Diagnostic efficacy of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for early detection of acute kidney injury in dogs with leptospirosis or babesiosis.

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice.

A novel loop-mediated isothermal amplification (LAMP) assay to diagnose feline panleukopenia.

Protoparvovirus carnivoran1, known commonly as feline panleukopenia virus (FPV) is a highly contagious and environmentally stable parvovirus of domestic as well as wild felids. A rapid and robust diagnostic tool will aid in implementing prompt treatment and control measures. A loop-mediated isothermal amplification (LAMP) as a point-of-care diagnostic tool for diagnosing feline panleukopenia was standardised using faecal samples of cats. The assay will reduce the cost and time required to diagnose feline panleukopenia. A set of two outer primers (F3 and B3) and two inner primers (FIP and BIP) were designed to target the viral polypeptide (VP2) gene of FPV. Optimisation of the LAMP reaction was done at 60 °C for one hour after an initial denaturation at 95 °C for five minutes. Visualisation of the result based on the addition of SYBR Green 1 dye offered an easy and reliable diagnosis. The detection limit of the standardised LAMP assay was as low as 1.25 ng/µl of the target DNA. Species specificity of the LAMP primers revealed no amplification of the non-target DNA of any other species except that of the canine parvovirus DNA template. DNA extracted from 100 PCR-positive and 20 PCR-negative faecal samples were subjected to the standardised assay and compared with PCR. Analysis of the results revealed that the LAMP assay was 100% sensitive and 90% specific compared to PCR. The LAMP assay could be a reliable tool for the point-of-care diagnosis of feline panleukopenia in limited resource settings.

In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation - Targeting Mpro and pan-coronavirus post-fusion Spike protein.

Background and aim: Novel nature of the viral pathogen SARS-CoV-2 and the absence of standard drugs for treatment, have been a major challenge to combat this deadly infection. Natural products offer safe and effective remedy, for which traditional ethnic medicine can provide leads. An indigenous poly-herbal formulation, Kabasura Kudineer from Siddha system of medicine was evaluated here using a combination of computational approaches, to identify potential inhibitors against two anti-SARS-CoV-2 targets - post-fusion Spike protein (structural protein) and main protease (Mpro, non-structural protein). Experimental procedure: We docked 32 phytochemicals from the poly-herbal formulation against viral post-fusion Spike glycoprotein and Mpro followed by molecular dynamics using Schrodinger software. Drug-likeness analysis was performed using machine learning (ML) approach and pkCSM. Results: The binding affinity of the phytochemicals in Kabasura Kudineer revealed the following top-five bioactives: Quercetin > Luteolin > Chrysoeriol > 5-Hydroxy-7,8-Dimethoxyflavone > Scutellarein against Mpro target, and Gallic acid > Piperlonguminine > Chrysoeriol > Elemol > Piperine against post-fusion Spike protein target. Quercetin and Gallic acid exhibited binding stability in complexation with their respective viral-targets and favourable free energy change as revealed by the molecular dynamics simulations and MM-PBSA analysis. In silico predicted pharmacokinetic profiling of these ligands revealed appropriate drug-likeness properties. Conclusion: These outcomes provide: (a) potential mechanism for the anti-viral efficacy of the indigenous Siddha formulation, targeting Mpro and post-fusion Spike protein (b) top bioactive lead-molecules that may be developed as natural product-based anti-viral pharmacotherapy and their pleiotropic protective effects may be leveraged to manage co-morbidities associated with COVID-19.

Nature-inspired Enzyme engineering and sustainable catalysis: biochemical clues from the world of plants and extremophiles.

