Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses

Significance Ketamine is an NMDA receptor (NMDAR) antagonist that elicits rapid antidepressant responses in patients with treatment-resistant depression. However, ketamine can also produce adverse side effects, which raised interest in whether the clinically tolerated NMDAR antagonist memantine can elicit similar fast antidepressant action. Rather surprisingly, clinical data have shown that memantine does not trigger rapid antidepressant effects for reasons that have yet to be elucidated. Here, we reconstitute the ketamine and memantine clinical findings in animal models and, combined with the analysis of synaptic function and subsequent intracellular signaling, demonstrate significant differences between the efficacies of ketamine and memantine on NMDAR-mediated neurotransmission and downstream intracellular signaling. These findings suggest a potential mechanism to explain the earlier clinical observations. Ketamine is an NMDA receptor (NMDAR) antagonist that elicits rapid antidepressant responses in patients with treatment-resistant depression. However, ketamine can also produce psychotomimetic effects that limit its utility as an antidepressant, raising the question of whether the clinically tolerated NMDAR antagonist memantine possesses antidepressant properties. Despite its similar potency to ketamine as an NMDAR antagonist, clinical data suggest that memantine does not exert rapid antidepressant actions for reasons that are poorly understood. In this study, we recapitulate the ketamine and memantine clinical findings in mice, showing that ketamine, but not memantine, has antidepressant-like effects in behavioral models. Using electrophysiology in cultured hippocampal neurons, we show that ketamine and memantine effectively block NMDAR-mediated miniature excitatory postsynaptic currents in the absence of Mg2+. However, in physiological levels of extracellular Mg2+, we identified key functional differences between ketamine and memantine in their ability to block NMDAR function at rest. This differential effect of ketamine and memantine extends to intracellular signaling coupled to NMDAR at rest, in that memantine does not inhibit the phosphorylation of eukaryotic elongation factor 2 or augment subsequent expression of BDNF, which are critical determinants of ketamine-mediated antidepressant efficacy. These results demonstrate significant differences between the efficacies of ketamine and memantine on NMDAR-mediated neurotransmission that have impacts on downstream intracellular signaling, which we hypothesize is the trigger for rapid antidepressant responses. These data provide a novel framework on the necessary functional requirements of NMDAR-mediated neurotransmission as a critical determinant necessary to elicit rapid antidepressant responses.
Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review

Allergen‐specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non‐invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on the efficacy of immunotherapy in all its different administration forms in youngsters. Therefore, we systematically reviewed randomized controlled trials (RCTs) to evaluate the effect of immunotherapy with inhalant allergens on symptoms and medication use in children and adolescents with allergic rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register and reference lists of recent reviews and published trials were searched. RCTs including youngsters aged 0–18 yr with allergic rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic treatment or a different administration form of immunotherapy were included. Primary outcome measures were rhinoconjunctivitis symptom and/or medication scores. Methodological quality was assessed using the validated Delphi list. A method of best evidence synthesis, a rating system with levels of evidence based on the overall quality and the outcome of the trials, was used to assess efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11 sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were included. Only 39% of the trials were of high methodological quality. For the SCIT and OIT subgroups the level of evidence for efficacy was conflicting. Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup showed no evidence of effect. The evidence for the perennial and seasonal allergen trials within the subgroups varied from moderate evidence of effect to no evidence of effect. In conclusion, there is at present insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in children and adolescents with allergic rhinoconjunctivitis.
Life After Burn Injury: Striving for Regained Freedom

Focusing beyond survival, the priority of modern burn care is optimal quality of life. Our aim with this study, which was informed by phenomenology, was to describe and identify invariant meanings in the experience of life after major burn injury. Fourteen adults having sustained a major burn were interviewed, on average, 14 months postinjury, and asked about their experience of important aspects of life. The accident meant facing an extreme situation that demanded vigilance, appropriate action, and the need for assistance. The aftermath of the burn injury and treatment included having to put significant effort into creating coherence in their disrupted personal life stories. Continuing life meant accepting the unchangeable, including going through recurrent processes of enduring, grief, fatalism, comparisons with others, and new feelings of gratefulness. Furthermore, a continuous struggle to change what was changeable, to achieve personal goals, independence, relationships with others, and a meaningful life, were all efforts to regain freedom, aiming for a life as it was before—and sometimes even better.
Combination of Machine Learning Methods for Optimum Chinese Word Segmentation

