Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era.

The recent success of gene therapy during the COVID-19 pandemic has underscored the importance of effective and safe delivery systems. Complementing lipid-based delivery systems, polymers present a promising alternative for gene delivery. Significant advances have been made in the recent past, with multiple clinical trials progressing beyond phase I and several companies actively working on polymeric delivery systems which provides assurance that polymeric carriers can soon achieve clinical translation. The massive advantage of structural tunability and vast chemical space of polymers is being actively leveraged to mitigate shortcomings of traditional polycationic polymers and improve the translatability of delivery systems. Tailored polymeric approaches for diverse nucleic acids and for specific subcellular targets are now being designed to improve therapeutic efficacy. This review describes the recent advances in polymer design for improved gene delivery by polyplexes and covalent polymer-nucleic acid conjugates. The review also offers a brief note on novel computational techniques for improved polymer design. The review concludes with an overview of the current state of polymeric gene therapies in the clinic as well as future directions on their translation to the clinic.

Novel Bioactive Magnesium-Hopeite composite by friction stir processing for orthopedic implant applications.

Magnesium (Mg) shows excellent potential for orthopedic implant applications owing to its equivalent mechanical properties compared to cortical bone and its biocompatibility. However, the rapid degradation rate of magnesium and its alloys in the physiological environment results in losing their mechanical integrity before complete bone healing. In light of this, friction stir processing (FSP), a solid-state process, is used to fabricate Hopeite (Zn(PO4)2.4H2O) reinforced novel magnesium composite. As a result of the novel composite fabricated by FSP, grain refinement of the matrix phase occurs significantly. The samples were immersed in simulated body fluid (SBF) for in-vitro bioactivity and biodegradability tests. The corrosion behavior of pure Mg, FSP Mg, and FSP Mg-Hopeite composite samples was compared using electrochemical and immersion tests in SBF. It found that Mg-Hopeite composite has better corrosion resistance than FSP Mg and pure Mg. Because of grain refinement and the presence of secondary phase Hopeite in the composite, the mechanical properties and corrosion resistance improved. The bioactivity test was performed in the SBF environment, and a rapid apatite layer was formed on the surface of Mg-Hopeite composite samples during the test. Osteoblast-like MG63 cells were exposed to samples, and the MTT assay confirmed the non-toxicity of the FSP Mg-Hopeite composite. The wettability of the Mg-Hopeite composite was improved than pure Mg. The present research findings showed that the novel Mg-Hopeite composite fabricated by FSP is a promising candidate for orthopedic implant applications, unreported in the literature.

Do Spinopelvic Parameters Relate with Secondary Hip Spine Syndrome in Secondary Hip Arthritis?

Background: The prevalence of low back pain (LBP) with primary osteoarthritis (OA) hip undergoing total hip replacement (THA) has been studied. However, secondary OA hip affects younger individuals where changes in the sagittal spinal parameters (SSPs) could be reversible to reduce LBP. The study aims to document changes in clinical and radiological parameters following THA. Methods: Thirty patients with secondary OA hip were included in the prospective analysis, excluding anyone with previous spine/hip surgery of known spinal diseases, including deformity, inflammatory or infective pathology. Visual analog scale for (VAS) hip and LBP, Oswestry disability index (ODI), and Harris core (HHS) along with SSPs were measured at baseline and three months and analyzed. Results:  Mean age was 42.8 ± 8.9 years which 17 unilateral (U/L) and 13 bilateral (B/L) OA. Overall, no significant changes were seen in SSPs that included pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), pelvic incidence-lumbar lordosis (PI-LL) was seen except for an improvement in the sagittal vertical axis (SVA) [40.22 ± 36.67 to 24.06 ± 21.93, p < 0.001]. However, clinical variables such as VAS hip and LBP, ODI, and HHS improved post-hip THA. Similar findings were seen in sub-group analysis when U/L affected were compared to B/L affected. Conclusion: The sagittal SSPs except SVA does not change significantly following THA in patients with secondary OA, though LBP improves clinically. Hence, we assume routine measurement of these parameters is not mandatory when planning for THA in these patients.

The computational quantum mechanical investigation of the functionalized boron nitride nanocage as the smart carriers for favipiravir drug delivery: a DFT and QTAIM analysis.

