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To compare breast milk volume between manual method and breast pump expression in mothers of preterm infants at different time point of first week.Randomized controlled trial.Postpartum ward of Obstetrics department and tertiary level neonatal intensive care unit (NICU) in a single institution in Orissa between October, 2020 and May, 2021.Mothers who delivered before 34 completed weeks of gestation.Manual breastmilk expression (ME) group using Marmet technique and breast pump milk expression (PE) group using pigeon manual breast pump, initiated milk expression within one hour of delivery.Expressed breast milk (EBM) volume in mothers of preterm infants at different time point of first week, and cumulative milk volume.Out of 170 mothers (83 PE and 87 ME group), 7-days milk volume data was available for 137 (71 ME and 66 PE) mothers. In per protocol analysis for 126 mothers (63 in each group), the median (IQR) EBM volume on day 2 and day 7 of ME and PE groups were similar [10 (5,20) vs 12 (5,28), P=0.10] and [280 (220-356) vs 280 (220-360), P=0.66]. The median (IQR) cumulative EBM volume over first 7 days in ME group was not significantly different from PE group [733 (593-995) vs 848.5 (571-1009)] P=0.55). A similar number of mothers in the PE and ME group [56 (88.9%) vs 58 (92%); P=0.14] provided exclusive breast milk for their neonates during the first week. Similar results were found on intention to treat analysis.EBM volume expressed was comparable between mothers expressing manually or with breast pump.

Abstract: Nuclear factor-kappa B (NF-κB) is one of the principal inducible proteins and a predominant transcription factor that is known to control gene expression in mammals. It plays a pivotal role in regulating cell signalling in the body under certain physiological and pathological conditions. In cancer cells, such as colon, breast, pancreatic, ovarian, melanoma, and lymphoma, the NF-κB pathway is active. In cellular proliferation, promoting angiogenesis, invasion, metastasis of tumour cells, and blocking apoptosis, the constitutive activity of NF-κB signalling has been reported. Therefore, immense attention has been given to developing drugs targeting NF-κB signalling pathways to treat many types of tumours. They are a desirable therapeutic target for drugs, and many studies have concentrated on recognizing compounds. They may be able to reverse or standstill the growth and spread of tumours that selectively interfere with this pathway. Recently, numerous substances derived from plants have been evaluated as possible inhibitors of the NF-κB pathway. These include various compounds, such as flavonoids, lignans, diterpenes, sesquiterpenes, polyphenols, etc. A study supported by folk medicine demonstrated that plant-derived compounds could suppress NF-κB signalling. Considering this, the present review revealed the anticancer potential of naturally occurring compounds that inhibit the NF-κB signalling and suppress the growth and spread of cancer.

Preterm neonates perceive multiple painful procedures during Neonatal Intensive Care Unit (NICU) stay, having long term neurobehavioral effects. This study aims to compare the analgesic efficacy of oral melatonin with 24% sucrose in neonates during retinopathy of prematurity (ROP) screening.A prospective, non-blinded, randomized controlled trial was conducted in a tertiary care NICU. All preterm neonates with gestational age (GA)34 weeks or birth weight (BW)2000 grams eligible for ROP screening were randomized into oral melatonin (4 mg/kg) and oral 24% sucrose (0.5 ml) groups. Both groups received standard non-pharmacological measures and topical proparacaine. The intensity of pain was measured by Premature Infant Pain Profile (PIPP) score during the procedure, at 1st and 5th minutes following the procedure and compared between the two groups by Mann-Whitney U test with p value0.05 considered as significant.A total of 60 preterm neonates were randomized with 30 neonates in the melatonin (median [interquartile range] GA: 30.86 [3.78] weeks, BW: 1160 [430] grams) and 30 neonates in the 24% sucrose (median [IQR] GA: 29.29 [4.68] weeks, BW: 1070 [315] grams) group. The median PIPP score during the procedure in the melatonin and sucrose groups were 17 and 16, respectively (p=0.64). The median (Q1-Q3) PIPP score at the 1st minute was significantly lower among the melatonin group (7 [5.25-10]) vs 24% sucrose group (9.5 [7.25-11]) (p=0.02); and at the 5th minute, the median (Q1-Q3) PIPP scores in the melatonin group (5 [4-6]) was comparable to the 24% sucrose group (5.5 [3.25-7]) (p= 0.52).Oral melatonin is not inferior to oral 24% sucrose for pain management during ROP screening.