This article presents our recent work for participation in the Second International Chinese Word Segmentation Bakeoff. Our system performs two procedures: Out-ofvocabulary extraction and word segmentation. We compose three out-of-vocabulary extraction modules: Character-based tagging with different classifiers – maximum entropy, support vector machines, and conditional random fields. We also compose three word segmentation modules – character-based tagging by maximum entropy classifier, maximum entropy markov model, and conditional random fields. All modules are based on previously proposed methods. We submitted three systems which are different combination of the modules.
Dual Effects of Hexanol and Halothane on the Regulation of Calcium Sensitivity in Airway Smooth Muscle

Background Contraction of airway smooth muscle is regulated by receptor-coupled mechanisms that control the force developed for a given cytosolic calcium concentration (i.e., calcium sensitivity). Halothane antagonizes acetylcholine-induced increases in calcium sensitivity by inhibiting GTP-binding (G)–protein pathways. The authors tested the hypothesis that hexanol, like halothane, inhibits agonist-induced increases in calcium sensitivity in airway smooth muscle by inhibiting G-protein pathways. Methods Calcium sensitivity was assessed using &agr;-toxin–permeabilized canine tracheal smooth muscle. In selected experiments, regulatory myosin light chain phosphorylation was also determined by Western blotting in the presence and absence of 10 mm hexanol and/or 100 &mgr;m acetylcholine. Results Hexanol (10 mm) and halothane (0.76 mm) attenuated acetylcholine-induced calcium sensitization by decreasing regulatory myosin light chain phosphorylation during receptor stimulation. Hexanol also inhibited increases in calcium sensitivity due to direct stimulation of heterotrimeric G-proteins with tetrafluoroaluminate but not with 3 &mgr;m GTP&ggr;S, consistent with prior results obtained with halothane. In contrast, in the absence of receptor stimulation, both compounds produced a small increase in calcium sensitivity by a G-protein–mediated increase in regulatory myosin light chain phosphorylation that was not affected by pertussis toxin treatment. Conclusions The authors noted dual effects of hexanol and halothane. In the presence of muscarinic receptor stimulation, hexanol, like halothane, decreases calcium sensitivity by interfering with heterotrimeric G-protein function. However, in the absence of muscarinic receptor stimulation, hexanol and halothane slightly increase calcium sensitivity by a G-protein–mediated process not sensitive to pertussis toxin. Hexanol may represent a useful experimental tool to study the effect of anesthetics on heterotrimeric G-protein function.
The big five and well-being outcomes during the revolution in Romania

Studiul investighează relaţiile dintre dimensiunile de personalitate ale Big Five si starea de bine declarată, investigate in ţări vestice si replicate in România după 1990. Inventarul Psihologic California si 16PF, precum si măsurători ale stării de bine au fost aplicate la 290 de ingineri români. Dimensiunile de personalitate ale Big Five au fost derivate prin intermediul unei analize factoriale. Studiul a confirmat că extraversiunea este corelată negativ cu depresia si problemele somatice, că neuroticismul este corelat negativ cu satisfacţia la locul de muncă si pozitiv cu depresia si problemele somatice, iar constiinciozitatea corelează pozitiv cu satisfacţia la locul de muncă. Au fost evidenţiate si unele relaţii neasteptate. In concluzie, majoritatea relaţiilor dintre personalitate si starea de bine evidenţiate in ţările vestice s-au regăsit si in cercetarea est-europeană, iar diferenţele obţinute pot fi explicate prin prisma factorilor socio-economici ai momentului respectiv.
Consumption, Aggregate Wealth and Expected Stock Returns

This paper studies the role of detrended wealth in predicting stock returns. We call a transitory movement in wealth one that produces a deviation from its shared trend with consumption and labor income. Using U.S. quarterly stock market data, we find that these trend deviations in wealth are strong predictors of both real stock returns and excess returns over a Treasury bill rate. We also find that this variable is a better forecaster of future returns at short and intermediate horizons than is the dividend yield, the earnings yield, the dividend payout ratio and several other popular forecasting variables. ; Why should wealth, detrended in this way, forecast asset returns? We show that a wide class of optimal models of consumer behavior imply that the log consumption-aggregate (human and nonhuman) wealth ratio forecasts the expected return on aggregate wealth, or the market portfolio. Although this ratio is not observable, we demonstrate that its important predictive components may be expressed in terms of observable variables, namely in terms of consumption, nonhuman wealth and labor income. The framework implies that these variables are cointegrated, and that deviations from this shared trend summarize agents' expectations of future returns on the market portfolio.
Health Impacts of Environmental Mycobacteria

SUMMARY Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.
Immunocytochemical analysis of beta keratins in the epidermis of chelonians, lepidosaurians, and archosaurians.

