Exploring the evolutionary and pathogenic role of Acinetobacter baumannii biofilm-associated protein (Bap) through in silico structural modeling.

Acinetobacter species encode for extracellularly secreted Biofilm-associated protein (Bap), a multi-domain protein with variable molecular weights reaching several hundred kilodaltons. Bap is crucial for the development of multi-dimensional structures of mature biofilms. In our investigation, we analyzed 7338 sequences of A. baumannii from the NCBI database and found that Bap or Bap-like protein (BLP) was present in 6422 (87.52%) isolates. Further classification revealed that 12.12% carried Type-1 Bap, 68.44% had Type-2, 6.91% had Type-3, 0.05% had Type-6 or SDF-Type, and 12.51% lacked Bap or BLP. The majority of isolates with Type-1, Type-2, and Type-3 Bap belonged to ST1, ST2, and ST25, respectively. Phylogenetic analysis suggested that Type-1 Bap is the most ancient, while Type-3 and SDF-Type have evolved recently. Studying the interaction of predicted Bap structures with human CEACAM-1 and PIgR showed that Bap with its BIg13 and BIg6 domains interact with the N-terminal domain of CEACAM-1, involving Arg43 and Glu40, involved in CEACAM-1 dimerization. Also, we found that recently evolved Type-3 and SDF-Type Bap showed greater interaction with CEACAM-1 and PIgR. It can be asserted that the evolution of Bap has conferred enhanced virulence characteristics to A. baumannii with increased interaction with CEACAM-1 and PIgR. Using in silico approaches, this study explores the evolutionary, physicochemical, and structural features of A. baumannii Bap and unravels its crucial role in mediating interaction with human CEACAM-1 and PIgR through detailed structure modelling. These findings advance our understanding of A. baumannii Bap and highlight its role in pathogenesis.

Red cell abnormalities characterized by ektacytometry in children with cholestasis.

BACKGROUND: Spur-cell anemia sometimes accompanies cholestasis. We postulated that even in the absence of spur-cells, cholestasis might alter red blood cell (RBC) osmotic fragility and deformability. Therefore, we assessed these RBC measures by ektacytometry in pediatric patients. METHODS: We conducted a single center, prospective, cross-sectional investigation of RBC membrane characteristics by ektacytometry in pediatric patients with intra- and extrahepatic cholestasis followed at Cincinnati Children's Hospital Medical Center. We measured red cell membrane fragility and deformability in 17 patients with cholestasis and 17 age-matched controls without cholestasis. RESULTS: Patients with cholestasis had decreased RBC osmotic fragility compared to controls, with a significant left shift in Omin, indicating increased RBC surface-to-volume ratio. One showed spur cell morphology. However, the other 16 had no spurring, indicating that ektacytometry is a sensitive method to detect RBC membrane abnormalities. Left shift of Omin positively correlated with serum conjugated bilirubin levels and even more negatively with serum vitamin E concentration. CONCLUSIONS: This study suggests that subclinical red blood cell membrane abnormalities exist in most pediatric patients with cholestasis, increasing risk for hemolysis when subjected to oxidative stress. Hence minimizing pro-oxidants exposure and maximizing antioxidant exposure is advisable for this group. GOV IDENTIFIER: NCT05582447 https://clinicaltrials.gov/ct2/show/NCT05582447?cond=Cholestasis&cntry=US&state=US%3AOH&city=Cincinnati&draw=2&rank=2 . IMPACT: Spur cell anemia due to decreased red cell osmotic fragility and decreased deformability has been reported among patients with cholestasis. Ektacytometry is a reliable, reproducible method to measure red cell osmotic fragility and deformability. Few data describe red cell osmotic fragility or deformability in patients with cholestasis who may or may not have spur cell anemia. Ektacytometry shows that red cell osmotic fragility and deformability are decreased in many children with cholestasis even when spur cell anemia has not yet occurred. Factors associated with decreased osmotic fragility include elevated serum bilirubin, elevated serum bile acids, and decreased serum vitamin E.

