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In recent decades, many studies have been carried out on heterocycles, especially imidazole rings. The pharmacological properties such as antibacterial, antifungal, anticancer, antiviral and antidiabetic properties Apart from that, there are few side effects. The search for new biologically active imidazoles remains an area of interest An overview of medicinal chemistry. This white paper aims to collect and explain a wealth of information. Antibacterial profile of imidazole. Therefore, it can be used for future development to obtain new effective drug molecules. These heterocycles are important building blocks of functional molecules used in various fields. Used on a daily basis. Emphasis was placed on the bonds that form during the formation of imidazole. The usefulness of these methods is based on functional group compatibility. Processes around the ring and the resulting permutation patterns are described, including domain descriptions. Limitations, Reaction Mechanisms, and Future Challenges. The imidazole ring is part of several important natural products Products containing purines, histamine, histidine, nucleic acids. as polar and ionic Aromatic compounds that improve the pharmacokinetic properties of lead molecules Used as a remedy to optimize poorly proposed solubility and bioavailability parameters soluble lead molecule. Imidazole derivatives occupy a unique position in the art medicinal chemistry. Imidazole drugs have expanded the scope of eliminating various dispositions in clinics dose.

A non-aromatic five membered heterocycle known as hydantoin, imidazolidine-2,4-dione, is regarded as a desirable, preferred scaffold in medicinal chemistry. In addition to phenytoin, Nitrofurantoin, and Enzalutamide, the importance of the hydantoin scaffold in drug discovery has been supported by a number of medications currently in use. Hydantoin has two hydrogen bond acceptors and two hydrogen bond donors among its five possible substituent sites. Because they display a variety of biological and pharmacological activity in therapeutic and agrochemical applications, hydantoin and the hybrids they form with other molecules represent a particularly significant group of heterocycles. Additionally, they play a crucial role in the chemical or enzymatic synthesis of important, non-natural -amino acids and their conjugates that have potential medical applications. The production of hydantoin using the Bucherer-Bergs reaction is thoroughly discussed in this article, although it is only applicable to free carbonyl compounds or carbonyl compounds protected as acetals (ketals) and cyanohydrins used as starting reaction components. In this respect, the Bucherer–Bergs reaction provides an efficient and simple method in the synthesis of important natural products as well as for the preparation of new organic compounds applicable as potential therapeutics. The scope and limitations, as well as a comparison with some other methods for preparing hydantoin, are also discussed

Triazolo-thiodiazole and related fused heterocyclic compounds are of interest as potential bioactive molecules. Triazolo-thiodiazole derivatives have attracted the attention of organic chemists due to their biological and chemotherapeutic significance. Research in the field of anti-mycobacterium, anti-inflammatory and anti-microbial therapies is ongoing and studies are seeking. Therefore, the discovery of new effective anti-mycobacterium, anti-inflammatory and antimicrobial agents is imperative. The literature survey indicates that the fuse ring of triazolo-thiazazole derivatives has proven to be a good bioactive molecule. They showed various biological activities such as antibacterial, antifungal, anti-inflammatory, tubercular, anticancer, anticonvulsant, antioxidant, analgesic. In view of the above facts it was felt that some were interested in triazo- synthesis. All drugs were screened for their anti-diabetic activity with the standard drug Acarbose by an in vitro alpha-amylation method. The compounds C1 and C3 have been shown to have significant anti-diabetic activity.

Hypohidrotic Ectodermal Dysplasia (HED) is characterized by a triad of hypotrichosis (sparse hair), hypodontia (multiple missing teeth), and hypohidrosis (inability to sweat adequately). Consequently, patients’ quality of life is severely affected due to impairments in mastication, speech, and esthetics. Timely oral rehabilitation of patients with HED can enable them to lead a normal life by helping them perform their functions adequately and prevent the psychological ill-effects; in which dental professionals play a key role. The present case report describes the oral rehabilitation and management of a 7-year-old male patient with HED.

