Correlation between retinal vein pulse amplitude, estimated intracranial pressure, and postural change.

Spaceflight associated neuro-ocular syndrome (SANS) is common amongst astronauts on long duration space missions and is associated with signs consistent with elevated cerebrospinal fluid (CSF) pressure. Additionally, CSF pressure has been found to be elevated in a significant proportion of astronauts in whom lumbar puncture was performed after successful mission completion. We have developed a retinal photoplethysmographic technique to measure retinal vein pulsation amplitudes. This technique has enabled the development of a non-invasive CSF pressure measurement apparatus. We tested the system on healthy volunteers in the sitting and supine posture to mimic the range of tilt table extremes and estimated the induced CSF pressure change using measurements from the CSF hydrostatic indifferent point. We found a significant relationship between pulsation amplitude change and estimated CSF pressure change (p < 0.0001) across a range from 2.7 to 7.1 mmHg. The increase in pulse amplitude was highest in the sitting posture with greater estimated CSF pressure increase (p < 0.0001), in keeping with physiologically predicted CSF pressure response. This technique may be useful for non-invasive measurement of CSF pressure fluctuations during long-term space voyages.

RAMPVIS: Answering the challenges of building visualisation capabilities for large-scale emergency responses.

The effort for combating the COVID-19 pandemic around the world has resulted in a huge amount of data, e.g., from testing, contact tracing, modelling, treatment, vaccine trials, and more. In addition to numerous challenges in epidemiology, healthcare, biosciences, and social sciences, there has been an urgent need to develop and provide visualisation and visual analytics (VIS) capacities to support emergency responses under difficult operational conditions. In this paper, we report the experience of a group of VIS volunteers who have been working in a large research and development consortium and providing VIS support to various observational, analytical, model-developmental, and disseminative tasks. In particular, we describe our approaches to the challenges that we have encountered in requirements analysis, data acquisition, visual design, software design, system development, team organisation, and resource planning. By reflecting on our experience, we propose a set of recommendations as the first step towards a methodology for developing and providing rapid VIS capacities to support emergency responses.

Zero retinal vein pulsation amplitude extrapolated model in non-invasive intracranial pressure estimation.

Intracranial pressure (ICP) includes the brain, optic nerve, and spinal cord pressures; it influences blood flow to those structures. Pathological elevation in ICP results in structural damage through various mechanisms, which adversely affects outcomes in traumatic brain injury and stroke. Currently, invasive procedures which tap directly into the cerebrospinal fluid are required to measure this pressure. Recent fluidic engineering modelling analogous to the ocular vascular flow suggests that retinal venous pulse amplitudes are predictably influenced by downstream pressures, suggesting that ICP could be estimated by analysing this pulse signal. We used this modelling theory and our photoplethysmographic (PPG) retinal venous pulse amplitude measurement system to measure amplitudes in 30 subjects undergoing invasive ICP measurements by lumbar puncture (LP) or external ventricular drain (EVD). We estimated ICP from these amplitudes using this modelling and found it to be accurate with a mean absolute error of 3.0 mmHg and a slope of 1.00 (r = 0.91). Ninety-four percent of differences between the PPG and invasive method were between - 5.5 and + 4.0 mmHg, which compares favourably to comparisons between LP and EVD. This type of modelling may be useful for understanding retinal vessel pulsatile fluid dynamics and may provide a method for non-invasive ICP measurement.

A current novel perspective approach for coronavirus disease-2019 pandemic outbreak.

Coronavirus disease-2019 is a serious health threat around the globe. Across the world, approximately 142 million people were infected, and three million deaths happened. The fast propagation is also associated with constant anxiety, mental stress, and discomfort in public and health-care professionals. Lack of approved drugs regimen to combat the pandemic challenge concretely is a challenging project for all who are committed to developing remedial assistance. However, the successful development of three vaccines gives a solid roadmap to combat this disease. In this review, we highlighted the current development and challenges of this pandemic.

Spectroscopic and molecular modeling studies of binding interaction between bovine serum albumin and roflumilast.

BACKGROUND: The binding interaction between bovine serum albumin (BSA) and roflumilast (ROF) was explored in this study. The binding of drugs to albumin plays a vital role in their pharmacokinetics and pharmacodynamics in vivo. The mechanisms involved in the interaction between BSA and ROF was studied using multi-spectroscopic experimental and computational approaches. MATERIALS AND METHODS: Spectrofluorometric experiments were used to determine the method of quenching involved and the conformational changes in the BSA. UV-visible spectroscopy synchronous and three-dimensional fluorescence spectroscopy were used to further explore the binding interaction mechanism. RESULTS: The results suggested that the intrinsic fluorescence of BSA was quenched due to the formation of a static complex between ROF and BSA. Conformational changes in BSA were determined based on its interaction with ROF. The thermodynamic results suggested that the interaction between ROF and BSA was spontaneous and a hydrophobic interaction occurred between them. Site I of BSA was suggested as the site of interaction between ROF and BSA based on the site marker experiments. CONCLUSION: The molecular simulation results and the experimental outcomes were complimentary to each other and helped to identify the binding site and nature of bonds involved in the interaction between ROF and BSA.

