Search

Context: Concerns about brolucizumab’s (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. Purpose: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. Settings and Design: Retrospective multicentric, survey-based study. Methods: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. Results: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1–65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. Conclusions: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.

Abstract The inhibition of tumor necrosis factor (TNF)-α trimer formation renders it inactive for binding to its receptors, thus mitigating the vicious cycle of inflammation. We designed a peptide (PIYLGGVFQ) that simulates a sequence strand of human TNFα monomer using a series of in silico methods, such as active site finding (Acsite), protein–protein interaction (PPI), docking studies (GOLD and Flex-X) followed by molecular dynamics (MD) simulation studies. The MD studies confirmed the intermolecular interaction of the peptide with the TNFα. Fluorescence-activated cell sorting and fluorescence microscopy revealed that the peptide effectively inhibited the binding of TNF to the cell surface receptors. The cell culture assays showed that the peptide significantly inhibited the TNFα-mediated cell death. In addition, the nuclear translocation of the nuclear factor kappa B (NFκB) was significantly suppressed in the peptide-treated A549 cells, as observed in immunofluorescence and gel mobility-shift assays. Furthermore, the peptide protected against joint damage in the collagen-induced arthritis (CIA) mouse model, as revealed in the micro focal-CT scans. In conclusion, this TNFα antagonist would be helpful for the prevention and repair of inflammatory bone destruction and subsequent loss in the mouse model of CIA as well as human rheumatoid arthritis (RA) patients. This calls upon further clinical investigation to utilize its potential effect as an antiarthritic drug.

Inter-appointment pain (IAP) is a subtype of postoperative pain which occurs between endodontic appointments. It may begin within a few hours after the first appointment and may continue for several days. Apart from mechanical instrumentation and thorough irrigation, intracanal medicaments play a central role in the disinfection of root canals and thus decreasing IAP. The aim of this study was to evaluate the effect of Curcuma Longa as an intracanal medicament on IAP in patients with symptomatic irreversible pulpitis (SIP). One hundred healthy adult patients having SIP in one of their single-rooted maxillary or mandibular teeth participated in this randomized, parallel, single-blinded clinical trial. After thorough biomechanical preparation, the root canals were randomly medicated with one of the following medicaments, Control (no medicament), Calcium Hydroxide, triple antibiotic paste (TAP), and Curcuma Longa. The pain was recorded using Visual analog scale at 4 h, 24 h, and every day until the seventh day. Data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. No statistical difference in pain scores was observed between Calcium Hydroxide, TAP or Curcuma Longa groups. It can be concluded that Curcuma Longa, Calcium hydroxide, and TAP are equally effective in controlling IAP.

The current pronunciation scoring based on Goodness of Pronunciation (GOP) uses posterior probabilities of the Acoustic Models. Such algorithms suffer from generalization since they are utilized to determine a score metric for each phoneme rather than on the completeness or comparison with the ideal utterance of the words. This paper proposes a novel method to overcome such limitations by using combined scores of prosodic, fluency, completeness, and accuracy. This is achieved using context-aware GOP in conjugation with dynamic time warping (DTW) matching of the pitch contours of a weighted average of the context tokens found in the audio file that is rich in mispronounced phonemes. The proposed work gives flexibility in tuning the results according to different speech aspects based on a single hyperparameter. The results achieved are encouraging and have been validated on the speechocean762 dataset, where Automatic Speech Recognition (ASR) model has been trained on the Librispeech dataset. The resultant mean error of the proposed approach is 3.38% and the value of the correlation coefficient achieved is 0.652.

The purpose of the current study was to prepare and evaluate a citronella oil-loaded microemulsion-based micro-emulgel for the treatment of Candida albicans. The primary objective was to use the skin to transfer hydrophobic medications into the bloodstream. The formulation included cinnamon oil as an antifungal oil and citronella oil as an active pharmaceutical ingredient, respectively. Tween 80 and PEG 200 were used as the surfactant and co-surfactant, respectively, to create phase diagrams. Carbopol 940, one of the frequently used polymers, was investigated for its ability to prepare gel formulations. The optimized (F3) batch contained the highest percentage (87.05 ± 0.03%) of drug content and, according to the statistics provided, had the highest drug release rate of around 87.05% within 4 h. The Korsmeyer–Peppas model with n value of 0.82, which is in the range 0.5–1, had the highest r2 value, indicating that release following non-Fickian/anomalous diffusion provided a better dimension for all of the formulations. The optimized (F3) formulation had stronger antifungal activity in comparison to other formulations. This leads to the conclusion that citronella oil can be made into a micro-emulgel, which may improve its release in aqueous systems while maintaining a high level of drug release at the target site.

