Delineation of acute myocardial infarction with dysprosium DTPA-BMA: influence of dose of magnetic susceptibility contrast medium.

OBJECTIVES. The contrast enhancement of acutely infarcted myocardium produced by the nonionic magnetic susceptibility-enhancing agent dysprosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA [S-043 Injection]) was assessed in the current study to establish the lowest dose that would yield optimal contrast between normal and acutely infarcted myocardium. BACKGROUND. Magnetic susceptibility contrast agents enhance differences between normal and ischemic tissue by reducing the signal of the normally perfused tissue to which they distribute. METHODS. Acute myocardial infarctions were produced by ligation of the left coronary artery. At 3 to 4 h after occlusion, a dose of 0.1, 0.3 or 0.5 mmol/kg of DyDTPA-BMA was injected intravenously into eight rats each in group 1, 2 or 3, respectively; a fourth group of seven rats served as a control group. Nuclear magnetic resonance (NMR) transverse relaxation time (T2)-weighted images (electrocardiographically gated to every 5th beat, echo delay time [TE] = 60 ms) were acquired before and for 1 h after administration of contrast agent. RESULTS. Images obtained before the injection of contrast agent showed moderate differences in signal intensity between normal and infarcted myocardium (p < 0.05). The contrast enhancement and the duration of delineation between infarcted and normal myocardium produced by this agent were dose dependent. At doses of 0.1, 0.3 and 0.5 mmol/kg, DyDTPA-BMA produced signal loss in normal myocardium: 63 +/- 5%, 41 +/- 4% and 28 +/- 4% of the baseline values, respectively, without any significant reduction in signal intensity of the infarcted region. The reduction in signal of normal myocardium and delineation of the infarct persisted for 5 min at a dose of 0.1 mmol/kg, for 20 min at a dose of 0.3 mmol/kg and for 40 min at a dose of 0.5 mmol/kg. No change in signal intensity or signal intensity ratio between normal and infarcted myocardium was observed in the control group during the same observation period. CONCLUSIONS. These results suggest that low doses of this agent, comparable to those of longitudinal relaxation time (T1)-enhancing agents, can delineate acutely infarcted myocardium. A dose of 0.3 mmol/kg of DyDTPA-BMA (S-043 Injection) provides reasonably persistent demarcation of acute myocardial infarction. Because this dose dramatically suppresses the NMR signal of normal myocardium, it shows the infarcted region as a region of high intensity (bright spot) on NMR images.     

High sustained response to daily dosing of interferon with ribavirin in chronic hepatitis C patients naïve to therapy

Background : Viral kinetics suggests that daily administration of α‐interferon (IFN) will clear hepatitis C virus (HCV) RNA earlier and more frequently compared with standard t.i.w. To reduce the likelihood of viral replication, mutation and subsequent development of resistance, daily dosing with IFN may be appropriate. To determine the safety and efficacy of daily IFN with ribavirin in chronic HCV infection we performed a prospective study. Methods : Thirty‐five naïve adult HCV‐positive patients (25 male/10 female) were treated with IFN‐α2b; 5 MU daily for 2 weeks followed by 3 MU daily for 22 weeks and ribavirin 800–1200 mg/day depending on weight. Liver biopsy, performed in 25 patients, showed mild to moderate activity in 19 patients (76%) and severe activity in six patients (24%). Two patients showed staged IV fibrosis. Serotyping was performed in 29 patients by an enzyme immunoassay‐based Murex assay. Type 3 was the predominant serotype, present in 14 cases. Hepatitis C virus RNA was measured by the Chiron bDNA assay. Results : Mean baseline HCV‐RNA level was 14.2 ± 18.7 MEq/mL (median 6.09; range 0.2–92.5), which became undetectable in all but three patients at week 4. Normalization of alanine aminotransferase (ALT) at week 4 was seen in 27 patients. Three patients withdrew due to non‐compliance. Thirty‐two patients completed 24 weeks of therapy as per the protocol. At the end of treatment, the HCV‐RNA level was negative in 29 of 32 patients (90.6%) and ALT was normal in 31 of 32 patients (97%). Sustained viral response at 6 months follow up was seen in 28 of 32 patients (88%). The ALT level was normal in 28 of 32 patients (88%). Conclusion : Daily administration of IFN with ribavirin is well tolerated in the majority of patients. There is rapid elimination of virus with normalization of ALT and a significantly high sustained viral response. © 2002 Blackwell Publishing Asia Pty Ltd     

Glycosylated hemoglobin levels in Sudanese sickle cell anemia patients

Glycosylated hemoglobin was measured, by a colorimetric method, in 49 patients with sickle cell anemia attending Khartoum Teaching Hospital. The level obtained (4.9%, SD 1.3) was significantly lower than the control value (5.6%, SD 0.2; p less than 0.0025). Expressed as percentage of the control value, the glycosylated hemoglobin level in these patients was 81%. This falls midway between the 90% reported in a benign form of sickle cell anemia in Saudi Arabia and the 58% reported in a severe form in an American Black group, which gives support to the observed heterogeneity of sickle cell anemia. Alternatively, glycosylated hemoglobin level in 27 subjects with sickle cell trait (5.6%, SD 0.2) was identical to that of the controls. The state of hemolysis in the sickle cell anemia patients, as indicated by bilirubin levels, did not correlate with the glycosylated hemoglobin values. Although glycosylated hemoglobin measurement is affected by red cell survival, it does not reflect the state of ongoing hemolysis.     