The use of enzymes to accelerate chemical reactions for the synthesis of industrially important products is rapidly gaining popularity. Biocatalysis is an environment-friendly approach as it not only uses non-toxic, biodegradable, and renewable raw materials but also helps to reduce waste generation. In this context, enzymes from organisms living in extreme conditions (extremozymes) have been studied extensively and used in industries (food and pharmaceutical), agriculture, and molecular biology, as they are adapted to catalyze reactions withstanding harsh environmental conditions. Enzyme engineering plays a key role in integrating the structure-function insights from reference enzymes and their utilization for developing improvised catalysts. It helps to transform the enzymes to enhance their activity, stability, substrates-specificity, and substrate-versatility by suitably modifying enzyme structure, thereby creating new variants of the enzyme with improved physical and chemical properties. Here, we have illustrated the relatively less-tapped potentials of plant enzymes in general and their sub-class of extremozymes for industrial applications. Plants are exposed to a wide range of abiotic and biotic stresses due to their sessile nature, for which they have developed various mechanisms, including the production of stress-response enzymes. While extremozymes from microorganisms have been extensively studied, there are clear indications that plants and algae also produce extremophilic enzymes as their survival strategy, which may find industrial applications. Typical plant enzymes, such as ascorbate peroxidase, papain, carbonic anhydrase, glycoside hydrolases and others have been examined in this review with respect to their stress-tolerant features and further improvement via enzyme engineering. Some rare instances of plant-derived enzymes that point to greater exploration for industrial use have also been presented here. The overall implication is to utilize biochemical clues from the plant-based enzymes for robust, efficient, and substrate/reaction conditions-versatile scaffolds or reference leads for enzyme engineering.

Targeting lipid-sensing nuclear receptors PPAR (α, γ, ß/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists.

The global prevalence of obesity-related systemic disorders, including non-alcoholic fatty liver disease (NAFLD), and cancers are rapidly rising. Several of these disorders involve peroxisome proliferator-activated receptors (PPARs) as one of the key cell signaling pathways. PPARs are nuclear receptors that play a central role in lipid metabolism and glucose homeostasis. They can activate or suppress the genes responsible for inflammation, adipogenesis, and energy balance, making them promising therapeutic targets for treating metabolic disorders. In this study, an attempt has been made to screen novel PPAR pan-agonists from the ZINC database targeting the three PPAR family of receptors (α, γ, ß/δ), using molecular docking and molecular dynamics (MD) simulations. The top scoring five ligands with strong binding affinity against all the three PPAR isoforms were eprosartan, canagliflozin, pralatrexate, sacubitril, olaparib. The ADMET analysis was performed to assess the pharmacokinetic profile of the top 5 molecules. On the basis of ADMET analysis, the top ligand was subjected to MD simulations, and compared with lanifibranor (reference PPAR pan-agonist). Comparatively, the top-scoring ligand showed better protein-ligand complex (PLC) stability with all the PPARs (α, γ, ß/δ). When experimentally tested in in vitro cell culture model of NAFLD, eprosartan showed dose dependent decrease in lipid accumulation and oxidative damage. These outcomes suggest potential PPAR pan-agonist molecules for further experimental validation and pharmacological development, towards treatment of PPAR-mediated metabolic disorders.

Nutraceutical and flavor profiles in underutilized desert legumes of India: gene editing strategies towards sustainable food development.

Climate change has posed a challenge for food security all over the world in the form of fluctuating crop yields and novel disease outbreaks in plants. Human society's overdependence on a few food crops does not seem a wise precedence. There are numerous underutilized/orphan/neglected legumes growing in the Indian desert regions that can come to the rescue and act as balanced and sustainable sources of nutrients and health-benefitting nutraceuticals. However, challenges such as low plant yield, unidentified metabolic pathways and off-flavor in the food products derived from them prevent the realization of their full potential. Conventional breeding techniques are too slow to achieve the desired modifications and cater to the sharply rising demand for functional foods. The novel gene editing tools like CRISPR-Cas provide more precise tool to manipulate the target genes with or without introduction of foreign DNA and therefore, have better chances to be accepted by governments and societies. The current article reports some of the relevant 'gene editing' success stories with respect to nutraceutical and flavor profiles in the popular legumes. It highlights gaps and future potential, along with areas requiring caution, in underutilized edible legumes of the Indian (semi) arid regions like Prosopis cineraria, Acacia senegal and Cyamopsis tetragonoloba.