Background Fibroids of the uterus are the most common benign pelvic tumors in women worldwide. Their diagnosis is usually not missed because of the widespread and well-established use of ultrasound in gynecological clinics. Hence, the development of an unusually large myoma is a rare event, particularly in first-world countries such as Germany. It is even more uncommon that a myoma is misdiagnosed as a dietary failure. Case presentation Herein, we report the case of a Caucasian woman with a giant fibroid that reached a size of over 50 cm, growing slowly over the past 15 years, and was misdiagnosed as abdominal fat due to weight gain. We aim to discuss the factors that lead to the growth of such a huge tumoral mass, including misdiagnosis and treatment, and the psychological impact. Through this case, we intend to increase the awareness among general physicians and gynecologists. Although menstrual disorders incorporate several pathologies, adequate assessment remains the primary responsibility of health care providers. A literature review revealed approximately 60 cases of giant uterine fibroids. Conclusion The use of clinical and diagnostic devices, especially ultrasound, in this case, is indispensable. In conclusion, the growth of a giant fibroid can have disastrous effects on a woman’s health, including surgical trauma and psychological issues.

Background: Cancer is one of the major causes of human mortality worldwide. A number of existing antineoplastic medications and treatment regimens are already working in the field, and several new compounds are in different phases of clinical trials. An extensive series of anticancer drugs exist in the market, and studies suggest that these molecules are associated with different types of adverse side effects. The reduction of the cytotoxicity of drugs to normal cells is a major problem in anticancer therapy. : Therefore, researchers around the globe are involved in the development of more efficient and safer anticancer drugs. The output of extensive research is that the quinazoline scaffold and its various derivatives can be explored further as a novel class of cancer chemotherapeutic agents that has already shown promising activities against different tumours. Quinazoline derivatives have already occupied a crucial place in modern medicinal chemistry. Various research has been performed on quinazoline and their derivatives for anticancer activity and pharmacological importance of this scaffold has been well established. Objective: The aim of this review is to compile and highlight the developments concerning the anticancer activity of quinazoline derivatives as well as to suggest some new aspects of the expansion of anticancer activity of novel quinazoline derivatives as anticancer agents in the near future. Methods: Recent literature related to quinazoline derivatives endowed with encouraging anticancer potential is reviewed. With a special focus on quinazoline moiety, this review offers a detailed account of multiple mechanisms of action of various quinazoline derivatives: inhibition of the DNA repair enzyme system, inhibition of EGFR, thymidylate enzyme inhibition and inhibitory effects for tubulin polymerization by which these derivatives have shown promising anticancer potential. Results: Exhaustive literature survey indicated that quinazoline derivatives are associated with properties of inhibiting EGFR and thymidylate enzymes. It was also found to be involved in disturbing tubulin assembly. Furthermore, quinazoline derivatives have been found to inhibit critical targets such as DNA repair enzymes. These derivatives have shown significant activity against cancer. Conclusion: In cancer therapy, Quinazoline derivatives seems to be quite promising and act through various mechanisms that are well established. This review has shown that quinazoline derivatives can further be explored for the betterment of chemotherapy. A lot of potentials are still hidden, which demands to be discovered for upgrading quinazoline derivatives efficacy.

TB is becoming a worldwide problem and it was declared since 1993 by the World Health Organization (WHO), a global health emergency. The current problem of tuberculosis therapy is the emergence of multi-drug resistant (MDR) strains, caused by the improper use of antibiotics in chemotherapy of TB patients. Azatidinones, a β-lactam cyclic amide with four atoms in a ring, has been considered as a magic moiety (wonder nucleus) which possesses almost all types of biological activities. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. Present article is sincere attempt to review chemistry, method of synthesis of azatidinones and to study azatidinones synthesized in last few years which have shown potent antitubercular activity.

Alzheimer’s disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.

