Biomechanical Analysis of Age-Dependent Changes in Fontan Power Loss.

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits.

Impact of Age-related change in Caval Flow Ratio on Hepatic Flow Distribution in Fontan.

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac (EC) conduit or a lateral tunnel (LT) connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. Objective: The effect of age-related changes in caval inflows on HFD was evaluated using cardiac MRI (CMR) data and patient-specific computational fluid dynamics (CFD) modeling. Methods: SVC and IVC flow from 414 Fontan patients were collected to establish a relationship between SVC:IVC flow ratio and age. CFD modeling was performed in 60 (30 EC and 30 LT) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. Results: SVC:IVC flow ratio inverted at ∼8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC = 2,1, and 0.5 corresponded to ages 3, 8, and 15+ respectively) was not significant for EC but statistically significant for LT cohorts. For all three caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2→0.5 (age 3→15+), the correlation's strength decreased from 0.87→0.64, due to potential flow perturbation as IVC flow momentum increased. Conclusion: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of including SVC:IVC variations over time to understand Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes. Clinical Perspective: With improvement in standard of care and management of single ventricle patients with Fontan physiology, the population of adults with Fontan circulation is increasing. Consequently, there is a clinical need to comprehend the impact of patient growth on Fontan hemodynamics. Using CMR data, we were able to quantify the relationship between changing caval inflows and somatic growth. We then used patient-specific computational flow modeling to quantify how this relationship affected the distribution of long-term hepatic flow in extracardiac and lateral tunnel Fontan types. Our findings demonstrated the significance of including SVC:IVC changes over time in CFD modeling to learn more about the long-term hemodynamics of Fontan. Fontan surgical approaches are increasingly planned and optimized using computational flow modeling. For a patient undergoing a Fontan procedure, the workflow presented in this study that takes into account the variations in Caval inflows over time can aid in predicting the long-term hemodynamics in a planned Fontan pathway.

Evaluation of Bond Durability, Surface Morphology, and Remineralization at the Adhesive Interface with Dentin Bonding Agents Modified with Silica-doped Nanohydroxyapatite.

Objectives: To compare and evaluate the bond durability, surface morphology, and remineralization of the adhesive layer with newer adhesive systems modified with novel bioactive nanoparticles. Methodology: Bonding agents evaluated in this study include (a) Conventional dentin bonding agent (CN-DBA) (b) Nanohydroxyapatite (nanoHAP) incorporated dentin bonding agent (NH DBA); (c) Silica doped nanohydroxyapatite (Si nanoHAP) incorporated dentin bonding agent (Si NH DBA). A total of 104 human dentin discs (5 mm × 5 mm × 2 mm) were sectioned. Elemental analysis (Ca/P ratio) and surface morphology of the adhesive layer with different dentin adhesives were evaluated under scanning electron microscopy with energy-dispersive X-ray analysis after speculated storage time of 1 day and 6 months. Microshear bond strength of adhesive restorations with different dentin adhesives was evaluated under universal testing machine and fractographic analysis under scanning electron microscope after speculated storage time of 1 day and 6 months. The results were analyzed using analysis of variance and post hoc analysis. Results: Si-NH-DBA showed highest mean microshear bond strength for both 1 day and 6 months, which was significantly higher compared to conventional nanofilled dentin bonding agent (CN-DBA) and NH-DBA. Si-NH-DBA group showed only 10% reduction in bond strength after 6 months, which was less compared to that of other groups. Similarly, Si-NH-DBA showed higher remineralization with stellate-shaped crystals at the adhesive layer after 6 months with hydrolytic resistant hybrid layer, compared to CN-DBA and NH-DBA. Conclusion: Silica-doped nanohydroxyapatite proved its efficiency on bond stability, remineralization, and hydrolytic resistance when incorporated into dentin bonding agents because of its bioactivity and carbonate-containing apatite-forming ability.

To Compare the Accuracy of 0.022 Inch Slot of Stainless Steel and Ceramic Orthodontic Brackets Marketed by Different Manufacturers.