Initial experience with 3D laparoscopic choledochal cyst (CDC) excision and hepatico-duodenostomy (HD) in 21 children.

INTRODUCTION: Minimal access surgery has gradually become the standard of care in the management of choledochal cysts (CDC). Laparoscopic management of CDC is a technically challenging procedure that requires advanced intracorporeal suturing skills, and hence, has a steep learning curve. Robotic surgery has the advantages of 3D vision, articulating hand instruments making suturing easy and thus is ideal. However, the non-availability, high costs and necessity for large-size ports are the major limiting factors for robotic procedures in the paediatric population. Use of 3D laparoscopy incorporates the advantage of 3D vision and at the same time allows the use of small-sized conventional laparoscopic instruments. With this background, we discuss our initial experience with the use of 3D laparoscopy using conventional hand instruments in CDC management. AIM: To study our initial experience in the management of CDC in paediatric patients with 3D laparoscopy in terms of feasibility and peri-operative details. MATERIALS AND METHOD: All patients under 12 years of age treated for choledochal cyst in a period of initial 2 years were retrospectively analysed. Demographic parameters, clinical presentation, intra-operative time, blood loss, post-operative events and follow-up were studied. RESULTS: The total number of patients were 21. The mean age was 5.3 years with female preponderance. Abdominal pain was the most common presenting symptom. All patients could be completed laparoscopically. No patient needed conversion to open procedure or re-exploration. The average blood loss was 26.67 ml. None of the patients required a blood transfusion. One patient developed a minor leak postoperatively and was managed conservatively. CONCLUSION: 3D laparoscopic management of CDC in the paediatric age group is safe and feasible. It offers the advantages of depth perception aiding intracorporeal suturing, with the use of small-sized instruments. It is thus a 'bridging the gap' asset between conventional laparoscopy and robotic surgery. LEVEL OF EVIDENCE: Treatment study level IV.

Investigating the antioxidant activity enhancer effect of Cyamopsis tetragonoloba seed extract on phenolic phytochemicals.

Introduction: Phenolic phytochemicals are known for antioxidant-mediated pharmacological effects in various diseases (diabetes, cancer, CVDs, obesity, inflammatory and neurodegenerative disorders). However, individual compounds may not exert the same biological potency as in combination with other phytochemicals. Cyamopsis tetragonoloba (Guar), an underutilized semi-arid legume which has been used as a traditional food in Rajasthan (India), is also a source of the important industrial product guar gum. However, studies on its biological activity, like antioxidant, are limited. Methods: We tested the effect of C. tetragonoloba seed extract to enhance the antioxidant activity of well-known dietary flavonoids (quercetin, kaempferol, luteolin, myricetin, and catechin) and non-flavonoid phenolics (caffeic acid, ellagic acid, taxifolin, epigallocatechin gallate (EGCG), and chlorogenic acid) using DPPH radical scavenging assay. The most synergistic combination was further validated for its cytoprotective and anti-lipid peroxidative effects in in vitro cell culture system, at different concentrations of the extract. LC-MS analysis of purified guar extract was also performed. Results and discussion: In most cases, we observed synergy at lower concentrations of the seed extract (0.5-1 mg/ml). The extract concentration of 0.5 mg/ml enhanced the antioxidant activity of Epigallocatechin gallate (20 µg/ml) by 2.07-folds, implicating its potential to act as an antioxidant activity enhancer. This synergistic seed extract-EGCG combination diminished the oxidative stress nearly by double-fold when compared with individual phytochemical treatments in in vitro cell culture. LC-MS analysis of the purified guar extract revealed some previously unreported metabolites, including catechin hydrate, myricetin-3-galactoside, gossypetin-8-glucoside, and puerarin (daidzein-8-C-glucoside) which possibly explains its antioxidant enhancer effect. The outcomes of this study could be used for development of effective nutraceutical/dietary supplements.