Favipiravir (FPV) is an antiviral drug used for the cure of Influenza virus, Ebola virus, Lassa virus etc. because it has excellent preventing ability of entry/exit of the virus into/from the human cells. Boron nitride nanocages have already drawn enormous attention as the delivery vehicle of various drug molecules for their nontoxicity and other lucrative properties. In this research, we have scrutinized the adsorption mechanism of FPV molecule on the exterior surface of pristine, Zn functionalized, and Ni functionalized B12N12 (BN, Zn f-BN, and Ni f-BN) nanocages by applying the DFT/QTAIM method and B3LYP/6-31G(d,p) approach. The adsorption energy (EAd) data reveal that the functionalized BN adsorbents can adsorb FPV drug very efficiently compared with the pristine adsorbent (Highest EAd is -56.40 kcal/mol for FPV adsorbed Ni f-BN complex). The reduction of the HOMO-LUMO gap up to 67.79% indicates that this drug can be detected by the produced electrical signal very promisingly in the case of f-BN nanocages. The topological parameters also validate the ability of the f-BN nanocages to adsorb the FPV molecule. The effect of the biological environment of our investigated structures has been studied by using water as a solvent, and spontaneous adsorption with high solubility is observed in our calculations. This analysis also reveals that f-BN nanocages can be a potential nanocarrier for the delivery of FPV drug molecule.Communicated by Ramaswamy H. Sarma.

Non-coding Single Nucleotide Variants of Renin and the (Pro)renin Receptor are Associated with Polygenic Diseases in a Bangladeshi Population.

Non-coding variants or single-nucleotide polymorphisms (SNPs) play pivotal roles in orchestrating pathogeneses of polygenic diseases, including hypertension (HTN) and diabetes. Renin-angiotensin system (RAS) components-renin and (pro)renin receptor [(P)RR]-maintain homeostasis of body fluids. Genetic variants of RAS components are associated with risk of HTN and type 2 diabetes (T2D) in different ethnic groups. We identified associations of SNPs within the renin and (P)RR genes with HTN, T2D, and T2D-associated hypertension in 911 unrelated Bangladeshi individuals. Five non-coding SNPs were involved in modulating regulatory elements in diverse cell types when tagged with other SNPs. rs61827960 was not associated with any disease; rs3730102 was associated with increased risk of HTN and T2D while under dominant model, it showed protective role against T2D-associated HTN. SNP rs11571079 was associated with increased risk of HTN and T2D-associated HTN and decreased risk of T2D, exerting a protective effect. Renin haplotypes GCA and GTG were related to increased risk of T2D and T2D-associated HTN, respectively. Heterogeneous linkage of genotypic and allelic frequencies of rs2968915 and rs3112298 of (P)RR was observed. The (P)RR haplotype GA was associated with increased risk of HTN and significantly decreased risk of T2D. These findings highlight important roles of non-coding variants of renin and (P)RR genes in the etiology of several polygenic diseases.

Multifunctional hydroxyapatite and hopeite coatings on SS254 by laser rapid manufacturing for improved osseointegration and antibacterial character: A comparative study.

Orthopaedic metallic implant's long-term success strongly depends upon the two main factors: osseointegration and antibacterial character. Bioceramic (hydroxyapatite and hopeite) coatings have been proven effective for getting strong osseointegration and antibacterial character. However, deterioration of bioceramic coatings during the implantation period can adversely affect its overall biological performance. To conquer this issue, this research work recommends an innovative process route of laser rapid manufacturing for depositing bioceramic (hydroxyapatite and hopeite) coatings with metallurgical bonding. Microstructure, phase composition, antibacterial efficacy and bioactivity were evaluated using scanning electron microscopy, X-ray diffraction, fluorescence-activated cell sorting technique and simulated body fluid immersion test. The promising results obtained from these characterizations and testing establish the new process route laser rapid manufacturing as an effective alternative to deposit multifunctional bioceramic (hydroxyapatite and hopeite) coatings on metallic prosthetic-orthopaedic implants.

Evaluation of Hemodynamics in a Prestressed and Compliant Tapered Femoral Artery Using an Optimization-Based Inverse Algorithm.