The coagulation abnormalities and thromboembolic complications of coronavirus 2 (SARS-CoV-2) are now a well-established fact. The hypercoagulable state, the tendency for thromboembolism, and a cytokine surge state have been the exclusive reasons for multiorgan failure and other morbidities that have been regularly reported in COVID-19 patients. Ocular involvement in patients with active disease and those who have recovered is uncommon but not rare. We report a case series of four patients with CRVO, BRVO, CRAO, and vitreous hemorrhage in patients with proven COVID-19 infection and no other systemic ailments. The case series also tries to correlate the elevated D-dimer values, which signify a plausible prothrombotic state with the vaso-occlusive phenomenon in the retina leading to significant visual morbidity.

A 32-year-old male with no known systemic illness presented with unilateral Purtscher-like retinopathy in his left eye 2 weeks after recovering from a severe COVID-19 infection. Fundus examination revealed areas of intraretinal whitening and few cotton wool spots. Multimodal imaging findings were consistent with embolic occlusion of capillaries seen in Purtscher-like retinopathy. The case highlights the effect of virus-directed coagulation cascade activation leading to unilateral microvasculopathy in our patient. The case adds to the spectrum of COVID-19 retinopathy and presses that retina screening strategies should be established for patients suffering from or recovering from severe COVID-19 infection.

BackgroundHeart failure (HF) is a prevalent chronic disease and is associated with increases in mortality and morbidity. HF is a leading cause of hospitalizations and readmissions in the United States. A potentially promising area for preventing HF readmissions is continuous remote patient monitoring (CRPM). ObjectiveThe primary aim of this study is to determine the feasibility and preliminary efficacy of a CRPM solution in patients with HF at NorthShore University HealthSystem. MethodsThis study is a feasibility study and uses a wearable biosensor to continuously remotely monitor patients with HF for 30 days after discharge. Eligible patients admitted with an HF exacerbation at NorthShore University HealthSystem are being recruited, and the wearable biosensor is placed before discharge. The biosensor collects physiological ambulatory data, which are analyzed for signs of patient deterioration. Participants are also completing a daily survey through a dedicated study smartphone. If prespecified criteria from the physiological data and survey results are met, a notification is triggered, and a predetermined electronic health record–based pathway of telephonic management is completed. In phase 1, which has already been completed, 5 patients were enrolled and monitored for 30 days after discharge. The results of phase 1 were analyzed, and modifications to the program were made to optimize it. After analysis of the phase 1 results, 15 patients are being enrolled for phase 2, which is a calibration and testing period to enable further adjustments to be made. After phase 2, we will enroll 45 patients for phase 3. The combined results of phases 1, 2, and 3 will be analyzed to determine the feasibility of a CRPM program in patients with HF. Semistructured interviews are being conducted with key stakeholders, including patients, and these results will be analyzed using the affective adaptation of the technology acceptance model. ResultsDuring phase 1, of the 5 patients, 2 (40%) were readmitted during the study period. The study completion rate for phase 1 was 80% (4/5), and the study attrition rate was 20% (1/5). There were 57 protocol deviations out of 150 patient days in phase 1 of the study. The results of phase 1 were analyzed, and the study protocol was adjusted to optimize it for phases 2 and 3. Phase 2 and phase 3 results will be available by the end of 2022. ConclusionsA CRPM program may offer a low-risk solution to improve care of patients with HF after hospital discharge and may help to decrease readmission of patients with HF to the hospital. This protocol may also lay the groundwork for the use of CRPM solutions in other groups of patients considered to be at high risk. International Registered Report Identifier (IRRID)DERR1-10.2196/36741

Introduction: Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose. Methods: We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival. Results: Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07). Conclusion: A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