The Rising Status of Phenobarbital: A Case for Use in Severe Refractory Hyperactive Poststroke Delirium.

INTRODUCTION: Up to 48% of patients who have had a stroke will experience poststroke delirium (PSD) that can be hyperactive, hypoactive, or mixed. Literature on treatment of the hyperactive subtype is specifically lacking. This case report describes the rapid resolution of severe refractory hyperactive PSD with phenobarbital. CASE REPORT: A 58-year-old man with a left middle cerebral artery stroke presented with severe hyperactive PSD of 12 days duration, refractory to antipsychotics, alpha-2 agonists, gabapentin, therapeutic valproic acid, benzodiazepines, and ketamine infusion. An oral dose of phenobarbital 30.4 mg, followed by oral maintenance therapy was initiated on day 13 of admission with dramatic improvement. As his Richmond Agitation-Sedation score trended downwards to 0, he was able to cooperate with therapies. This allowed for discharge to a skilled nursing facility for rehabilitation and subsequently home 2 weeks later. CONCLUSION: Hyperactive PSD is a common complication of stroke with little evidence to guide treatment strategies. This report suggests that phenobarbital, because of its varied mechanisms of action and unique neurochemistry, may be an unrecognized potential therapy.

COVID-19 infection and metabolic comorbidities: Mitigating role of nutritional sufficiency and drug - nutraceutical combinations of vitamin D.

The vulnerability of human health is amplified in recent times with global increase in non-communicable diseases (due to lifestyle changes and environmental insults) and infectious diseases (caused by newer pathogens and drug-resistance strains). Clinical management of diseases is further complicated by disease severity caused by other comorbid factors. Drug-based therapy may not be the sole approach, particularly in scenarios like the COVID-19 pandemic, where there is no specific drug against SARS-CoV-2. Nutritional interventions are significant in armouring human populations in disease prevention, and as adjunctive therapy for disease alleviation. Amidst ongoing clinical trials to determine the efficacy of Vit. D against infections and associated complications, this review examines the pleiotropic benefits of nutritional adequacy of vitamin D (Vit. D) in combating viral infections (COVID-19), its severity and complications due to co-morbidities (obesity, diabetes, stroke and Kawasaki disease), based on research findings and clinical studies. Supplements of Vit. D in combination with other nutrients, and drugs, are suggested as promising preventive-health and adjunct-treatment strategies in the clinical management of viral infections with metabolic comorbidities.

Acute Generalized Exanthematous Pustulosis in a Setting of Cutaneous Lymphoma.

Acute generalized exanthematous pustulosis (AGEP) is a rare dermatological manifestation of the adverse drug reaction that occurs for a varied duration after the receipt of certain drugs. It manifests as an acute onset of generalized exanthematous pustular reaction with an edematous base. It has a characteristic clinical presentation and rapid resolution soon after the removal of the offending drug. The unique histological finding is that of single-cell necrosis of keratinocytes with edema of papillary dermis accompanied by components of vasculitis and/or exocytosis of eosinophils. Management consists of moist antiseptic dressings, topical steroids, infliximab, the use of systemic steroids if needed, and avoiding antibiotics as much as possible. Here, we present a case of AGEP in a setting of usages of antibiotics like vancomycin, cefepime, and ceftriaxone in a patient with cutaneous lymphoma that resolved after withdrawal of the offending antibiotics.

Effect of Different Proportions of Phenolics on Antioxidant Potential: Pointers for Bioactive Synergy/Antagonism in Foods and Nutraceuticals.