Serum Galectin-3 and Subsequent Risk of Coronary Heart Disease in Subjects With Childhood-Onset Type 1 Diabetes: A Cohort Study

OBJECTIVETo study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes.RESEARCH DESIGN AND METHODSA population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at <15 years of age during 1973–1982 was examined in 2002–2003 at a mean age of 33 years (range 21–44), with mean diabetes duration of 24 years (range 19–30). Subjects were followed through 31 December 2017 for their first CHD event registered by a hospitalization or cause of death using nationwide registries. Stored serum samples were available for 296 subjects and analyzed for interleukin-6 (IL-6), IL-6 receptor, IL-18, hs-CRP, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), galectin-3, and high-sensitivity troponin T. Adjusted hazard ratios (aHRs) for CHD per SD increase in biomarker were estimated using Cox regression.RESULTSOf 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5–16). IL-6 (aHR 1.32 [95% CI 1.07–1.63]), galectin-3 (aHR 1.44 [95% CI 1.09–1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04–1.81]) were significant predictors of CHD after adjustment for conventional risk factors.CONCLUSIONSGalectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.     

Oriented nanofibrous silk as a natural scaffold for ocular epithelial regeneration

The aim of this study was to develop nanofibrous silk substrates for limbal stem cell expansion that can serve as a potential alternative substrate to replace human amniotic membrane. The human limbal stem cell was used to evaluate the biocompatibility of substrates (random and oriented nanofibrous mats, and human amniotic membrane) based on their phenotypic profile, viability, proliferation, and attachment ability. Biocompatibility results indicated that all substrates were highly biocompatible, as limbal stem cells could favorably attach and proliferate on the nanofibrous surfaces. Microscopic figures showed that the human limbal stem cells were firmly anchored to the substrates and were able to retain a normal corneal stem cell phenotype. Microscopic analyses illustrated that cells infiltrated the nanofibers and successfully formed a three-dimensional corneal epithelium, which was viable for 15 days. Immunocytochemistry and real-time PCR results revealed no change in the expression profile of limbal stem cells grown on nanofibrous substrates when compared to those grown on human amniotic membrane. In addition, electrospun nanofibrous silk substrates especially oriented mat provides not only a milieu supporting limbal stem cells expansion, but also serve as a useful alternative carrier for ocular surface tissue engineering and could be used as an alternative substrate to amniotic membrane.     

Thoracic imaging outcomes in COVID-19 survivors

The coronavirus disease 2019 (COVID-19) pandemic presents a significant global public health challenge. One in five individuals with COVID-19 presents with symptoms that last for weeks after hospital discharge, a condition termed “long COVID”. Thus, efficient follow-up of patients is needed to assess the resolution of lung pathologies and systemic involvement. Thoracic imaging is multimodal and involves using different forms of waves to produce images of the organs within the thorax. In general, it includes chest X-ray, computed tomography, lung ultrasound and magnetic resonance imaging techniques. Such modalities have been useful in the diagnosis and prognosis of COVID-19. These tools have also allowed for the follow-up and assessment of long COVID. This review provides insights on the effectiveness of thoracic imaging techniques in the follow-up of COVID-19 survivors who had long COVID.     

The relative locations of the supraorbital,infraorbital, and mental foramina: A cadaveric study

The purpose of this study is to investigate the applicability of the current surgical guideline stating that the main facial foramina that transmit cutaneous nerves to the face (supraorbital notch/foramen, infraorbital foramen, and mental foramen) are equidistant from the midline in European and Hispanic populations. Previous studies suggest this surgical guideline is not applicable for all ethnicities; however, to our knowledge, no data have been published regarding the accuracy of this guideline pertaining to the Hispanic population. An experimental study was performed on 67 cadavers donated to the Human Anatomy Program at UT Health San Antonio. The supraorbital, infraorbital, and mental foramina were dissected and midline structures including the crista galli, internasal suture, anterior nasal spine, and mandibular symphysis were identified. The distance from each foramen to midline was recorded using a digital caliper. For all cadavers/ethnicities studied, the supraorbital, infraorbital, and mental foramina were 25.32 mm, 29.57 mm, and 25.55 mm to the midline, respectively. Thus, the infraorbital foramen is located significantly more lateral compared to the supraorbital (p < 0.0001) and mental foramina (p < 0.0001). After dividing the sample based on ethnicity, this relationship was also true for the European sample and tended to be true for the Hispanic sample. Significant anatomical variations exist in the current surgical guideline stating that the supraorbital foramen, infraorbital foramen, and mental foramen are equidistant from the midline. Clinicians may need to adjust their methodology during surgical procedures of the face in order to optimize patient care.     

Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model

Background

Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia.

Objective

This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep.

Methods

Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers.

Results

Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05).

Conclusion

Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.     

Combined NGS Approaches Identify Mutations in the Intraflagellar Transport Gene IFT140 in Skeletal Ciliopathies with Early Progressive Kidney Disease

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.     

Van der Waals heterostructures of SiC and Janus MSSe (M = Mo,W) monolayers: a first principles study

Favorable stacking patterns of two models with alternative orders of chalcogen atoms in SiC-MSSe (M = Mo, W) vdW heterostructures are investigated using density functional theory calculations. Both model-I and model-II of the SiC-MSSe (M = Mo, W) vdW heterostructures show type-II band alignment, while the spin orbit coupling effect causes considerable Rashba spin splitting. Furthermore, the plane-average electrostatic potential is also calculated to investigate the potential drops across the heterostructure and work function. The imaginary part of the dielectric function reveals that the first optical transition is dominated by excitons with high absorption in the visible region for both heterostructures. Appropriate band alignments with standard water redox potentials enable the capability of these heterostructures to dissociate water into H⁺/H₂ and O₂/H₂O.

Using DFT calculations, we have investigated the electronic structure, Rashba effect, optical and photocatalytic performance of SiC-MSSe (M = Mo, W) van der Waals heterostructures with different stacking patterns of chalcogen atoms.