The important factors that affect the arterial wall compliance are the tissue properties of the arterial wall, the in vivo pulsatile pressure, and the prestressed condition of the artery. It is necessary to obtain the load-free geometry for determining the physiological level of prestress in the arterial wall. The previously developed optimization-based inverse algorithm was improved to obtain the load-free geometry and the wall prestress of an idealized tapered femoral artery of a dog under varying arterial wall properties. The compliance of the artery was also evaluated over a range of systemic pressures (72.5-140.7 mmHg), associated blood flows, and artery wall properties using the prestressed arterial geometry. The results showed that the computed load-free outer diameter at the inlet of the tapered artery was 6.7%, 9.0%, and 12% smaller than the corresponding in vivo diameter for the 25% softer, baseline, and 25% stiffer arterial wall properties, respectively. In contrast, the variations in the prestressed geometry and circumferential wall prestress were less than 2% for variable arterial wall properties. The computed compliance at the inlet of the prestressed artery for the baseline arterial wall property was 0.34%, 0.19%, and 0.13% diameter change/mmHg for time-averaged pressures of 72.5, 104.1, and 140.7 mmHg, respectively. However, the variation in compliance due to the change in arterial wall property was less than 6%. The load-free and prestressed geometries of the idealized tapered femoral artery were accurately (error within 1.2% of the in vivo geometry) computed under variable arterial wall properties using the modified inverse algorithm. Based on the blood-arterial wall interaction results, the arterial wall compliance was influenced significantly by the change in average pressure. In contrast, the change in arterial wall property did not influence the arterial wall compliance.

Pulsatile arterial wall-blood flow interaction with wall pre-stress computed using an inverse algorithm.

BACKGROUND: The computation of arterial wall deformation and stresses under physiologic conditions requires a coupled compliant arterial wall-blood flow interaction model. The in-vivo arterial wall motion is constrained by tethering from the surrounding tissues. This tethering, together with the average in-vivo pressure, results in wall pre-stress. For an accurate simulation of the physiologic conditions, it is important to incorporate the wall pre-stress in the computational model. The computation of wall pre-stress is complex, as the un-loaded and un-tethered arterial shape with residual stress is unknown. In this study, the arterial wall deformation and stresses in a canine femoral artery under pulsatile pressure was computed after incorporating the wall pre-stresses. A nonlinear least square optimization based inverse algorithm was developed to compute the in-vivo wall pre-stress. METHODS: First, the proposed inverse algorithm was used to obtain the un-loaded and un-tethered arterial geometry from the unstressed in-vivo geometry. Then, the un-loaded, and un-tethered arterial geometry was pre-stressed by applying a mean in-vivo pressure of 104.5 mmHg and an axial stretch of 48% from the un-tethered length. Finally, the physiologic pressure pulse was applied at the inlet and the outlet of the pre-stressed configuration to calculate the in-vivo deformation and stresses. The wall material properties were modeled with an incompressible, Mooney-Rivlin model derived from previously published experimental stress-strain data (Attinger et al., 1968). RESULTS: The un-loaded and un-tethered artery geometry computed by the inverse algorithm had a length, inner diameter and thickness of 35.14 mm, 3.10 mm and 0.435 mm, respectively. The pre-stressed arterial wall geometry was obtained by applying the in-vivo axial-stretch and average in-vivo pressure to the un-loaded and un-tethered geometry. The length of the pre-stressed artery, 51.99 mm, was within 0.01 mm (0.019%) of the in-vivo length of 52.0 mm; the inner diameter of 3.603 mm was within 0.003 mm (0.08%) of the corresponding in-vivo diameter of 3.6 mm, and the thickness of 0.269 mm was within 0.0015 mm (0.55%) of the in-vivo thickness of 0.27 mm. Under physiologic pulsatile pressure applied to the pre-stressed artery, the time averaged longitudinal stress was found to be 42.5% higher than the circumferential stresses. The results of this study are similar to the results reported by Zhang et al., (2005) for the left anterior descending coronary artery. CONCLUSIONS: An inverse method was adopted to compute physiologic pre-stress in the arterial wall before conducting pulsatile hemodynamic calculations. The wall stresses were higher in magnitude in the longitudinal direction, under physiologic pressure after incorporating the effect of in-vivo axial stretch and pressure loading.