Phenolic compounds include a broad variety of antioxidant plant substances such as flavonoids that have in common an aromatic ring with one or more hydroxyl groups. Nutraceuticals and health food supplements are designed from flavonoids as well as pure phytochemicals, often in isolation. However, studies on synergistic and antagonistic effects of such compounds are relatively few. In the current study, dual combinations prepared from five phenolic compounds (flavonoid and non-flavonoid) including rutin hydrate, quercetin dihydrate, hydroquinone, kaempferol, and resveratrol were tested for their antioxidant activities using DPPH · radical scavenging assay. The synergistic antioxidant interactions among these phenolics were evaluated by comparing their individual antioxidant effect with that obtained by a mixture of two compounds in various ratios. Quercetin dihydrate showed the highest antioxidant activity. Many combinations were found statistically synergistic in particular ratios. Rutin hydrate and resveratrol showed maximum synergy (1:1, 2:1, and 3:1 ratio). Antagonistic interactions were also identified. The results of this study could be used by industries to develop more potent nutraceutical supplements or guide the researchers for further bioactivity validation using in vivo assays.

In silico and in vitro analysis of PPAR - α / γ dual agonists: Comparative evaluation of potential phytochemicals with anti-obesity drug orlistat.

Obesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (-10.96 kcal/mol against PPARα and -10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (-14.88 kcal/mol against PPARα and -13.64 kcal/mol against PPARγ), and its aglycone, quercetin (-10.08 kcal/mol in PPARα and -9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment.

Chitosan nanoparticles augmented indole-3-acetic acid production by rhizospheric Pseudomonas monteilii.

Rhizospheric Pseudomonas spp. are widely used for upgrading sustainable agriculture because of their ability to execute multifaceted plant beneficial functions. In the current study, chitosan nanoparticles (CNPs) were used to analyze their effect on plant beneficial properties of rhizospheric Pseudomonas monteilii. The CNPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. The impact of CNPs on indole-3-acetic acid (IAA) production of P. monteilii was analyzed and quantified by spectrophotometric and confirmed high-performance liquid chromatography analysis. This revealed the beneficial effect of CNPs (1 mg/ml) by enhancing the IAA production of P. monteilii. In planta effect of varied bacterial IAA production was further demonstrated in Vigna unguiculata. Here, enhancement in shoot length (35.79 ± 0.37 cm), leaf number (7 ± 0.54), and fresh weight (3.07 ± 0.11 g) were observed in the plants treated with the culture filtrate collected from P. monteilii cultivated with 1 mg/ml CNPs. The results of the study highlight the beneficial effect of the CNPs to augment the rhizobacterial functioning by inducing the expression of plant beneficial properties.

Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS). We aimed to assess relationships between cerebral arterial blood flow (CABF) and serum neurofilament light chain (sNfL) as neuronal damage biomarkers. METHODS AND MATERIALS: Total CABF was measured in 137 patients (86 with clinically isolated syndrome/relapsing-remitting (RR) MS and 51 with progressive MS [PMS]) and 48 healthy controls using Doppler ultrasonography. sNfL was quantitated using a single-molecule assay (Simoa). Examination using 3.0-T magnetic resonance imaging (MRI) allowed quantification of T2 lesions and whole-brain volume (WBV). Multiple linear regression models determined the sNfL association with CABF after correction for demographic and MRI-derived variables. RESULTS: After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained an additional 2.6% of the sNfL variance (ß = -0.167, p = 0.044). CABF also remained significant in a stepwise regression model (ß = 0.18, p = 0.034) upon the inclusion of T2 lesion burden and WBV effects. Patients in the lowest CABF quartile (CABF ≤ 761 ml/min) had significantly higher sNfL levels (34.6 vs. 23.9 pg/ml, age and BMI-adjusted-p = 0.042) when compared to the highest quartile (CABF ≥ 1130 ml/min). CONCLUSION: Lower CABF is associated with increased sNfL in MS patients, highlighting the relationship between cerebral hypoperfusion and axonal pathology.