Beta (beta) keratins are present only in the avian and reptilian epidermises. Although much is known about the biochemistry and molecular biology of the beta keratins in birds, little is known for reptiles. In this study we have examined the distribution of beta keratins in the adult epidermis of turtle, lizard, snake, tuatara, and alligator using light and electron immunocytochemistry with a well-characterized antiserum (anti-beta(1) antiserum) made against a known avian scale type beta keratin. In lizard, snake, and tuatara epidermis this antiserum reacts strongly with the beta-layer, more weakly with the oberhautchen before it merges with the beta-layer, and least intensely with the mesos layer. In addition, the anti-beta(1) antiserum reacts specifically with the setae of climbing pads in gekos, the plastron and carapace of turtles, and the stratum corneum of alligator epidermis. Electron microscopic studies confirm that the reaction of the anti-beta(1) antiserum is exclusively with characteristic bundles of the 3-nm beta keratin filaments in the cells of the forming beta-layer, and with the densely packed electron-lucent areas of beta keratin in the mature bet- layer. These immunocytochemical results suggest that the 3-nm beta keratin filaments of the reptilian integument are phylogenetically related to those found in avian epidermal appendages.
Relationship between the gut and the spine: a pilot study of first-degree relatives of patients with ankylosing spondylitis

Patients with ankylosing spondylitis (AS) have a high frequency of asymptomatic acute and chronic gut inflammation resembling inflammatory bowel disease (IBD), with as many as 60% displaying evidence of microscopic gut inflammation in the absence of gastrointestinal (GI) symptoms.1 Further, there is considerable overlap in susceptibility loci between AS and IBD but this pleiotropic phenomenon likely only explains part of the clinical co-occurrence.2 3 Animal model data investigating molecular mechanisms point to a critical relationship between the gut and AS and the potential role of the gut in the pathogenesis of AS.4 5 Several markers are utilised in clinical practice to determine the likelihood that a patient has IBD, the most common of which is the faecal calprotectin which has an estimated sensitivity and specificity of upwards of 80% for identification of patients with IBD and thus serves as a very useful marker of gut inflammation.6 Similarly, various IBD-related antibodies including anti - Saccharomyces cerevisiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), anti-I2 (associated with anti- Pseudomonas activity), anti- Escherichia coli outer membrane porin C (anti-OmpC) and antiflagellin antibodies (anti-CBir1) have been shown to have very good utility in distinguishing individuals with IBD from healthy controls, particularly when these tests are used in combination and thus serve as useful serological biomarkers for IBD.7 Using the above biomarkers along with advanced imaging studies, this pilot study investigated if first-degree relatives (FDRs) of patients with AS, who themselves do not carry a diagnosis of AS or IBD, have evidence of mucosal dysregulation, subclinical gut or sacroiliac joint inflammation that could potentially precede the development of overt IBD or AS. We postulate that this group will provide insights into the relationship between the gut and AS. The investigators collaborate in a large AS and IBD consultation and research centre where …
Histological studies of the effects of monosodium glutamate of the fallopian tubes of adult female Wistar rats

Background: The effect of monosodium glutamate used as food additive on the fallopian tubes of adult Wistar rat was investigated. Material and Methods: Adult female Wistar rats (n=24) of average weight of 230g were randomly assigned into three groups A, B and C in each group (n=8). The treatment groups (A & B) were given 0.04mg/kg and 0.08mg/kg of monosodium glutamate thoroughly mixed with the growers’ mash, respectively on a daily basis. The control group (C) received equal amount of feeds (Growers’ mash) without monosodium glutamate added for fourteen days. The growers’ mash was obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and the rats were given water liberally. The rats were sacrificed on day fifteen of the experiment. The fallopian tubes were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological procedures. Result: The histological findings in the treated groups showed evidence of cellular hypertrophy, degenerative and atrophic changes, and lysed red blood cells in lumen with the group that received 0.08mg/kg of monosodium glutamate more severe. Conclusion: MSG may have some deleterious effects on the fallopian tubes of adult female Wistar rats at higher doses and by extension may contribute to the causes of female infertility. It is recommended that further studies aimed at corroborating these findings be carried out.
An investigation into best practices in training para-educators of students with autism