Nanosheet field-effect transistors (NSFETs) have emerged as a novel device replacement for sub-7nm CMOS technology nodes. However, due to smaller fin thickness (Tfin = 5nm), NSFETs are more vulnerable to the process-induced variations. Among various types of process-induced variations, Line edge roughness (LER) is becoming a significant concern for multi-gate field-effect transistors (MugFETs) with smaller feature sizes. In this article, we have reported and compared the impact of LER on the electrical characteristics of NSFETs and nanowire field-effect transistors (NWFETs) for the sub-7nm technology node. We have generated a 3-D LER profile using 2-D Auto Covariance Function (ACVF) that considers two degrees of freedom for a realistic roughness analysis at advanced CMOS technology nodes. For a complete study of 3-D LER effect in NSFET, we have considered roughness along the nanosheet's sidewalls as well as top and bottom surfaces. We have shown using 3D TCAD simulations that the sidewall roughness in NSFETs contributes to a negligible mismatch in threshold voltage and ON current. The mismatch performance of NSFET is compared with that of the NWFET for sub-7nm technology node. NSFET appears to be more immune to mismatch in ON current than NWFETs considered in this work. On the other hand, as compared with NSFET, owing to its superior gate all-around control, the NWFET achieves lower mismatch in drain induced barrier lowering (DIBL) and subthreshold slope (SS) in presence of LER. In addition to this, FETs with different channel doping modes such as inversion (IM) and Junction less (JL) mode have been compared for their matching performance against 3-D LER. It can be concluded from the results that IM FETs are more immune to 3-D LER as compared to JL FETs.

Recommendation systems suggest relevant items to a user based on the similarity between users or between items. In a collaborative filtering approach for generating recommendations, there is a symmetry between the users. That is, if user A has similar interests with user B, then an item liked by B can be recommended to A and vice versa. To provide optimal and fast recommendations, a recommender system may generate and keep clusters of existing users/items. In this research work, a hybrid sparrow clustered (HSC) recommender system is developed, and is applied to the MovieLens dataset to demonstrate its effectiveness and efficiency. The proposed method (HSC) is also compared to other methods, and the results are compared. Precision, mean absolute error, recall, and accuracy metrics were used to figure out how well the movie recommender system worked for the HSC collaborative movie recommender system. The results of the experiment on the MovieLens dataset show that the proposed method is quite promising when it comes to scalability, performance, and personalized movie recommendations.

Mutant IDH1 (mIDH1) inhibitors have shown single-agent activity in relapsed/refractory AML, though most patients eventually relapse. We evaluated the efficacy and molecular mechanism of the combination treatment with azacitidine, which is currently the standard of care in older AML patients, and mIDH1 inhibitor BAY1436032. Both compounds were evaluated in vivo as single agents and in combination with sequential (azacitidine, followed by BAY1436032) or simultaneous application in two human IDH1 mutated AML xenograft models. Combination treatment significantly prolonged survival compared to single agent or control treatment (P

Polypoidal choroidal vasculopathy (PCV) is increasingly recognized as an important cause of exudative maculopathy in Asians as against Wet age-related macular degeneration in Caucasians. A panel of retinal experts methodically evaluated pertinent updated literature on PCV with thorough PubMed/MEDLINE search. Based on this, the panel agreed upon and proposed the current consensus recommendations in the diagnosis (clinical and imaging), management and follow-up schedule of PCV. Diagnosis of PCV should be based on the gold standard indocyanine green angiography which demonstrates early nodular hyperfluorescence signifying the polyp with additional features such as abnormal vascular network (AVN). Optical coherence tomography is an excellent adjuvant for diagnosing PCV, monitoring disease activity, and decision-making regarding the treatment. Current treatment modalities for PCV include photodynamic therapy, anti-vascular endothelial growth factor agents, and thermal laser. Choice of specific treatment modality and prognosis depends on multiple factors such as the location and size of PCV lesion, presence or absence of polyp with residual AVN, amount of submacular hemorrhage, presence or absence of leakage on fundus fluorescein angiography, visual acuity, and so on. Current recommendations would be invaluable for the treating physician in diagnosing PCV and in formulating the best possible individualized treatment strategy for optimal outcomes in PCV management.