Myocarditis in Duchenne Muscular Dystrophy After Changing Steroids.

Importance: Cardiac dysfunction is a leading cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). This case highlights the importance of steroids in treating cardiac complications of DMD and the dangers of discontinuing or switching between steroid classes. Objective: To recognize the presentation of acute myocardial inflammation, or dystrophinitis, in DMD, which presents as myocarditis and to treat the myocardial inflammation and dilated cardiomyopathy associated with DMD through guideline-directed medical therapy, steroids, and serial surveillance for cardiac dysfunction. Design, Setting, and Participant: A case report of an 18-year-old patient with DMD and with steroid withdrawal-induced myocarditis followed up for 3 years to observe for cardiac function recovery and the natural history of cardiomyopathy in DMD, who was hospitalized in the cardiac care unit and followed up between November 3, 2016, and March 27, 2017. Exposures: Switching from deflazacort to underdosed prednisone for 7 days. Main Outcomes and Measures: Increased myocardial inflammation, edema, and fibrosis after stopping deflazacort abruptly. Results: An 18-year-old male patient with DMD presented to the emergency department with acute-onset chest pain. Ischemic changes were present on electrocardiogram, and elevated cardiac enzymes were detected. Depressed cardiac function and potential evidence of inflammation were seen on cardiac magnetic resonance (CMR) imaging, characterized by elevated T2 values and late gadolinium enhancement. These findings were all consistent with acute myocarditis but without a viral prodrome. Several days prior to presentation, the patient's deflazacort was abruptly discontinued and converted to an equivalent dose of prednisone. After restarting deflazacort, his symptoms improved, and subsequent CMR showed resolution of myocardial edema and improved left ventricular function. Conclusions and Relevance: This case highlights adverse effects associated with changing between corticosteroid classes in DMD cardiomyopathy and also demonstrates the utility of CMR in detecting myocardial inflammation and monitoring response to treatment.

Comparison of Goldmann Applanation, Noncontact Air Puff, and Tono-Pen XL Tonometry in Normal Controls versus Glaucoma Patients at a University Hospital in Riyadh, Saudi Arabia.

PURPOSE: The purpose of this study is to compare intraocular pressure (IOP) measured by the Goldmann applanation tonometer (GAT), the Tono-Pen XL (TPXL), and a noncontact airpuff tonometer (NCT) in glaucoma patients and normal controls. METHODOLOGY: In the current study, two groups of individuals were recruited; the first group included glaucoma patients (glaucoma group) while the second one was a glaucoma-free group. The IOP was measured through GAT, NCT, and TPXL for the same participants by three different physicians in both groups. Measurements through the three devices were compared statistically. Correlations between different methods of assessment were also assessed. RESULTS: In the glaucoma group, the mean IOP measured was 16.0 ± 5.5 mmHg (range, 6-40 mmHg) with GAT 20.5 ± 6.9 mmHg (range, 10-52 mmHg) with the TPXL, and 20.2 ± 6.5 mmHg (range, 8-50 mmHg) with the NCT. In the control group, the mean IOP was 14.0 ± 2.7 mmHg (range, 9-19 mmHg) with GAT, 17.3 ± 3.8 mmHg (range 6-30 mmHg) with the TPXL, and 17.9 ± 3.9 mHg (range 10-27 mmHg) with the NCT. CONCLUSION: IOP measurements were approved among the three devices with relatively higher readings using both NTC and TPXL. All three methods are required to address different situations that present in the daily clinical and surgical practice.

Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice.

