Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxybutynin-Nanoemulgel Formulation as a Successful Skin Permeation Strategy: In-vitro and ex-vivo Evaluation

Among different topical drug delivery systems, nanoemulsions (NEs) are attractive due to enhanced skin permeation potential and minimum toxicity. Topical nanoemulgels (NEMGELs) contain both gelling agents and NEs and thus can enhance skin permeation with sustained effects at the site of application. Oxybutynin (OXB) is an anti-muscarinic agent that is administered orally to treat hyperhidrosis but its systemic side effects may decrease patient compliance. Therefore, it assumes that oxybutynin-nanoemulgel (OXB-NEMGEL) with sustained release properties and skin permeation ability may be a suitable alternative. Using Design Expert software®, 17 OXB-NE formulations were prepared and optimized based on particle size, zeta potential and physical stability. Three polymers were used to prepare and optimized OXB-NEMGEL based on spreadability and viscosity. In-vitro drug release and ex-vivo skin permeation were investigated for optimized formulation. The model suggested by Design-Expert was quadratic and there was significant association between response variables including particle size and zeta potential and independent variables (Oil:Surfactant ratio, Oil:Water ratio, and surfactants HLB) with P-values of 0.0334 and 0.0173, respectively. Also, the lack of fit was not significant (P-values 0.057 and 0.569, respectively) which confirms the fitness of this model. Average size and zeta potential of optimized nanoemulsions were 99 ± 0.1 nm and -57.3 ± 0.5 mv, respectively. Carboxymethyl cellulose-based nanoemulgels (CMC-NEMGEL) showed acceptable viscosity with a shear thinning rheological pattern and good spreadability which released OXB within 8 h. Ex-vivo OXB skin permeation revealed OXB flux of 1.5 ± 0.3 and 3.6 ± 0.2 μg/cm2/h after 12 and 24 h, respectively, which was equal to 5.3 ± 1.1% and 11.9 ± 0.7% of drug, while simple OXB gel did not permeate through skin layers. Thus, OXB-NEMGEL with effective skin permeation potential would be a novel promising drug delivery system for hyperhidrosis management which may lower systemic side effects.
Relation of maternal hypertension with infant growth in a prospective birth cohort: the ABCD study

The aim of this study was to investigate the assumed positive association of pre-existent and pregnancy-induced hypertension with the offspring’s weight and length gain in the first 14 months of life. We studied 3994 pregnant women and their offspring in a prospective community-based cohort study, starting between 2003 and 2004 (Amsterdam Born Children and their Development, ABCD study). Questionnaires obtaining information about hypertension during pregnancy were completed, and this was complemented with additional information from the obstetric caregiver. Anthropometry of the offspring was followed during the first 14 months of life. Main outcome measures were presence or absence of growth acceleration in weight or length (normal: ΔSDS ⩽ 0.67 v. growth acceleration: ΔSDS > 0.67). The relation between hypertension during pregnancy and weight and length gain was addressed by logistic regression analyses. We found that pre-existent hypertension was related to growth acceleration in weight and length. After correction for birth weight and pregnancy duration, the effect remained significant for growth acceleration in weight (OR 1.89; 95% CI 1.21–2.97; P < 0.01). Pregnancy-induced hypertension showed similar results, although correction for birth weight and pregnancy duration rendered the associations non-significant. In conclusion, infants of women with pre-existent hypertension during pregnancy more frequently have growth acceleration in weight and length, and yet the mechanisms acting on postnatal growth appear to be different.
Somatic Cell Hybrid Mapping of Expressed Sequence Tags For Genes Showing Early Embryonic Death-Associated Changes of Expression Patterns in the Fetal Placenta of the Cow Carrying Somatic Nuclear-Derived Cloned Embryo