Aim: The aim of this study is to comparatively evaluate “internal limiting membrane (ILM) blue (0.025% brilliant blue G (BBG) +4% polyethylene glycol” and “Brilliant Peel (0.025% BBG + heavy water)” in idiopathic full-thickness macular hole (FTMH) surgery with respect to anatomical and functional outcome and surgical ease of ILM peeling. Materials and Methods: It was a prospective comparative study. Thirty patients with idiopathic FTMH selected for pars-plana vitrectomy with ILM peeling were included in the study. Cataract extraction was combined with vitrectomy if cataract was significant. Fifteen eyes underwent ILM peeling with ILM blue – Group 1 and fifteen eyes with Brilliant Peel – Group 2. The adequacy of ILM staining was noted intraoperatively. All patients followed up next day, at 1 week, 6 weeks, and 3 months. Macular hole closure rate and gain in visual acuity (VA) and contrast sensitivity (CS) were noted. Statistical Analysis: Student's t-test was used to assess the baseline numeric differences among groups. Repeated measures ANOVA was used to assess VA improvement over time in each group. Chi-square test was used to compare two groups in terms of stage of macular hole. Means test was used to check the effect of lens status in visual recovery. Results: Both groups were well matched in demographic data, baseline VA, stage of macular hole, and percentage of eyes undergoing simultaneous cataract extraction. Macular hole closed in 100% of eyes. Mean pre- and postoperative logMAR best-corrected VA was 0.80 and 0.40 in ILM blue group and 0.993 and 0.527 in the Brilliant Peel group. VA improvement was clinically and statistically significant in both ILM blue (P = 0.004) and Brilliant Peel (P = 0.003) groups. The groups did not differ from each other at 3 months in terms of gain in VA (P = 0.291) and CS. Intraoperatively, both the dyes stained the ILM well. Conclusion: ILM peeling with ILM blue and Brilliant Peel dyes showed comparable intraoperative staining and good postoperative anatomic and functional outcome.

Abstract Background To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. Methods Multimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA). Results Ten patients were identified. Three patients had a prior RPE-rip and were excluded. Seven patients with a mean follow-up period of 47 ± 38 months after the occurrence of the RPE-defect were included (age range 71–87 years). Mean distance Best corrected visual acuity (BCVA) at initial presentation was 0.36 ± 0.29logMAR and at last follow-up visit 0.51 ± 0.43logMAR. Patients presented with clinically apparent GA on funduscopy and FAF, but preserved photoreceptor layers on optical coherence tomography (OCT). On FA there was early hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid material right above the Bruch’s membrane with concomitant decrease of hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid pigment epithelium detachment (PED) preceding the lesion. Conclusions Beside GA and characteristic RPE-tears, another atypical form of RPE-defect with overlying preserved photoreceptor layers are found in AMD. This so far disregarded subgroup of patients present with reasonable visual function and long-term survival of photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid material and persistent subretinal fluid (SRF), but also a RPE-independent visual cycle for cone photopigment within the neurosensory retina may contribute to their favorable course.

Direct perfluorocarbon liquid (PFCL)-silicone oil exchange presents its own set of challenges in the micro incision vitreous surgery era. We propose a simple bimanual technique to circumvent this problem. Thirteen eyes of patients with retinal detachment associated with giant retinal tears underwent vitrectomy followed by self-retaining endo illuminator (Chandelier) assisted direct PFCL-silicone exchange. No intra or postoperative complications related to the surgical technique were noted. All patients had attached retinas and satisfactory visual recovery at 6 months. Direct bimanual PFCL silicone oil exchange using a Chandelier seems to be a safe and effective technique.

A tonic pupil is usually caused due to parasympathetic denervation of the iris sphincter muscles. It's usually seen in females and in 80 % cases it's unilateral, and 4% of these cases progress to bilateral involvement. Adie's tonic pupil has been reported in literature to have multiple syndromic associations. Simultaneous bilateral occurrence of Adie's tonic pupil in an asymptomatic healthy adult male is sparsely reported in literature. The diagnostic dilemma in the setting of a busy clinical practice is henceforth discussed.

Large traumatic macular holes (TMHs) tend to be irregular and have a variable predictability. The inverted flap technique makes use of remnants of internal limiting membrane (ILM) at the periphery of the MH. The peeled-off ILM contains Müller cell fragments which can induce gliosis and help in closure of MH. We operated on a case of large TMH (~899 μ minimum linear diameter) with choroidal rupture and subretinal hemorrhage in a young female with the inverted flap technique of ILM peeling and observed successful closure of the MH. The excellent anatomical and surgical results achieved in our case seem to suggest this to be a safe and effective surgical manoeuvre for such cases.