Introduction: Previous research studies show high prevalence of stress among the adolescents. It is significant to explore the factors responsible for stress among the adolescents so that preventive and remedial strategies may be planned. Therefore, the present study was conducted with the objectives (1) to assess the level of stress among adolescents, (2) to explore the factors causing stress among adolescents, and (3) to find out association of stress with their selected demographical variables. Materials and Methods: An exploratory study was conducted on 100 adolescents studying at select school of the Rahata Tehsil, M. S. Participants were recruited in the study by adapting purposive sampling technique. Data were collected using interview technique with the help of adolescent stress questionnaires which are a 56 items checklist with five point rating scale. Data were analyzed using descriptive and inferential statistics. Results: Findings of the study revealed factors responsible for stress among the adolescents which included home life, school performance, school attendance, peer pressure, interaction with the teachers, future uncertainty, conflicts in the school, financial pressure, and emerging adult responsibility. About 67% and 33% adolescents were having moderate and low stress, respectively. There was a significant association of stress with occupation of mother, religion, and family income. Conclusion: The present study reported moderate stress among 67% of the adolescents, which is alarming. This study highlights the need to orient parents and teachers to factors of stress and ways of modifying them.

The masticatory muscles may undergo fatigue due to prolonged mouth opening during the endodontic procedures. Low-level laser can be used to treat muscle fatigue due its capacity to produce reactive oxygen species and improve function of mitochondria. Aim: To determine the effectiveness of low-level laser therapy in the management of masticatory muscle fatigue caused after long endodontic procedure under Local anesthesia. MATERIAL AND METHODS: 44 patients complaining of reduced mouth opening and pain while mouth opening, after long endodontic therapy were considered for the study and were randomly allocated into study and control group. In the study group, low-level laser was applied while patients of control group didn't receive any therapy. In the study group, Visual analogue scale (VAS) score of pain was taken after endodontic therapy, immediately after laser therapy and 4 hours after endodontic therapy. Mouth opening of the patients was measured, before and after endodontic procedure and immediately after laser therapy. In the control group, VAS score of pain was recorded immediately after endodontic therapy and 4 hours after endodontic therapy. Statistical analysis used: ANOVA test and un-paired t-test was used for the data analysis. RESULTS: When both groups were compared, a statistically significant (P=0.0000) reduction with fatigue was found. CONCLUSIONS: The low-level laser can be a useful procedure immediately post long endodontic procedure causing masticatory muscle fatigue. Hence, this therapy can be considered as an add-on therapeutic procedure along with prolonged endodontic appointments to relieve the patient from the discomfort. Key words:Muscle fatigue, Masticatory muscles, Low-level laser therapy.

Ion exchange resigns are suitable for usage as flavor masking agents and sustained pharmaceutical release due to their inherent properties such as high ion exchangeability, modified administration capacity, physiochemical stability, and non-solubility in any solvent. Ion-exchange resins (IERs) are macromolecular polymers with differing cationic and anionic functional groups qualitatively as well as quantitatively. The polymer chain is fabricated in such a way that it consists of different salt-forming groups in repeating mode. In this study, we have tried to create a rapid dissolving oro-film of lamivudine using the ion exchange resins indion 204, tulsion 335, and doshion P551. FDOFs attempt to boost patient compliance by shortening the time it takes for the treatment to take effect, in addition to having a quick onset of action and higher bioavailability and also it’s a conventional dosage form. Out of three different resins, indion 204 gives a very excellent result with 1:1.5 ratio, where the maximum amount of complexation is within 4 hours of stirring. Their resinate are converted into granules and exhibit satisfactory value of angle of repose, bulk density, and flow property. Drug loading with indion 204 resin showed above 94%.”

Stress is the disturbed homeostatic condition of the organism, and it is represented by non-specific response of the body to any demand imposed on it. Stress brings various changes in physiological condition of the organism, but various mechanism of the body will counteract to maintain homeostasis. Neurotip capsule is effective Ayurvedic treatment for stress related disorders. Neurotip capsules have unique combination of herbs like Jatamansi, Guduchi, Shankapushpi, Ashwagandha, and Probiotics. These herbs are known to sooth the mind, promote calmness and act as a stress buster. In present research study Neurotip formulation was screened for acute toxicity study and sub chronic oral toxicity study on adult albino mice. Animals were observed for behavioural changes, neurological changes and autonomic profile changes. There was no noticeable toxicity and death observed in animals when treated with highest dose of 5000mg/ kg of the formulation. Neurotip was tested on swimming endurance of mice. The results were compared with standard group treated with Geriforte. Test formulation was evaluated by chronic stress model in rats using Omeprazole as standard drug. Assessment of ulcer induction was done to check adaptogenic potential of Neurotip. Ulcer protection by test formulation was found to be 68.44% showing good antistress effects.

