Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and comparison of 0.5% levobupivacaine with 0.75% ropivacaine for peribulbar anaesthesia in cataract surgery

Background and objective: The low cardiovascular and neurological toxicity of levobupivacaine has led to its application as a local anaesthetic in a wide variety of specialist applications including peribulbar block for cataract surgery. The aim of this study was to evaluate the efficacy of levobupivacaine 0.5% and to compare block quality vs. ropivacaine 0.75% in peribulbar anaesthesia. Methods: We examined 208 patients subjected to cataract surgery by phacoemulsification who were randomized into two groups according to the anaesthetic used for peribulbar block, namely levobupivacaine 0.5% or ropivacaine 0.75%, both with the addition of hyaluronidase. Nerve block was carried out by injection of 6 mL of the anaesthetic mixture equally distributed between the inferotemporal and superonasal areas. The success of the block was evaluated by determining the time of motor and sensory onset, akinesia score, times of motor and sensory offset and satisfaction of the patient and surgeon after 24 h. Pre‐block, post‐block and postoperative intraocular pressure as well as the duration of surgical intervention was also determined. Results: With respect to ropivacaine, levobupivacaine showed a significant reduction (P < 0.001) in the average motor and sensory onset. Both the akinesia score (P < 0.01) and mean motor and sensory offset times were also higher (P < 0.001). Neither the average intervention times nor the satisfaction of the patient/surgeon showed any significant differences between the two groups. Conclusions: Levobupivacaine (0.5%) has better anaesthetic properties with respect to 0.75% ropivacaine and is well‐suited for peribulbar block in cataract surgery.
Population genetic structure and diversity of the Apennine endemic stream frog, Rana italica– insights on the Pleistocene evolutionary history of the Italian peninsular biota

For most species in the Western Palaearctic region, southern Mediterranean peninsulas have been identified as major Quaternary refugia and hotspots of intraspecific diversity, and thus, as areas of particular relevance for the conservation of the evolutionary potential. We analysed the patterns of geographical variation among 26 populations of the Italian stream frog, using both nuclear (allozymes) and mitochondrial (partial cytochrome b sequences) markers. Phylogenetic, phylogeographical and population genetic analyses suggested that the species survived the last glacial–interglacial cycles in two distinct refugia, one restricted to the tip of the Calabrian peninsula, at the extreme south of the species’ range, the other spanning from central Calabria to central Apennines and showing evidences for further population subdivision therein. Historical demographic tests suggested a significant population expansion from the latter, which most likely began around the last pleniglacial. This expansion would have led to the rapid colonization of the northern Apennines to the north, and to a secondary contact and population admixture with the population from the southern refugium in southern central Calabria. A comparison of the evolutionary history inferred for the Italian stream frog with the data emerging for other codistributed species suggests: (i) the generality of a multiple‐refugia scenario for the Italian peninsula, (ii) the possible occurrence of at least one suture zone in southern Italy, and (iii) that for most species, this Pleistocene refugium is not only a hotspot, but also a melting pot of intraspecific genetic diversity. Finally, the conservation implications of these results are also briefly highlighted.
Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch

The targeted inactivation of oncogenes offers a rational therapeutic approach for the treatment of cancer. However, the therapeutic inactivation of a single oncogene has been associated with tumor recurrence. Therefore, it is necessary to develop strategies to override mechanisms of tumor escape from oncogene dependence. We report here that the targeted inactivation of MYC is sufficient to induce sustained regression of hematopoietic tumors in transgenic mice, except in tumors that had lost p53 function. p53 negative tumors were unable to be completely eliminated, as demonstrated by the kinetics of tumor cell elimination revealed by bioluminescence imaging. Histological examination revealed that upon MYC inactivation, the loss of p53 led to a deficiency in thrombospondin-1 (TSP-1) expression, a potent antiangiogenic protein, and the subsequent inability to shut off angiogenesis. Restoration of p53 expression in these tumors re-established TSP-1 expression. This permitted the suppression of angiogenesis and subsequent sustained tumor regression upon MYC inactivation. Similarly, the restoration of TSP-1 alone in p53 negative tumors resulted in the shut down of angiogenesis and led to sustained tumor regression upon MYC inactivation. Hence, the complete regression of tumor mass driven by inactivation of the MYC oncogene requires the p53-dependent induction of TSP-1 and the shut down of angiogenesis. Notably, overexpression of TSP-1 alone did not influence tumor growth. Therefore, the combined inactivation of oncogenes and angiogenesis may be a more clinically effective treatment of cancer. We conclude that angiogenesis is an essential component of oncogene addiction.
Ambulatory blood pressure monitoring in the primary care setting: assessment of therapy on the circadian variation of blood pressure from the MICCAT-2 Trial

