Miracle-dz/UniFAR-FTUs huggingface dataset:
Remifentanil Pharmacokinetics in Obese versus Lean Patients

Background Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics. Methods Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed. Results The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations. Conclusions The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.
Use of the Amplatzer Vascular Plug as an Anchoring Scaffold for Coil-mediated Parent Vessel Occlusion: Technical Case Report

OBJECTIVE: Parent vessel sacrifice is a useful treatment strategy for fusiform intracranial aneurysms. Originally performed using the detachable silicone balloon, endovascular arterial occlusion is currently achieved using coils, a process which can be limited by coil mass migration. METHODS: We demonstrate the use of the Amplatzer vascular plug as a fixed anchor within the target parent vessel to facilitate coil-mediated occlusion, especially in vascular segments not encased by a bony canal. The technique was used successfully in two patients: a 90-year-old woman presenting with IIIrd and VIth cranial nerve palsy from a fusiform left cavernous internal carotid aneurysm and a 44-year-old man with distal thromboemboli from a fusiform dissecting-type right vertebral artery involving the origin of the posterior inferior cerebellar artery. RESULTS: Both patients were treated successfully with proximal parent vessel occlusion using coils after deployment of an Amplatzer vascular plug proximal to the target lesion. With the Amplatzer device acting as a fixed anchor in the parent vessel, coils were deployed proximally in a compact configuration. After deployment of the vascular plugs and coils, hermetic occlusion of the parent vessel was documented angiographically. CONCLUSION: The Amplatzer vascular plug can facilitate coil occlusion of large cervical vessels by acting as a focal coil and embolic material immobilizer, which can prevent coil mass migration and lead to improved packing density.
Long‐term course of post‐transplant mesangial IgA deposition: clinicopathologic study of nine cases

Abstract: We conducted the present study to elucidate the fate of post‐transplant mesangial IgA deposit under the long‐term observation. Out of a total of 45 cases with post‐transplant mesangial IgA deposition, nine cases with more than 4 yr of follow‐up term were enrolled in this study, and clinicopathologic characteristics were described. The study included three men and six women with a mean age of 34.2 yr. The average observation time from the detection of mesangial IgA deposition was 6.1 yr. Three cases were categorized as recurrent IgA nephropathy, while six cases were classified into latent mesangial IgA deposition. One case with hypertension developed end‐stage renal disease. The significant improvement in microscopic hematuria was observed in one recurrent IgA nephropathy case. Microscopic findings included mild mesangial stalk thickening in all but one case. IgA deposition demonstrated a significant decrease in three latent mesangial IgA deposition cases. No apparent reduction in dense deposit quantity was observed on electron microscopy. There was no association between clinicopathologic findings and the regimen of anti‐immunosuppressive agents. This study showed the improvement of the disease activity did occur in both recurrent IgA nephropathy and latent mesangial IgA deposition. Further investigation of latent mesangial IgA deposition may present the important clue to the pathogenesis of IgA nephropathy.
A Sequential Panel Selection Approach to Cointegration Analysis: An Application to Wagner’s Law for South African Provincial Data

This study extends the recently introduced sequential panel selection method (SPSM) to a cointegration framework which is particularly used to investigate Wagner’s law for 9 South African provinces between 2001 and 2016. We note that when applying single country/region estimates we fail to find evidence of cointegration whereas within panel regressions, cointegration effects are present for the entire dataset. In further applying the SPSM we observed significant Wagner’s effects for panels inclusive of Gauteng, Eastern Cape and Kwazulu-Natal provinces and when these provinces are excluded from the panels, cointegration effects are unobserved.
Parathyroid hormone synergizes with non‐cyclic AMP pathways to activate the cyclic AMP response element