Artemether oily injection is recommended for the treatment of severe malaria by the intramuscular route. The major limitations of the artemisinin combination therapy are erratic absorption from the injection site and high dosing frequency due to a very short elimination half-life of the drug. Advanced drug delivery systems have shown significant improvement in the current malaria therapy; the desired drug concentration within infected erythrocytes is yet the major challenge. Recently, we have reported the fabrication of artemether-loaded polymeric nanorods for intravenous malaria therapy which was found to be biocompatible with THP-1 monocytes and rat erythrocytes. The objective of the present study was the evaluation of pharmacokinetics, biodistribution, and antimalarial efficacy of artemether-loaded polymeric nanorods. Scanning electron microscopy and confocal microscopy studies revealed that both nanospheres and nanorods were adsorbed onto the surface of rat erythrocytes after an incubation of 10 min. After intravenous administration to rats, artemether nanorods showed higher plasma concentration and lower elimination rate of artemether when compared with nanospheres. The biodistribution studies showed that, at 30 min, the liver concentration of DiR-loaded nanospheres was higher than that of DiR-loaded nanorods after intravenous administration to BALB/c mice. The

The medicinal plants are important source for pharmaceutical manufacturing. Medicinal plants & herbal medicines account for a significant percentage of the pharmaceutical market. There is increasing awareness and general acceptability of the use of herbal drugs in today’s medical practice although most of these applications are not scientific. Herbal medicines are not a simple task since many factors influence the biological efficacy and Reproducible therapeutic effect. So it is necessary to improve safety of herbal drugs by developing certain quality control parameters and by following the WHO guidelines for herbal medicine WHO specific criteria for assessing the safety, efficacy, and quality of herbal medicines are critical for global harmonisation. The term “standardisation” refers to the assurance of a drug’s identification, quality, and purity at all stages of its life cycle. This study examines the need for and breadth of herbal medicine standardisation techniques for optimal quality assurance.To provide a platform for the quality control of traditional herbal medicines and to discover novel therapeutics composed of multiple chemical compounds, it is necessary to combine chemistry, pharmacology, medicine, and even statistics.

Analytical techniques used to determine chemical or physical property of analyte, chemical substance, chemical element or mixture. There are different types of analytical techniques used in pharmaceutical field for qualitative and quantitative estimation of drugs in biological fluids such as human plasma, human serum, human urine etc. and its formulations such as tablet, capsule, bulk drugs etc. This review work aims to provide most of existing analytical methods for analysis of Dipeptidyl peptidase-4 (DPP4) inhibitor and Peroxisome proliferator activated (PPAR) agonist. Estimation of Sitagliptin, Saxagliptin, Alogliptin, Gemifibrozil, Troglitazone, Pioglitazone, Linagliptin, and Rosiglitazone in active pharmaceutical ingredients, biological fluids and in various formulations which is reported in various research articles are reviewed. The analytical techniques which are utilised for the estimation of these drugs involves RP-HPLC, HPTLC, UPLC-MS/MS, LC-MS/MS, MALDI-TOF mass spectrometry, Raman spectroscopy, Liquid chromatography and Tandem mass spectrometry, TLC-densitometry with fluorescent detector, LC-ESI-MS-MS etc. are involved. The review assist in appropriate selection of analytical technique, mobile phase, column and detector based on available analytical instruments and chemicals by referring tabulated extensive condition. DPP4 inhibitor used in treatment of type 2 diabetes, hypoglycemia, weight loss etc. PPAR agonist also used in treatement of type 2 diabetes, in metabolic syndrome mainly for lowering triglycerides and blood sugar etc.

