Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of life over time in dialysis: the Netherlands Cooperative Study on the Adequacy of Dialysis. NECOSAD Study Group.

BACKGROUND Information on the longitudinal quality of life (QL) of patients treated by different dialysis modalities is lacking. Therefore, we performed a prospective cohort study on the QL over time in hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS New chronic dialysis patients from 13 Dutch dialysis centers were consecutively included. The patients' self-assessment of QL was measured with the SF-36 form at 3, 6, 12, and 18 months after the start of dialysis treatment. RESULTS Out of 230 patients who completed the QL questionnaire at least once, 139 patients stayed on their initial dialysis modality, 26 patients switched dialysis modality, 35 patients were transplanted, 28 patients died, and two patients had a recovery of renal function. The QL of patients who died during the study period was considerably worse at baseline and worsened at a faster rate than in the other patient groups. In patients who stayed on their initial dialysis modality, the physical QL decreased over time, whereas the mental QL tended to remain stable. After an adjustment for the initial value of QL and comorbidity, a consistently favorable effect of HD on physical QL over time was found compared with PD, whereas mental QL values remained similar. Parameters of adequacy of dialysis were not associated with QL over time. CONCLUSION This prospective cohort study shows that physical QL over time in HD patients is better than in PD patients.
Bonding of mild self-etching primers/adhesives to dentin with thick smear layers.

PURPOSE To compare the microtensile bond strength (microTBS) and the ultrastructure of resin-dentin interfaces of four self-etching systems that were applied to dentin with thick smear layers. METHODS Human third molars were ground with 180-grit silicon carbide papers to expose deep coronal dentin. A 3-mm vertical slit was made along the diameter of each tooth to fit a glass cover slip, dividing each tooth into two bonding surfaces. Two 2-step, self-etching primers (ABF experimental system and Imperva Fluoro Bond) and two single-step, self-etching adhesives (One-Up Bond F and AQ Bond) were examined. Adhesives were applied to one side of the teeth passively, and to the other side with continuous agitation for the same self-etching period. Incremental composite buildups were performed and beams with cross-sectional areas of 0.81 mm2 were prepared for microTBS evaluation. Demineralized, bonded specimens were processed for TEM examination. RESULTS Two-way ANOVA showed that both the adhesive type and the application mode significantly affected microTBS results. However, the interaction of these two factors was not statistically significant (P > 0.05). For each adhesive, agitation produced significantly higher microTBS than passive application. With passive application, all systems diffused through thick smear layers and formed thin hybrid layers in intact dentin. With continuous agitation, smear layers were completely dispersed or dissolved, and thicker hybrid layers with upstanding collagen fibrils were observed.
Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia

Background and Objectives Commonly used local anesthetics (eg, lidocaine) are nonselective in blocking sodium channel subtypes, potentially resulting in adverse events, such as prolonged muscle paralysis and unstable hemodynamics. Subtype-selective sodium channel block might avoid these unwanted adverse effects while preserving desirable anesthetic effects. The contributions of sodium channel subtypes in different components of regional anesthesia are unclear and this study assumed that selective sodium channel subtype block might produce selective nerve block. Methods Sciatic nerve block was performed in mice with lidocaine (nonselective sodium channel blocker), tetrodotoxin (TTX, TTX-sensitive sodium channel blocker), and A-803467 (selective Nav1.8 subtype blocker). Tactile sensory, pinprick, and thermal sensory block as well as motor block were evaluated after injection of study drugs. Median effective concentration (EC50) of lidocaine, TTX, and A-803467 as well as their blocking durations were determined. Results Lidocaine produced regional anesthetic effects including tactile, pinprick, and thermal sensory block as well as motor block, with EC50 [mean, 95% confidence intervals (CIs)] of 4.4 (3.7–5.2), 9.4 (8.0–10.9), 5.2 (4.3–6.2), and 3.7 (3.3–4.2) mmol/L, respectively. Tetrodotoxin produced tactile sensory block and motor block with EC50 (mean, 95% CIs) of 7.7 (6.0–11.0) and 8.3 (7.4–9.8) &mgr;mol/L, respectively; whereas A-803467 produced tactile sensory block only, with EC50 (mean, 95% CIs) of 12.6 (11.7–15.6) &mgr;mol/L. Conclusions Sodium channel subtype selective blockers could induce selective nerve blocks. Tetrodotoxin-sensitive sodium channel subtypes contribute to low-threshold sensory block (eg, tactile) and motor block. Unexpectedly, selective Nav1.8 subtype block induced low-threshold sensory block rather than nociceptive or motor block.
Comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome

Background. Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV) is currently invading the germline of the koala (Phascolarctos cinereus) and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized. Results. To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS) and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW) koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized. Conclusions. Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small.
Extracorporeal Membrane Oxygenation after Liver Transplantation in a Patient with Hepatopulmonary Syndrome and an Atrial Septal Defect

Introduction Hepatopulmonary syndrome (HPS) is a rare complication of liver cirrhosis that may result in refractory hypoxemia even after liver transplantation. ECMO has been rarely used after liver transplantation or in patients with HPS. Methods We present a patient with HPS who underwent liver transplantation and developed refractory hypoxemia requiring postoperative ECMO support at our institution. During our review of literature we found nine reports of ECMO use for cardiorespiratory failure after liver transplant in the past. Results Our patient had persistent intrapulmonary shunting and developed severe respiratory failure after liver transplant. Additionally, the patient was found to have an atrial septal defect (ASD) and required percutaneous closure while receiving ECMO support. Literature review suggests that survival among these patients who were supported with ECMO after liver transplant was 50% and catastrophic bleeding complications were described in only one report. Conclusions With careful selection of post-liver transplant patients and judicious management of anticoagulation, ECMO can be safely instituted in this cohort.
Influence of airway pressure on minimum occlusive endotracheal tube cuff pressure.

OBJECTIVE To examine the in vivo relationship between peak inflation pressure and the minimum occlusive pressure of a "high-volume, low-pressure" endotracheal tube cuff that may in some circumstances promote tracheal ischemic complications. DESIGN Prospective, clinical study. SETTING Surgical suite in a university hospital. PATIENTS Fifteen patients undergoing mechanical ventilation and general anesthesia for surgery. INTERVENTIONS After the regularly assigned anesthesia personnel established adequate general anesthesia, the investigator deflated and then reinflated the endotracheal tube cuff until tracheal seal was reestablished by auscultation. Peak inflation pressure and minimum occlusive pressure were determined using fluid-filled transducers to simultaneously record airway pressure just proximal to the endotracheal tube and cuff pressure via the pilot tube. MEASUREMENTS AND MAIN RESULTS Peak inflation pressure ranged from 12.1 to 43.7 mm Hg, and was associated with a minimum occlusive pressure of 2.2 to 39.7 mm Hg. Minimum occlusive pressure increased linearly over the range of measured peak inflation pressure values (r2 = .85, p < .001). CONCLUSIONS Knowledge of the linear relationship between peak inflation pressure and minimum occlusive pressure can help the clinician identify patients who may be at risk for cuff-induced tracheal ischemic complications, such as tracheoesophageal fistula and tracheal stenosis. In our series, a cuff pressure of 25 mm Hg corresponded to a peak inflation pressure of 35.3 mm Hg (48 cm H2O). Patients with higher peak inflation pressures may be at risk for ischemic tracheal injury, despite proper cuff inflation techniques.
COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream

While the cortical interneurons derived from the medial ganglionic eminence (MGE) migrate rather diffusely into the cortex, interneurons that migrate out from the caudal ganglionic eminence (CGE) mainly move caudally into the caudal cerebral cortex and the hippocampus in the form of the caudal migratory stream (CMS) (Yozu et al., 2005). Although transplantation experiments at embryonic day 13.5 had revealed that the migrating cells in these two populations are already intrinsically different in regard to their ability to respond to the CGE environment (Yozu et al., 2005), it is not known how the CGE cells are specified and how their migratory behavior is determined. In this study we showed that, although CGE and lateral ganglionic eminence (LGE) express almost the same marker molecules, LGE cells do not migrate caudally when transplanted into the CGE, suggesting that LGE cells are intrinsically different from CGE cells. We therefore compared the transcriptomes of the CGE, MGE, and LGE, and the results showed that COUP-TFII was expressed preferentially in the CGE as well as in the migrating interneurons in the CMS. Transplantation experiments revealed that COUP-TFII is sufficient to change the direction of MGE cell migration to caudal when transplanted into the CGE environment, and knockdown of COUP-TFII inhibited the caudal migration of the CGE cells. These results suggest that COUP-TFII is both required and sufficient for the CGE-cell-specific migratory behavior in the caudal direction. Thus, a locally expressed transcription factor determines the migratory direction of the cortical interneurons in a region-specific manner.
Intracranial pressure pulse morphological features improved detection of decreased cerebral blood flow