A vast advancement has been made in the treatment related to central nervous system disorders especially Parkinson’s disease. The development in therapeutics and a better understanding of the targets results in upsurge of many promising therapies for Parkinson’s disease. Parkinson’s disease is defined by neuronal degeneration and neuroinflammation and it is reported that the presence of the neurofibrillary aggregates such as Lewy bodies is considered as the marker. Along with this, it is also characterized by the presence of motor and non-motor symptoms, as seen in Parkinsonian patients. A lot of treatment options mainly focus on prophylactic measures or the symptomatic treatment of Parkinson’s disease. : Neuroinflammation and neurodegeneration are the point of interest which can be exploited as a new target to emphasis on Parkinson’s disease. : A thorough study of these targets helps in modifications of those molecules which are particularly involved in causing the neuronal degeneration and neuroinflammation in Parkinson’s disease. : A lot of drug regimens are available for the treatment of Parkinson’s disease, although levodopa remains the choice of drug for controlling the symptoms, yet is accompanied with significant snags. It is always suggested to use other drug therapies concomitantly with levodopa. : A number of significant causes and therapeutic targets for Parkinson’s disease have been identified in the last decade, here an attempt was made to highlight the most significant of them. It was also found that the treatment regimen and involvement of therapies are totally dependent on individuals and can be tailored to the needs of each individual patient.

Background: Vision impairment remains a major health problem worldwide. Elevated intraocular pressure is a prime risk factor for blindness in the elderly. Netarsudil is a Rho-associated protein kinase (ROCK) inhibitor, which also inhibits norepinephrine transport. This narrative review summarizes the properties and clinical significance of netarsudil, a promising drug in topical glaucoma therapy. Methods: We searched PubMed, Medline and Scopus databases using relevant keywords to retrieve information on the physicochemical properties, formulation, mechanism of action, clinical pharmacokinetics, dose and toxicity of netarsudil. Results: Netarsudil showed promising effects in lowering the elevated intraocular pressure by two mechanisms. The US FDA approved netarsudil for clinical use in 2017 under the trademark of Rhopressa® while European Medicines Agency approved Rhokiinsa® in 2019. This drug is available as a 0.02% ophthalmic solution for once-daily topical application. Conclusion: The discovery of netarsudil is a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and is well tolerated in cases with ocular hypertension and chronic glaucoma.

Diabetes mellitus is one of the aggressive disorders in global society. No pharmacotherapy is available for permanent diabetes cure, although management is possible with drugs and physical activities. One of the recent complications noticed in type 2 diabetes mellitus includes diabetes-induced Alzheimer. It has been proposed that the possible diabetes-induced Alzheimer could be of type 3 diabetes. A variety of cross-sectional studies have proved that type 2 diabetes mellitus is one of the factors responsible for the pathophysiology of Alzheimer. New drug molecules developed by pharmaceutical companies with adequate neuroprotective effect have demonstrated their efficacy in treatment of Alzheimer in various preclinical diabetic studies. Patients of type 2 diabetes mellitus may show the benefit with existing drugs but may not cause complete cure. Extensive studies are being carried out to find new drug molecules that show their potential as antidiabetic drug and could treat type 2 diabetes–induced Alzheimer as well. This review provides an overview about the recent advancement in pharmacotherapy of diabetes-induced Alzheimer. The pathomechanistic links between diabetes and Alzheimer as well as neurochemical changes in diabetes-induced Alzheimer are also briefed.

Background: Radiotherapy in head-and-neck cancer (HNC) is a challenging task, and the anatomical alterations occurring during the course of intensity-modulated radiotherapy (IMRT) can be compensated by adaptive radiotherapy (ART) which utilizes repeat computed tomography (CT) scans during the treatment course for replanning. In this study, the clinical and dosimetric benefits of ART were compared with the conventional IMRT. Materials and Methods: Sixty patients with locally advanced HNC were randomized into two arms to receive IMRT up to a curative dose of 70 Gy with concurrent weekly chemotherapy and were prospectively analyzed between March 2018 and March 2019. Repeat CT scan was acquired after the 3rd week of radiation. Patients in the study arm underwent replanning, whereas those in the control arm continued with the first IMRT plan. Assessment was done weekly till the end of treatment and at 1, 3, and 6 months post IMRT for disease response and toxicities. Tumor volume reduction rate (TVRR) and dose reduction to organs at risk were also recorded. Results: Complete response was observed in 90% and 96.7% patients in the control and study arms, respectively, at the end of 6 months. Insignificant differences were found between the two arms in terms of toxicities. Xerostomia was statistically significantly higher in the control arm at 6 months (P = 0.01). TVRR was found to be 31.85%. Dose to spinal cord, ipsilateral, and contralateral parotid reduced by 4.3%, 6%, and 2.2%, respectively, with ART. Conclusion: Mid-treatment adaptive replanning can help in better target coverage and minimize toxicities in HNC patients.