BackgroundWe conducted a large-scale, practice-based trial (MICCAT-2) to evaluate the effects of telmisartan alone and in combination with a diuretic on 24-h blood pressure (BP) profiles, including the early morning period, a time when cardiovascular risk is excessive. MethodsPatients with hypertension, either untreated or currently on treatment, were started on, or switched to, the angiotensin receptor blocker telmisartan 40 mg daily; after 2 weeks, if office blood pressure (BP) remained ≥140/85 mmHg, the dose was increased to 80 mg; and if necessary, hydrochlorothiazide 12.5 mg was added after a further 4 weeks and continued for a final 4-week period. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at baseline and at the end of the treatment period. Baseline and treatment ABPM measurements were completed in 1619 patients. ResultsThere were highly significant reductions in both the daytime (−11.8/−7.2 mmHg) and night-time (−9.6/−5.7 mmHg) mean BP following telmisartan alone or in combination with the diuretic. Evaluation of the 24-h profiles showed evidence for sustained pharmacodynamic effects of telmisartan over the entire dosing period. Ninety-five (6%) patients had a marked surge in early morning BP defined as >30 mmHg post-awakening change in systolic BP. The average reduction of in the early morning (post-awakening) BP in the entire cohort was −11.5/−7.0 mmHg (P<0.001; reductions were similar for monotherapy and combination therapy groups. The early morning post-awakening BPs fell by an average of −17.2/−10.1 mmHg in patients with large morning BP surges (P<0.05 versus non-surge patients). ConclusionsIn a community based study using ambulatory BP monitoring, telmisartan-based therapy induced highly significant reductions in systolic and diastolic BP over 24 h and was particularly effective in reducing BP during the early morning period.
The potential impact of neighborhood empowerment on dental caries among adolescents.

OBJECTIVE Empowerment has been considered a dimension of social capital. It refers to social interaction processes that enable people to enhance their individual and collective skills and to exert greater control over their lives. This relationship has not been explored in relation to dental health. The objective of this study was to investigate the association between neighborhood empowerment and dental caries in adolescents. METHODS A multilevel study was designed to assess the individual and neighborhood effects on the oral health of adolescents. Four sources of data were used: (a) clinical examinations (WHO), (b) students' questionnaires, (c) parents' questionnaires and (d) census data. The study population was 1302, 14/15-year-old students from 39 public schools of two cities of the Distrito Federal (DF), Brazil. Data analysis used logistic multilevel modeling at two levels: students (sources a and b) and neighborhood as defined by catchment areas of schools (sources c and d). RESULTS High DMFT (DMFT > median, DMFT > or =3) rates were significantly lower in areas with higher levels of empowerment. This relationship was independent of socioeconomic variables at the individual and area levels and of all other individual risk factor variables such as sex, fluoride, sugar consumption, tooth brushing and dental attendance [OR for low compared with high empowerment was 1.54 (95% CI = 1.09-2.18), P = 0.014]. CONCLUSIONS Neighborhood empowerment may play an important role in explaining inequalities in the levels of dental caries. New perspectives are needed so that more effective interventions can be implemented using area-based perspectives.
Does agglomeration explain regional income inequalities

This paper seeks to explain regional income inequalities in Norway. Similar to the EU countries, Norway is characterized by substantial income disparities. I use sub-regional NUTS 4 data for the Norwegian manufacturing sector to analyze to what extent agglomeration effects and skills can explain regional variation in productivity and income. Both intra-sectoral and inter-sectoral agglomeration effects are analyzed. The reported estimates suggest the presence of both types, and that the latter are slightly stronger than the former. Contrary to popular views, I moreover find that location and agglomeration effects have become more, not less, important. In contrast to empirical evidence on sources of regional inequalities in other European countries skill composition as a determinant of regional income variations appears to have declined in importance over time. Hence, high income appears to be an outcome of high activity density — agglomeration — rather than being due to differences in education and skills. ∗Thanks to Victor D. Norman for valuable comments.
Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy

Aims Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF).
Reduction of voltage harmonics in three-phase inverters using discrete observers

