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Novel 6-arylethyl-1,2,4-trioxanes6a-i and 7a-i are easily accessible in one step from the diimide reduction of 6-arylvinyl-1,2,4-trioxanes 5a-i. All of these new trioxanes were assessed for their oral antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in a Swiss mice model. Most of the saturated trioxanes 6c, 6f, 6g, 6h, and 6i, the active compounds of the series, provided 100% protection to the malaria-infected mice at a dose of 24 mg/kg × 4 days. Further, trioxane 6i, the most active compound of the series, also showed 100% protection even at a dose of 12 mg/kg × 4 days and 20% protection at a dose of 6 mg/kg × 4 days. In this model, β-arteether provided 100% protection at a dose of 48 mg/kg × 4 days and only 20% protection at a dose of 24 mg/kg × 4 days via the oral route, which was found to exhibit 4-fold antimalarial activity compared with the currently used drug β-arteether.

Introduction: Coronary Artery Disease (CAD) is a leading cause of morbidity and mortality in India as well as worldwide. CT angiography is an excellent imaging modality for evaluation of CAD. Previous studies with 64 or lesser slice CT scanner have failed to show consistent and optimal Image Quality (IQ) at Heart Rate (HR) more than 70 bpm and required beta blockers. Aim: To evaluate the diagnostic accuracy of 256-slice Dual Source CT Angiography (DSCTA) in comparison with Catheter Coronary Angiography (CCA) in evaluation of Coronary Arteries (CA) in patients with clinical suspicion of CAD and to study its effectiveness at higher HR without using beta blockers. Materials and Methods: This cross-sectional study was conducted on patients (n=46) with suspected CAD using ECG triggered 256-slice Dual Source Computed Tomography (DSCT) over a period of nine months. Patients were sub grouped according to HR (Group I: 50-70 (18 patients), Group II: 71-90 (24 patients) and Group III ≥91 (8 patients). A total of 48% patients had HR of 71-90 bpm while 16% had HR ≥91 bpm. Scan protocols included prospective ECG triggering (HR 75 bpm). CA segments were analysed for IQ on a 4 point scale (1 is worst while 4 is best) by two independent readers who were blinded to the patient details. Accuracy to detect significant luminal stenosis was correlated with CCA (gold standard). Statistical significance of the study was established by Chi-square test (p

The aim of current study is to provide a significant traditional knowledge on wild medicines used for ethnoveterinary purposes in the rural area of Maraog region in district Shimla. The medicinal plants have played a significant role in the treatment of human as well as animal’s diseases. The rural people of the Maraog region were interviewed through a questionnaire and extensive field surveys were conducted from June 2020 to July 2021. The discussion, observations and interviews were conducted in study site and included 96 informants. The information gathered from the residents is presented in a table format and includes scientific and local names, different parts used, diseases treated and mode administration. The most commonly used taxa are calculated with used value. The study revealed 100 plants in which trees (7), shrubs (26), herbs (56), ferns (5), grasses (3) and climbers (3) were identified. The most commonly documented livestock diseases were found to be hoof infections, eyes infections, poisoning and skin infections. In the current study, the Rosaceae family was reported as being the highest number (11), followed by Asteraceae (10) and then Lamiaceae (6). It was found that leaves, roots, flowers and fruits are the commonly used parts for ethnoveterinary medications. The phytochemicals present in the plant, such as alkaloids, sterols, glycosides, flavonoids, lignin, coumarins and terpenoids, etc., may be responsible for their medicinal properties. In this documentation, it was observed that the younger generation does not have good knowledge of medicinal plants as compared to the older ones. Therefore, it is necessary to preserve the traditional knowledge of these medicinal plants before their permanent loss. The documentation and conservation of medicinal plants can be a good start for novel phytopharmacological research in the veterinary field.