Mutation in OSTM1 give rise to the rarest and most lethal subtype of malignant infantile osteopetrosis (MIOP), and an improved understanding of OSTM1-associated MIOP would help with informed decision-making regarding symptom management and early palliative care referral. This retrospective study describes the clinical and laboratory features of patients with a genetic diagnosis of OSTM1 MIOP made between January 2011 and December 2021 in the Department of Pediatrics, Al-Adan Hospital, Kuwait. Twenty-two children had confirmed homozygous deletion in OSTM1 (13 females, nine males). Consanguinity was reported in almost all parents. 72.7% were diagnosed before the age of two months, most commonly incidentally with a high clinical suspicion. All 22 patients developed upper respiratory symptoms, hepatosplenomegaly, poor feeding, and had severe developmental delay. 80% of patients developed pain and/or irritability, and 40.9% were diagnosed with primary seizures. Bone fractures developed in 27% of patients, most likely iatrogenic, and some patients had hernia and gum abnormalities. The mean survival was 10.9 months. The clinical presentation, symptomatology, and mortality of our cohort were compared with other cases of OSTM1 MIOP identified through a comperhensive search of the PubMed database. The findings conclude that OSTM1 MIOP is a multi-systemic disease with distinct clinical features, of which neurological complications are the most severe and include nociplastic pain and irritability. Although orthopedic complications influence the trajectory of most patients with other forms of osteopetrosis, OSTM1 MIOP is driven by its neurological complications. Hence, OSTM1 should be regarded as a neurodegenerative disease with osteopetrosis as a comorbidity that warrants early palliative care referral.

Program evaluation, as a learning process, offers promise for nonprofit leaders. Rather than conducting research on organizations, evaluators partner with organizational leaders, helping them, in real-time, understand their programs, policies, and systems; prioritize their informational needs; and generate credible and actionable knowledge to answer their questions. This article 1) outlines why evaluation may be a more responsive learning process for nonprofit leaders, in contrast to other research processes; 2) describes the field of program evaluation and its contributions to knowledge creation for nonprofits; 3) explains an evaluation approach, called developmental evaluation, that produces real-time, complexity-informed knowledge resources for nonprofit leaders; and 4) concludes by encouraging nonprofit leaders to make the most of processes, like developmental evaluation, by building their capacity to promote sustained organizational learning and knowledge creation that is conducted for them and by them as opposed to on them.

The interior of Earth’s core can be explored using weak interactions of atmospheric neutrinos. This would complement gravitational and seismic measurements, paving the way for multimessenger tomography of Earth. Oscillations of atmospheric neutrinos passing through Earth are affected by the ambient electron density. We demonstrate that atmospheric neutrinos can probe the possible existence of dark matter inside Earth’s core in a unique way—by measuring the amount of baryonic matter using neutrino oscillations. We find that a detector like ICAL at INO with muon charge identification capability can be sensitive to dark matter with ∼5%–6% mass of Earth, at 1σ level with 500 kt yr exposure. We show that, while it will not be possible to identify the dark matter profile using neutrino oscillation experiments, the baryonic matter profile inside the core can be probed with atmospheric neutrinos.

ED health care professionals are at the frontline of evaluation and management of patients with acute, and often undifferentiated, illness. During the initial phase of the SARS-CoV-2 outbreak, there were concerns that ED health care professionals may have been at increased risk of exposure to SARS-CoV-2 due to difficulty in early identification of patients. This study assessed the seroprevalence of SARS-CoV-2 antibodies among ED health care professionals without confirmed history of COVID-19 infection at a quaternary academic medical center.This study used a cross-sectional design. An ED health care professional was deemed eligible if they had worked at least 4 shifts in the adult emergency department from April 1, 2020, through May 31, 2020, were asymptomatic on the day of blood draw, and were not known to have had prior documented COVID-19 infection. The study period was December 17, 2020, to January 27, 2021. Eligible participants completed a questionnaire and had a blood sample drawn. Samples were run on the Roche Cobas Elecsys Anti-SARS-CoV-2 antibody assay.Of 103 health care professionals (16 attending physicians, 4 emergency residents, 16 advanced practice professionals, and 67 full-time emergency nurses), only 3 (2.9%; exact 95% CI, 0.6%-8.3%) were seropositive for SARS-CoV-2 antibodies.At this quaternary academic medical center, among those who volunteered to take an antibody test, there was a low seroprevalence of SARS-CoV-2 antibodies among ED clinicians who were asymptomatic at the time of blood draw and not known to have had prior COVID-19 infection.