AIM OF THE STUDY: The aim of the present study was to analyze the accuracy of 0.022 inch slot of stainless steel and ceramic orthodontic brackets marketed by different manufacturers. MATERIALS AND METHODS: An in vitro study was done on upper left central incisor bracket of MBT 0.022 slot of American orthodontics (AO), 3M Unitek, Ormco with each 20 of stainless steel and ceramic brackets divided into six groups, and the total sample was 120. The brackets were scanned with stereo microscope of Magnus Company and Image Pro plus analysis software was used to evaluate the mesial face and base, distal face and base. RESULTS: Comparison in between the groups of stainless steel showed that 3M Unitek brackets showed higher slot widths as compared to AO and Ormco which was statistically significant (P < 0.05). Comparison in between the groups of ceramic brackets of AO brackets showed higher slot widths as compared to Ormco and 3M Unitek ceramic brackets which was statistically significant (P < 0.05). CONCLUSION: By this study, there was a difference between stated values and measured values of brackets displaying inaccuracies in dimension. A clear impreciseness about the appliance could be needed during the finishing and detailing stage to avoid loss of torque control due to slot oversize and the divergence of slot walls.

Retrospective analysis of EMR database to assess the effectiveness of Saccharomyces boulardii CNCM I-745 in children with acute diarrhoea during routine clinical practice.

This study aimed to assess the efficacy of Saccharomyces boulardii, a yeast probiotic, in the management of acute diarrhoeal disorders in the paediatric population in outpatient settings. It was a multicentre retrospective analysis of medical records of children who were treated for acute diarrhoea by routine treatment (oral rehydration solution and zinc) with or without S. boulardii. Overall, 160 children presenting with acute diarrhoea at seven different outpatient paediatric settings were included in the study. Children were divided into two categories based on their treatment with S. boulardii (SB group) or without S. boulardii (Non-SB group). Baseline demographic, anthropometric and clinical variables were compared between the two groups. The median duration of diarrhoea post-treatment was significantly shorter in the S. boulardii group (3 days) than in the non-SB group (4 days). A significant reduction in the frequency of stools was observed post-treatment in the S. boulardii group (1.7 versus 2.5 in the non-SB group). There was a significant weight gain in the S. boulardii group post-treatment (300 g) in comparison with the non-SB group (mean loss of 400 g). This study established the positive role of S. boulardii in the management of acute diarrhoeal diseases in children. Moreover, the S. boulardii probiotic was seen to be effective in diarrhoeal diseases in children with dehydration.

Hyaluronic acid coating of gold nanoparticles for intraocular drug delivery: Evaluation of the surface properties and effect on their distribution.

Due to the unique anatomical structure of the eye, ocular drug delivery is a promising delivery route for the treatment of several ocular diseases, such as the ocular neovascularization that contributes to diabetic retinopathy. This disease is triggered by inflammation, retinal ischemia, and/or deposits of advanced-glycation end-products (AGEs), as well as increased levels of vascular endothelial growth factor (VEGF), interleukins, or reactive oxygen species (ROS). Gold has unique antioxidant and antiangiogenic properties and can inhibit angiogenic molecules. Furthermore, gold nanoparticles (GNPs) are not only biocompatible, they are easy to synthesize, they absorb and scatter visible light, and they can be made with precise control over size and shape. GNPs are an excellent candidate for ocular drug delivery because they can be conjugated to an extraordinarily diverse array of different biomolecules, and surface functionalization can improve the mobility of GNPs across the physiological barriers of the eye, such as the vitreous humour or the inner limiting membrane. For this purpose, we employed low molecular weight hyaluronan (HA) to increase the mobility of the nanoparticles as well as target them to HA receptors that are expressed in different cells of the eye. In this study, the combination of gold and HA enhanced the stability of the whole carrier and promoted their distribution across ocular tissues and barriers to reach the retina. Moreover, analysis in vitro, ex vivo, and in ovo revealed the protective and antiangiogenic effect of GNPs as inhibitors of AGEs-mediated- retinal pigment epithelial cell death and neovascularization. We demonstrated that conjugation with HA enhances GNP stability and distribution due to a specific CD44 receptor interaction. The capacity of HA-GNPs to distribute through the vitreous humour and their avidity for the deeper retinal layers ex vivo, suggest that HA-GNPs are a promising delivery system for the treatment of ocular neovascularization and related disorders.

