. Both groups were continued on beta-blockers. Symptoms, echocardiographic gradients and Brain natriuretic peptide (NTproBNP) measurements were assessed on follow-up. Twelve patients aged 5-23 years (11-98 kg) formed the study group. Indications for PTSMA in 8 patients included abnormal mitral valve anatomy warranting replacement (n = 3), Jehovah's witness (n = 2), severe neurodevelopmental and growth retardation (n = 1) and refusal of surgery (n = 2). PTSMA targeted first perforator (n = 5), second perforator (n = 2) and anomalous septal artery from left main trunk (n = 1). Outflow gradient reduced from 92.5 ± 19.7 to 33.1 ± 13.5 mmHg. At a median follow-up of 38 months (range 3-120 weeks), the peak instantaneous echocardiographic gradient was 32 ± 16.5 mmHg. Gradient reduced in four surgical patients from 86.5 ± 16.3 mmHg to 42 ± 14.7 mm Hg. All patients were in NYHA class I/II on follow-up. The mean NTproBNP in PTSMA group reduced from 6084 ± 3628 pg/ml to 3081 ± 2019 pg/ml; it was 1396 and 1795 pg/ml in surgery. PTSMA may be considered in medically refractory high-risk young patients. It relieves symptoms and reduces gradient. Though surgery is preferred in young patients, PTSMA may have a role in selected patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Hipertrófica , Adulto , Humanos , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Coração , Procedimentos Cirúrgicos Vasculares , Miocárdio
5.
Chem Biodivers ; : e202401756, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146235

RESUMO

Diploknema butyracea (Roxb) H.J Lam, also referred as "Kalpavriksha", is commonly known as Gophal, Cheura, or Indian butter tree. It is a deciduous tree with straight trunks of 15-20 m in height and white-yellow-coloured fragile flowers with fragrance, found at altitudes of 300-1500 m in the sub-Himalayan region of India, China, Nepal, and Bhutan. Diploknema have 11 taxa and 8 species, out of which 3 species are found in Uttarakhand hills, Sikkim, Darjeeling, Arunachal Pradesh, and Assam. The tree holds significant economic importance, serving various purposes within ethnic communities. Its high lipid content makes it valuable for food, medicine, construction, and the production of various value-added products. The ethno-pharmacological applications encompass treating rheumatism, burns, asthma, and various skin conditions. The plant's different components-bark, leaves, flowers, seeds, and fruits-contain a diverse array of phytoconstituents, including alkaloids, tannins, flavonoids, steroids, terpenoids, and palmitic acid, along with essential nutrients like sodium, calcium, potassium, iron, magnesium, zinc, and various sugars which shows diverse pharmacological and therapeutic activities. Beyond traditional uses, Diploknema is important for diverse industrial application in pharmaceuticals, confectionery, nutraceuticals, and cosmetics. Present paper is an attempt to understand comprehensive details on different aspects of this plant to explore new avenues for various value-added products.

6.
Drug Dev Ind Pharm ; 50(2): 89-101, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38175566

RESUMO

OBJECTIVE: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions. SIGNIFICANCE, METHODS, AND RESULTS: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints. CONCLUSION: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.


Assuntos
Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Alimentos Fortificados , Calcitriol/fisiologia , Calcitriol/uso terapêutico , Vitaminas , Deficiência de Vitamina D/tratamento farmacológico
7.
Arch Psychiatr Nurs ; 52: 89-100, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260990