Objectives: To explore the potential of Radiomics alone and in combination with a diffusion-weighted derived quantitative parameter, namely the apparent diffusion co-efficient (ADC), using supervised classification algorithms in the prediction of outcomes and prognosis. Materials and Methods: Retrospective evaluation of the imaging was conducted for a study cohort of uterine cervical cancer, candidates for radical treatment with chemo radiation. ADC values were calculated from the darkest part of the tumor, both before (labeled preADC) and post treatment (labeled postADC) with chemo radiation. Post extraction of 851 Radiomics features and feature selection analysis—by taking the union of the features that had Pearson correlation &gt, 0.35 for recurrence, &gt, 0.49 for lymph node and &gt, 0.40 for metastasis—was performed to predict clinical outcomes. Results: The study enrolled 52 patients who presented with variable FIGO stages in the age range of 28–79 (Median = 53 years) with a median follow-up of 26.5 months (range: 7–76 months). Disease recurrence occurred in 12 patients (23%). Metastasis occurred in 15 patients (28%). A model generated with 24 radiomics features and preADC using a monotone multi-layer perceptron neural network to predict the recurrence yields an AUC of 0.80 and a Kappa value of 0.55 and shows that the addition of radiomics features to ADC values improves the statistical metrics by approximately 40% for AUC and approximately 223% for Kappa. Similarly, the neural network model for prediction of metastasis returns an AUC value of 0.84 and a Kappa value of 0.65, thus exceeding performance expectations by approximately 25% for AUC and approximately 140% for Kappa. There was a significant input of GLSZM features (SALGLE and LGLZE) and GLDM features (SDLGLE and DE) in correlation with clinical outcomes of recurrence and metastasis. Conclusions: The study is an effort to bridge the unmet need of translational predictive biomarkers in the stratification of uterine cervical cancer patients based on prognosis.

The Indian Society of Gastroenterology (ISG) Task Force on Inflammatory Bowel Disease and the Indian Radiological and Imaging Association (IRIA) developed combined ISG-IRIA evidence-based best-practice guidelines for imaging of the small intestine in patients suspected to have or having Crohn’s disease. The 29 consensus statements, developed through a modified Delphi process, are intended to serve as reference for teaching, clinical practice, and research.

Ethnomedicinal plants have a significant role in the lives of people of rural and tribal areas. Thousands of medicinal plant species are used to treat various diseases, including jaundice, and are considered an important therapeutic resource to minimize these diseases. Jaundice (icterus) is a chronic disease that occurs when the amount of bilirubin in the blood increases. This review describes different ethnomedicinal plants used for curing jaundice by tribal and rural people of Himachal Pradesh. The study reveals 87 ethnomedicinal plant species belonging to 51 different families, which are used for treating jaundice in Himachal Pradesh. These plants are arranged in a systematic way, which includes a description of their common name, botanical name, along with its family, plant parts used, region, and mode of use in tabulated form. Some of the plant extracts have already been explored for their phytochemical and pharmacological significance and proved their potential in the preparation of new medicines or drugs against the treatment of jaundice. This review is an attempt to highlight the indigenous knowledge of medicinal plants, which are specifically used for the treatment of jaundice. The data mentioned in the present review is compiled from various sources like existing literature, books, Google Scholar, and Scopus publications. Among all the observed plant species, most used medicinal plants for the treatment of jaundice include Justicia adhatoda, Emblica officinalis, Ricinus communis, Saccharum officinarum, Terminalia chebula, Berberis aristata, Cuscuta reflexa, and Tinospora cordifolia. Plants that are mostly utilized for the treatment of jaundice need to be scientifically validated by pharmacological analysis and should be subsequently used for the preparation of new drugs, which may prove far more beneficial than the existing one.

Extra-axial cavernous sinus haemangioma are rare extra-axial parasellar lesions. These are non-neoplastic lesions, but can behave in a manner like that of neoplastic lesions as their slow growth with progressive enlargement of thin-walled vascular channels may result in extrinsic compression on adjacent retro-orbital neural structures. It is important to diagnose these lesions preoperatively as surgery in these lesions is often complicated by incomplete removal, severe intraoperative haemorrhage and significant operative morbidity and mortality. A parasellar lesion showing homogeneous markedly increased signal on T2 or proton density weighted images with progressive centripetal “filling-in” with contrast on dynamic Magnetic Resonance Imaging (MRI) should suggest the diagnosis. We are presenting three interesting cases of cavernous sinus haemangioma.

Aging is a complicated biological process in which functional and structural alterations in a living organism take place over time. Reactive oxygen species is one of the main factors responsible for aging and is associated with several chronic pathologies. The relationship between aging and diet is quite interesting and has attained worldwide attention. Healthy food, in addition to dietary antioxidants, are required to delay the process of aging and improve the quality of life. Many healthy foods such as fruits are a good source of dietary nutrients and natural bioactive compounds which have antioxidant properties and are involved in preventing aging and other age-related disorders. Health benefits linked with healthy consumption of fruit have drawn increased interest. A significant number of studies have documented the advantages of fruit intake, as it suppresses free-radical development that further reduces the oxidative stress created in the body and protects against several types of diseases such as cancer, type 2 diabetes, inflammatory disorders, and other cardiovascular diseases that ultimately prevent aging. In addition, fruits have numerous other properties like anti-inflammatory, anti-cancerous, anti-diabetic, neuroprotective, and have health-promoting effects. Mechanisms of various bioactive compounds that aids in preventing various diseases and increases longevity are also described. This manuscript provides a summary of various bioactive components present in fruits along with their health-promoting and antiaging properties.