Development and optimization of Clitoria teratea synthesized silver nanoparticles and its application to nanogel systems for wound healing.

OBJECTIVE: The present research deals with sequential optimization strategy based on Central Composite Design to optimize the process variables for efficient production of Clitoria teratea (CLT) synthesized silver nanoparticles (AgNPs) using biological synthesis. METHODS: Two substantial factors influencing the dependent variables viz UV-visible absorbance, particle size, zeta potential and polydispersity index (PDI) were identified as NaOH concentration, RH concentration, temperature as independent variables. In-vitro and ex-vivo studies of prepared CLT-AgNPs gel and marketed gel were carried out using dialysis membrane and egg membrane, respectively. In addition, antimicrobial study was also performed on the bacterial strains. RESULTS: The particles size (114 nm), PDI (0.45), and zeta potential (-29.5 mV) of optimized formulation were found, respectively. In-vitro profile of AgNPs from prepared CLT-AgNPs gel was noted (95.6%) in 8 h. It was found that the prepared CLT-AgNPs gel stimulates fibroblast and agranulocytosis development resulting better and timely wound healing. CONCLUSIONS: The prepared CLT-AgNPs gel can be as a potential substitute in the management and treatment of acute and chronic wounds.

Probing plasmon-induced surface reactions using two-dimensional correlation vibrational spectroscopy.

Surface plasmon resonance (SPR) has the ability to drive catalytic conversion of the reactant molecules via the production of hot electrons, which in general requires high activation energy. The reactions driven by these hot electrons are critical and essential in various heterogeneous surface catalytic reactions. However, there is a need to understand the dynamics of surface reactions and the underlying mechanism, which are influenced by several factors such as the constitution of the nanoparticle, exposure time, and reaction conditions to name a few. However, the effect of solvent in stabilizing the electron-hole pair, the orientation, and the surface coverage of the analyte are poorly understood due to the limitations of current methods. To get deeper insights into the reaction dynamics, we have demonstrated the combined utility of plasmon-enhanced Raman spectroscopy and Two-dimensional correlation spectroscopy (2DCOS) to study the plasmon-driven conversion of 4-nitrothiophenol on the surface of plasmonic nanoparticles. Interestingly, this combined technique provided us with previously unobservable results regarding surface catalysis by conventional spectroscopic analysis alone. Specifically, for the first time, 2DCOS provided critical insights in bridging the gap in our understanding of the interplay of solvent effect, orientation, and surface packing of the analyte molecules. It was observed that certain species like 4,4-dimercaptoazobenzene (DMAB) or 4-aminothiophenol (4-ATP) can be selectively formed based on the ordered or disordered phases of the analytes on the surface, thus paving the way to precisely control light-driven reactions through operando spectroscopy.

Exaggerated response to pattern reversal visual evoked potential among migraineurs.

OBJECTIVE: Visual evoked potential recording has reported ambiguous results among migraineurs, thus the present study explored the association of check-size and reversal rates on the latency and amplitude of pattern reversal VEP among migraineurs. METHOD AND MATERIAL: Monocular VEP responses for both eyes were recorded in 133 migraineurs and 111 controls. Checkerboard pattern with phase reversal frequency of 0.5, 1, 2 and 4 Hz and check-size of 16 × 16, 32 × 32, 64 × 64 and 128 × 128, i.e. spatial frequency of 0.475, 1.029, 2.056 and 4.112 cycle per degree (cpd) were used to record 100 responses each. Three-minutes gap was given after change of reversal frequency to a higher rate for next cycle of 4 check-size records. RESULT: A linear increase in latencies was observed with decreasing check-size in both groups, but migraineurs had significantly higher latencies at a given reversal rate. Amplitudes A1 and A2 were higher among migraineurs and amplitude A2 showed an inverted 'U' shaped trend with maximum amplitude at 32 × 32 check size (1.029 cpd) in both groups, with an exaggerated response among migraineurs. Check-size 32 × 32 i.e. spatial frequency of 1.029 behaves differently than other larger or smaller check-sizes. CONCLUSION: Variable VEP response for different visual stimuli may be due to differential activation of respective retinocortical pathways and cortical areas. The highest amplitude at modest check-size suggests a contributory role of foveal-parafoveal fibres in migraineurs. Exaggerated physiological response to visual stimuli may be responsible for higher amplitudes and prolonged latencies among migraineurs.