This paper proposes a simple harmonic feedback strategy for reduction of output voltage harmonics and the removal of any voltage unbalance due to unbalanced linear and non-linear loads in three-phase inverters. The fundamental components of the voltage and current are controlled in dq frame. Two-phase observers have been used for estimating the fundamental αβ components of the inverter voltage and the load current, which in turn helps to segregate the harmonics from the signal. The observer based control strategy, reduction of harmonic distortion and load voltage balancing by the simple harmonic feedback approach has been verified by simulation and experiments.
Expression of surface hydrophobic proteins by Candida albicans in vivo

Candida albicans modulates cell surface hydrophobicity during growth and morphogenesis in vitro. To determine if surface hydrophobicity is expressed during pathogenesis, we generated a polyclonal antiserum against yeast hydrophobic proteins. The antiserum was then used for indirect immunofluorescence analysis of tissues from mice colonized and chronically infected with C. albicans. Results demonstrated that yeast hydrophobic proteins are exposed on fungal cells present in host tissues. The polyclonal antiserum distinguished between hydrophobic and hydrophilic cell surfaces in vitro and gave similar staining patterns and intensities for C. albicans cells in vivo. Of the yeast forms present within tissue lesions, approximately half exhibited moderate to intense immunofluorescence with the antiserum. Immunoblot analysis indicated that antigens recognized by the antiserum are predominantly low-molecular-mass hydrophobic proteins that are expressed by different C. albicans isolates and are expressed regardless of growth temperature. Taken together, the immunofluorescence and immunoblot analyses of antigens indicate that C. albicans displays surface hydrophobic proteins during pathogenesis and these proteins are available for hydrophobic interactions with host tissues. The effect of hydrophobic protein exposure on the virulence of C. albicans is discussed.
Cytotoxicity and aromatase (CYP19) activity modulation by organochlorines in human placental JEG-3 and JAR choriocarcinoma cells.

The human placental JEG-3 and JAR choriocarcinoma cell lines have been used as placental models for the study of aromatase (CYP19) activity and endocrine functions. In the present study, 21 organochlorines (OCs) mediated decreases in aromatase activity and protein and DNA content and increases in the percent lactate dehydrogenase (LDH) leakage in JEG-3 cells. These effects were highly variable among the types of OC and their treatment concentrations. Lowest observed effective concentrations reached 0. 001 microM for several OCs. Aromatase activity decreases and OC-mediated cytotoxicity were related. Thus, it was not possible to clearly assess the capacity of the OCs to modulate aromatase activity. Similar to 1,4-naphthoquinone, the most cytotoxic OCs contained a hydroxyl (4'-OH-2,4,6-trichlorobiphenyl and tris(4-chlorophenyl)methanol) or methylsulfonyl- (3- and 4-MeSO(2)-2, 2',5,5'-tetrachlorobiphenyl and -2,3',4',5-tetrachlorobiphenyl, and 3'- and 4'-MeSO(2)-2,2',3,4,5'-pentachlorobiphenyl and -2,2',4,5, 5'-pentachlorobiphenyl) functional group. Modulation of aromatase activity and LDH leakage were less for 3,3',4,4', 5-pentachlorobiphenyl and benzo[a]pyrene and insignificant for five alkyl-substituted trichloro-dibenzofurans and 2,3,7, 8-tetrachloro-dibenzo-p-dioxin (up to 10 microM). Cytotoxicity-related effects were influenced by the cell density and the presence of 10% fetal calf serum in the medium during compound incubation. Similar cytotoxic effects were observed for the JAR cell line. The involvement of an apoptotic mechanism of cytotoxicity in OC-treated JEG-3 cells was suggested by the binding of APO2.7 (an antibody specific to apoptotic cells), DNA fragmentation, and trypan blue staining. JEG-3 and JAR cells appear too sensitive toward OC-mediated cytotoxicity for use as in vitro bioassays to evaluate the potential modulation of aromatase activity. However, these cell lines may prove useful for examining the capacity of xenobiotics to modulate placental toxicity.
Structure of TatA Paralog, TatE, Suggests a Structurally Homogeneous Form of Tat Protein Translocase That Transports Folded Proteins of Differing Diameter