Tomato is one of the important crop in the family solanaceae. It is the third most important cultivated crop in India but it is adversely affected by various abiotic factors. This article will help growers in understanding various physiological disorders that impact the crop, and remedies which should be followed to control them. The major physiological disorders which are affecting the crop are blossom end rot, fruit cracking (radial and concentric cracking), puffiness, sunscald, blotchy ripening etc., The visible symptoms of the blossom end rot affected fruits are showing small darkened or water soaked area near the blossom end of the fruit which is majorly caused due to Calcium deficiency. Fruit cracking is associated with cracks develop at the stem end of the fruit, due to heavy rainfall or irrigation followed by long dry spell. The fruits affected with puffiness are looks normal from outside, but the fruit are hollow inside. One of the seed cavities is usually empty. Causes of puffiness are extreme high or low temperature, excessive fertilization and poor pollination and fertilization. Sunscald occurs on fruit exposed to the sun during periods of extreme heat and the affected fruits are shiny white or yellow patches would be on the sides of the fruit exposed to the sun. So this article will help the growers on various physiological disorders which are affecting the crop and the remedial measures to be followed to grow the healthy crop.

Most of the nutrients required for plant growth come from the soil. But to some extent, this nutrient requirement of crops can be meet by chemical fertilizers, green manures, manures, compost, crop rotation, inclusion of leguminous crops etc. It is necessary to have scientific information about the quantity, form, availability of major nutrients in the soil and also the method, quantity, etc. of chemical fertilizers. A total of 17 different nutrients are required for proper growth of crops. An element is essential if a plant cannot complete its life cycle without it, if no other element can perform the same function, and if it is directly involved in nutrition. An essential nutrient required by the plant in large amounts is called a macronutrient, while one required in very small amounts is termed a micronutrient. Missing or inadequate supplies of nutrients adversely affect plant growth, leading to stunted growth, slow growth, chlorosis, or cell death. About half the essential nutrients are micronutrients such as boron, chlorine, manganese, iron, zinc, copper, molybdenum, nickel, silicon, and sodium. These nutrients are secondary nutrients and called as micronutrients. The present research topic gathers several studies that focus on the beneficial role of micronutrients in plant nutrition, while aiming at the same time to set the borderlines between excessive use and deficiencies in plant development.

Osteopetrosis describes a heterogeneous group of diseases characterised by increased bone density due to impaired osteoclast. The malignant infantile autosomal recessive (MIOP) form caused by mutations in OSTM1 is the most severe form of osteopetrosis. Children with this phenotype exhibit multisystemic complications, of which the neuropathic manifestations are the most severe. Infants with MIOP may present with pain and irritability that are likely to become continuous and debilitating as the disease progresses. There is limited understanding of the aetiology and management of pain in MIOP. Here, we describe a 2 month-old infant with OSTM1 mutation-related MIOP presenting with severe irritability and pain. This case provides the opportunity to discuss the cause and management of these distressing symptoms. We also review similar cases and the possible underlying mechanisms of pain and irritability to help provide a conceptual framework for the management of these symptoms in infants with OSTM1 MIOP.