RESUMO

AIMS AND OBJECTIVES: To develop and evaluate the effectiveness of a structured therapeutic communication module on psychological distress and perceived needs among caregivers of critically ill patients. BACKGROUND: Caregivers of critically ill patients experience intense psychological distress, and their needs often go unexpressed or unidentified. Structured therapeutic communication enables nurses to explore and fulfill these needs. METHOD: A mixed-method study was conducted among 30 caregivers of critically ill patients. During phase one, a qualitative interview was conducted, and a structured therapeutic communication module was developed based on Hildegard Peplau's Interpersonal Relations Theory. In the second phase, one group pre-test and post-test design was adopted. The Hospital Anxiety and Depression Scale (HADS) and a Semi-structured interview schedule were used to assess psychological distress and perceived needs, respectively. RESULTS: Half of (50 %) the caregivers reported a high level of anxiety before intervention, with a mean of 11.30 (SD: 4.0), and 66.7 % of them had a high level of depression, with a mean of 12.03 (SD: 0.08). There was a statistically significant difference in anxiety (CI: 0.451-2.016) and depression (CI: 0.261-1.538) before and after the intervention. The qualitative analysis revealed unmet needs perceived by caregivers. CONCLUSION: Using a structured therapeutic communication module helps nurses to alleviate the psychological distress experienced by caregivers of CCU patients. RELEVANCE TO CLINICAL PRACTICE: Nurses need to be sensitive to the unexpressed needs of caregivers of critically ill patients. The structured therapeutic communication modules can be integrated into routine nursing care practice to ensure family-centered care.


Assuntos
Cuidadores , Comunicação , Estado Terminal , Unidades de Terapia Intensiva , Angústia Psicológica , Humanos , Estado Terminal/psicologia , Feminino , Masculino , Cuidadores/psicologia , Adulto , Pessoa de Meia-Idade , Depressão/psicologia , Ansiedade/psicologia , Estresse Psicológico/psicologia , Pesquisa Qualitativa
8.
J Anaesthesiol Clin Pharmacol ; 40(3): 516-522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39391650

RESUMO

Background and Aims: Pneumoperitoneum creation for laparoscopic surgery increases the intraabdominal pressure and causes alveolar atelectasis. We investigated the influence of an increase in intra-abdominal pressure (IAP) on ventilatory mechanical power (MP) delivery during pneumoperitoneum creation for laparoscopic cholecystectomy. Material and Methods: In a prospective cohort design, we enrolled 42 patients undergoing laparoscopic cholecystectomy. During pneumoperitoneum creation, the IAP was sequentially raised to three predefined IAP levels (8, 11 and 14 mmHg), keeping identical ventilatory settings (timepoints T1, T2, and T3). After that, positive end-expiratory pressure (PEEP) was sequentially raised from 5 to 8 to 11 cmH2O (timepoint T4 and T5). The primary outcome included ventilatory MP delivery at each timepoint. Other variables included respiratory driving pressure (DP), airway resistance (AR), and respiratory compliance (RC). Results: The MP increased linearly with a rise in IAP from T1 to T3 (r = 0.71, P < 0.001); the MP increased by 0.19 per unit rise in IAP (effect size 0.90, P < 0.001). A similar positive correlation was also observed between DP and IAP from T1 to T3 (r = 0.73, P < 0.001); the DP increased by 0.72 per unit rise in IAP (effect size 0.89, P < 0.001). The MP increased significantly on increasing PEEP from T3 to T5, while the DP decreased concomitantly (P < 0.001). The AR increased significantly from T1 to T3, while RC decreased concomitantly; vice-versa was observed at T4 and T5 (P < 0.001). Conclusions: The ventilatory MP delivery rises linearly with an increase in IAP. Targeting an IAP-guided MP level could be an attractive approach to minimize lung injury.

9.
J Anaesthesiol Clin Pharmacol ; 40(2): 312-317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919449

RESUMO

Background and Aims: The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same. Material and Methods: Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h. Results: A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 µg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14). Conclusion: The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread.

10.
Environ Res ; 233: 116454, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37343751

RESUMO

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.


Assuntos
Canabidiol , Nanoestruturas , Neoplasias Cutâneas , Humanos , Absorção Cutânea , Canabidiol/metabolismo , Canabidiol/farmacologia , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Pele , Fluoruracila/metabolismo , Fluoruracila/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Lipídeos , Tamanho da Partícula
11.
Drug Resist Updat ; 65: 100889, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403342

RESUMO

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Oncologia , Microambiente Tumoral/genética , Resistência a Múltiplos Medicamentos/genética
12.
Inflammopharmacology ; 31(5): 2571-2585, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37432554