Background: The Tat system transports folded proteins in bacteria. Results: Unlike TatA, the paralogous TatE is found as small, homogeneous complexes. Conclusion: TatE cannot form a variable translocation channel as suggested for TatA. Significance: This work suggests a new model in which a structurally homogeneous form of translocase uses a flexible channel. The twin-arginine translocation (Tat) system transports folded proteins across bacterial and plant thylakoid membranes. Most current models for the translocation mechanism propose the coalescence of a substrate-binding TatABC complex with a separate TatA complex. In Escherichia coli, TatA complexes are widely believed to form the translocation pore, and the size variation of TatA has been linked to the transport of differently sized substrates. Here, we show that the TatA paralog TatE can substitute for TatA and support translocation of Tat substrates including AmiA, AmiC, and TorA. However, TatE is found as much smaller, discrete complexes. Gel filtration and blue native electrophoresis suggest sizes between ∼50 and 110 kDa, and single-particle processing of electron micrographs gives size estimates of 70–90 kDa. Three-dimensional models of the two principal TatE complexes show estimated diameters of 6–8 nm and potential clefts or channels of up to 2.5 nm diameter. The ability of TatE to support translocation of the 90-kDa TorA protein suggests alternative translocation models in which single TatA/E complexes do not contribute the bulk of the translocation channel. The homogeneity of both the TatABC and the TatE complexes further suggests that a discrete Tat translocase can translocate a variety of substrates, presumably through the use of a flexible channel. The presence and possible significance of double- or triple-ring TatE forms is discussed.
A Multi-Stub Lowpass Filter

The stepped-impedance lowpass filter is modified by replacing the low-impedance lines with lowpass transmission lines. The modified stepped-impedance lowpass filter is called a multi-stub lowpass filter because it is largely composed of open-circuited stubs. For experimental verification of the multi-stub filters, we design a 1 GHz seventh-order Butterworth LPF. The proof-of-concept prototype is a compact design that fits into a circuit size of 0. 09λg × 0. 136λg on an RO4003 substrate. The measurement results show that the multi-stub lowpass filter retains the characteristics of a Butterworth filter in the passband, while substantially improves the performance in the transition and stopband regions. It achieves state-of-the-art performance compared to lowpass filters in the literature.
Estradiol Prevents Neural Tau Hyperphosphorylation Characteristic of Alzheimer's Disease

Abstract: Alzheimer's disease (AD) is three times more prevalent in women than men, and epidemiological studies have shown that estrogen replacement in aging women forestalls the onset of AD. Hyperphosphorylation of the tau protein that forms the neurofibrillary tangles found in AD brains might be responsible for the breakdown of microtubules in affected neurons. The mechanisms by which tau protein is phosphorylated in the AD brain are not fully understood. Using a human neuroblastoma cell line (SH‐SY5Y) and primary cultures of newborn male or female rat cerebral cortical neurons, we investigated the effect of 17β‐estradiol on tau protein expression and phosphorylation. We found that estradiol increased total tau and induced dephosphorylation at the proline‐directed site of themolecule. Further, estradiol prevented okadaic acid‐induced hyperphosphorylation of tau in both proline‐ and non‐proline‐directed sites, and antiestrogens blocked this effect. To our knowledge, this is the first report of an effect of estradiol on naturally occurring and induced tau phosphorylation. This assumes special significance because the estrogen action was found to be sexually dimorphic in rat cortical neurons and differentiation‐sensitive in human neuroblastoma cells.
Beneficial Effect of Donepezil Augmentation for the Management of Comorbid Schizophrenia and Dementia

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (p < 0.01) and for CGI scores (p < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.
Memory Stacking in Hierarchical Networks

Robust representations of sounds with a complex spectrotemporal structure are thought to emerge in hierarchically organized auditory cortex, but the computational advantage of this hierarchy remains unknown. Here, we used computational models to study how such hierarchical structures affect temporal binding in neural networks. We equipped individual units in different types of feedforward networks with local memory mechanisms storing recent inputs and observed how this affected the ability of the networks to process stimuli context dependently. Our findings illustrate that these local memories stack up in hierarchical structures and hence allow network units to exhibit selectivity to spectral sequences longer than the time spans of the local memories. We also illustrate that short-term synaptic plasticity is a potential local memory mechanism within the auditory cortex, and we show that it can bring robustness to context dependence against variation in the temporal rate of stimuli, while introducing nonlinearities to response profiles that are not well captured by standard linear spectrotemporal receptive field models. The results therefore indicate that short-term synaptic plasticity might provide hierarchically structured auditory cortex with computational capabilities important for robust representations of spectrotemporal patterns.