BACKGROUND: Dependence on antipsycotic drugs like aripriprazole (ARI) is increasing at alarming rate, hence, this study was undertaken to support the hypothesis that supplementation of Citrus paradisi (Grapefruit) juice having high concentration of polyphenols might potentiate and synergize the therapeutic effect of ARI, by increasing its bioavailability and inherent antioxidant potential. These benefits together might decrease the daily dosage of the ARI and thus alleviate the possible side effects of drug. METHODS: In this study the antioxidant and anti-inflammatory potential of ARI alone and in combination with GFJ was evaluated for hydrogen peroxide (H2O2) induced oxidative stress in mice. Seventy mice (4 weeks old), were randomly divided into seven groups. Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated. Serum levels of alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine kinase (CK), creatinine and total protein were measured. Furthermore, pro-inflammatory cytokines Interleukin (IL)-1α, IL-2, IL-10 and tumor necrosis factor-α (TNF-α) concentrations were also measured. RESULTS: The mice group that was treated with ARI, GFJ or combination of the two showed significant improvement in the H2O2 altered parameters with the combination group showing more significant improvement than the ARI and GFJ alone groups indicating a synergistic and potentiating effect of the antioxidant and anti-inflammatory potential of GFJ on ARI. CONCLUSION: Supplementing GFJ to ARI might increase an anti-oxidative potential of ARI due to inherent antioxidant and anti-inflammatory activity of GFJ and thus could alleviate the possible dosage dependent side effects of ARI.

A case report of congenital glycogen storage liver cirrhosis treated with bone marrow derived stem cells.

Liver cirrhosis represents a state of end-stage failure that is usually fatal. The condition results in liver dysfunction, recurrent ascites, encephalopathy, renal failure, splenomegaly, bleeding, and a poor quality of life in general. With the current severe shortage of donated organs, the only available treatment in the developing countries remains palliative care. We report a case of congenital metabolic liver cirrhosis due to glycogen storage disease diagnosed at age eight. The patient, a male, received bone marrow derived mononuclear cells (BMMC) at age 16 and again at age 17 with significant improvement of his biochemical liver function tests, ascites build-up, asthenia, splenomegaly and quality of life. Furthermore, liver biopsies showed clear reduction of the inflammation and fibrosis from Ishak score dropped from 3 to 1 paralleling the symptomatic improvement of the patient.

Study of the Interactions of Bovine Serum Albumin with the New Anti-Inflammatory Agent 4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-N'-[(4-ethoxy-phenyl)methylidene]benzohydrazide Using a Multi-Spectroscopic Approach and Molecular Docking.

The lipophilic derivative of thalidomide (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N'-[(4-ethoxyphenyl)methylidene]benzohydrazide, 6P) was synthesized to enhance its characteristics and efficacy. Earlier studies have proved the immunomodulatory and anti-inflammatory effects of 6P. In this study the interaction between bovine serum albumin (BSA) and 6P was studied using a multi-spectroscopic approach which included UV spectrophotometry, spectrofluorimetry and three dimensional spectrofluorometric and molecular docking studies. Static quenching was involved in quenching the fluorescence of BSA by 6P, because a complex formation occurred between the 6P and BSA. The binding constant decreased with higher temperature and was in the range of 2.5 × 105-4.8 × 10³ L mol-1 suggesting an unstable complex at higher temperatures. A single binding site was observed and the the site probe experiments showed site II (sub-domain IIIA) of BSA as the binding site for 6P. The negative values of ∆G°, ∆H° and ∆S° at (298/303/308 K) indicated spontaneous binding between 6P and BSA as well as the interaction was enthalpy driven and van der Waals forces and hydrogen bonding were involved in the interaction. The docking results and the results from the experimental studies are complimentary to each other and confirm that 6P binds at site II (sub-domain IIIA) of BSA.

Late Diagnosis of 5-α-Reductase Type 2 Deficiency in an Adolescent Girl with Primary Amenorrhoea.

Deficiency of the 5-α-reductase enzyme has been found to affect male sexual development. We report an 18-year-old patient who was referred to an endocrinology clinic in Jizan, Saudi Arabia, in April 2014 with primary amenorrhoea, virilisation and a lack of secondary sex characteristics. As female external genitalia were present at birth, she had been raised as a female. Magnetic resonance imaging revealed no uterine or ovarian tissue in the pelvis and the presence of a scrotal sac. She was diagnosed with 5-α-reductase type 2 deficiency, a 46,XY disorder of sexual development. Typically, affected males have pseudovaginal perineoscrotal hypospadias and ambiguous genitalia at birth. Individuals who have been raised as female manifest characteristics of virilisation at puberty, including deepening of the vocal tone, phallus enlargement, scrotal hyperpigmentation and increased muscle mass.

Cloning and characterization of recombinant Hc-CPL-1 from gastrointestinal nematode Haemonchus contortus isolate from goat (Capra hircus) population in Penang, Malaysia.

