Miracle-dz/UniFAR-FTUs huggingface dataset:
Patterns of hippocampal abnormalities in malformations of cortical development

Objective: To assess whether different types of malformation of cortical development (MCD) are associated with specific patterns of hippocampal abnormalities. Methods: A total of 122 consecutive patients with MRI diagnosis of MCD (53 males, age range 1–58 years) were included in the study. Hippocampal measurements were made on 1–3 mm coronal T1-weighted MRIs and compared with MRIs of normal controls. Results: A total of 39 patients had focal cortical dysplasia, 5 had hemimegalencephaly, 5 had lissencephaly-agyria-pachygyria, 11 had SLH, 11 had PNH, 12 had bilateral contiguous PNH, 5 had schizencephaly, and 34 had polymicrogyria. The frequency of hippocampal abnormalities in these patients with MCD was 29.5%. A small hippocampus was present in all types of MCD. Only patients with lissencephaly and SLH had an enlarged hippocampus. Abnormalities in hippocampal rotation and shape were present in all types of MCD; however, these predominated in PNH. None of the patients with lissencephaly-agyria-pachygyria or SLH had hyperintense signal on T2 or FLAIR images or abnormal hippocampal internal architecture. Conclusion: A small hippocampus was present in all types of MCD; however, the classic MRI characteristics of hippocampal sclerosis were often lacking. Abnormal enlargement of the hippocampus was associated with only diffuse MCD due to abnormal neuronal migration (lissencephaly-agyria-pachygyria and SLH).
A small bispecific protein selected for orthogonal affinity purification

A novel protein domain with dual affinity has been created by randomization and selection. The small alkali‐stabilized albumin‐binding domain (ABD*), used as scaffold to construct the library, has affinity to human serum albumin (HSA) and is constituted of 46 amino acids of which 11 were randomized. To achieve a dual binder, the binding site of the inherent HSA affinity was untouched and the randomization was made on the opposite side of the molecule. Despite its small size and randomization of almost a quarter of its amino acids, a bifunctional molecule, ABDz1, with ability to bind to both HSA and the Z2 domain/protein A was successfully selected using phage display. Moreover, the newly selected variant showed improved affinity for HSA compared to the parental molecule. This novel protein domain has been characterized regarding secondary structure and affinity to the two different ligands. The possibility for affinity purification on two different matrices has been investigated using the two ligands, the HSA matrix and the protein A‐based, MabSelect SuRe matrix, and the new protein domain was purified to homogeneity. Furthermore, gene fusions between the new domain and three different target proteins with different characteristics were made. To take advantage of both affinities, a purification strategy referred to as orthogonal affinity purification using two different matrices was created. Successful purification of all three versions was efficiently carried out using this strategy.
Effect of intraluminal thrombus on wall stress in patient-specific models of abdominal aortic aneurysm.

PURPOSE The role of intraluminal thrombus (ILT) on abdominal aortic aneurysm rupture is still not clear. Rupture of an aneurysm occurs when the wall stress exceeds the wall strength at any location on the wall. The purpose of this study was to address the hypothesis that the presence of ILT alters the wall stress distribution or wall stress magnitude in AAA. METHODS Patient-specific 3D AAA geometries were reconstructed from computed tomographic images. Two geometric features, ILT surface ratio (ILT surface area divided by the total AAA surface area) and ILT volume ratio (ILT volume divided by the total AAA volume), were calculated for each AAA. Two models were created for each patient: one with ILT and one without ILT. Systolic pressure measured at the time of computed tomographic imaging was applied to the internal surface of each model. A nonlinear large deformation algorithm was used to compute wall stress distribution with the finite element method. The Wilcoxon matched pairs test was used to compare the peak wall stress between the two models of each patient. RESULTS Four patients were studied with ILT surface ratios that ranged from 0.29 to 0.72 and ILT volume ratios that ranged from 0.12 to 0.66. The peak wall stress was reduced (range, 6% to 38% reduction; P =.067) for all models with ILT included (range, 28 to 37 N/cm(2)) as compared with models with no ILT (range, 30 to 44 N/cm(2)). Visual inspection also revealed a marked effect of ILT on the wall stress distribution. CONCLUSION The presence of ILT alters the wall stress distribution and reduces the peak wall stress in AAA. For this reason, ILT should be included in all patient-specific models of AAA for evaluation of AAA wall stresses.
In Vitro and In Vivo Properties of Adenovirus Vectors with Increased Affinity to CD46