Utilization of the increased biomass of corn (Zea mays L.) after adoption of hybrid cultivars and to avoid problems like residue burning, its textile application can be explored for sustainable agriculture. Extraction of fibre was done by optimizing alkali extraction parameters. The effect of corn stalk fibre loading on the properties of composite material was analyzed. In epoxy resin composite sample, 10 g fibre loading with matrix resulted tensile strength as 4.33 MPa. With the increase in fibre loading in the matrix, material strength of fibre also increased, whereas the differential increase in flexural strength from 10–30 g was seen as 13.23 MPa in epoxy resin composite. The impact strength in epoxy resin composite of 10–20 g fibre loading was 30.92 J/m and 45.67 J/m thickness, respectively whereas at 30 g fibre loading impact strength was maximum i.e. 60.45 J/m thickness. In polyester resin composite, one layered composite sample (10 g fibre’s volume) has 7.74 MPa tensile strength while two layered composite material have 15.09 MPa. Impact strength in three layered corn stalk composite material reinforced with polyester was much higher (60.29 J/m thickness) which is very appreciable for high impact/shock applications. From these results it was concluded that 100% corn stalk 3 layered composite sample have better mechanical properties than the other layered composites and can be used in high strength application if the fibre loading is increased in appropriate amount. It was also concluded that the epoxy resin applied specimens have better strength properties as compared to polyester resin specimen.

β-arrestins initially contact with the phosphorylated carboxyl-terminus of GPCRs before engaging with the GPCR core. Here, the authors use a chimeric GPCR partially and fully engaged with β-arrestin1 and show that the core interaction is dispensable for receptor endocytosis and signalling.

The heritability of hypertension (HTN) is widely recognized and as a result, extensive studies ranging from genetic linkage analyses to genome-wide association studies are actively ongoing to elucidate the etiology of both monogenic and polygenic forms of HTN. Due to the complex nature of essential HTN, however, single genes affecting blood pressure (BP) variability remain difficult to isolate and identify and have rendered the development of single-gene targeted therapies challenging. The roles of other causative factors in modulating BP, such as gene–environment interactions and epigenetic factors, are increasingly being brought to the forefront. In this review, we discuss the various monogenic HTN syndromes and corresponding pathophysiologic mechanisms, the different methodologies employed in genetic studies of essential HTN, the mechanisms for epigenetic modulation of essential HTN, pharmacogenomics and HTN, and finally, recent advances in genetic studies of essential HTN in the pediatric population.

Reduced number of teeth with underdeveloped alveolar ridges poses a greatest prosthetic challenge in rehabilitation of ectodermal dysplasia patients (ED). Furthermore, surgical risks and financial constraints may preclude the implant supported prosthesis, the most desirable treatment option in an adult ED patient. Long edentulous span does not permit fixed dental prosthesis (FDP) as well. Telescopic denture by incorporating the best of both fixed and removable prosthesis can be a viable treatment alternative for ED patients with compromised dentition and limited finances. A 21-year-old young girl presented with chief complaint of esthetics and mastication due to missing upper and lower teeth. A provisional diagnosis of ED was made based on familial history, physical, and oral examination. This clinical report describes management of an adult ED patient by means of telescopic overdenture prosthesis in mandibular arch and FDP in maxillary arch which restored esthetics, function, and social confidence of the patient in a cost effective manner.

Geriatrics is a medical practice that addresses the complex needs of older patients and emphasizes maintaining functional independence even in the presence of chronic disease. Treatment of geriatric patients requires a different strategy and is very complex. Geriatric medicines aim to promote health by preventing and treating diseases and disabilities in older adults. Development of effective dietary interventions for promoting healthy aging is an active but challenging area of research because aging is associated with an increased risk of chronic disease, disability, and death. Aging populations are a global phenomenon. The most widespread conditions affecting older people are hypertension, congestive heart failure, dementia, osteoporosis, breathing problems, cataract, and diabetes to name a few. Decreased immunity is also partially responsible for the increased morbidity and mortality resulting from infectious agents in the elderly. Nutritional status is one of the chief variables that explains differences in both the incidence and pathology of infection. Elderly people are at increased risk for micronutrient deficiencies due to a variety of factors including social, physical, economic, and emotional obstacles to eating. Thus there is an urgent need to shift priorities to increase our attention on ways to prevent chronic illnesses associated with aging. Individually, people must put increased efforts into establishing healthy lifestyle practices, including consuming a more healthful diet. The present review thus focuses on the phytochemicals of nutraceutical importance for the geriatric population.