Desert legume Prosopis cineraria as a novel source of antioxidant flavonoids / isoflavonoids: Biochemical characterization of edible pods for potential functional food development.

Flavonoids and isoflavonoids in foods are attracting attention as they are significant antioxidant and phytoestrogenic compounds that are beneficial for human health. In this study, the edible pods of the underutilized desert legume Prosopis cineraria from Rajasthan, India were used to extract flavonoids. The pods from semi-arid zone showed the highest flavonoid content (432 mg Rutin hydrate/gm). UV spectrophotometric analysis was also done to characterize flavonoids. The flavonoids and isoflavonoids were further purified from semi-arid zone plants using column chromatography with Amberlite XAD7HP and Sephadex LH-20. LC-MS analysis revealed the presence of medicinally valuable antioxidant flavonoids and isoflavonoids in the pods, viz. vitexin, puerarin, phloridzin, and daidzein. It was seen that the flavonoids/isoflavonoids are present in the selected legume in different forms i.e. pure aglycone, C-glycoside as well as O-glycoside. This finding makes P. cineraria an attractive source candidate for extraction of these nutraceuticals with a potential for development into functional food.

Real-world comorbidities of atopic dermatitis in the US adult ambulatory population.

BACKGROUND: Atopic dermatitis (AD) is a pruritic, inflammatory skin disease associated with various comorbidities. However, comprehensive analyses of real-world comorbidities in adult patients with AD are limited. OBJECTIVE: To characterize the real-world comorbidities associated with adult AD in an ambulatory population. METHODS: We queried the MarketScan Commercial Claims and Encounters database from January 1, 2017 to December 31, 2017. Multivariable logistic regressions were performed to compare comorbidities in adult patients with AD versus age- and sex-matched controls. RESULTS: A total of 39,779 patients with AD and 353,743 controls were identified. Increased odds of psychiatric conditions, including anxiety (odds ratio [OR] 1.44) and mood disorders (OR 1.31), were observed in patients with AD. Patients with AD had higher likelihoods of autoimmune diseases, including vitiligo (OR 4.44) and alopecia areata (OR 6.01). Adult AD was also associated with infections, including impetigo (OR 9.72), methicillin-resistant Staphylococcus aureus (OR 3.92), and cellulitis (OR 2.52). Patients with AD were more likely to have systemic conditions, including lymphoid/hematopoietic malignancy (OR 1.91), atherosclerosis (OR 1.69), and metabolic syndrome (OR 1.47). For all the above, P < .001. LIMITATIONS: Retrospective analysis of health care claims data. CONCLUSION: Adult AD is associated with various psychiatric and systemic comorbidities, emphasizing the systemic nature of AD and the need for the collaborative management of these patients.

Brain atrophy and lesion burden are associated with disability progression in a multiple sclerosis real-world dataset using only T2-FLAIR: The NeuroSTREAM MSBase study.

BACKGROUND: Methodological challenges limit the use of brain atrophy and lesion burden measures in the follow-up of multiple sclerosis (MS) patients on clinical routine datasets. OBJECTIVE: To determine the feasibility of T2-FLAIR-only measures of lateral ventricular volume (LVV) and salient central lesion volume (SCLV), as markers of disability progression (DP) in MS. METHODS: A total of 3,228 MS patients from 9 MSBase centers in 5 countries were enrolled. Of those, 2,875 (218 with clinically isolated syndrome, 2,231 with relapsing-remitting and 426 with progressive disease subtype) fulfilled inclusion and exclusion criteria. Patients were scanned on either 1.5 T or 3 T MRI scanners, and 5,750 brain scans were collected at index and on average after 42.3 months at post-index. Demographic and clinical data were collected from the MSBase registry. LVV and SCLV were measured on clinical routine T2-FLAIR images. RESULTS: Longitudinal LVV and SCLV analyses were successful in 96% of the scans. 57% of patients had scanner-related changes over the follow-up. After correcting for age, sex, disease duration, disability, disease-modifying therapy and LVV at index, and follow-up time, MS patients with DP (n = 671) had significantly greater absolute LVV change compared to stable (n = 1,501) or disability improved (DI, n = 248) MS patients (2.0 mL vs. 1.4 mL vs. 1.1 mL, respectively, ANCOVA p < 0.001, post-hoc pair-wise DP vs. Stable p = 0.003; and DP vs. DI, p = 0.002). Similar ANCOVA model was also significant for SCLV (p = 0.03). CONCLUSIONS: LVV-based atrophy and SCLV-based lesion outcomes are feasible on clinically acquired T2-FLAIR scans in a multicenter fashion and are associated with DP over mid-term.