RESUMO

Cerium oxide nanoparticles (CONPs), owing to their radical scavenging property, have recently emerged as a therapeutic candidate for oxidative stress-mediated neurological diseases. However, oral and intravenous administration of CONPs is limited due to their poor physicochemical characteristics, low bioavailability, rapid systemic clearance, poor blood-brain penetration and dose-dependent toxicity. To overcome these challenges, we developed intranasal CONPs and evaluated their potential in the experimental PD model. CONPs were prepared by homogenous precipitation using tween 80 as a stabilizer and methanol/water as solvent. The optimization was done using Central Composite Design (CCD). The CONPs synthesis was confirmed by UV and FTIR. The optimized CONPs were small-sized (105.1 ± 5.78 nm), spherical (TEM), uniform (PDI, 0.119 ± 0.006) and stable (ZP, -22.7 ± 1.02 mV). Energy-dispersive X-ray analysis showed characteristic signals of Ce in developed CONPs. The X-ray diffraction pattern described the cubic fluorite structure and nano-crystalline nature of CONPs. The CONP anti-oxidant activity was found to be 93.60 ± 0.32% at 25 µg/mL concentration. Finally, motor manifestation studies like the forced swim test, locomotor test, akinesia, catalepsy, and muscle coordination test were conducted to assess the motor dysfunctions and behavioral activity in all four animal groups. Results of the in vivo motor manifestation studies in the haloperidol-induced PD rat model showed that co-administration of intranasal CONPs along with a half dose of levodopa resulted in significant protection, and results were significantly different from the untreated group but not significantly different from the healthy group. In conclusion, intranasal CONPs can be useful in ameliorating oxidative stress through their antioxidant effect and could be prospective therapeutics for the treatment of motor manifestations in Parkinson's disease.


Assuntos
Nanopartículas , Transtornos Parkinsonianos , Ratos , Animais , Haloperidol/farmacologia , Estresse Oxidativo
13.
Indian J Crit Care Med ; 27(3): 222-224, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36960112

RESUMO

Background: High mortality due to COVID-19 disease has been a serious concern, a few of the causes being disseminated intravascular coagulation (DIC) and venous thromboembolism. Considering this, some experts have used heparin. However, its role still needs to be validated. Materials and methods: This study predicts the role of nebulized heparin in decreasing the severity of lung injury caused by COVID-19. Thirty patients admitted with COVID-19 acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) of All India Institute of Medical Sciences, Rishikesh, were included in this study, which was conducted over a period of 3 months. Patients were nebulized with 2 mL of heparin 5,000 units/mL IV formulation diluted with 3 mL of 0.9% sodium chloride, every 6 hours for a total duration of 7 days. Improvement in oxygenation (ratio of partial pressure of oxygen in blood and fraction of inspired oxygen delivered, pO2/FiO2 ratio) was calculated as the primary outcome. Other parameters like effect on inflammatory markers (neutrophil-lymphocyte ratio, total leukocyte count, interleukin (IL-6), and D-dimer values), time to liberate from mechanical ventilation, and hospital stay were calculated as secondary outcomes. Results: In our study population, the mean age was 54.5 years and the majority of patients were males (79.0%). All patients received prone ventilation and none of them required tracheostomy. However, 5 patients (16.6%) succumbed to illness. After nebulization with unfractionated heparin, no statistically significant difference was seen in the neutrophil-lymphocyte ratio (mean = 6.87, p = 0.318) and interleukin (IL-6) levels (mean = 62.85, p = 0.6) over 7 days. Similarly, the D-dimer level also had no statistically significant change (mean = 1853.73 p = 0.570). However, there was a statistically significant improvement in oxygenation (pO2/FiO2 ratio) over 7 days (mean = 184.96, p = 0.00). Similarly, there was a significant improvement in PaO2 (84.17 ± 33.82) and SO2 (92.30 ± 3.49). Although, no significant changes were seen in the partial pressure of carbon dioxide on nebulized heparin administration. Conclusion: Administration of nebulized heparin in COVID-19 pneumonia with mild ARDS may improve oxygenation and result in the improvement of inflammatory markers with variable sensitivity and specificity. How to cite this article: Gupta B, Chandrakar S, Gupta N, Jain G. Nebulized Heparin to Reduce COVID-19-induced Acute Lung Injury: A Prospective Observational Study. Indian J Crit Care Med 2023;27(3): 222-224.