Segmental dilatation of ileum (SDI) is a less known uncommon entity with a confusing clinical scenario and no definite etiopathogenesis. The preoperative diagnosis is of exclusion. However, it has an excellent prognosis after surgery. We describe a case of a young patient who presented with anemia without any overt gastrointestinal (GI) bleed. Thorough radiological examinations were needed to reach the diagnosis of SDI which was confirmed postoperatively.

A survey of wild edible plants of Gaddi tribes of Himachal Pradesh was carried out in Chamba and Kangra districts of Himachal Pradesh located in Western Himalayas. The inhabitants subsisted primarily on pastoralism and agriculture and have traditional knowledge on wild edible plants. A total of 49 edible plants belonging to 24 families were recorded in the study area. These were commonly used as vegetables, fruits, spices, and chutney. Nearly half of the species belong to Polygonaceae and Rosaceae families. Herbs, shrubs, climbers, and trees form the habit of these plants. The highest proportion of edible species were herbs (29) followed by trees (10), shrubs (8), climber (1), and Morchella esculenta (fungi) (1).

In a focused exploration, we designed, synthesized, and biologically evaluated chiral conjugated new chloroquine (CQ) analogues with substituted piperazines as antimalarial agents. In vitro as well as in vivo studies revealed that compound 7c showed potent activity (in vitro 50% inhibitory concentration, 56.98 nM for strain 3D7 and 97.76 nM for strain K1; selectivity index in vivo [up to at a dose of 12.5 mg/kg of body weight], 3,510) as a new lead antimalarial agent. Other compounds (compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c) also showed moderate activity against a CQ-sensitive strain (3D7) and superior activity against a CQ-resistant strain (K1) of Plasmodium falciparum. Furthermore, we carried out docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of all in-house data sets (168 molecules) of chiral CQ analogues to explain the structure-activity relationships (SAR). Our new findings specify the significance of the H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against the 3D7 strain indicated the favorable and unfavorable sites of CQ analogues for incorporating steric, hydrophobic, and electropositive groups to improve the antimalarial activity.

The choledochal cysts, which refer to the cystic dilatation of the biliary duct, are rare lesions generally seen in children. Choledochal cyst of the cystic duct is an uncommon entity. Often, it is associated with the choledochal cyst of the rest of the biliary tree. Isolated cystic duct choledochal cyst is quite rare. Most of these lesions have been recognized only on surgery. Modern cross-sectional imaging methods have facilitated preoperative recognition and characterization of cystic duct cyst enabling formulation of appropriate management strategy. We report the imaging findings in three cases of choledochal cyst involving the cystic duct. All these cases were correctly diagnosed preoperatively. A review of cases reported in the literature and the role of imaging in guiding the management are also presented.

Osteochondroma is the most common benign skeletal tumour. It frequently causes pain and local symptoms, however, vascular complications are rare. The popliteal artery is more commonly affected and there are isolated case reports of popliteal artery pseudoaneurysm in literature. However, venous complications are extremely rare. We hereby report a case of 21-year-old male patient with distal femoral osteochondroma complicated by a popliteal venous aneurysm and deep vein thrombosis. This association has not been described in the past. The patient was put on anticoagulants as he refused surgery and was asymptomatic at six months follow-up. Awareness of this complication is important for timely diagnosis and surgical management as it is a source of life threatening pulmonary thromboembolism.

We report an interesting case of coronary cameral fistula with associated aneurysmal dilatation of coronary artery. The complete evaluation including anatomical relationships with surrounding vascular and non-vascular structures can be achieved with ECG gated multi-detector computed tomography (MDCT). MDCT has many advantages over echocardiography and digital subtraction catheter angiography, because of its ability to demonstrate the fistula separate from surrounding cardiovascular structures along with any aneurysm or obstruction in its course. Thus, MDCT is emerging as the initial non-invasive imaging technique for comprehensive preoperative evaluation of these rare congenital anomalies for cardiovascular surgeons to achieve better operative assessibity and outcome.