Variations in the levels of acute-phase proteins and lactoferrin in serum and milk during bovine subclinical mastitis.

Variations in the levels of acute phase proteins and lactoferrin in serum and milk for diagnosis of subclinical mastitis in dairy cows are described in this research paper. Milking animals from two organized dairy farms in Kerala, India, were screened by California Mastitis Test (CMT), Electrical Conductivity test (EC) and Somatic Cell Count (SCC) test to identify animals affected with sub clinical mastitis (SCM). The concentrations of acute phase proteins (APP) Haptoglobin (Hp), C- reactive protein (CRP), Albumin, Lactoferrin (Lf) and α- 1 acid glycoprotein (AGP) in milk and Hp, Albumin, Serum Amyloid A (SAA) and CRP in the serum of 40 normal cows and 40 cows affected with sub clinical mastitis were assessed. Solid phase ELISA was employed for assessment of all parameters except the albumin levels, for which spectrophotometry was used. The values of Hp in milk; and SAA, AGP and Lf in serum, were significantly elevated in the group with sub clinical mastitis. Such variations were found to be independent of the specific bacterial organism causing the disease. These results show that significant variations exist in the levels of acute phase proteins Hp, AGP and Lf in milk, and SAA in serum of animals affected with subclinical bovine mastitis that are not affected by specific bacterial etiology.

Quantifying disease pathology and predicting disease progression in multiple sclerosis with only clinical routine T2-FLAIR MRI.

BACKGROUND: Although quantitative measures from research-quality MRI provide a means to study multiple sclerosis (MS) pathology in vivo, these metrics are often unavailable in legacy clinical datasets. OBJECTIVE: To determine how well an automatically-generated quantitative snapshot of brain pathology, measured only on clinical routine T2-FLAIR MRI, can substitute for more conventional measures on research MRI in terms of capturing multi-factorial disease pathology and providing similar clinical relevance. METHODS: MRI with both research-quality sequences and conventional clinical T2-FLAIR was acquired for 172 MS patients at baseline, and neurologic disability was assessed at baseline and five-years later. Five measures (thalamus volume, lateral ventricle volume, medulla oblongata volume, lesion volume, and network efficiency) for quantifying disparate aspects of neuropathology from low-resolution T2-FLAIR were applied to predict standard research-quality MRI measures. They were compared in regard to association with future neurologic disability and disease progression over five years. RESULTS: The combination of the five T2-FLAIR measures explained most of the variance in standard research-quality MRI. T2-FLAIR measures were associated with neurologic disability and cognitive function five-years later (R2 = 0.279, p < 0.001; R2 = 0.382, p < 0.001), similar to standard research-quality MRI (R2 = 0.279, p < 0.001; R2 = 0.366, p < 0.001). They also similarly predicted disability progression over five years (%-correctly-classified = 69.8, p = 0.034), compared to standard research-quality MRI (%-correctly-classified = 72.4%, p = 0.022) in relapsing-remitting MS. CONCLUSION: A set of five T2-FLAIR-only measures can substitute for standard research-quality MRI, especially in relapsing-remitting MS. When only clinical T2-FLAIR is available, it can be used to obtain substantially more quantitative information about brain pathology and disability than is currently standard practice.