Parathyroid hormone (PTH) activates multiple signaling pathways following binding to the PTH1 receptor in osteoblasts. Previous work revealed a discrepancy between cAMP stimulation and CRE reporter activation of truncated PTH peptides, suggesting that additional signaling pathways contribute to activation of the CRE. Using a CRE‐Luciferase reporter containing multiple copies of the CRE stably transfected into the osteoblastic cell line Saos‐2, we tested the ability of modulators of alternative pathways to activate the CRE or block the PTH‐induced activation of the CRE. Activators of non‐cyclic AMP pathways, that is, EGF (Akt, MAPK, JAK/STAT pathways); thapsigargin (intracellular calcium pathway); phorbol myristate acetate (protein kinase C, PKC pathway) induced minor increases in CRE‐luciferase activity alone but induced dramatic synergistic effects in combination with PTH. The protein kinase A (PKA) inhibitor H‐89 (10 µM) almost completely blocked PTH‐induced activation of the CRE‐reporter. Adenylate cyclase inhibitors SQ 22536 and DDA had profound and time‐dependent biphasic effects on the CRE response. The MAPK inhibitor PD 98059 partially inhibited basal and PTH‐induced CRE activity to the same degree, while the PKC inhibitor bisindolylmaleimide (BIS) had variable effects. The calmodulin kinase II inhibitor KN‐93 had no significant effect on the response to PTH. We conclude that non‐cAMP pathways (EGF pathway, calcium pathway, PKC pathway) converge on, and have synergistic effects on, the response of a CRE reporter to PTH. J. Cell. Biochem. 106: 887–895, 2009. © 2009 Wiley‐Liss, Inc.
A simplified maximal power controller for terrestrial photovoltaic panel arrays

Perusal of the V-I characteristics of commercial solar panels with insolation, ambient temperature and production spreads as parameter, indicate that the maximum power is obtained from such a panel when it is loaded to a working voltage that is a fixed percentage of its open circuit voltage within (+2)%. This contribution describes a system that uses this characteristic to achieve maximum power control by determining the open circuit voltage and automatically loading the panel to the maximum power point as applied to a battery charging installation. The description includes the application of a novel modified darlington circuit to boost the efficiency of a pulse width controlled switch mode type regulator by reducing the darlington saturation voltage by a compensating voltage. Advanced switching technology is applied to reduce switching losses, and maximise efficiency.
Detection of herpes simplex virus type 1 latency-associated transcript expression in trigeminal ganglia by in situ reverse transcriptase PCR

One of the defining characteristics of herpes simplex virus type 1 (HSV-1) infection is the ability of the virus to establish a lifelong latent state in neurons. We previously demonstrated (R. Ramakrishnan, A.J. Fink, G. Jiang, P. Desai, J. C. Glorioso, and M. Levine, J. Virol. 68:1864-1873, 1994) by in situ PCR that many more neurons contain viral genomes than are detected by in situ hybridization for HSV latency-associated transcripts (LATs). To determine whether all cells which contain genomes express LATs, we examined trigeminal ganglia for LATs 1 and 8 weeks after corneal scarification with ribonucleotide reductase-deficient HSV-1 by in situ reverse transcriptase PCR. The number of LAT-positive cells detected by in situ reverse transcriptase was substantially greater than the number of cells positive by in situ hybridization and appeared to be similar to the number of cells containing HSV genomes by in situ PCR and the number of ganglionic neurons that project to the cornea as detected by retrograde labeling with Fluorogold. These results demonstrate LAT expression in many neurons containing HSV-1 genomes.
Sustainable Consumer Behaviour in the Market of Cultural Services in Central European Countries: The Example of Poland

In the second decade of the 21st century, in the developed countries of Central Europe, we can observe the transfer of free time to consumption, including the consumption of cultural services. This change, however, has led to some disturbances in the consumption of cultural services. Disturbances, which in particular relate to the sphere of needs, the sphere of the means of meeting needs and, finally, the sphere of consumer behaviour; for example, in relation to transport. In this article, most of the attention was devoted to the last category of disturbances (the sphere of consumer behaviour) and specifically concerned the culture service customers’ choice of means of transport to a specific cultural event. The research carried out by the authors shows that the most popular means of transport used on the way to a symphonic concert held in Katowice is still one’s own car. This applies to both residents of the city of Katowice, who could easily get to the concert using public transport (bus, tram) or on foot, as well as people from outside Katowice (who, as the research shows, very rarely use Katowice’s extensive rail network and well-developed intercity bus service). Thus, it has been proved that despite various legal regulations conducive to sustainable consumption, the majority of Polish consumers of cultural services in the analysed area of consumer behaviour do not follow this concept. The article opens with a review of the literature on free time and the sustainable consumption of cultural services. The next part of the study presents the results and conclusions of research conducted on a group of 515 consumers of philharmonic services. The last part of the article discusses the results obtained and indicates the existing management implications.
Acute blood loss during burn and soft tissue excisions: An observational study of blood product resuscitation practices and focused review