Para-educators have become the backbone of special education classes providing services for students with Autism Spectrum Disorder (ASD), (Crawford, 2005). As a result, they have been assigned more responsibility in the classroom that includes providing instructional support, while often left to fend for themselves, functioning as primary teacher (Giangreco, 2010). Para-educators are often hired with little or no previous experience in working with students with ASD and little or no course work or professional development training in special education. The purpose of this qualitative multiple case study was to determine how four paraeducators perceive and respond to an individual training program designed to assist paraeducators working with students on the autism spectrum, and identify training strategies and themes that are important to their work. This study was based on a social cognitive and constructivist theoretical framework where students learn best by taking control of their own learning, and developing their own goals. The coaching and professional development format used in the study encouraged para-educators to take an active role in their own learning. This study provides preliminary research-based guidelines so that practitioners may begin to develop training programs that will meet the needs of students with ASD. Additional research that would support the findings of this study, may lead to the implementation of a standardized training program and certification for para-educators working with students with ASD.
ENGAGING MOTHERS: SELF-EFFICACY AND MOTHER/INFANT INTERACTION AMONG MOTHERS EXPERIENCING MULTIPLE LIFE STRESSORS

OF THESIS ENGAGING MOTHERS: SELF-EFFICACY AND MOTHER/INFANT INTERACTION AMONG MOTHERS EXPERIENCING MULTIPLE LIFE STRESSORS The purpose of this project was to interview mothers of newborns who participated in early intervention services focusing on the implementation of a tool developed at the Family, Infant and Preschool Program (FIPP) in North Carolina. The intent was to examine the experience of mothers and home visitors employing the tool, which was designed to enhance the mother/infant relationship. However, a stronger focus on the relationship between mother and home visitor emerged throughout the interviews. Among some participants the relationship among practitioner and parent appeared to create a safe space to share, practice strategies and grow. Although characteristics of FIPP practices associated with the tool remained consistent among home visitors, the way in which services were implemented were unique to each home visitor and parent. Mothers participating in the project were identified as coping with numerous life stressors associated with poverty at the time of the interviews.
Adequacy and accuracy of nontrauma center computed tomography: What are we missing?

BACKGROUND Timely and appropriate use of computed tomography (CT) scans is critical to the evaluation of traumatic injuries. The objective of this study was to assess the adequacy of CT scans performed at nontrauma centers (NTCs) as they pertain to the management of trauma patients. METHODS Adult patients transferred to our ACS-verified Level I trauma center from any NTC between May and December 2012 were enrolled prospectively. Available CT images from NTCs were reviewed in a blinded fashion by our facility’s trauma radiologist; his interpretations were compared with those from the NTC. Interpretations of the trauma centers (TCs) images were compared with the NTC interpretations. Means and proportions were used to summarize the data. RESULTS A total of 235 consecutive patients with a complete dataset were included, of which, 203 (86.4%) had a CT scan performed at an NTC. Additional imaging was obtained at the TC in 76% of patients with outside CT (154 of 203), with inadequacy of outside CTs for patient workup based on mechanism of injury (76%) and technical inadequacy of outside images (31%) being the main, nonexclusive reasons to repeat imaging. Image interpretation by the trauma radiologist at the TC using NTC images identified missed injuries in 49% of the patients, and 90% of these missed injuries were deemed clinically significant, meaning the injury would have altered patient care had they been identified. When the same body region was imaged at the TC, 54% had missed injuries, of which 76% were deemed significant. CONCLUSION This study demonstrates inaccuracy in the interpretation of NTC images, which can lead to inappropriate management of trauma patients. Parameters other than imaging need to be used to identify patients requiring a higher level of care. LEVEL OF EVIDENCE Therapeutic and care management study, level V.