We previously detected 368 expressed sequence tags showing early embryonic death-associated changes of expression patterns in the fetal placenta of the cow carrying somatic nuclear-derived cloned embryo. In the present study 7 (presumed expressed sequence tags for HYPC, SPTBN1 and TNNC2, and four expressed sequence tags for unknown novel genes) out of the 368 expressed sequence tags were mapped to bovine chromosomes by analyzing deoxyribonucleic acids of bovine/murine somatic cell hybrid panel with polymerase chain reaction using primers specific for those bovine genes.
Predicting Survival of Patients with Amyotrophic Lateral Sclerosis at Presentation: A 15-Year Experience

Objective: To describe the clinical features at first evaluation that best predict survival of the amyotrophic lateral sclerosis (ALS) population from the Salpêtrière Hospital between 1995 and 2009. Methods: Data are collected and entered into a clinical database from all patients seen at the Paris ALS Center. Variables analyzed were demographic and baseline information, strength testing (manual muscle testing; 1995-2009), the revised ALS Functional Rating Scale (ALSFRS-R; 2002-2009) and survival status. The χ2 test and ANOVA assessed differences in variables by region and across time period. Univariate and multivariate Cox proportional hazards models determined which variables best predicted survival. Flexible modeling of continuous predictors (splines) assessed trends in survival for different variables. Results: 3,885 patients with ALS were seen in 1995-2009, of whom 2,037 had ALSFRS-R scores. Age, weight, strength, and site of onset varied by region of residence. The proportion of patients living outside Paris, the time to first visit, patient age, and motor function differed across time periods. In Cox models, site of onset, time to first visit greater than 18 months, strength and the year of visit after 2006 predicted survival (all p values <0.0001). Compared to patients first seen between 1999 and 2002, the hazard ratio of death was 1.04 (95% CI = 0.95-1.14) for 2003-2006, and 0.76 (95% CI = 0.66-0.87) after 2006, while adjusting for other predictors of survival. The use of noninvasive ventilation increased during 2004-2008 from 16 to 51% of patients. Conclusions: Older age, bulbar onset, shorter delay to first visit and poor motor function at first visit predicted shorter survival rates in this large center-based sample from France, showing marked consistency across time and region of residence. Survival improved after 2006, concurrent with increasing rates of noninvasive ventilation use. Clinicopathologic correlation could better define subgroups, but identification of etiologies may be needed to elucidate individual forms of ALS with unique survival patterns.
Inefficient Cross-Presentation Limits the CD8+ T Cell Response to a Subdominant Tumor Antigen Epitope1

CD8+ T lymphocytes (TCD8) responding to subdominant epitopes provide alternate targets for the immunotherapy of cancer, particularly when self-tolerance limits the response to immunodominant epitopes. However, the mechanisms that promote TCD8 subdominance to tumor Ags remain obscure. We investigated the basis for the lack of priming against a subdominant tumor epitope following immunization of C57BL/6 (B6) mice with SV40 large tumor Ag (T Ag)-transformed cells. Immunization of B6 mice with wild-type T Ag-transformed cells primes TCD8 specific for three immunodominant T Ag epitopes (epitopes I, II/III, and IV) but fails to induce TCD8 specific for the subdominant T Ag epitope V. Using adoptively transferred TCD8 from epitope V-specific TCR transgenic mice and immunization with T Ag-transformed cells, we demonstrate that the subdominant epitope V is weakly cross-presented relative to immunodominant epitopes derived from the same protein Ag. Priming of naive epitope V-specific TCR transgenic TCD8 in B6 mice required cross-presentation by host APC. However, robust expansion of these TCD8 required additional direct presentation of the subdominant epitope by T Ag-transformed cells and was only significant following immunization with T Ag-expressing cells lacking the immunodominant epitopes. These results indicate that limited cross-presentation coupled with competition by immunodominant epitope-specific TCD8 contributes to the subdominant nature of a tumor-specific epitope. This finding has implications for vaccination strategies targeting TCD8 responses to cancer.
Optimization of the auxiliary switch components in a flying capacitor ZVS PWM converters