Exaggerated physiological VEP response as higher amplitudes and prolonged latencies, among migraineurs may be due to differential activation of respective retinocortical pathways and cortical areas.

Identification of plastic rice in adulterated raw and cooked rice.

In the present study, attempts have been made to identify the presence of plastic rice in adulterated raw and cooked rice by comparing the compositional and morphological properties of fake rice and real rice using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) techniques. Various rice samples from the national capital region of India were studied for their compositional and morphological properties. The surface morphology of real rice and plastic rice was analyzed using scanning electron microscopy. Results suggest that plastic rice used as an adulterant in raw or cooked rice is made up of polystyrene, which is a well-known toxic chemical entity. The studies suggest that these techniques can be used as a scientific tool to detect and identify the presence of plastic rice in adulterated raw and cooked rice.

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

BACKGROUND AND AIMS: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

Sarcopenia is highly prevalent in children with autoimmune liver diseases and is linked to visceral fat and parent-perceived general health.

BACKGROUND: Patients with autoimmune hepatitis (AIH) and primary or autoimmune sclerosing cholangitis are at nutritional risk; their body composition and has not been extensively studied. We aimed to describe their body composition and identify clinical links. METHODS: Using magnetic resonance imaging (MRI), two reviewers segmented total psoas muscle area (tPMSA), visceral fat area (VFA) and subcutaneous fat area (mm2 ) and measured visceral and subcutaneous thickness (mm). Clinical, laboratory and quality of life (QoL; using PedsQL) data were collected. Sarcopenia was defined as tPMSA ≤5th percentile. Analysis of variance, Wilcoxon rank test and multivariable modelling were performed. A paediatric cohort with non-alcoholic fatty liver disease (NAFLD) was used as a comparator following propensity score matching. RESULTS: Fifty-eight patients with autoimmune liver disease (AILD) (33 [57%] with AIH) were included: median age 16 years (interquartile range [IQR]: 13-18), 33 (57%) male. Median time from diagnosis to MRI was 15 months (IQR: 2-39 months). Two patients (3%) had a BMIz indicative of mild malnutrition. tPMSA was measurable in 52 subjects (90%). Of those, 25 (48%) had sarcopenia. Sarcopenic patients had a lower blood urea nitrogen compared to non-sarcopenic (median [IQR]: 9.5 [8.0, 12.0] vs 11 [10, 14] mg/dL; P = .023). There was no difference in corticosteroid use between groups. The VFA of sarcopenic patients was higher (3156 [2064, 7492]) vs 2084 [688, 3092]) mm2 ; P = .005). Patient-reported QoL negatively associated with VFA and general health negatively associated with VFA. Compared with NAFLD, the odds ratio for sarcopenia with AILD was 14.5 (95% confidence interval: 2.3-90.7). CONCLUSION: In autoimmune liver diseases, sarcopenia is highly prevalent, associated with increased visceral fat and QoL.