Methodology for implementing patient-specific spatial boundary condition during a cardiac cycle from phase-contrast MRI for hemodynamic assessment.

Pulmonary insufficiency (PI) can render the right ventricle dysfunctional due to volume overloading and hypertrophy. The treatment requires a pulmonary valve replacement surgery. However, determining the right time for the valve replacement surgery has been difficult with currently employed clinical techniques such as, echocardiography and cardiac MRI. Therefore, there is a clinical need to improve the diagnosis of PI by using patient-specific (PS) hemodynamic endpoints. While there are many reported studies on the use of PS geometry with time varying boundary conditions (BC) for hemodynamic computation, few use spatially varying PS velocity measurement at each time point of the cardiac cycle. In other words, the gap is that, there are limited number of studies which implement both spatially- and time-varying physiologic BC directly with patient specific geometry. The uniqueness of this research is in the incorporation of spatially varying PS velocity data obtained from phase-contrast MRI (PC-MRI) at each time point of the cardiac cycle with PS geometry obtained from angiographic MRI. This methodology was applied to model the complex developing flow in human pulmonary artery (PA) distal to pulmonary valve, in a normal and a subject with PI. To validate the methodology, the flow rates from the proposed method were compared with those obtained using QFlow software, which is a standard of care clinical technique. For the normal subject, the computed time average flow rates from this study differed from those obtained using the standard of care technique (QFlow) by 0.8 ml/s (0.9%) at the main PA, by 2 ml/s (3.4%) at the left PA and by 1.4 ml/s (3.8%) at the right PA. For the subject with PI, the difference was 7 ml/s (12.4%) at the main PA, 5.5 ml/s (22.6%) at the left PA and 4.9 ml/s (18.0%) at the right PA. The higher percentage differences for the subject with PI, was the result of overall lower values of the forward mean flow rate caused by excessive flow regurgitation. This methodology is expected to provide improved computational results when PS geometry from angiographic MRI is used in conjunction with PS PC-MRI data for solving the flow field.

Energy transfer ratio as a metric of right ventricular efficiency in repaired congenital heart disease.

OBJECTIVE: With the success of early repair, continued functional assessment of repaired congenital heart disease is critical for improved long-term outcome. Pulmonary regurgitation, which is one of the main postoperative sequelae of congenital heart disease involved with the right ventricle (RV) such as tetralogy of Fallot and transposition of the great arteries, results in progressive RV dilatation coupled with pulmonary artery (PA) obstruction causing elevated RV pressures. The appropriate timing of intervention to correct these postoperative lesions remains largely subjective. In the present study, we evaluated an energy-based end point, namely energy transfer ratio (eMPA ), to assess the degree of RV and PA inefficiency in a group of congenital heart disease patients with abnormal RV-PA physiology. METHODS: Eight patients with abnormal RV-PA physiology and six controls with normal RV-PA physiology were investigated using a previously validated technique that couples cardiac magnetic resonance imaging and invasive pressure measurements. RESULTS: The mean eMPA of the patient group (0.56 ± 0.33) was significantly lower (P <.04) than that of the control group (1.56 ± 0.85), despite the fact that the patient group had a significantly higher RV stroke work indexed to body surface area (RV SWI ) than the control group (0.205 ± 0.095 J/m(2) vs. 0.090 ± 0.038 J/m(2) ; P <.02). CONCLUSION: We determined that the patients had inefficient RV-PA physiology due to a combination of RV dilatation with pulmonary regurgitation and RV outflow obstruction leading to an elevated end-systolic pressure. Using coupled magnetic resonance imaging and invasive pressure measurements, eMPA is determined to be a sensitive energy-based end point for measuring RV-PA efficiency. It may serve as a diagnostic end point to optimize timing of intervention.

Comparison of stroke work between repaired tetralogy of Fallot and normal right ventricular physiologies.