A family of PWM converters with an Auxiliary Switch Assisted Soft Switcher (AASS) is studied. The basic AASS cell includes an inductor connected in series with the auxiliary switch of the converter, a capacitor connected in parallel with the main switch or main diode of the converter and an additional capacitor (designated a 'Flying' capacitor) connected through an auxiliary diode parallel to the inductor and through an extra auxiliary diode parallel to the main diode of the converter. The unified analysis of steady-state processes in a generalized AASS converter, carried out in this investigation, is applicable to various PWM topologies. It is shown that AASS ensures soft switching of all power devices and that the voltage and current stresses are not appreciably higher than in the corresponding hard switched PWM topologies. A design procedure for optimization of AASS parameters is developed. Experimental investigation (a Boost DC-DC converter 130/380 V, 1.1 kW, switching frequency 100.160 kHz) confirmed the results of the theoretical analysis.
Taxonomic Relationships of Ansonia anotis Inger, Tan, and Yambun, 2001 and Pedostibes maculatus (Mocquard, 1890), with a Description of a New Genus (Amphibia, Bufonidae)

Abstract Examination of types and recently collected specimens revealed that Ansonia anotis Inger, Tan, and Yambun, 2001 and Pedostibes maculatus (Mocquard, 1890), both described from Kinabalu, Sabah, Malaysia, are hardly differentiated morphologically. Analyses of a total of 2,427 bp of the 12S rRNA, tRNAval, and 16S mitochondrial rRNA genes revealed that the two species are very close genetically. Thus A. anotis is regarded as conspecific and is synonymized with P. maculatus. Genetically, this species proved to form a lineage distinct from other bufonids from Southeast Asia, including species of Ansonia and Pedostibes. Because the species has also some unique morphological traits different from known bufonid genera, we propose to establish a new genus for Nectophryne maculata Mocquard, 1890.
Networks and webs in ecosystems and financial systems

This paper briefly outlines our growing understanding of the relationships between the network structure of ecological networks—both in mathematical models and in the real world—and their consequent dynamical properties. These are interesting, inter alia, because they affect the system’s ability to withstand disturbance, whether natural or human-created. The paper also sketches recent interest in the potential relevance of this work to ‘systemic risk’ and regulatory measures in banking systems, emphasizing the similarities and differences. I conclude with some cautions against drawing excessively general conclusions from any such models.
Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch.

OBJECTIVES Hemospan (Sangart Inc, San Diego, CA) (MP4) is a hemoglobin-based oxygen carrier consisting of human hemoglobin modified with polyethylene glycol. This study evaluated the effects of MP4 on blood volume, hemodynamics, and metabolic stability in a rat model of hemodilution and hemorrhage. MP4 was compared with hydroxyethyl starch solutions of differing concentrations (ie, HES 260/0.45 and HES 130/0.4). DESIGN An open-label, randomized comparison of treatments. SETTING Pharmaceutical industry. PARTICIPANTS Sprague Dawley rats. INTERVENTIONS Rats underwent 50% hemodilution with one of the solutions. Control rats were not hemodiluted. Blood volume was determined at baseline and 0, 60, and 120 minutes after exchange. In separate groups, hemodilution and subsequent 60% hemorrhage were examined to determine effectiveness of hemodilution. MEASUREMENTS AND MAIN RESULTS Endpoints were blood volume after hemodilution and survival, hemodynamics, and acid-base status during hemorrhage. Volume expansion was similar with MP4 (159% of infused volume) and HES 260/0.45 (145%) and less with HES 130/0.4 (104%). The duration of expansion was longest with MP4 (1-2 hours). In the hemorrhage studies, 2-hour survival was 90% with MP4, 50% with controls, and 10% and 0% with HES 260/0.45 and HES 130/0.4, respectively. The severity of hemodynamic and acid-base changes paralleled the survival, with the least disturbance observed in MP4-treated animals. CONCLUSIONS Hemodilution with MP4 was more effective in maintaining hemodynamic and metabolic stability than starch solutions or no hemodilution before simulated intraoperative hemorrhage. The benefit of MP4 is not ascribed solely to volume expansion. The results suggest that perioperative administration of MP4 may improve outcomes in surgical settings.
Involvement of vascular endothelial growth factor (VEGF) gene polymorphism in hepatocellular carcinoma of HCV patients from local population