Associations Between Quantitative MRI Metrics and Clinical Risk Scores in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. The Mayo risk score and SCOPE (Sclerosing Cholangitis Outcomes in Pediatrics) index are clinical risk scores for monitoring the progression of primary sclerosing cholangitis (PSC) and predicting clinically important endpoints. OBJECTIVE. The purpose of this study was to evaluate relationships between quantitative MRI measures of liver disease and clinical risk scores in children and young adults with autoimmune liver disease (AILD). METHODS. This prospective study included 58 patients (35 male and 23 female patients; mean age, 15.1 ± 1.1 [SD] years [range, 6-24 years]) with AILD (16 with PSC, 30 with autoimmune hepatitis, and 12 with autoimmune sclerosing cholangitis) who underwent research liver MRI examinations including MR elastography, T2*-corrected T1 (cT1), and quantitative MRCP measurements. Associations between quantitative MRI metrics and clinical risk scores were evaluated using Spearman rank-order correlation coefficients and multivariable regression analyses. RESULTS. The mean Mayo risk score was -1.1 ± 0.9 (SD) (range, -2.9 to 1.1); the mean SCOPE index was 2.7 ± 2.2 (range, 0-9). Mean liver stiffness was 2.8 ± 1.1 kPa, whole-liver mean cT1 was 874.7 ± 77.7 ms, and whole-liver cT1 interquartile range (IQR) was 150.8 ± 55.6 ms. The Mayo risk score was significantly correlated with liver stiffness (ρ = 0.56; p < .001), whole-liver mean cT1 (ρ = 0.31; p = .02), whole-liver cT1 IQR (ρ = 0.58; p < .001), and multiple quantitative MRCP measures (ρ = 0.36-0.45, p < .001). SCOPE index was significantly correlated with liver stiffness (ρ = 0.68; p < .001), whole-liver cT1 IQR (ρ = 0.51; p < .001), and multiple quantitative MRCP measures (ρ = 0.47-0.49; p < .001). Multivariable linear regression analyses identified liver stiffness, whole-liver cT1 IQR, and left hepatic duct maximum diameter as significant independent predictors of the Mayo risk score (adjusted R2 = 0.45), and liver stiffness, whole-liver cT1 IQR, maximum common bile duct (CBD) diameter, and median CBD diameter as significant independent predictors of the SCOPE index (adjusted R2 = 0.69). On logistic regression analysis, greater than low risk by SCOPE index was best predicted by liver stiffness [odds ratio [OR] = 49.6; 95% CI, 3.1-793.6) and maximum CBD diameter (OR = 2.5; 95% CI, 1.3-4.7). CONCLUSION. Increased liver stiffness, increased cT1 IQR, and larger bile duct diameters are independently associated with higher (worse) Mayo risk score and SCOPE index among children and young adults with AILD and may be surrogate markers of clinically meaningful endpoints. CLINICAL IMPACT. Multiparametric MRI of the liver incorporating quantitative metrics may serve as a noninvasive diagnostic and prognostic tool in pediatric AILD. TRIAL REGISTRATION. ClinicalTrials.gov: NCT03175471.

Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani.

In the absence of adequate diagnosis and treatment, leishmaniasis remains a major public health concern on a global scale. Drug resistance remains a key obstacle in controlling and eliminating visceral leishmaniasis. The therapeutic gap due to lack of target-specific medicine and vaccine can be minimized by obtaining parasite's genomic information. This study compared whole-genome sequence of paromomycin-resistant parasite (K133PMM) developed through in vitro adaptation and selection with sensitive Leishmania clinical isolate (K133WT). We found a large number of upstream and intergenic gene variations in K133PMM. There were 259 single nucleotide polymorphisms (SNPs), 187 insertion-deletion (InDels), and 546 copy number variations (CNVs) identified. Most of the genomic variations were found in the gene's upstream and non-coding regions. Ploidy estimation revealed chromosome 5 in tetrasomy and 6, 9, and 12 in trisomy, uniquely in K133PMM. These contain the genes for protein degradation, parasite motility, autophagy, cell cycle maintenance, and drug efflux membrane transporters. Furthermore, we also observed reduction in ploidy of chromosomes 15, 20, and 23, in the resistant parasite containing mostly the genes for hypothetical proteins and membrane transporters. We chronicled correlated genomic conversion and aneuploidy in parasites and hypothesize that this led to rapid evolutionary changes in response to drug induced pressure, which causes them to become resistant.

Exploratory study to understand association of emotional comorbidities and sleep with migraine.