Retinoblastoma is the most common primary intraocular malignancy of childhood. The present study was undertaken to overcome the scarcity of data regarding the epidemiology, demographic and clinical profile, and nature of the first health-care professional consulted.A retrospective analysis of medical records was performed for all cases of retinoblastoma who presented to the department of ophthalmology and oncology between 2010 and 2017. A total of 54 cases were reviewed.Unilateral disease was seen in 85.2% while 14.8% presented with bilateral disease with a median age of 3 years and 2 years, respectively, at diagnosis. The male: female ratio was 2:1. The most common presenting symptom was leukocoria which was noticed in 42 patients (77.7%), followed by red eye (33.3%) and proptosis (20.3%). The most common stage of presentation was Stage I (44.4%), followed by Stage IV (20.4%), Stage III (9.3%), and Stage II (5.6%). The median time to diagnosis was 8.7 months (range, 0.5-98.7 months), and the median time to treatment was 37.4 days (range, 0-645 days). Majority of the patients were referred by local ophthalmologists (48%), followed by general practitioners (20%), nurses (19%), and quacks (13%). Enucleation was the most preferred treatment modality (48.1%), followed by chemotherapy (33.3%), radiotherapy (13%), photocoagulation (3.7%), and exenteration (1.9%). The overall remission rate was 79.6%, while 12.3% had relapse and 7.4% died.The study showed a dire need for timely detection and treatment of retinoblastoma which is possible with improved awareness and better accessibility to health-care facilities. It also revealed a decrease in histopathological risk factors with chemoreduction.

Vaginal infection is widespread and80% of females encounter such infections during their lives. Topical treatment and prevention of vaginal infection allows direct therapeutic action, reduced drug doses and adverse effects, convenient administration and improved compliance. The advent of nanotechnology results in the use of nanoparticulate vehicle to control drug release, to enhance dosage form mucoadhesive properties and vaginal retention, and to promote mucus and epithelium permeation for both extracellular and intracellular drug delivery.This review discusses the conflicting formulation requirements on polymeric nanoparticles in order to have them mucoadhesive and retentive in vaginal tract, while able to penetrate through mucus to reach adherent mucus layer or epithelium surfaces to prolong extracellular drug release, or facilitate mucosal permeation and intracellular drug delivery.Nanoscale systems are potentially useful in topical vaginal drug delivery. A thorough understanding of their mucus penetration and retention behavior as a function of their formulation, size and surface properties, biorecognition, pH, temperature or other stimuli responsiveness is essential for design of therapeutically effective nanomatrices.

The unique properties of carbon nanotubes (CNTs) make them a highly interesting and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and lot more. Even though highly beneficial, the biocompatibility of CNTs is a major issue in their questioning their potential application in targeting drug delivery. Studies confirmed subdued toxicity of CNTs following slight modifications like functionalization, controlled dimensions, purification etc. A well-established mechanism for cellular internalization is an insistent need to attain a more efficient and targeted delivery. Recent patents have been thoroughly discussed in the text below.

Extensive attempts to overcome problems related to solubility of drugs for maximizing bioavailability at targeted sites in the body have been made. The issue of drug solubility appears to attract the continued interest of pharmaceutical manufacturers. In this context, nanocrystallization has emerged as an important tool. In the present review, the authors discuss the advantages of nanocrystallized drugs and examine the products available in the market as well as drugs in the pipeline using nanocrystal-based formulations, which are being developed by pharmaceutical companies for drug delivery.