ABSTRACT Gene transfer vectors containing adenovirus (Ad) serotype 35 (Ad35) fibers have shown promise for cancer and stem cell gene therapy. In this study, we attempted to improve the in vitro and in vivo infection properties of these vectors by increasing their affinity to the Ad35 fiber receptor CD46. We constructed Ad vectors containing either the wild-type Ad35 fiber knob (Ad5/35) or Ad35 knob mutants with 4-fold- and 60-fold-higher affinity to CD46 (Ad5/35+ and Ad5/35++, respectively). In in vitro studies with cell lines, the higher affinities of Ad5/35+ and Ad5/35++ to CD46 did not translate into correspondingly higher transduction efficiencies, regardless of the CD46 receptor density present on cells. However, in vivo, in a mouse model with preestablished CD46high liver metastases, intravenous injection of Ad5/35++ resulted in more-efficient tumor cell transduction. We conclude that Ad5/35 vectors with increased affinity to CD46 have an advantage in competing with non-CD46-mediated sequestration of vector particles after intravenous injection.
Viral RNA and p24 Antigen as Markers of HIV Disease and Antiretroviral Treatment Success

HIV-1 RNA has become the standard for monitoring antiretroviral therapies. Dogma predicts, however, that a viral protein like p24 should be at least as good a marker of HIV disease activity, provided that it is measured with sufficient sensitivity and accuracy. Simple modifications including use of a more efficient virus lysis buffer, heat-mediated destruction of antibodies interfering with antigen detection, and tyramide signal amplification for increased sensitivity have highly improved the HIV-1 p24 antigen assay. The p24 antigen assay is inferior to RT-PCR in detecting viral particles, but the presence of extraviral p24 antigen in most samples makes largely up for this. p24 antigen testing is similarly sensitive and specific in diagnosing pediatric HIV infection, in predicting CD4+ T cell decline and clinical progression at early and late stage of infection, and suitable for antiretroviral treatment monitoring in both adults and children. Notably, p24 antigen was measurable even in patients with stably suppressed viremia, and its concentrations were correlated negatively with the concentrations of CD4+ T cells and positively with the concentrations of activated CD8+ T cell subsets. p24 antigen is an excellent marker of HIV expression and disease activity and can be used in the same fields of application as HIV RNA is used. The test is validated for subtype B, but requires further studies for non-B subtypes.
Spray Characterization of Ultra-low–volume Sprayers Typically Used in Vector Control1

Abstract Numerous spray machines are used to apply pesticides for the control of human disease vectors, such as mosquitoes and flies, and the selection and setup of these machines significantly affects the level of control achieved during an application. The droplet spectra produced by 9 different ultra-low–volume sprayers with oil- and water-based spray solutions were evaluated along with 2 thermal foggers with the use of diesel-based spray solutions. The droplet spectra from the sprayers were measured with the use of laser diffraction droplet sizing equipment. The volume median diameter from the sprayers ranged from 14.8 to 61.9 µm for the oil-based spray solutions and 15.5 to 87.5 µm for the water-based spray solutions. The 2 thermal foggers generated sprays with a volume median diameter of 3.5 µm. The data presented will allow spray applicators to select the spray solution and sprayer that generate the droplet-size spectra that meet the desired specific spray application scenarios.
Risk of acute promyelocytic leukemia in multiple sclerosis