A 55-year-old male patient presented with a slowly enlarging, painless, large soft mass lesion in left scrotal sac for 6 month. On clinical examination the mass lesion could not be separated from testis, hence provisional diagnosis of testicular tumour was made. For further evaluation scrotal ultrasound was performed. In the region of the clinically palpable lump, ultrasound revealed a unilocular, well-circumscribed cystic lesion with moderately thick wall and fine internal echoes [Table/Fig-1]. The size of lesion was approximately 4.5 x 5 cm. It was located cranial to testis, partially replacing left epididymis. No internal or peripheral flow was detected on colour Doppler study. Mild fluid was also noted in scrotal sac, which was consistent with hydrocele. Right testis and epididymis were normal. [Table/Fig-1]: Gray scale ultrasound image of left scrotal sac shows a well circumscribed, rounded, unilocular cystic lesion with low level internal echoes located superior to left testis consistent with the diagnosis of spermatocele Ultrasound examination also revealed a cluster of multiple, small, anechoic cysts located in the region of testicular mediastinum [Table/Fig-2]. No solid component or calcification was seen. No evidence of any obvious arterial or venous flow was noted in the cysts on colour Doppler study [Table/Fig-3]. [Table/Fig-2]: Transverse (A), longitudinal (B) gray scale ultrasound images of left testis shows a cluster of multiple small anechoic cystic structures noted in the region of testicular mediastinum with hydrocele [Table/Fig-3]: Transverse colour Doppler ultrasound image of left testis shows numerous small cysts with no colour flow On the basis of characteristic ultrasound and Doppler findings final diagnosis was made of tubular ectasia of rete testis and spermatocele. Because of benign nature of this condition patient was reassured and ask for 6 monthly follow up. Tubular ectasia of the rete testis is a benign clinical entity in which cystic dilation of rete testis results from partial or complete obliteration of the efferent ducts [1]. The obstruction may occur at different levels and may be classified into intra- or extra-testicular. In testicular lesions, the obstruction generally resulting from previous inflammatory episodes like orchitis, while in extra-testicular lesions, traumatic tearing of epididymis, obstruction from epididymitis, spermatoceles and tunica albuginea cyst and post-vasectomy or other scrotal surgeries are the common causes [2]. Typically this condition affects patients older than 50 year of age. Bilateral lesions have been reported in 29 to 69% of cases [3]. Spermatocele and epididymis cysts are commonly associated with this condition. Ultrasonography is usually the first and only modality needed to diagnose this condition. Sonographic findings of tubular ectasia of rete testis consists of a cluster of several anechoic rounded and serpiginous tubular structures located in the mediastinum testis without any solid areas or calcific foci. They do not cause mass effect on the adjacent testicular parenchyma. Colour Doppler shows no arterial or venous flow within cystic lesions [4]. Spermatoceles are common extra-testicular lesions caused by cystic dilation of efferent ductules in the region of head of epididymis. On ultrasonography, it appears as a unilocular or multilocular hypoechoic cystic lesion located superior to and separate from testis. It is usually small in size ranging from 1-2cm in size. However large lesions upto 8 cm in size have been reported in the literature [5]. Spermatocele may show low-level echogenic internal echoes due to proteinaceous fluid containing dead sperms. MRI is usually not indicated because of typical appearance on ultrasound. However, if done in doubtful cases, reveals a cluster of round or serpiginous lesions in the hilum of testis, which appear hypointense TI-weighted and hyperintense on T2- weighted images. The main differential diagnosis includes intra-testicular varicocele and cystic dysplasia of testis. Intra-testicular varicocele is a rare entity, which can give similar appearance on B-mode ultrasonography, however colour Doppler and pulsed Doppler evaluation shows colour flow with characteristic venous spectral waveform that augments during Valsalva maneuver [6]. Cystic dysplasia of testis is thought to be a congenital condition unlike tubular ectasia of rete testis which is an acquired condition. It is seen in children and has similar appearance to tubular ectasia of rete testis [7]. Other differential diagnosis includes epididymal cystadenoma, teratoma, non-Hodgkin’s lymphoma and seminiferous tubules dilatation secondary to testicular neoplasms [1]. Tubular ectasia of rete testis and spermatocele are benign entities With characteristics features on gray scale and colour Doppler examination. This condition should be recognized in older individuals and its awareness can prevent unnecessary investigations and surgical intervention.

Filariasis is an endemic infection seen in the tropical and subtropical regions of the world, presenting with lymphatic dysfunction in the form of lymphocele, hydrocele, chyluria, or groin lymphadenovarix. We report a rare presentation of filariasis as an intra-abdominal cystic mass.