Adult patients who underwent tetralogy of Fallot repair surgery (rTOF) confront life-threatening ailments due to right ventricular (RV) myocardial dysfunction. Pulmonary valve replacement (PVR) needs to be performed to restore the deteriorating RV function. Determination of correct timing to perform PVR in an rTOF patient remains subjective, due to the unavailability of quantifiable clinical diagnostic parameters. The objective of this study is to evaluate the possibility of using RV body surface area (BSA)-indexed stroke work (SW(I)) to quantify RV inefficiency in TOF patients. We hypothesized that RV SW(I) required to push blood to the lungs in rTOF patients is significantly higher than that of normal subjects. Seven patients with rTOF pathophysiology and eight controls with normal RV physiology were registered for this study. Right ventricular volume and pressure were measured using cardiac magnetic resonance imaging and catheterization, respectively. Statistical analysis was performed to quantify the difference in SW(I) between the RV of the rTOF and control groups. Right ventricular SW(I) in rTOF patients (0.176 ± 0.055 J/m(2)) was significantly higher by 93.4% (P = 0.0026) than that of controls (0.091 ± 0.030 J/m(2)). Further, rTOF patients were found to have significantly higher (P < 0.05) BSA normalized RV end-systolic volume, end-systolic pressure, and regurgitation fraction than control subjects. Ejection fraction and peak ejection rate of rTOF patients were significantly lower (P < 0.05) than those of controls. Patients with rTOF pathophysiology had significantly higher RV SW(I) compared with subjects with normal RV physiology. Therefore, RV SW(I) may be useful to quantify RV inefficiency in rTOF patients along with currently used clinical end points such as RV volume, pressure, regurgitation fraction, and ejection fraction.

Gastroprotective effect of Achyranthes aspera Linn. leaf on rats.

OBJECTIVE: The study was aimed at evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera (EEAA) leaf. METHODS: The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulcer model. The effects of the EEAA on gastric content volume, pH, free acidity, total acidity and ulcer index were evaluated. RESULTS: The percentage of ulcer protection (59.55% and 35.58%) was significantly (P < 0.001) higher in the groups treated with the high dose of EEAA (600 mg/kg), it also reduced the volume of gastric juice and total acidity whereas, gastric pH was increased significantly. CONCLUSIONS: The results of this study show significant gastroprotective activity of EEAA may be due to presence of phyto-constituents like flavanoids, saponins and tannins.

Influence of arterial wall compliance on the pressure drop across coronary artery stenoses under hyperemic flow condition.

Hemodynamic endpoints such as flow and pressure drop are often measured during angioplasty procedures to determine the functional severity of a coronary artery stenosis. There is a lack of knowledge regarding the influence of compliance of the arterial wall-stenosis on the pressure drop under hyperemic flows across coronary lesions. This study evaluates the influence in flow and pressure drop caused by variation in arterial-stenosis compliance for a wide range of stenosis severities. The flow and pressure drop were evaluated for three different severities of stenosis and tested for limiting scenarios of compliant models. The Mooney-Rivlin model defined the non-linear material properties of the arterial wall and the plaque regions. The non-Newtonian Carreau model was used to model the blood flow viscosity. The fluid (blood)-structure (arterial wall) interaction equations were solved numerically using the finite element method. Irrespective of the stenosis severity, the compliant models produced a lower pressure drop than the rigid artery due to compliance of the plaque region. A wide variation in the pressure drop was observed between different compliant models for significant (90% area occlusion) stenosis with 41.0, 32.1, and 29.8 mmHg for the rigid artery, compliant artery with calcified plaque, and compliant artery with smooth muscle cell proliferation, respectively. When compared with the rigid artery for significant stenosis the pressure drop decreased by 27.7% and 37.6% for the calcified plaque and for the smooth muscle cell proliferation case, respectively. These significant variations in pressure drop for the higher stenosis may lead to misinterpretation and misdiagnosis of the stenosis severity.

Comparison of hemodynamic endpoints between normal subject and tetralogy patient using Womersley velocity profile and MR based flow measurements.