Background: Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ). Methods: Using MassARRAY high-throughput DNA analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we genotyped patients with sAPL (n = 20) developed after treatment of MS (18 out 20 treated with MTZ) for the presence of 210 SNPs of 22 genes mostly involved in DNA repair and drug detoxification. Patients with MS who did not develop sAPL including 41 treated with MTZ (n = 253 and 41, respectively) and healthy blood donors (n = 310) were also genotyped as controls. Results: We observed risk allele frequency between MS and sAPL for BRCA2 (rs1801406): 6% and 26%, p = 0.007; XRCC5 (rs207906): 2.5% and 15%, p = 0.016; CYP3A4 (rs2740574): 4.5% and 25%, p = 0.0035. The association of homozygous variants of BRCA2 and XRCC5 yielded higher risk of sAPL (MS vs sAPL: 0.4% and 18%, p = 0.001). We also observed a significant association between a SNP in the promoter region (rs2740574) of CYP3A4, an enzyme involved in the metabolism of chemotherapeutic agents and development of sAPL. Conclusions: Increased susceptibility to develop sAPL in patients with MS receiving MTZ may be linked to genetic variants in DNA repair and drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage.
Diabetic Glycemic Control and Retinal Blood Flow

The effect of strict glycmic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 ± 0.9 μU/min (P < 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 ± 1.7 μU/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P <0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy.
Donors in Chains: Psychosocial Outcomes of Kidney Donors in Paired Exchange

Background Kidney paired donation chains are initiated by nondirected donors and propagated by donors within the chain of transplants, or chain donors. Objective To compare psychosocial and functional outcomes, and to test coercion, of chain donors in paired exchange versus traditional directed donors who have an established relationship with the recipient. Methods Thirty chain donors from a transplant center who were part of the National Kidney Registry paired exchange program were compared with 34 traditional donors who donated around the same time. Participants completed online surveys: the post-donation section of the Living Donor Expectancies Questionnaire was used to assess psychosocial and functional outcomes 1 to 6 years after donation. A survey to assess coercion was used as well. Results Chain donors and traditional donors were similar in terms of sex, race, age, and time after donation. The 2 groups had similar altruistic motives in donating their kidney, and both types of donors mentioned psychological benefits. No differences were found on questions regarding psychosocial outcomes save for the “quid pro quo scale” (P = .01), which suggested that the traditional donors felt more that the recipients are indebted to them. The 2 groups did not differ significantly in the coercion measure. Pressure to donate and stress of donation were not greater in chain donors than traditional donors (P = .60). Conclusion Kidney donors in kidney paired donation chains do as well as traditional donors psychosocially without any increased tendency toward experiencing coercion.
Hepatotoxicity of statins and other lipid‐lowering agents

Statins are generally well tolerated and adverse effects are relatively rare. Clinical trials are underpowered to detect uncommon adverse effects such as idiosyncratic drug‐induced liver injury. This review is aimed at covering the current knowledge on the hepatotoxicity associated with statins and other lipid lowering drugs. Both atorvastatin and simvastatin have been associated with more than 50 case reports of liver injury and other statins have been implicated in this type of liver injury as well. Idiosyncratic liver injury due to statins has been reported to occur 1.9%‐5.5% of patients in prospective series of drug‐induced liver injury. Atorvastatin and simvastatin have been associated with positive rechallenge and some case reports have described liver injury following dose escalation of the implicated statin. Mortality from liver injury and/or liver transplantation has been documented in a few patients with statin induced liver injury although the vast majority of patients with liver injury have recovered after cessation of therapy.
Circadian Phase-Dependent Modulation of cGMP-Gated Channels of Cone Photoreceptors by Dopamine and D2 Agonist