BACKGROUND: Migraine is often associated with psychiatric and emotional co-morbidities. Several studies have shown association of sleep problems and/or emotional co-morbidities among migraineurs. However, less is known about the association of migraine disability with sleep and emotional co-morbidities. OBJECTIVE: To explore the association of emotional co-morbidities and sleep quality with migraine disability among migraineurs in the central part of India. METHODS AND MATERIAL: A cross-sectional study enrolling 132 patients of migraine was conducted at a tertiary care centre. They were evaluated for migraine disability by Migraine Disability Assessment Test (MIDAS), emotional co-morbidities by depression, anxiety, stress scale (DASS-21) and sleep quality by Pittsburgh Sleep Quality Index (PSQI). RESULT: Mean age of participants was 32.9 ± 9.8 and 83.3% (n = 110) were females. Fourty seven percentage(n = 62) patients reported moderate to severe disability on MIDAS. Anxiety was most frequent (n = 87; 65.9%) emotional co-morbidity followed by depression (n = 70;53%) and stress (n = 52;39.4%). Severity of emotional co-morbidities increased while sleep quality deteriorated with increasing migraine disability. However, migraine frequency had positive correlation only with sleep quality. Stress showed a linear relationship with migraine disability at highest second-third decile of MIDAS. CONCLUSION: Migraineurs in central India have higher emotional co-morbidities. These co-morbidities increased and sleep quality deteriorated with increasing migraine disability. Frequency of migraine has no association with emotional co-morbidities. Linear association of stress at higher migraine disability prompts possible role of stress management to break the complex relationship between stress and migraine.

Isolation and characterization of a novel flavanone glycoside from an endemic plant Haplanthodes neilgherryensis.

The chemical characterization study of an endemic plant, Haplanthodes neilgherryensisis (Wight) R.B. Majumdar from Western Ghats of India, resulted in to the isolation of a new flavanone glycoside, 5-hydroxy-7-methoxy-8-O-ß-D-glucopyranosyl-2S-flavanone (1), along with 3 known flavonoids, 7-O-methyl dihydrowogonin (2), 7-O-methyl wogonin (3), andrographidine C (4). The structure of 1 was elucidated by using 1 D and 2 D NMR and HRMS experimental data, while for the known compounds, 1H NMR and mass spectrometry data were compared with the reported literature. Compound 1 was tested in vitro to check the improvement in uptake of glucose by the L6 rat skeletal muscle tissues and the observed EC50 value was 5.8 µM, while rosiglitazone showed EC50 of 2.7 µM.

Pharmacokinetic Study of Withanosides and Withanolides from Withania somnifera Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS).

Withania somnifera is a traditional Indian herb described under the 'Rasayana' class in Ayurveda, which gained immense popularity as a dietary supplement in the USA, Europe, Asia, and the Indian domestic market. Despite enormous research on the pharmacological effect of withanosides and withanolides, bioanalytical method development and pharmacokinetics remained challenging and unexplored for these constituents due to isomeric and isobaric characteristics. In current research work, molecular descriptors, pharmacokinetic, and toxicity prediction (ADMET) of these constituents were performed using Molinspiration and admetSAR tools. A rapid, selective, and reproducible bioanalytical method was developed and validated for seven withanosides and withanolides as per USFDA/EMA guidelines, further applied to determine pharmacokinetic parameters of Withania somnifera root extract (WSE) constituents in male Sprague Dawley rats at a dose of 500 mg/kg. Additionally, an ex vivo permeability study was carried out to explore the absorption pattern of withanosides and withanolides from the intestinal lumen. In silico, ADMET revealed oral bioavailability of withanosides and withanolides following Lipinski's rules of five with significant absorption from the gastrointestinal tract and the ability to cross the blood-brain barrier. Upon oral administration of WSE, Cmax was found to be 13.833 ± 3.727, 124.415 ± 64.932, 57.536 ± 7.523, and 7.283 ± 3.341 ng/mL for withanoside IV, withaferin A, 12-Deoxy-withastramonolide, and withanolide A, respectively, with Tmax of 0.750 ± 0.000, 0.250 ± 0.000, 0.291 ± 0.102, and 0.333 ± 0.129 h. Moreover, at a given dose, withanoside V, withanolide B, and withanone were detected in plasma; however, the concentration of these constituents was found below LLOQ. Thus, these four major withanoside and withanolides were quantified in plasma supported by ex vivo permeation data exhibiting a time-dependent absorption of withanosides and withanolides across the intestinal barrier. These composite findings provide insights to design a clinical trial of WSE as a potent nutraceutical.

Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis.

Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC).1-3 We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.

Utility of Blood as the Clinical Specimen for the Molecular Diagnosis of Post-Kala-Azar Dermal Leishmaniasis.

The countries in the Indian subcontinent have reported a dramatic decline in visceral leishmaniasis (VL) cases. However, the presence of the parasite reservoir in the form of post-kala-azar dermal leishmaniasis (PKDL), a dermal sequel of VL, is a hurdle in attaining VL elimination. Presently employed clinical specimens for the diagnosis of PKDL include skin biopsy specimens and slit skin smears. In this study, the use of blood as a clinical specimen was investigated in different manifestations of PKDL in India. This is a bicentric study (National Institute of Pathology, Indian Council of Medical Research [ICMR], New Delhi, and Institute of Medical Sciences [IMS], Banaras Hindu University, Varanasi), with 215 participants (120 PKDL patients and 95 controls). Highly sensitive quantitative real-time PCR (Q-PCR) and field-deployable loop-mediated isothermal amplification (LAMP) were employed using blood samples for diagnosis. Promising sensitivities of 77.50% (95% confidence interval [CI], 69.24 to 84.05%) for Q-PCR and 70.83% (95% CI, 62.16 to 78.22%) for LAMP were obtained for the diagnosis of PKDL. Further, enhanced sensitivities of 83.33% (95% CI, 71.28 to 90.98%) and 77.78% (95% CI, 65.06 to 86.80%) for Q-PCR and LAMP, respectively, were recorded for the detection of macular cases. The study revealed an inverse correlation between the parasite load estimated in slit and blood samples, thereby favoring the use of blood for the diagnosis of the macular variant, which may be missed due to scant parasite loads in the slit. This study is the first to propose the promising potential of blood as a clinical specimen for accurate diagnosis of PKDL, which would aid in fast-tracking VL elimination.

A panoramic view on phytochemical, nutritional, and therapeutic attributes of Ziziphus mauritiana Lam.: A comprehensive review.

Ziziphus mauritiana (Rhamnaceae), commonly known as Indian jujube, is a pharmacologically diverse medicinal plant. A plethora of active phytochemical constituents of this plant has been revealed so far, namely, berberine, quercetin, kaempferol, sitosterol, stigmasterol, lanosterol, diosgenin, and so forth. Several studies demonstrated the exploration of pharmacological potential of various parts such as fruits, leaves, and stems of the plant as antioxidant, cytotoxic, antimicrobial, anti-diarrhoeal, antidepressant, immunomodulator, and hepatoprotective. This review gives a unique summary including phytochemistry, nutritional value, and significant pharmacological importance of Z. mauritiana. The literature search was carried out via search engine PubMed, Science Direct, and so on. The data were heterogeneous in terms of leaves, stem, roots, and fruits which were used for different experimental findings, which made the comparison a lengthy task. Study findings suggested that the extracts from this plant may possess numerous types of pharmacological activities. As the search for novel drugs from botanical sources continues, there is need for future investigations to isolate and characterize pharmacologically active agents that confer medicinal properties on Z. mauritiana, as well as to elucidate the structures of these agents by which they exert their healing properties and to scientifically validate the existing traditional practices concerning its health benefits.

Assessing the Efficacy and Safety of Liposomal Amphotericin B and Miltefosine in Combination for Treatment of Post Kala-Azar Dermal Leishmaniasis.