Cathepsin L (CPL) cysteine protease is a proteolytic enzyme that involves in many biological processes in a wide range of organisms. In free-living nematode Caenorhabditis elegans, CPL plays important roles in embryogenesis and development processes. The CPL protein is also believed to have a role in degradation of blood meal in the gut of parasitic nematodes. Considering this enzyme might play the same functions in parasitic nematodes, CPL became a potential candidate for vaccination against Haemonchus contortus, a gastrointestinal nematode of small ruminants. H. contortus has been shown to have variations in term of morphology and genetic materials that correlated with different hosts and geographical areas. These variations could hinder the development of effective vaccines. Thus, the present study was conducted to clone and characterize recombinant Hc-CPL-1 from H. contortus isolated from a goat population in Penang, Malaysia. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify target complimentary DNA (cDNA) from total RNA and protein expression using Escherichia coli expression system was performed from constructed cDNA clone library. The identity of each protein band was confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis followed by De novo sequencing and database matching. The protein structure and its evolutionary relationship were also studied using several bioinformatics approaches. Basic local alignment search tool (BLAST) analysis of the strain retrieved from clone library showed 99% sequence similarity to the Haemonchus cathepsin L cysteine protease and a 47 kDA protein was successfully expressed. Bioinformatic analysis indicated that this protease has a close relationship with Dv-CPL-1, Sv-CPL-1 and Ce-CPL-1. These data might provide an insight on manipulating this enzyme for future novel vaccine development.

Oral acute toxicity study as well as tissues oxidative stress and histopathological disorders in edible camphor administered rats.

In the South-western part of Nigeria, edible camphor (EC) infusions are used to treat pile, back pain, and erectile dysfunction, especially in preparation for sexual intercourse. We therefore carried out oral acute toxicity study, and then investigated the effects of various doses of EC on the activities of lactate dehydrogenase (LDH), catalase (CAT), and superoxide dismutase (SOD), as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels in wistar rats. Oral LD50 of EC was estimated to be 9487mg/kg body weight. Based on this, thirty animals were divided into six groups of five rats each, and were orally administered various doses of EC (1, 2, 4, and 6g/kg body weight) for seven days. Comparing all results with control, EC significantly increased serum LDH activity (4 and 6g/kg), liver (6g/kg) and kidney (4 and 6g/kg) MDA levels, as well testis GSH levels (1g/kg). CAT activities were significantly decreased in liver, kidney, and testis, and also lung GSH level by all the tested doses. For SOD, activities were significantly increased in liver and lung, but significantly decreased in kidney (2, 4, and 6g/kg). Various pathological disorders were also seen following the various doses of EC administered, especially in liver, kidney and lung. Therefore, from our findings, it is evident that incessant, misuse or overconsumption of EC could lead to oxidative tissue damage in rats.

Losartan: Comprehensive Profile.

Losartan (Cozaar™) is an angiotensin II receptor antagonist with antihypertensive activity. It is used in the management of hypertension and heart failure. Nomenclature, formulae, elemental analysis, and appearance of the drug are included in this review. The uses, applications, and the variety of synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum with fragmentation patterns, and NMR (1H and 13C) spectra of losartan together with the corresponding figures and/or tables are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including: spectrophotometric, electrochemical, chromatographic, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior and the pharmacology of the drug are also provided.

Re-examination of renal allograft biopsy blocks for C4d positivity: missed cases of antibody mediated rejection.

INTRODUCTION: C4d immunostaining of renal allograft biopsies is recommended for the diagnosis of antibody-mediated rejection (ABMR), but it was not available to us prior to June 2012. In June 2012, we were able to obtain anti-human C4d polyclonal antibody and decided to retrospectively evaluate archived kidney allograft biopsies at our center for C4d deposition. METHODS: Twenty-four paraffin blocks were available for this study. Immunostaining for C4d was performed using anti-human C4d polyclonal antibody by Immunohistochemistry. The score and pattern of C4d positivity were determined according to the Banff 2007 guidelines. RESULTS: All grafts were from living related donors with negative CDC cross-match. The indications for biopsy were primary, acute and chronic graft dysfunction in 29.2%, 33.3% and 37.5% of patients respectively. Two biopsies revealed extensive necrosis rendering it difficult to interpret the result of C4d staining. Among the remaining 22 biopsies, C4d staining was categorized as negative in 40.9%, minimal in 13.6%, focal in 22.7% and diffuse in 22.7%. The prevalence of C4d positivity among biopsies taken due to primary, chronic and acute graft dysfunction was 71.4%, 44.4% and 12.5% respectively. CONCLUSION: C4d positivity was common in biopsies taken from this group of kidney transplant recipients and its prevalence was particularly high among biopsies taken due to primary graft non-function. This indicates that missed ABMR is an important cause for kidney allograft dysfunction in our setting.

Study of Cholesteryl Ester Transfer Protein (CETP) I405v Genotype and Its Association with Lipid Fractions in Myocardial Infarction Patients: A Case Control Study.