Right ventricular (RV) enlargement and pulmonary valve insufficiency (PI) are well-known, unavoidable long term sequelae encountered by patients who undergo tetralogy of Fallot (TOF) surgery. Despite their lifelong need for cardiac surveillance and occasional re-intervention, there is a paucity of numerical data characterizing blood flows in their pulmonary arteries (PA). Specifically, although PA regurgitation is well-known to be ubiquitously present in adult repaired TOF (rTOF) patients yet, there have been only limited numerical studies to fully characterize this process. The few studies available have utilized idealized, simplistic geometric models or overly simplistic boundary conditions that fail to account for flow reversals near the arterial walls as observed in in-vitro and MRI based in-vivo studies. The objective of this study was to establish and validate a numerical methodology of PA blood flow using actual patient specific geometry and flow measurements obtained using phase-contrast MRI, employing Womersley type velocity profiles that model flow reversals near walls. The results from computation were validated with measurements. For the normal subject, the time averaged right PA pressure from computation (13.8 mmHg) and experiment (14.6 mmHg) differed by 6%. The time-averaged main PA pressure from computation (16.5 mmHg) and experiment (16.3 mmHg) differed by 1%. The numerically computed left PA regurgitant fraction was 89% compared to measured 77.5%, while the same for the rTOF was 43% (computation), compared to 39.6% (measured). We conclude that the use of numerical computations using the Womersley boundary condition allows reliable modeling of the pathophysiology of PA flow in rTOF.

Influence of arterial wall-stenosis compliance on the coronary diagnostic parameters.

Functional diagnostic parameters such as Fractional Flow Reserve (FFR), which is calculated from pressure measurements across stenosed arteries, are often used to determine the functional severity of coronary artery stenosis. This study evaluated the effect of arterial wall-stenosis compliance, with limiting scenarios of stenosis severity, on the diagnostic parameters. The diagnostic parameters considered in this study include an established index, FFR and two recently developed parameters: Pressure Drop Coefficient (CDP) and Lesion Flow Coefficient (LFC). The parameters were assessed for rigid artery (RR; signifying high plaque elasticity), compliant artery with calcified plaque (CC; intermediate plaque elasticity) and compliant artery with smooth muscle cell proliferation (CS; low plaque elasticity), with varying degrees of epicardial stenosis. A hyperelastic Mooney-Rivlin model was used to model the arterial wall and plaque materials. Blood was modeled as a shear thinning, non-Newtonian fluid using the Carreau model. The arterial wall compliance was evaluated using the finite element method. The present study found that, with an increase in stenosis severity, FFR decreased whereas CDP and LFC increased. The cutoff value of 0.75 for FFR was observed at 78.7% area stenosis for RR, whereas for CC and CS the cutoff values were obtained at higher stenosis severities of 81.3% and 82.7%, respectively. For a fixed stenosis, CDP value decreased and LFC value increased with a decrease in plaque elasticity (RR to CS). We conclude that the differences in diagnostic parameters with compliance at intermediate stenosis (78.7-82.7% area blockage) could lead to misinterpretation of the stenosis severity.

Clinical features of children hospitalized with malaria--a study from Bikaner, northwest India.

Severe Plasmodium vivax malaria in adults has been reported from Bikaner (northwestern India) but the reports on children are scanty. This prospective study was done on 303 admitted children of malaria. The diagnosis was done by peripheral blood smear and rapid diagnostic test. Further confirmation of severe P. vivax monoinfection was done by polymerase chain reaction (PCR). The proportion of P. falciparum, P. vivax, and mixed (P. falciparum and P. vivax) infection was 61.01%, 33.99%, and 4.95%, respectively. Severe disease was present in 49.5% (150/303) children with malaria, with the risk greatest among P. vivax monoinfection (63.1% [65/103]) compared with P. falciparum, either alone (42.7% [79/185]; odds ratio [OR] = 2.3 [95% confidence interval (CI) = 1.40-3.76], P = 0.001) or mixed infections (40% [6/15]; OR = 2.57 [95% CI = 0.88-7.48]). In children < 5 years of age, the proportion of severe malaria attributable to P. vivax rose to 67.4% (31/46) compared with 30.4% (14/46) of P. falciparum (OR = 4.7 [95% CI = 2.6-8.6], P < 0.0001) and 2.2% (1/46) of mixed infection (OR = 92 [95% CI = 24.6-339.9], P < 0.0001). The proportion of patients having severe manifestations, which included severe anemia, thrombocytopenia, cerebral malaria, acute respiratory distress syndrome, hepatic dysfunction, renal dysfunction, abnormal bleeding was significantly high in association with P. vivax monoinfection in 0-5 year age group, while the same was significantly high in association with P. falciparum monoinfection in 5-10 year age group. Similarly P. vivax monoinfection had greatest propensity to cause multiorgan dysfunction in 0-5 year age group (34.1% [17/41], P < 0.0001) in comparison to P. falciparum monoinfection, which had similar propensity in 5-10 year age group (36.8% [35/95], P = 0.039). Plasmodium vivax monoinfection was almost equally serious to cause significant mortality in comparison to P. falciparum (case fatality rate of severe P. vivax was 3.9% versus 3.2% of severe P. falciparum malaria; P = 1.0). This study reaffirms the evidence of severe P. vivax malaria in children in Bikaner.