BACKGROUND: No satisfactory canonical treatment is available for post-kala-azar dermal leishmaniasis (PKDL), clinical sequela of visceral leishmaniasis. Confined treatment options and substantial increase in relapse rate after miltefosine (MIL) treatment warrant the need to adapt resilient combination therapies. In this study, we assessed the safety and efficacy of combination therapy using liposomal amphotericin B (LAmB) and MIL for treating PKDL. METHODS: Thirty-two PKDL patients, confirmed by microscopy or quantitative polymerase chain reaction (qPCR), were included in the study. An equal number of cases (n = 16) were put on MIL monotherapy (100 mg/day for 90 days) or MIL and LAmB combination for 45 days (3 injections of LAmB, 5 mg/kg body weight, and 100 mg/day MIL). Parasite load in slit aspirate was monitored using qPCR. RESULTS: Patients treated with combination therapy demonstrated a rapid decline in parasite load and achieved 100% cure, with no reports of relapse. Those treated with MIL monotherapy attained clinical cure with a gradual decrease in parasite load; however, 25% relapsed within 18 months of follow-up. CONCLUSIONS: Liposomal amphotericin B and MIL combination for treating PKDL is efficacious and safe, with high tolerability. Furthermore, this study established the utility of minimally invasive slit aspirate method for monitoring of parasite load and assessment of cure in PKDL.

Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis: Data From the Pediatric Primary Sclerosing Cholangitis Consortium.

OBJECTIVES: Most patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The liver and colon express MAdCAM-1, a target of lymphocyte homing integrins. Vedolizumab (VDZ) is an α4ß7 integrin antibody used to treat IBD. We investigated liver outcomes in children with PSC-IBD treated with VDZ. METHODS: Patients were identified within the Pediatric PSC Consortium, a multicenter research registry. Retrospective demographic, phenotypic, biochemical, radiological, histopathologic and IBD data for up to 1 year of VDZ therapy were collected. Liver biochemical and IBD responses were defined as: a 75% or greater reduction in initial γ-glutamyltransferase (GGT), or a GGT that fell to <50 IU/L and improved Mayo endoscopy grade or IBD activity scores after 9 to 12 months. RESULTS: Thirty-seven patients were identified from 19 centers. VDZ was initiated at median age of 16 years [IQR 15-18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response after 9 to 12 months. For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response. Final GGT after 9 to 12 months was 51 [IQR 28-71] in IBD patients in remission versus 127 [IQR 63-226] in those with active IBD, (P = 0.066). CONCLUSIONS: Liver biochemistry worsened over time in IBD unresponsive to VDZ but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically refractory IBD.

Comparison of liver T1 relaxation times without and with iron correction in pediatric autoimmune liver disease.

BACKGROUND: Magnetic resonance imaging (MRI) T1 relaxometry (mapping) has been reported as a quantitative biomarker of liver injury due to inflammation and fibrosis. OBJECTIVE: To assess the relationship between liver MRI T1 relaxometry measurements obtained using a modified Look-Locker inversion recovery (MOLLI) pulse sequence without and with iron (T2*) correction (cT1) in pediatric autoimmune liver disease. MATERIALS AND METHODS: This cross-sectional study was institutional review board-approved, with informed consent obtained. MRI was acquired at 1.5 T in patients participating in an autoimmune liver disease registry. T1 relaxometry was performed using a MOLLI sequence with a 5(3)3-s acquisition strategy. A multi-echo gradient echo sequence was used to measure liver T2*. Non-iron-corrected native T1 (ms), calculated as the mean of four slices through the mid-liver, was measured using T1 parametric maps generated off-line. A proprietary T2* correction (Perspectum Diagnostics, Oxford, UK), blinded to native T1 values, calculated cT1 values. The relationship between native T1 and cT1 measurements was assessed using Spearman rank correlation and Bland-Altman analyses. RESULTS: Forty-eight patients with a mean (standard deviation [SD]) age of 15.2 (4.1) years were included. Mean (SD) liver native T1 was 651.2 (123.9) ms and mean (SD) cT1 was 919.5 (86.8) ms, with excellent positive correlation between values (r=0.91 [95% confidence interval (CI): 0.85-0.95]; P<0.0001). Mean bias between native T1 and cT1 measurements was 268.3 ms (95% limits of agreement: 131.9-404.7 ms). CONCLUSION: There is excellent positive correlation between liver native T1 and cT1 measurements in pediatric patients with autoimmune liver disease. This relationship brings into question the need to perform T1 iron correction in this patient population. T1 and cT1 measurements are not interchangeable, however, due to considerable systematic bias with cT1 values being considerably higher.