Development of Hepatocellular carcinoma (HCC) after Hepatitis C virus (HCV) infection is common cause of poor long-term survival. This study aimed to evaluate the effect of Vascular Endothelial growth factor (VEGF) genes polymorphism as a risk factor of Hepatocellular carcinoma (HCC) in chronic hepatitis C virus in Pakistani population. VEGF regulates angiogenesis so it is mainly involved in progression and development of solid tumor. The results showed that HCC patients had a higher frequency of the VEGF-634 GG genotype. In this study results revealed that VEGF Genotype GG is not associated with the risk of HCC in HCV infected patients in Punjab region of Pakistan. Keywords: HCV; HCC; VEGF Polymorphism http://dx.doi. org/10.19045/bspab.2017. 60077
Thalamocortical pathway specialization for sound frequency resolution

Core auditory cortices are organized in parallel pathways that process incoming sensory information differently. In the rat, sound filtering properties of the primary (A1) and ventral (VAF) auditory fields are markedly different, yet both are core regions that by definition receive most of their thalamic input from the ventral nucleus (MGBv) of the medial geniculate body (MGB). For example, spike rate responses to sound intensity and frequency are more narrowly resolved in VAF vs. A1. Here we question whether there are anatomic correlates of the marked differences in response properties in these two core auditory fields. Combined Fourier optical imaging and multiunit recording methods were used to map tone frequency responses with high spatial resolution in A1, VAF, and neighboring cortices. The cortical distance representing a given octave was similar, yet response frequency resolution was about twice as large in VAF as in A1. Retrograde tracers were injected into low‐ and high‐isofrequency contours of both regions to compare MGBv label patterns. The distance between clusters of MGBv neurons projecting to low‐ and high‐isofrequency contours in the cortex was twice as large in caudal as in rostral MGB. This suggests that differences in A1 and VAF frequency resolution are related to the anatomic spatial resolution of frequency laminae in the thalamus, supporting a growing consensus that antecedents of cortical specialization can be attributed in part to the structural and functional characteristics of thalamocortical inputs. J. Comp. Neurol. 519:177‐193, 2011. © 2010 Wiley‐Liss, Inc.
The effect of indoor air pollutants on otitis media and asthma in children

This case-control study investigated the possible association between home environmental air pollutants and their effect on otitis media and asthma in children. Patients with physician-diagnosed otitis (n = 125, 74% response), with asthma (n = 137, 80% response), and controls (n = 237, 72% response) from a private pediatric practice seen between October 1986 and May 1987 were studied. A questionnaire inquired about housing characteristics (i.e., age, insulation, heating system) and sources of indoor air pollution such as cigarette smoking, use of woodburning stoves, household pets, etc. Analysis of the responses confirmed previous findings of significant relationships between maternal smoking (P = .021), and the presence of pets (P = .034) and the occurrence of asthma. A newly reported relationship between exposure to woodburning stoves and the occurrence of otitis (P less than .05) was reported. This implicates yet another risk factor (wood burning) in the etiology of otitis media.
Silver fluoride as a treatment for the disease dental caries