The affinity of cGMP-gated ion channels (CNGCs) for cGMP in chick retinal cone photoreceptors is under circadian control. Here we report that dopamine (DA) and D2 receptor agonists evoke phase-dependent shifts in the affinity of CNGCs for activating ligand. Inside-out patch recordings from cultured chick cones were performed at circadian time (CT) 4–7 and CT 16–19 on the second day of constant darkness. Exposing intact cells to DA or the D2 agonist quinpirole for 2 hr before patch excision caused a significant increase in theKD for cGMP during the night (CT 16–19) but had no effect during the day (CT 4–7). DA or quinpirole treatment had no effect on the Hill slope or the average number of channels per patch. The effect of DA was blocked by the D2 antagonist eticlopride and was not mimicked by D1 agonists or blocked by D1 antagonists. By contrast, a brief (15 min) exposure to DA or quinpirole caused a decrease in KD during the subjective day and had no effect during the subjective night. Thus, the effect of D2 agonists depends on both the duration of agonist exposure and the time of day. Application of DA or quinpirole evoked a transient activation of the MAP kinase Erk (extracellular signal-related kinase) during the day but caused a sustained inhibition during the night. Conversely, D2 agonists caused activation of Ca2+/calmodulin-dependent protein kinase II during the night and inhibited this enzyme during the day. A circadian oscillator in cones appears to regulate the nature of the transduction cascade used by D2 receptors.
What Is the Best Method for Treating Osmidrosis?

Axillary osmidrosis is caused by excessive secretion of apocrine, which causes an acrid odor and extreme social embarrassment. Elimination of the apocrine glands by a radical surgical procedure is known as the best solution for axillary osmidrosis; however, it is often accompanied by marked complications. The purpose of this study was to seek a more effective surgical procedure by comparing the various preexisting subcutaneous apocrine gland elimination methods using four parameters: odor, scar, immobilization period, and other surgical complications such as hematoma, seroma, flap necrosis, and wound dehiscence. From March 1995 to March 2000, a total of 189 patients underwent surgery for axillary osmidrosis via manual subdermal shavings (N = 117), liposuction curettage (N = 32), CO2 laser vaporization (N = 18), and ultrasonic aspiration (N = 22). Of these procedures, manual shaving had the lowest recurrence rate for malodor. However, the disadvantages of this procedure included wide scar, a long immobilization period, and moderate cases of surgical complications. CO2 laser vaporization had results similar to manual shaving except for a clinically higher recurrence rate. Liposuction had advantages such as small invisible scars, a short-term immobilization period, and the least number of surgical complications, but it had a high rate of dissatisfaction in postoperative malodor (46.9%). Ultrasonic aspiration offered better results such as short surgical scar and relatively low recurrence rate, but it had some surgical complications (3 of 44 axillas). Therefore, removal of subcutaneous apocrine glands by manual subdermal shaving is the treatment of choice for axillary osmidrosis, with a low recurrence rate (7.7%). Other adjuvant procedures were effective in achieving short scars and low surgical complications, but there was dissatisfaction in the rate of recurrence.
Alterations in the Renin-Angiotensin System in a Rat Model of Human Preeclampsia

Background/Aims: Preeclampsia is a hypertensive disorder unique to pregnancy in which elevated levels of marinobufagenin (MBG) have been reported. The renin-angiotensin system (RAS) may also play a role in the pathogenesis of preeclampsia. The aim of our study was to evaluate the status of the RAS in a rat model of preeclampsia characterized by hypertension, proteinuria, excessive weight gain and intrauterine growth restriction. Methods: We evaluated the components of the RAS in 5 groups of animals: nonpregnant control; normal pregnant (NP); pregnant rats which received injections of desoxycorticosterone acetate and 0.9% saline as their drinking water (PDS); normal pregnant rats injected with MBG (NPM), and PDS rats to which resibufogenin (RBG) had been administered (PDSR). RBG is an antagonist of MBG differing in structure from MBG only in the absence of a hydroxyl group in the β-5 position. Results: Plasma levels of active renin, renin and Ang II were significantly lower in PDS and NPM compared to NP and PDSR rats (p < 0.05). However, placental levels of these components were increased significantly in PDS and NPM compared to NP and PDSR rats (p < 0.05). Placental AT1 receptor expression was significantly higher in PDS and NPM compared to NP and PDSR rats (p < 0.05). Conclusions: (1) The peripheral RAS is downregulated, and the uteroplacental RAS is upregulated in this rat model of preeclampsia; (2) MBG is involved in the causation of these alterations, and (3) RBG prevents these changes.
Successful pregnancies on nocturnal home hemodialysis.