14.
J Anaesthesiol Clin Pharmacol ; 39(2): 201-207, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564855

RESUMO

Background and Aims: Postoperative sore throat (POST) is a minor but distressing complication following general anesthesia. The current literature on the effect of preoperative nebulization with dexmedetomidine, or ketamine on POST is, however, sparse. So, we compared the effect of preoperative nebulization with these drugs on POST. Material and Methods: One hundred and thirty-two American Society of Anaesthesiology (ASA) grade I-II patients undergoing elective laparoscopic surgeries under general anesthesia were randomized into three equal groups: D, K, or C to receive dexmedetomidine, ketamine, or saline as preoperative nebulization, respectively. The primary objective was to compare the incidence and severity of POST, as inferred from the patient interviews at 2, 6, 12, 24-h postoperatively. Results: Group D had a significantly lower incidence (29.5%) and severity (12: mild; 1: moderate) of POST compared to group K (54.5% [21: mild; 3: moderate]) and group C (56.8% [19: mild; 6: moderate]), at 2-h postoperatively. The same trend was observed at 6-h postoperatively (group D: 22.7% [9: mild; 1: moderate]); group K: (40.9% [17: mild; 1: moderate]); group C (50% [17: mild; 5: moderate]). The mean arterial pressure was significantly lower in group D at 15 min intraoperatively (84.09 mmHg, P = 0.018) and immediate postoperatively (97.60 mmHg, P = 0.034). The postoperative sedation, nausea, and vomiting was not statistically significant. Conclusion: Preoperative nebulization with dexmedetomidine is effective in the reduction of the incidence and severity of early POST.

15.
Semin Cancer Biol ; 69: 249-267, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31442570

RESUMO

Cancer, being the most prevalent and resistant disease afflicting any gender, age or social status, is the ultimate challenge for the scientific community. The new generation therapeutics for cancer management has shifted the approach to personalized/precision medicine, making use of patient- and tumor-specific markers for specifying the targeted therapies for each patient. Peptides targeting these cancer-specific signatures hold enormous potential for cancer therapy and diagnosis. The rapid advancements in the combinatorial peptide libraries served as an impetus to the development of multifunctional peptide-based materials for targeted cancer therapy. The present review outlines benefits and shortcomings of peptides as cancer therapeutics and the potential of peptide modified nanomedicines for targeted delivery of anticancer agents.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanomedicina , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Animais , Humanos , Nanopartículas/química , Neoplasias/patologia , Fragmentos de Peptídeos/química , Proteínas/química
16.
Opt Express ; 30(12): 20194-20202, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224770

RESUMO

This paper describes the characterization of a novel directly modulated multi-section laser with a master-slave configuration. Amplitude and phase noise measurements show relative intensity noise values of around -150 dB/Hz and a 3-dB linewidth of around 3 MHz. The laser's suitability for optical access networks, enabled by the chirp reduction from the external injection locking, is shown by demonstrating unamplified 30 Gbit/s C-band transmission over 25 km and 50 km of single mode fiber using PAM4, as well as 30 Gbit/s PAM4 and PAM8 amplified transmission over 75 km.

17.
J Clin Psychopharmacol ; 42(5): 475-479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35977035

RESUMO

BACKGROUND: Extrapyramidal symptoms (EPSs) are adverse effects of antipsychotics. Different risks of EPSs have been attributed to the 3 classes of antipsychotics. This study aimed to assess EPS in a clinical sample of schizophrenia patients who are on LAI and compare the severity of EPSs among the following 3 antipsychotic groups: (1) partial agonist, (2) second-generation antipsychotics, and (3) first-generation antipsychotics. METHODS: Ninety-two patients were recruited from the Schizophrenia Program Injection Clinic. Using the Extrapyramidal Symptom Rating Scale (ESRS), severity of EPS was assessed and information regarding factors associated with risk of EPS, including coprescriptions, comorbidities, and demographics, was obtained from medical charts. Group differences in ESRS scores and subscores were analyzed using 1-way analyses of variances. RESULTS: Among the 3 groups, there was no significant difference in total ESRS scores and subscores. Risperidone was associated with higher ESRS scores when compared with paliperidone, aripiprazole, and flupenthixol. Doses above maximum were commonly used in the paliperidone group, and there was no significant difference in total ESRS scores between the low, average, or above-maximum doses of paliperidone. CONCLUSIONS: Our results demonstrated a comparative risk of EPS across all 3 antipsychotic classes. Risperidone was associated with more EPS compared with other medications. A higher threshold for the "maximum dose" of paliperidone could be considered and higher doses used with the same cautions as low-average doses.