Codrug or mutual prodrug is an approach where various effective drugs, which are associated with some drawbacks, can be modified by attaching with other drugs of same or different categories directly or via a linkage. More appropriately one can say combining two different pharmacophores with similar or different pharmacological activities elicit synergistic action or help to target the parent drug to specific site/organ/cells respectively. This approach is commonly used to improve physicochemical, biopharmaceutical and drug delivery properties of therapeutic agents.

Solid- phase synthesis is an approach, where synthetic transformation in carbohydrates are carried out with one of the reactant molecule attached to an insoluble material referred as polymeric support via linker. In recent years, it has been extensively accepted as fast and accurate method for the synthesis of biologically active oligosaccharides. This re- view attempts to focus on various methods of oligosaccharide synthesis by solid- phase including their applications. In the recent years, development of efficient and yet sim- ple procedures for the synthesis of oligosaccharides has been a major goal of carbohydrate chemistry. It is highly desirable to establish methodology for rapid oligosaccharide assembly. Several methods and strategies have been developed so far, which include synthesis in the solution phase leading to ste- reo controlled and high yield reactions. Chemical and enzy- matic synthesis of oligosaccharides on soluble or insoluble polymeric support has also been reported. The advantages associated with the use of an insoluble polymeric support justify further efforts to improve the solid phase strategy. The solid- phase synthesis has been demonstrated to be extremely valuable for routine preparation of oligopeptides and oligonucleotides. The potential usefulness of this proce- dure for the synthesis of other biomolecules is obvious. In past few years, the interest in solid-phase synthesis has in- creased dramatically due to the excitement engendered by the concept of combinatorial chemistry. The Solid-phase synthesis of oligosaccharides, when carried out combinatori- aly, offers the possibility of easy access to a very large num- ber of well-defined oligosaccharides. This can be used as potential tools in glycobiology (1-5).

Epilepsy is the most common chronic neurological disorder of the brain. For several decades different kinds of medications have been used to treat epilepsy. Even though many surgical advances has been made and implemented, medications remain the basis of treatment. The search for noble antiepileptic drugs (AEDs) with more selective activity and lower toxicity continues to be an area of intensive investigation in medicinal chemistry. Additionally, drug resistance is an important clinical problem in epilepsy and is associated with an increased risk of morbidity and mortality. This review intends to present a comprehensive overview on AED in particular along with discussion on some aspects of associated drug resistance and combination therapy.

Malaria, a vector-borne infectious disease, is currently a grave and universal concern with a significant social, economic, and human cost, mainly in developing countries. In addition, the emergence and spread of resistance to antimalarial therapies have further aggravated the global situation. Currently most of the research is focused on development of antimalarial drugs, drug resistance, and novel formulations to maximize the therapeutic effect. A number of novel molecules potentially active against malarial parasites are being developed. A vaccine is still viewed as a critical part of a long-term malaria control strategy. In the last several years various studies have shown significant progress in the development of vaccines against malaria. Advancement in vaccine technology and immunology is being used to develop malaria subunit vaccines that would open up new vistas for effective treatment and control of malaria. The development of an effective malaria vaccine represents one of the most important approaches that would provide a cost-effective intervention in addition to currently available malaria control strategies. An overview on progress in antimalarial vaccines is presented.

Soluble Epoxide Hydrolase (sEH) is an important and promising new pharmacologic target for the treatment of acute systemic inflammation. Inhibition of sEH by a highly selective and potent sEH inhibitor (sEHI) elevates the epoxyeicosatrienoic acids (EETs) level in vivo leading to decreased inflammation. To explore the necessary structural requirement of 1, 3-disubstituted ureas as sEH inhibitors for anti-inflammatory activity, the molecular modeling studies have been pursued. A ligand-based pharmacophoric model and atom-based 3D-QSAR have been generated by Phase. Binding interaction as determined by the docking study revealed that these inhibitors interact at active site (ASP 335 & TYR 383) of sEH enzyme. The pharmacophore model was further used as a 3D query for virtual screening to retrieve potential inhibitors.

Malaria is a global health problem that needs attention of drug discovery scientists to investigate novel compounds with high drug efficacy, safety and low cost to counter the malaria parasites that are resistant to existing drug molecules. This is an overview of past to present status of antimalarial drugs including newly researched candidates and also the alternative approaches for the complete control of malaria.