BACKGROUND Many military and civilian centers have shifted to a damage-control resuscitation approach, focused on providing oxygen-carrying capacity while simultaneously mitigating coagulopathy with a balanced ratio of platelets and plasma to red blood cells. It is unclear to what degree this strategy is used during burn or soft tissue excision. Here, we characterized blood product transfusion during burn and soft tissue surgery and reviewed the published literature regarding intraoperative coagulation changes. We hypothesized that blood product resuscitation during burn and soft tissue excision is not hemostatic and would be insufficient to address hemorrhage-induced coagulopathy. METHODS Consented adult patients were enrolled into an institutional review board–approved prospective observational study. Number, component type, volume, and age of the blood products transfused were recorded during burn excision/grafting or soft tissue debridement. Component bags (packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate) were collected, and the remaining sample was harvested from the bag and tubing. Aliquots of 1/1,000th the original volume of each blood product were obtained and combined, producing an amalgam sample containing the same ratio of product transfused. Platelet count, rotational thromboelastometry, and impedance aggregometry were measured. Significance was set at p < 0.05. RESULTS Amalgamated transfusate samples produced abnormally weak clots (p ⩽ 0.001) particularly if they did not contain platelets. Clot strength (48.8 [2.6] mm; reference range, 49–71 mm) for platelet-containing amalgams was below the lower limit of the reference range despite platelet–red blood cell ratios greater than 1:1. Platelet aggregation was abnormally low; transfused platelets were functionally inferior to native platelets. CONCLUSION Our study and focused review demonstrate that further work is needed to fully understand the needs of patients undergoing tissue excision. The three studies reviewed and the results of our observational work suggest that coagulopathy and thrombocytopenia may contribute to intraoperative hemorrhage. Blood product resuscitation during burn and soft tissue excision is not hemostatic. LEVEL OF EVIDENCE Epidemiologic study, level V.
Treatment: Evaluation Evaluation of a Therapeutic Community Treatment Program: A Long-Term Follow-up Study in Spain

The aims of this study is to carry out a long-term follow-up evaluation of a wellestablished therapeutic community treatment for addictions in Navarre (Spain) and to make a comparison between the program completers and the dropouts, as well as between relapsing and nonrelapsing patients, on a broad set of variables. A long-term follow-up design (mean of 6 years after leaving treatment) was used to analyze the outcomes of the therapeutic program. The sample consisted of 155 subjects (113 completers and 42 dropouts). A personal interview was carried out with each one of the located subjects. The interviews took place between September 2000 and September 2004. Treatment “dropouts” manifested a higher and earlier rate both of relapses, and of new treatments for their drug addiction than the completion group. The program was also effective in reducing criminal behavior and improving the state of health. Significant differences were found across outcome variables when comparison was made between treatment completers and “dropouts. ” All subjects improved on outcome variables after receiving the treatment. When relapsing and nonrelapsing patients were compared, significant outcome differences were also found between groups. The study’s limitations are noted and future needed research is suggested.
The role of endoscopic retrograde cholangiopancreatography in infants with cholestasis.

BACKGROUND/PURPOSE Endoscopic retrograde cholangiopancreatography (ERCP) was assessed in the diagnosis of cholestatic liver disease in infants. METHODS ERCP was performed in 50 infants who had prolonged cholestasis. Their ages ranged from 25 to 274 days (mean, 69 days), and their weight ranged from 2.6 to 6.7 kg (mean, 4.7 kg). Incomplete visualization of the biliary tree or visualization of only the pancreatic duct was followed by exploratory laparotomy. In those in whom the biliary tree was visualized completely, the caliber of the bile duct was compared with that of the pancreatic duct. RESULTS ERCP was completed in 43 patients (success rate, 86%) without complications. In the 7 patients in whom ERCP failed, 6 had biliary atresia (BA) diagnosed by exploratory laparotomy. The other patient had congenital biliary dilatation (CBD). In 29 of the 43 patients, the biliary tree was seen partially or only the pancreatic duct was visualized. These patients had BA diagnosed by laparotomy. Complete visualization of the biliary tree was obtained in 14 patients. Of these, 9 had neonatal hepatitis (NH), 2 had a paucity of intrahepatic bile ducts (PIBLD), and 3 had CBD. In all of the patients with NH, cholestasis improved spontaneously. The 2 patients with PIBLD had biopsy-proven disease. The caliber of the bile duct was larger than that of the pancreatic duct in NH. This relationship was not observed in PIBLD. CONCLUSIONS ERCP is safe in infants. It is useful in the diagnosis of prolonged cholestasis.
Investigation of colon cancers for human papillomavirus genomic sequences by polymerase chain reaction

Two previous studies have reported the presence of human papillomavirus (HPV) genomic sequences in colorectal cancers. We examined DNAs from 50 colorectal tumors for HPV sequences by polymerase chain reaction (PCR), using HPV consensus L1 primers for amplification. The PCR products were screened with a generic HPV probe consisting of amplimers of HPV‐16 and HPV‐18. All tumor DNAs were negative for HPV sequences. These results call into the question the reported association of colorectal cancers with HPVs. © 1992 Wiley‐Liss, Inc.
Delayed maturation of the frontal cortex in childhood autism.