The current paradigm of treatment for dental caries (tooth decay) in primary teeth is dangerous, fails to reach many children, and suffers high recurrence. Acceptance of the paradigm arises from a misperception that untreated caries in primary teeth is a threat to life. We show a linear relationship between age and deaths in the United States from 1999 through 2015 caused by dental caries, pulpal / periapical abscess, or facial cellulitis. The intercept of 6 years coincides with emergence of the first permanent tooth: it appears that caries in primary teeth is not a threat to life. Thus, treatment goals should be to avoid pain, which is not possible with operative dentistry, as it causes pain. Medical management of caries is a distinct treatment philosophy which employs topical minimally invasive therapies that treat the disease, and is not merely prevention. Silver diamine fluoride (SDF) is a central agent to enable effective non-invasive treatment. The announcement of FDA Breakthrough Therapy designation suggests that SDF will become the first FDA approved drug for treating the disease dental caries. Since our last review, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety and concern of diminished effectiveness by dilution, and to start patients with an intensive regimen of multiple applications over the first few weeks. Breakthroughs in elucidating the impact of SDF on tooth structure and the plaque microbiome inform potential opportunities for bioengineering and understanding caries arrest, respectively. Dentists have been surprised by preference of this treatment over traditional invasive approaches. Renewed interest in this old material has delivered progress to optimize the judicious use of SDF, and enable a revolution in caries management – particularly for primary teeth. ONE SENTENCE SUMMARY Anesthesia is inappropriate for first-line treatment of early childhood caries now that safe topical treatments such as silver diamine fluoride are available.
Factors Associated with Survival and Neurological Outcome after Cardiopulmonary Resuscitation of Neurosurgical Intensive Care Unit Patients

OBJECTIVE:We investigated predictors of survival and the neurological outcomes of neurosurgical patients who experienced cardiac arrest and received cardiopulmonary resuscitation after being admitted to the neurosurgical intensive care unit. METHODS:A retrospective study was conducted of adult patients in the neurosurgical intensive care unit who had experienced cardiac arrest and received cardiopulmonary resuscitation. Factors relevant to the cardiac arrest (before and after arrest) were used to study association with survival (immediate or short-term) and neurological outcome (unconscious or conscious) via statistical methods. RESULTS:Immediate survival was seen in 105 patients (49%), 19 survived until hospital discharge, and 11 were still alive at the conclusion of this study. Of the immediate survivors, 41 patients were conscious and 64 were unconscious. Multivariate analysis showed increased mortality in patients with infection, asystole, or resuscitation time exceeding 30 minutes (P < 0.05). Additional factors associated with high in-hospital mortality included lack of spontaneous respiration, no caloric-vestibular reflex, and unconsciousness after resuscitation (P < 0.05). In addition, neurological recovery was poor in patients with infection, asystole, no caloric-vestibular reflex, conscious recovery, or resuscitation lasting more than 30 minutes (P < 0.05). CONCLUSION:Even after initially successful resuscitation, survival and neurological recovery is quite dismal in patients with cerebral lesions. Prognostic factors for neurosurgical patients should be assessed on an individual basis to determine medical futility in the early post-resuscitation period.
REGIONAL BIOSYNTHESIS OF ACETYLCHOLINE IN BRAIN FOLLOWING FORCED ORAL CHRONIC BARBITONE TREATMENT TO RAT

Rats received a solution of sodium barbitone as their only drinking fluid for 33 and 42–44 weeks. In three groups (A3, A12 and A30) the barbitone solution was withheld and replaced by water 3, 12 and 30 days respectively before death. Two other groups consisted of animals drinking barbitone until death (B) and untreated controls (C). Abstinence convulsions were recorded by jiggle cages.
Non-pharmacological interventions for Lewy body dementia: a systematic review

Abstract Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.
Transanal self‐expanding metal stents as an alternative to palliative colostomy in selected patients with malignant obstruction of the left colon

Palliative colostomy is still unavoidable in many patients with malignant obstruction of the left colon. This report describes an initial experience and follow‐up in a small series of patients with left‐sided colon obstruction in whom transanal self‐expanding metal stent (SEMS) placement was attempted for palliative purposes.