BACKGROUND AND OBJECTIVES Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal hemodialysis (NHD) (3 to 6 sessions per week, 6 to 8 h per treatment), by augmenting uremic clearance, leads to a more hospitable maternal environment and therefore superior outcomes in fertility and pregnancy compared with CHD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS This is a descriptive cohort study of all female patients achieving pregnancy and delivering a live infant while on NHD at the University Health Network, St. Michael's Hospital, and Humber River Regional Hospital from 2001 to 2006 in Toronto, Canada. Our primary objective was to describe maternal and fetal outcomes in addition to the changes in biochemical parameters after conception in our cohort. RESULTS Our cohort included five patients (age range, 31 to 37 yr) who had seven pregnancies while on NHD and delivered six live infants. All had previously been on CHD, but none conceived during that time. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 +/- 10 to 48 +/- 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean arterial BP were maintained within normal physiological parameters. The mean gestational age of the cohort was 36.2 +/- 3 wk and the mean birth weight was 2417.5 +/- 657 g. The maternal and fetal complications observed in the cohort included intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, an augmented dialysate phosphate supplementation regimen was required. CONCLUSIONS NHD may allow for improved fertility. Delivering a live infant at a mature gestational age is feasible for patients on NHD. Our cohort tended to have fewer maternal and fetal complications compared with historical controls. Hemoglobin and phosphate levels must be monitored with treatment adjusted accordingly.
Estrogen receptor‐alpha immunoreactive neurons in the ventrolateral periaqueductal gray receive monosynaptic input from the lumbosacral cord in the rhesus monkey

Estrogen affects female sexual behavior, analgesia, and micturition in mammals. One of the possible sites at which estrogen might exert its effect on these functions is the periaqueductal gray (PAG). The PAG is involved in each of these functions, it receives sensory input relevant to these functions from the lumbosacral cord, and contains estrogen receptor‐alpha immunoreactive (ER‐α IR) neurons. The present light (LM) and electron microscopic (EM) study seeks to determine whether there are monosynaptic projections from the lumbosacral cord to ER‐α IR neurons in the PAG of the female rhesus monkey. Tracer was injected into the lumbosacral cord to visualize the lumbosacral‐PAG projection, and the distribution of ER‐α IR neurons in the PAG was studied immunohistochemically. The medial part of the ventrolateral caudal PAG received the densest projection from the lumbosacral cord. Another prominent projection was found in the lateral PAG at the intercollicular level. Although ER‐α IR neurons were widely distributed throughout the PAG, approximately 40% of ER‐α IR PAG neurons were located as a distinct cluster in the medial portion of the ventrolateral, caudal PAG. Double labeling experiments showed that the location of this cluster precisely overlapped with the densest lumbosacral‐PAG projection. EM revealed that axons from the lumbosacral cord made asymmetrical synaptic contacts with unlabeled dendrites and ER‐α IR neuronal somata in the ventrolateral PAG. It is concluded that there exists a specific, monosynaptic pathway from lumbosacral neurons to ER‐α expressing PAG neurons in the rhesus monkey. This pathway might be involved in the mechanisms of analgesia, blood pressure, mating behavior, and micturition. J. Comp. Neurol. 443:27–42, 2002. © 2002 Wiley‐Liss, Inc.