Drug discovery initiatives, aimed at Chagas treatment, have been hampered by the lack of standardized drug screening protocols and the absence of simple pre-clinical assays to evaluate treatment efficacy in animal models. In this study, we used a simple Enzyme Linked Aptamer (ELA) assay to detect T. cruzi biomarker in blood and validate murine drug discovery models of Chagas disease. In two mice models, Apt-29 ELA assay demonstrated that biomarker levels were significantly higher in the infected group compared to the control group, and upon Benznidazole treatment, their levels reduced. However, biomarker levels in the infected treated group did not reduce to those seen in the non-infected treated group, with 100% of the mice above the assay cutoff, suggesting that parasitemia was reduced but cure was not achieved. The ELA assay was capable of detecting circulating biomarkers in mice infected with various strains of T. cruzi parasites. Our results showed that the ELA assay could detect residual parasitemia in treated mice by providing an overall picture of the infection in the host. They suggest that the ELA assay can be used in drug discovery applications to assess treatment efficacy in-vivo.

Milk whey—commonly known as cheese whey—is a by-product of cheese or casein in the dairy industry and contains usually high levels of lactose, low levels of nitrogenous compounds, protein, salts, lactic acid and small amounts of vitamins and minerals. Milk whey contains several unique components like immunoglobulins (Igs), lactoferrin (Lf), lactoperoxidase (Lp), glycomacropeptide (GMP) and sphingolipids that possess some important antimicrobial and antiviral properties. Some whey components possess anticancer properties such as sphingomyelin, which have the potential to inhibit colon cancer. Immunoglobulin-G (IgGs), Lp and Lf concentrated from whey participates in host immunity. IgGs binds with bacterial toxins and lowers the bacterial load in the large bowel. There are some whey-derived carbohydrate components that possess prebiotic activity. Lactose support lactic acid bacteria (such as Bifidobacteria and Lactobacilli). Stallic acids, an oligosaccharide in whey, are typically attached to proteins, and possess prebiotic properties. The uniqueness of whey proteins is due to their ability to boost the level of glutathione (GSH) in various tissues and also to optimize various processes of the immune system. The role of GSH is very critical as it protects the cells against free radical damage, infections, toxins, pollution and UV exposure. Overall GSH acts as a centerpiece of the body’s antioxidant defense system. It has been widely observed that individuals suffering from cancer, HIV, chronic fatigue syndrome and many other immune-compromising conditions have very poor levels of glutathione. The sulphur-containing amino-acids (cysteine and methionine) are also found in high levels in whey protein. Thus, the present review will focus on the therapeutic potential of milk whey such as antibiotic, anti-cancer, anti-toxin, immune-enhancer, prebiotic property etc.

Chagas disease affects about 5 million people across the world. The etiological agent, the intracellular parasite Trypanosoma cruzi (T. cruzi), can be diagnosed using microscopy, serology or PCR based assays. However, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. It is well documented that several parasite proteins called T. cruzi Excreted Secreted Antigens (TESA), are released into the blood of an infected host. These circulating parasite antigens could thus be used as highly specific biomarkers of T. cruzi infection. In this study, we have demonstrated that, using a SELEx based approach, parasite specific ligands called aptamers, can be used to detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer (ELA) assay, similar to ELISA, was developed using biotinylated aptamers to demonstrate that these RNA ligands could interact with parasite targets. Aptamer L44 (Apt-L44) showed significant and specific binding to TESA as well as T. cruzi trypomastigote extract and not to host proteins or proteins of Leishmania donovani, a related trypanosomatid parasite. Our result also demonstrated that the target of Apt-L44 is conserved in three different strains of T. cruzi. In mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of binding compared to non-infected mice suggesting that it could detect a biomarker of T. cruzi infection. Additionally, Apt-L44 could detect these circulating biomarkers in both the acute phase, from 7 to 28 days post infection, and in the chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44 could thus be used in a qualitative ELA assay to detect biomarkers of Chagas disease.