Acarbose improves glycemic control and reduces body weight: Subanalysis data of South Asia region.

Alpha-glucosidase inhibitors (AGIs) are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycaemia. However, data from South Asia region is very limited. In order to examine the effect of AGI in real-life setting, 10 PMS/NIS from all over the world from the launch of acarbose to date were pooled in one database and exploratory analysis was performed for glycemic parameters and weight. In total 62,905 patients were pooled from 21 countries and regions. Mean follow up (± SD) was 12.2 ± 4.8 weeks (range 0.1-108.9). From South Asia region (India and Pakistan), 8,738 Asian patients were enrolled. Mean PPG decreased from 240.0 and 261.1 mg/dl at baseline by 70.26 ± 65.10 and 82.96 ± 56.59 mg/dl at the last visit in total and South Asian populations, respectively (n = 53,883; n = 7,991, P < 0.0001 for both). Mean FPG decreased from 171.6 and 176.5 mg/dl at baseline by 38.48 ± 47.83 and 49.59 ± 41.41 mg/dl at the last visit in total and South Asian populations, respectively (n = 56,672; n = 7,837, P < 0.0001 for both). Mean HbA1c decreased from 8.4 and 8.4% at baseline by 1.11 ± 1.31% and 0.91 ± 0.93% at the last visit in total and South Asian populations, respectively (n = 38,843; n = 2,343, P < 0.0001 for both). Mean relative reduction of body weight (BW) was 1.40 ± 3.28% and 1.10 ± 3.39% at the last visit for mean baseline BW 73.6 and 74.2 kg in total and South Asian populations, respectively (n = 54,760; n = 7,718, P < 0.0001 for both). Consistent with RCT meta-analyses, post-hoc analysis of real-life data showed acarbose treatment improved glycaemic control and reduced the BW. Acarbose treatment in real life setting showed significant reductions in all glycemic parameters and BW in Asian patients from South Asia region.

Alpha-glucosidase inhibitor, acarbose, improves glycamic control and reduces body weight in type 2 diabetes: Findings on indian patients from the pooled data analysis.

Alpha-glucosidase inhibitors are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycemia (PPG). The higher carbohydrate in the Indian diets lead to greater prandial glycemic excursion, increased glucosidase, and incretin activity in the gut and may need special therapeutic strategies to tackle these glucose peaks. This is the subgroup analysis of Indian subjects who participated in the GlucoVIP study that investigated the effectiveness and tolerability of acarbose as add-on or monotherapy in a range of patients with type 2 diabetes mellitus. A total of 1996 Indian patients were included in the effectiveness analysis. After 12.5 weeks (mean), the mean change in 2-hour PPG from baseline was -74.4 mg/dl, mean HbA1c decreased by -1.0%, and mean fasting blood glucose decreased by -37.9 mg/dl. The efficacy of acarbose was rated "very good" or "good" in 91.1% of patients, and tolerability as "very good" or "good" in 88.0% of patients. The results of this observational study suggest that acarbose was effective and well tolerated in the Indian patients with T2DM.

Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab.

PURPOSE: The aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab. METHODS: The method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab. RESULTS: Three eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes. CONCLUSION: Intravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD.

Study of lead exposure to children residing near a lead-zinc mine.