OBJECTIVES: We determine the significant relation of HDL cholesterol and total cholesterol/HDL cholesterol between CETP I405V genotypes and activity of CETP. CETP is an essential for transfer of cholesterol ester to the liver from peripheral tissues which facilitating its transfer to TG rich VLDL. Reduction activity of CETP I405V may associate with genotypes of CETP I405V. This study is undertaken to assess the presence and impact of CETP I405V genotype in our population. MATERIALS AND METHODS: In this study 100 acute myocardial infarction patients and 100 normal age & sex matched healthy individuals were included. Serum Lipid profile was estimated by using universal standard methods whereas CETP I405V genotype was studied by ARMS PCR. RESULT: There is presence of CETP 405Val genotype both in patient as well as in control group. RESULTs show that HDL cholesterol (p<0.0001) and ratio of total cholesterol/HDL cholesterol are significantly (p<0.0043) associated with Val/Val genotype. In addition to that the CETP I405V genotype is associated with inhibition of CETP activity with higher HDL-C level and decreased total cholesterol/HDL cholesterol ratio. CONCLUSION: Our results show that the CETP I405V genotypes are very much significantly determinant of HDL cholesterol in patients with CHD.

Co-administration of ketoconazole and tacrolimus to kidney transplant recipients: cost minimization and potential metabolic benefits.

To evaluate the effects of the co-administration of tacrolimus and ketoconazole to a group of kidney transplant recipients, we studied 30 kidney transplant recipients with stable kidney function who were maintained on tacrolimus-based immunosuppression. They were prescribed ketoconazole (100 mg/day) with a concomitant reduction in daily tacrolimus dose to maintain its level within the therapeutic range. The study included 19 males and 11 females with a mean age of 36 ± 12 years. All patients were at least three months post-transplant and had tacrolimus trough levels within the therapeutic range of 5-7 ng/mL. Desired tacrolimus trough levels could be achieved in 29/30 patients after the addition of ketoconazole. This resulted in a significant reduction of the median tacrolimus dose from 5 mg/day (range 3-20 mg/day) at baseline to 2 mg/day (range 1-4 mg/day) (P = 0.00). The median reduction in the tacrolimus dose was 63% (range 50-83%). The median monthly tacrolimus cost dropped from 375 US$ per patient (range 225-1440 US$) to 150 US$ per patient (range 120-300 US$). There were no reported adverse drug effects during the study period. After one year of follow-up, there was a small but significant improvement in the estimated glomerular filtration rate (72 ± 18 versus 78 ± 20 mL/min, P = 0.01) and a significant reduction in serum uric acid levels (7.7 ± 1.7 versus 5.9 ± 0.8 mg/dL, P = 0.003). The co-administration of ketoconazole and tacrolimus to kidney trans-plant recipients is safe and significantly reduces the cost of immunosuppression. In addition, this combination appears to have a beneficial effect on kidney function.

Prevalence and Risk Factors of Central Venous Stenosis among Prevalent Hemodialysis Patients, a Single Center Experience.

INTRODUCTION: Central vein stenosis (CVS) is a common complication of central venous catheter (CVC) insertion. In this study we evaluated the prevalence and risk factors of CVS among hemodialysis (HD) patients in a single center in Sudan, using Doppler ultrasound as a screening tool. METHODS: The study included 106 prevalent HD patients. For every patient, we performed Duplex Doppler for the right and left jugular, subclavian and femoral veins. A patient was considered to have hemodynamically significant stenosis if the pre-stenosis to the post-stenosis velocities ratio was ≥ 2.5 or they had complete vein occlusion. RESULTS: Overall, 28.3% of patients had Doppler detected CVS, including 25.5% with hemodynamically significant stenosis and 2.8% with compromised flow. The prevalence of CVS was 68.4% among symptomatic patients compared to 19.5% in asymptomatic patients. The prevalence of CVS among patients with history of 0-1, 2-3 and ≥ 4 central venous catheters was 3.4%, 29.4% and 53.8% respectively (p=0.00). CVS was not more common in patients with history of previous/current jugular or femoral vein catheterization compared to no catheter placement in these veins (28.3% vs 28.6% and 35% vs 26.7% respectively; p >0.1). However, CVS was significantly more common in patients with previous/ current subclavian vein catheterization compared to no catheter placement in this vein (47.8% vs 22.9%, p = 0.02). CONCLUSION: CVS is highly prevalent among studied HD patients, particularly in the presence of suggestive clinical signs. The number of HD catheter placements and subclavian vein utilization for dialysis access impose a significantly higher risk of CVS.