Right ventricular inefficiency in repaired tetralogy of Fallot: proof of concept for energy calculations from cardiac MRI data.

Repaired tetralogy of Fallot (rTOF) patients develop right ventricular (RV) dilatation and dysfunction. To prevent their demise, pulmonary valve replacement is necessary, though appropriate timing for it is challenged by a paucity of reliable diagnostic parameters. In this pilot study, we hypothesized that stroke work (SW) and energy calculations would delineate the inefficiency of RV performance in rTOF. RV SW was calculated for both an rTOF and a normal subject by utilizing RV pressure and volume measurements obtained during cardiac catheterization and MRI studies. Energy transfer rate and ratio were computed at the main pulmonary artery (PA). Compared to the normal RV, the rTOF RV had higher operating pressure, lower computed SW (0.078 J vs. 0.115 J for normal), and higher negative energy transfer at the PA (0.044 J vs. 0.002 J for normal). Furthermore, the energy transfer ratio was nearly twice as high for the normal RV (1.06) as for the rTOF RV (0.56). RV SW and energy transfer ratio delineate important operational efficiency differences in blood flow from the RV to the PA between rTOF and normal subjects. Our pilot data suggest that the rTOF RV is significantly less efficient than normal.

Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India.

Epidemiologic studies and clinical description of severe Plasmodium vivax malaria in adults living in malaria-endemic areas are rare and more attention is needed to understand the dynamics and its interaction with the immune system. This observational study included 1,091 adult patients admitted to medical wards of S. P. Medical College and associated group of hospitals in Bikaner, India from September 2003 through December 2005. The diagnosis of P. vivax malaria was established by peripheral blood film (PBF), rapid diagnostic test (RDT), and polymerase chain reaction (PCR), and severe malaria was categorized as per World Health Organization guidelines. Of 1,091 patients with malaria, 635 had P. falciparum malaria and 456 had P. vivax malaria. Among patients with severe manifestations, 40 had evidence of monoinfection of P. vivax malaria diagnosed by PBF, RDT, and PCR. Complications observed were hepatic dysfunction and jaundice in 23 (57.5%) patients, renal failure in 18 (45%) patients, severe anemia in 13 (32.5%) patients, cerebral malaria in 5 patients (12.5%), acute respiratory distress syndrome in 4 patients (10%), shock in 3 patients (7.5%), and hypoglycemia in 1 (2.5%) patient. Thrombocytopenia was observed in 5 (12.5%) patients, and multi-organ dysfunction was detected in 19 (47.5%) patients. Further large-scale multicentric epidemiologic studies are needed to define the basic pathology of this less known entity.

Similarities and differences of MR findings between Japanese encephalitis and Wilson's disease.

Although Japanese Encephalitis (JE) and Wilson's disease (WD) are different entities, MR findings in both these conditions are quite similar. The purpose of this retrospective study was to find out the similarities and differences between JE and WD on MR imaging. The study group comprised 25 proven cases of JE and 10 cases of WD. Spin echo (SE) TI- and T2-weighted imaging was performed on a 1.5-T MR system. Fourteen of these 35 cases (10 JE, 4 WD) were also examined using T1-weighted magnetization transfer (MT) SE sequence before and after contrast administration. Although both JE and WD showed similar topographical distribution of lesions, predominant involvement of the basal ganglia and thalami, there were some differences. Brain stem lesion was more frequent for WD than for JE, and posteromedial part of the thalami was spared in WD. The lesion characteristics were also different between both; in WD mixed intensity in the basal ganglia and hyperintense linear rim at the peripheral putamen was observed frequently, whereas hyperintense basal ganglia on T2-weighted images, subacute hemorrhage in the thalami and meningeal enhancement were seen only in the patients with JE. These characteristic lesion criteria may help in differentiation of JE from WD on MR imaging.