This lead exposure study was conducted in a total of 452 school children in the age group of 9-14 years. Two hundred and ninety-eight exposed children came from the villages situated within a 2.5 km radius of the lead-zinc mine whereas the comparative group children were selected from the villages at least 10 km away from mine. Environmental monitoring study suggested that lead levels in air and water samples near the mining areas were within the Central Pollution Control Board prescribed standards. Lead levels in about 80% of the children were less than 10 µg/dl. Medical examination of all children did not show any signs related to lead toxicity but central nervous system-related symptoms, as reported by the subjects during medical examination, were found to be higher in the exposed group when compared with the comparative group. The values of physical growth parameters of the exposed group were comparable with that of the comparative group for both girls and boys. Hence, the physical growth of children was found to be unaffected by the observed level of lead exposure. To safeguard the health of the children residing near the mining area, various preventive and control measures were suggested.

Ultrasound-guided bilateral superior laryngeal nerve block to aid awake endotracheal intubation in a patient with cervical spine disease for emergency surgery.

Ultrasound has been widely used to locate nerves for various nerve blocks. The potential advantages of using ultrasound imaging for nerve blocks include reduction in the amount of local anaesthetic required, improved success rate, reduced time to perform the block and reduced complication rate. We describe the successful performance of ultrasound-guided bilateral superior laryngeal nerve block to facilitate awake fibreoptic intubation in a patient presenting for emergency surgery on the cervical spine.

Two unusual cases of histoplasmosis in human immunodeficiency virus-infected individuals.

Histoplasmosis, also called as Darling's disease, is caused by the dimorphic fungus, Histoplasma capsulatum. In India, several cases of histoplasmosis have been reported since 1954, but in only a few cases could the diagnosis be confirmed by fungal culture. Disseminated histoplasmosis in adults is often associated with immunosuppression, as in human immunodeficiency virus (HIV) infection. Oral lesions are seen in 30-50% of the patients. Here, we are reporting two histoplasmosis cases, one with disseminated histoplasmosis with extensive skin and oral lesions in a known HIV-positive patient and the second case presenting with ulcer of the tongue, found to be HIV positive on investigation. It is important to consider histoplasmosis as one of the differential diagnosis of oral lesions in HIV-infected individuals.

FDC of montelukast with levocetirizine: focus on bilayer technology.

Allergic rhinitis is the most common allergic disease worldwide and affects about 18% to 40% of the general population. Anti-allergic medicines (eg, some antihistamines) can cause adverse events such as somnolence and can have an additional negative impact on quality of life. Combining montelukast with levocetirizine gives additional benefits in comparison with either drug alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis. Montelukast sodium is alkaline, stable and levocetirizine dihydrochloride is acid stable, when we prepare a matrix tablet, both the drugs would be in contact and make it unstable during the shelf life of the formulation. Hence it is recommended to prepare bilayer tablet, as it improves and increases the stability of both the drugs in combination. Bilayer tablet of montelukast with levocetirizine is more stable with respect to stability studies, in comparison to matrix tablet.

Simulation of normal, carrier and affected controls for large-scale genotyping of cattle for factor XI deficiency.

An insertion mutation within exon 12 of the factor XI gene has been described in Holstein cattle. This has opened the prospect for large-scale screening of cattle using the polymerase chain reaction (PCR) technique for the rapid identification of heterozygous animals. To facilitate such a screening process, the mutant and normal alleles of factor XI gene, represented by 244- and 320-bp PCR amplified fragments, were individually cloned in Escherichia coli using a multicopy plasmid cloning vehicle to generate pFXI-N and pFXI-M, respectively. The authenticity of the inserts was confirmed by nucleotide sequencing. A nested PCR method was developed, by which PCR amplicons generated from primers with annealing sites on the recombinant plasmids and by flanking the insert were used as templates for amplification of the diagnostic products using factor XI gene-specific primers. An equimolar mixture of both PCR amplicons, originating from pFXI-N and pFXI-M, constituted the carrier control while the individual amplicons were the affected and normal controls. The controls were used as references for in-gel comparison to screen a population of 307 cattle and 259 water buffaloes; the frequency of the mutant allele was found to be 0. No DNA size standards were required in this study. The simulated control DNA samples representing normal, carrier and affected cattle have the potential to help in large-scale screening of a cattle population for individuals that are carriers or affected by factor XI deficiency.