We investigated whether intracranial pressure (ICP) pulse morphological metrics could be used to realize continuous detection of low cerebral blood flow. Sixty-three acutely brain injured patients with ICP monitoring, daily 133Xenon cerebral blood flow (CBF) and daily transcranial Doppler (TCD) assessments were studied. Their ICP recordings were time-aligned with the CBF and TCD measurements so that a 1 h ICP segment near the CBF and TCD measurements was obtained. Each of these recordings was processed by the Morphological Cluster and Analysis of Intracranial Pressure (MOCAIP) algorithm to extract pulse morphological metrics. Then the differential evolution algorithm was used to find the optimal combination of the metrics that provided, using the regularized linear discriminant analysis, the largest combined positive predictivity and sensitivity. At a CBF threshold of 20 ml/min/100 g, a sensitivity of 81.8 ± 0.9% and a specificity of 50.1 ± 0.2% were obtained using the optimal combination of conventional TCD and blood analysis metrics as input to a regularized linear classifier. However, using the optimal combination of the MOCAIP metrics alone we were able to achieve a sensitivity of 92.5 ± 0.7% and a specificity of 84.8 ± 0.8%. Searching the optimal combination of all available metrics, we achieved the best result that was marginally better than those from using MOCAIP alone. This study demonstrated that the potential role of ICP monitoring may be extended to provide an indicator of low global cerebral blood perfusion.
In-vivo sensitivity of Plasmodium vivax isolates from Rond nia (western Amazon region, Brazil) to regimens including chloroquine and primaquine.

Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rond nia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the 'classical' regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a 'short' regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re-infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region.
Retinoic acid hydroxylase (CYP26) is a key enzyme in neuronal differentiation of embryonal carcinoma cells.

Besides nuclear retinoid receptors and cellular retinoid binding proteins also retinoic acid (RA)-synthesizing enzymes (using all-trans-retinal as substrate) and RA-catabolizing enzymes (producing hydroxylated products) may explain the specific effects of retinoids. In the past we have established an active role for 4-hydroxy-RA and 4-oxo-RA, which originally were considered to be inactive retinoids, but in fact are highly active modulators of positional specification in Xenopus development. Here we present evidence for a specific role of hydroxylated RA metabolites in the onset of neuronal differentiation. 4-Hydroxy- and 18-hydroxy-RA are products of the hydroxylation of RA by a novel cytochrome P450 (CYP)-type of enzyme, CYP26, expression of which is rapidly induced by RA. P19 embryonal carcinoma (EC) cell lines stably expressing hCYP26 undergo extensive and rapid neuronal differentiation in monolayer at already low concentrations of RA, while normally P19 cells under these conditions differentiate only in endoderm-like cells. Our results indicate that the effects on growth inhibition and RARbeta transactivation of P19 EC cells are mediated directly by RA, while the onset of neuronal differentiation and the subsequent expression of neuronal markers is mediated by hCYP26 via the conversion of RA to its hydroxylated products.
The effect of dopaminergic medication on conflict adaptation in Parkinson's disease