Assuntos
Antipsicóticos , Doenças dos Gânglios da Base , Esquizofrenia , Antipsicóticos/efeitos adversos , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/epidemiologia , Preparações de Ação Retardada/efeitos adversos , Humanos , Pacientes Ambulatoriais , Palmitato de Paliperidona/efeitos adversos , Risperidona/efeitos adversos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico
18.
Natl Med J India ; 35(2): 105-107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36461857

RESUMO

Background Postgraduate residents' ability to understand and effectively manage their finances is variable. We conducted this study to assess the awareness of personal financial literacy among Indian residents. Methods We circulated a web-based cross-sectional Google Forms multiple-choice questionnaire having questions in three categories including financial awareness, current financial status and plans among 400 Indian residents. Results A total of 215 Indian residents (53.75%) responded to the survey (men 80.9%, unmarried 74.4% and pursuing broad specialties 83.3%). The majority were unaware of stocks, special student/doctor loans, tax planning, life insurance, professional indemnity and tax/financial planning. The majority opined that personal finance and investing should be taught at medical school/residency. A financial pyramid based on the hierarchy of needs is proposed. Conclusion Lack of financial literacy and planning was seen among the majority of Indian residents. Our study highlights this gap in the medical curriculum and the need for formal structured financial education during training.


Assuntos
Internato e Residência , Alfabetização , Masculino , Humanos , Estudos Transversais , Currículo , Faculdades de Medicina
19.
Int J Environ Health Res ; 32(8): 1815-1826, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33886400

RESUMO

At the end of 2019 and 2020s, a wave of coronavirus disease 19 (COVID-19) epidemics worldwide has catalyzed a new era of 'communicable infectious diseases'. However, the world is not currently prepared to deal with the growing burden of COVID-19, with the unexpected arrival of Hantavirus infection heading to the next several healthcare emergencies in public. Hantavirus is a significant class of zoonotic pathogens of negative-sense single-stranded ribonucleic acid (RNA). Hemorrhagic renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are the two major clinical manifestations. Till date, there is no effective treatments or vaccines available, public awareness and precautionary measures can help to reduce the spread of hantavirus disease. In this study, we outline the epidemiology, virology, clinical aspects, and existing HFRS and HCPS management approaches. This review will give an understanding of virus-host interactions and will help for the early preparation and effective handling of further outbreaks in an ever-changing environment.


Assuntos
COVID-19 , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , COVID-19/epidemiologia , Surtos de Doenças , Orthohantavírus/genética , Infecções por Hantavirus/epidemiologia , Febre Hemorrágica com Síndrome Renal/epidemiologia , Humanos
20.
Indian J Public Health ; 66(4): 498-500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37039181

RESUMO

In tobacco use disorders (TUDs), technology-based training of health-care professionals can reduce the treatment gap and bring attitudinal change. The study aimed to assess the practices and determine the change in knowledge and attitude among health-care professionals following an online training program (OTP). Half-day OTP on tobacco cessation using prepost quasi-experimental study design with a structured questionnaire-based assessment was conducted. Among 293 completed surveys, knowledge post-OTP was higher but insignificant (P = 1.2). Post-OTP, participants felt less angry and disappointed toward tobacco users (mean of difference (MOD) =0.21, P = 0.0007); more sympathetic and concerned (MOD = -0.22, P = 0.0005); and acknowledged tobacco users deserve the same medical care as nonusers (MOD = -0.177, P = 0.001). Post-OTP scores in attitudes did not change significantly for the responsibility domain (P < 0.05). In practice, relatively greater number of health-care professionals asked about tobacco use and advised cessation, however lesser assessed, assisted, and referred. To conclude, technology-based training program can result in attitudinal changes toward tobacco users.


Assuntos
Abandono do Uso de Tabaco , Humanos , Atitude do Pessoal de Saúde , Índia , Comportamentos Relacionados com a Saúde , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
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