Evaluating thyroid nodules to rule out malignancy is a very common clinical task. Image-based clinical and machine learning risk stratification schemas rely on the presence of thyroid nodule high-risk sonographic features. However, this approach is less suitable for diagnosing malignant thyroid nodules with a benign appearance on ultrasound. In this study, we developed thyroid cancer polygenic risk scoring (PRS) to complement deep learning analysis of ultrasound images. When the output of the deep learning model was combined with thyroid cancer PRS and genetic ancestry estimates, the area under the receiver operating characteristic curve (AUROC) of the benign vs. malignant thyroid nodule classifier increased from 0.83 to 0.89 (DeLong, p-value = 0.007). The combined deep learning and genetic classifier achieved a clinically relevant sensitivity of 0.95, 95 CI [0.88-0.99], specificity of 0.63 [0.55-0.70], and positive and negative predictive values of 0.47 [0.41-0.58] and 0.97 [0.92-0.99], respectively. An improved AUROC was consistent in ancestry-stratified analysis in Europeans (0.83 and 0.87 for deep-learning and deep learning combined with PRS classifiers, respectively). An elevated PRS was associated with a greater risk of thyroid cancer structural disease recurrence (ordinal logistic regression, p-value = 0.002). This study demonstrates that augmenting ultrasound image analysis with PRS improves diagnostic accuracy, paving the way for developing the next generation of clinical risk stratification algorithms incorporating inherited risk for developing thyroid malignancy.

Background: Heat shock protein is one of the most abundant and best characterized heat shock protein family that consists of highly conserved stress proteins. Amongst these heat shock protein family, HSP70 is expressed in response to stress and plays crucial roles in environmental stress tolerance and adaptation. Thermal stress alters the normal body homeostasis and causes severe detrimental effects on production and productivity of animals and impairs growth, immune status of animal. Therefore, the present study is proposed to study HSP70 gene expression pattern in peripheral blood mononuclear cells. Methods: The present study was conducted to study the relative mRNA expression pattern of HSP70 gene in peripheral blood mononuclear cells (PBMCs) during different seasons in Padharpuri buffaloes. 10 Apparently healthy, non - pregnant Pandharpuri buffaloes (above 2 years of age) were taken for study. Blood samples were collected thrice i.e. once in winter season, once in summer season and once in rainy season. Real-time polymerase chain reaction was applied to investigate mRNA expression of HSP70 gene during different seasons. Specificity of the desired products was documented using analysis of the melting temperature and high resolution gel electrophoresis to verify that the transcripts are of the exact molecular size predicted. Result: To investigate the variation in relative mRNA expression profile of HSP70 gene, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH gene) was used as a housekeeping gene. The relative expression values of HSP70 during summer and rainy seasons were found statistically significant in comparison to winter. These results suggest that HSP70 gene expression varies with season and this variation may play an imperative role in conferring thermo tolerance against heat stress during different seasons.

Supplementary Figure 3: Breast cancer cell lines (A) BT-474, (B) MCF-7 and (C) MDA-MB-231 were treated with anti-Notch1 MAb (602.101), MAPK inhibitor (PD98059), combination of MAb602.101 and PD98059 and appropriate controls (IgG and DMSO) and cell viability was assessed by MTT assay.

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Supplementary Figure 1: A) Photomicrographs show representative immunohistochemical staining for the expression of cleaved Notch1 and pErk1/2 in breast cancer patient samples based on which they were further sub-divided into clNotch1highpErkhigh and the 'rest' (including, clNotch1lowpErklow, clNotch1highpErklow and clNotch1lowpErkhigh ) categories. B) Representative images for the expression of stemness markers CD44, Oct-4 and Nanog in TNBC patient samples as determined by immunohistochemistry analysis.

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Supplementary Figure 4: Breast cancer cell lines were subjected to sphere formation in the presence of anti-Notch1 MAb602.101 (10microg/ml), 10microM MAPK inhibitor (PD98059), combination of MAb602.101 and PD98059 and appropriate controls (IgG and DMSO). After a week cells were dissociated and subjected for secondary sphere formation in the absence of any treatments. Photomicrographs represent phase contrast images of secondary spheres formed by MDA-MB-231 and BT-474 cells; magnification 10x.

Supplementary Figure 2: BT474 cells treated with anti-Notch1 MAb 602.101 (10microg/ml) and MEK inhibitor PD98059 (10microM), alone (A and C respectively) or together (D), for 48 hrs were subjected to real time PCR analysis using specified primer sets; treatment with IgG and DMSO served as controls. (B) MDA-MB-231 and HCC-1806 cells were treated with PD98059 (10 microM) for 48 hours and subjected to immunoblot analysis for the specified proteins.

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