Parkinson's disease (PD) is a neurological disorder associated primarily with motor symptoms such as tremor, slowness of movement, and difficulties with gait and balance. Most patients take dopaminergic medication to improve their motor functions. Previous studies reported indications that such medication can impair higher cognitive functions (cf. dopamine overdose hypothesis). In the present study, we examined the effect of medication status on conflict adaptation. PD patients performed a Stroop task in which we manipulated the proportion of congruent and incongruent items, thereby allowing us to explore conflict adaptation. The use of mouse movements allowed us to examine the action dynamics of conflict adaptation in PD, and their sensitivity to dopaminergic medication. Each patient performed the same task twice: once without making changes to their regular medication regime, and once after overnight withdrawal from their medication. Results showed that medication improved mouse movements and alleviated motor symptoms. Moreover, patients' mouse movements were modulated as a function of the proportion congruency manipulation, revealing conflict adaptation in PD, which was unaffected by medication status. The present study extends earlier work on conflict adaptation in PD where reduced transient (trial-by-trial) conflict adaptation was observed ON compared to OFF medication (Duthoo et al., 2013, Neuropsychology, 27, 556). Our findings suggest that more sustained cognitive control processes may not be sensitive to dopamine overdose effects.
The emerging diversity of transpososome architectures

Abstract DNA transposases are enzymes that catalyze the movement of discrete pieces of DNA from one location in the genome to another. Transposition occurs through a series of controlled DNA strand cleavage and subsequent integration reactions that are carried out by nucleoprotein complexes known as transpososomes. Transpososomes are dynamic assemblies which must undergo conformational changes that control DNA breaks and ensure that, once started, the transposition reaction goes to completion. They provide a precise architecture within which the chemical reactions involved in transposon movement occur, but adopt different conformational states as transposition progresses. Their components also vary as they must, at some stage, include target DNA and sometimes even host-encoded proteins. A very limited number of transpososome states have been crystallographically captured, and here we provide an overview of the various structures determined to date. These structures include examples of DNA transposases that catalyze transposition by a cut-and-paste mechanism using an RNaseH-like nuclease catalytic domain, those that transpose using only single-stranded DNA substrates and targets, and the retroviral integrases that carry out an integration reaction very similar to DNA transposition. Given that there are a number of common functional requirements for transposition, it is remarkable how these are satisfied by complex assemblies that are so architecturally different.
Evaluations of Unformulated and Formulated Dendrimer-Based Microbicide Candidates in Mouse and Guinea Pig Models of Genital Herpes

ABSTRACT Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.
Detection of nitrotyrosine in aging and osteoarthritic cartilage: Correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1.

OBJECTIVE To determine whether oxidative damage to cartilage proteins can be detected in aging and osteoarthritic (OA) cartilage, and to correlate the results with the local production of interleukin-1beta (IL-1beta) and the responsiveness of isolated chondrocytes to stimulation with insulin-like growth factor 1 (IGF-1). METHODS The presence of nitrotyrosine was used as a measure of oxidative damage. Histologic sections of knee articular cartilage, obtained from young adult and old adult cynomolgus monkeys, which develop age-related, naturally occurring OA, were evaluated. Each cartilage section was graded histologically on a scale of 0-7 for the presence of OA-like changes, and serial sections were immunostained using antibodies to nitrotyrosine and IL-1beta. Chondrocytes isolated and cultured from cartilage adjacent to the sections used for immunostaining were tested for their response to IGF-1 stimulation by measuring sulfate incorporation in alginate cultures. For comparison with the monkey tissues, cartilage sections from human tissue donors and from tissue removed at the time of OA-related joint replacement surgery were also immunostained for nitrotyrosine and IL-1beta. RESULTS The presence of nitrotyrosine was associated with aging and with the development of OA in cartilage samples from both monkeys and humans. All sections that were highly positive for IL-1beta also showed staining for nitrotyrosine. However, in a few sections from older adult monkeys and humans, nitrotyrosine was present but IL-1beta was absent, suggesting that some age-related oxidative damage is independent of IL-1beta. In chondrocytes that were isolated from monkey cartilage positive for nitrotyrosine or IL-1beta, the response to stimulation with IGF-1 was significantly reduced. In some samples from older adult monkeys, IGF-1 resistance was seen in cells isolated from tissue that did not stain for nitrotyrosine or IL-1beta. CONCLUSION Oxidative damage due to the concomitant overproduction of nitric oxide and other reactive oxygen species is present in both aging and OA cartilage. This damage can contribute to the resistance of chondrocytes to IGF-1 stimulation, but it is unlikely to be the sole cause of IGF-1 resistance in these chondrocytes.