OBJECTIVE The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. METHOD Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. RESULTS A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. CONCLUSIONS Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.
A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces

We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain‐of‐function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial MTOR mutation. We describe the findings in this family to highlight that (i) the path to determination of pathogenicity was confounded by the lack of genomic reference data for Australian Aboriginals and that (ii) the disease biology, functional analyses in this family, and studies on the tuberous sclerosis complex support consideration of an mTOR inhibitor as a therapeutic agent. © 2015 Wiley Periodicals, Inc.
Real time implementation of k fake location generation algorithm to protect location privacy in location based services

In today's world usage of location based services on mobile devices such as smartphones, tablet PCs and laptops has become progressively popular. Even though location based services are proved to be very useful and convenient, they may cause risk to the users' location privacy, because for the retrieval of useful information based on user's location, user has to send his/her present location and the query to the location based service provider and the service provider or intruders can misuse this private information of user to infer some delicate data, such as, users' home location, workplace, most frequently visited places etc. This problem gets riskier if the user often makes use of the location based services as the history of the gathered locations makes it very easy to sense such private data. Although a lot of work that addresses privacy security concerns in location based services have been carried out, most of it cannot be applied directly to a real life scenario. This is because their focus is on theoretical facets in location privacy protection and assumption of a simple system model in which users' mobility model doesn't take into account the real world characteristics. In this paper, we have implemented a real time model to protect the location privacy of the user by taking into account characteristics of the real world.
The Nuclear Tyrosine Kinase BRK/Sik Phosphorylates and Inhibits the RNA-binding Activities of the Sam68-like Mammalian Proteins SLM-1 and SLM-2*

Expression of the intracellular tyrosine kinase BRK/Sik is epithelial-specific and regulated during differentiation. Only a few substrates have been identified for BRK/Sik, including the KH domain containing RNA-binding protein Sam68 and the novel adaptor protein BKS. Although the physiological role of Sam68 is unknown, it has been shown to regulate mRNA transport, pre-mRNA splicing, and polyadenylation. Here we demonstrate that the Sam68-like mammalian proteins SLM-1 and SLM-2 but not the related KH domain containing heterogeneous nuclear ribonucleoprotein K are novel substrates of BRK/Sik. The expression of active BRK/Sik results in increased SLM-1 and SLM-2 phosphorylation and increased retention of BRK/Sik within the nucleus. The phosphorylation of SLM-1 and SLM-2 has functional relevance and leads to inhibition of their RNA-binding abilities. We show that SLM-1, SLM-2, and BRK/Sik have restricted patterns of expression unlike the ubiquitously expressed Sam68. Moreover, BRK/Sik, SLM-1, and Sam68 transcripts were coexpressed in the mouse gastrointestinal tract and skin, suggesting that SLM-1 and Sam68 could be physiologically relevant BRK/Sik targets in vivo. The ability of BRK/Sik to negatively regulate the RNA-binding activities of the KH domain RNA binding proteins SLM-1 and Sam68 may have an impact on the posttranscriptional regulation of epithelial cell gene expression.
β-Amyloid Induces Local Neurite Degeneration in Cultured Hippocampal Neurons: Evidence for Neuritic Apoptosis

Many apoptotic insults, including beta-amyloid, cause neuritic degeneration. The possibility that apoptotic insults act directly on neurites was investigated in experiments using compartmented cultures of hippocampal neurons. Neurites in modified Campenot chambers displayed morphological signs of degeneration, including beading or blebbing, when exposed to beta-amyloid. At short time points neurite degeneration was limited to the distal portions of neurites directly exposed to beta-amyloid. Furthermore, annexin V binding detected extracellular exposure of phosphatidylserine in portions of neurites directly exposed to apoptotic insults. Pretreatment of the cultures with zVAD-fmk blocked annexin V binding induced by beta-amyloid and concanavalin A, suggesting that caspase activity was required. Caspase activation was also visualized in neurites locally exposed to apoptotic insults. Together these results show that apoptotic insults cause local neurite degeneration which displays morphological and biochemical characteristics of apoptosis and suggest that neurite degeneration may use mechanisms common to apoptosis.