A 16-year-old girl presented with a progressively increasing pulsatile subcutaneous scalp swelling with linear tortuous structures in the frontoparietal region. A loud bruit was heard on auscultation. General examination and haematological investigations were unremarkable. In suspicion of arteriovenous malformation a CT angiography (CTA) was performed which showed a large vascular mass formed of bunch of dilated and tortuous vessels in the scalp. Feeders from bilateral superficial temporal arteries were identified with venous drainage by superficial scalp veins (figures 1⇓–3). On the basis of clinical and CTA findings a final diagnosis …

Progress towards a vaccine against Plasmodium falciparum malaria is advancing rapidly, with several candidate antigens being tested for safety and efficacy in humans (4); comparatively, however, the development of a vaccine against P. vivax malaria has lagged behind. Unlike P. falciparum, where sporozoite challenge studies using the chloroquine-sensitive 3D7 strain are available, the relapsing nature of P. vivax hepatic stages and the lack of an in vitro culture system precludes any sporozoite challenge studies of P. vivax vaccine candidates in humans. Therefore, as more recombinant vaccine products become available, there will be an increasing need to compare and down-select vaccine candidate antigens in preclinical studies using animal models of P. vivax infection. P. cynomolgi, which infects rhesus macaques in southeast Asia, is a closely related species to P. vivax; human transmission of P. cynomolgi has also been reported (25). The two parasites share a similar clinical course of infection (26), a reticulocyte-specific invasion (17), the presence of Schuffner's dots on infected erythrocytes (2), and a dormant liver hypnozoite stage that is responsible for a relapsing blood stage infection (23). P. cynomolgi and P. vivax have similar genomic GC content, and rRNA analysis confirms their close taxonomic relatedness (43). High homology of prime vaccine candidates such as the apical membrane antigen 1, 97% (13); circumsporozoite protein, 90% (16); erythrocyte binding protein, 76% (32); and the 42-kDa fragment of the merozoite surface protein 1 (MSP-1), 75% (31); have been reported. Although it is believed that the P. cynomolgi-rhesus model can serve as a model for testing P. vivax antigens, there is only one previous report where this model was used to test the efficacy of a recombinant P. vivax vaccine (22). The merozoite surface protein 1 (MSP-1), found on the surface of Plasmodium merozoites, has been a prime vaccine candidate for many years (10). Following its synthesis as a 200-kDa precursor, the MSP-1 molecule undergoes step-wise proteolytic processing resulting in a glycosyl-phosphatidylinositol-anchored 42-kDa protein (MSP-142) on the surface of free merozoites (7). This 42-kDa intermediate undergoes secondary processing at the time of invasion, releasing a 33-kDa soluble polypeptide (MSP-133) and leaving behind on the invading merozoite a glycosyl-phosphatidylinositol-anchored 19-kDa form (MSP-119) (7). Depending on the species, MSP-119 contains 10 or 11 cysteine residues that form five disulfide bonds. Immunization with recombinant MSP-142 and MSP-119 raises antibodies that inhibit invasion of merozoites in vitro (9) and protects the immunized animals against live parasite challenge (29). We have previously reported a process for the production of correctly folded human vaccine-grade P. vivax MSP-142 protein in the bacterial expression host Escherichia coli Origami(DE3) (14). This bacterial strain has mutations in both the thioredoxin reductase (trxB) and glutathione reductase (gor) genes, which greatly enhances the disulfide bond formation of recombinant proteins expressed in its cytoplasm, hence resulting in a soluble product (6). However, the transposon-mediated genetic modifications of E. coli carried both the tetracycline and the kanamycin resistance genes as selectable markers and therefore made the cells incompatible with the production of human use vaccines that relied on plasmids carrying the Tetr or the Kanr genes. The use of a compatible expression host E. coli BL21(DE3) resulted in the production of an MSP-142 protein that was insoluble and located in the inclusion body fraction of the cells. In this report we have shown that soluble MSP-142 protein can be obtained from the BL21(DE3) cells by in vitro refolding of the inclusion body-derived protein under controlled redox conditions. Both the soluble and refolded P. vivax MSP-142 products appeared to be structurally similar based on biophysical analysis and reactivity with conformational epitope-specific monoclonal antibodies. It was our goal, therefore, to seek evidence of the immunological equivalence of these proteins in a parasite challenge model. Towards that end we report here the results of a vaccination study comparing the immunogenicity and efficacy of the soluble and refolded P. vivax MSP-142 products in the P. cynomolgi-rhesus model. We have also produced equivalent homologous constructs of P. cynomolgi MSP-142 protein both in their soluble and refolded forms, and these two proteins were also used as positive control immunogens in this study.

Background Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats. Methods A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. In-situ permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC. Results For nominal doses increasing in a 1:2:4 proportion, the Cmax and AUC0-∞ values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the Cmax and the AUC0-t values for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10-5 cm/s) in permeability study. Conclusions The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the in-situ permeability study.