Miracle-dz/UniFAR-FTUs huggingface dataset:
Is Green Growth Possible?

ABSTRACT The notion of green growth has emerged as a dominant policy response to climate change and ecological breakdown. Green growth theory asserts that continued economic expansion is compatible with our planet’s ecology, as technological change and substitution will allow us to absolutely decouple GDP growth from resource use and carbon emissions. This claim is now assumed in national and international policy, including in the Sustainable Development Goals. But empirical evidence on resource use and carbon emissions does not support green growth theory. Examining relevant studies on historical trends and model-based projections, we find that: (1) there is no empirical evidence that absolute decoupling from resource use can be achieved on a global scale against a background of continued economic growth, and (2) absolute decoupling from carbon emissions is highly unlikely to be achieved at a rate rapid enough to prevent global warming over 1.5°C or 2°C, even under optimistic policy conditions. We conclude that green growth is likely to be a misguided objective, and that policymakers need to look toward alternative strategies.
SnoN Suppresses Maturation of Chondrocytes by Mediating Signal Cross-talk between Transforming Growth Factor-β and Bone Morphogenetic Protein Pathways*

Background: BMP signaling promotes chondrocyte maturation and, subsequently, endochondral ossification, whereas TGF-β signaling is inhibitory. Results: TGF-β induced SnoN to suppress BMP signaling and chondrocyte hypertrophy. Conclusion: SnoN mediates a signal cross-talk between TGF-β and BMP to regulate chondrocyte maturation. Significance: Our data revealed an effector of TGF-β signaling as a putative therapeutic molecular target for cartilage/bone regeneration or osteoarthritis. Hypertrophic maturation of chondrocytes is a crucial step in endochondral ossification, whereas abnormally accelerated differentiation of hypertrophic chondrocytes in articular cartilage is linked to pathogenesis of osteoarthritis. This cellular process is promoted or inhibited by bone morphogenetic protein (BMP) or transforming growth factor-β (TGF-β) signaling, respectively, suggesting that these signaling pathways cross-talk during chondrocyte maturation. Here, we demonstrated that expression of Tgfb1 was increased, followed by phosphorylation of Smad2, during BMP-2-induced hypertrophic maturation of ATDC5 chondrocytes. Application of a TGF-β type I receptor inhibitor compound, SB431542, increased the expression of Id1, without affecting the phosphorylation status of Smad1/5/8, indicating that the activated endogenous TGF-β pathway inhibited BMP signaling downstream of the Smad activation step. We searched for TGF-β-inducible effectors that are able to inhibit BMP signaling in ATDC5 cells and identified SnoN. Overexpression of SnoN suppressed the activity of a BMP-responsive luciferase reporter in COS-7 cells as well as expression of Id1 in ATDC5 cells and, subsequently, the expression of Col10a1, a hallmark of hypertrophic chondrocyte maturation. siRNA-mediated loss of SnoN showed opposite effects in BMP-treated ATDC5 cells. In adult mice, we found the highest level of SnoN expression in articular cartilage. Importantly, SnoN was expressed, in combination with phosphorylated Smad2/3, in prehypertrophic chondrocytes in the growth plate of mouse embryo bones and in chondrocytes around the ectopically existing hypertrophic chondrocytes of human osteoarthritis cartilage. Our results indicate that SnoN mediates a negative feedback mechanism evoked by TGF-β to inhibit BMP signaling and, subsequently, hypertrophic maturation of chondrocytes.
[Clinical evaluation of body hair in healthy women].

AIM to study the amount and distribution of terminal body hair in non-hirsute women consulting in a public outpatient clinic. PATIENTS AND METHODS two hundred thirty six premenopausal women consulting in a birth control clinic or consulting for acute non-endocrinological diseases were studied. Body hair was assessed with a semi-quantitative clinical method described by Ferriman and Gallwey. RESULTS Ninety-five percent of women had a score equal or less than 5. No correlations were found between the score and body mass index or age. Partial scores over 1 were found specially in the lower abdomen, chest, superior lip and thighs. CONCLUSIONS This sample of women, coming from middle and low socioeconomic levels, appears more hairless than European or North American Women. Thus, hirsutism must be suspected with scores over 5. These results cannot be extrapolated to all Chilean women, due to differences in ethnical backgrounds.
Herpes zoster, immunological deterioration and disease progression in HIV‐1 infection

ObjectiveTo study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. Design and methodsA total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. ResultsThe incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositivesthe incidence was 31.2 per 1000 PY at CD4+ cells ≥; 500 × 106/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (Cl), 0.78–2.94] at CD4+ cells 200–499 × 106/l and 97.5 per 1000 PY (RR, 3.13; 95%Cl, 1.54–6.32) at CD4+ cells < 200 × 106/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% Cl, 1.1–2.4) and for death 1.7 (95% Cl, 1.1–2.5), but these were not independent from CD4+ cell counts. ConclusionIn HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.
Laboratory diagnosis of syphilis with automated immunoassays

The serological detection of specific antibodies to Treponema pallidum is of particular importance in the diagnosis of syphilis. The purpose of this study was to evaluate diagnostic performances of automated immunoassays in comparison with T. pallidum hemagglutination test (TPHA) and Western Blot (WB). The retrospective study was performed with different panels of sera: 244 clinical and serological characterized syphilitic sera and 203 potentially interfering samples. All the sera were tested by Enzygnost Syphilis, ARCHITECT Syphilis TP, TPHA, and homemade WB. The diagnostic performances of the two assays were very similar: both Enzygnost Syphilis and ARCHITECT Syphilis TP performed with a sensitivity of 99.2%, whereas the specificity was 98.5 and 98.4%, respectively. Considering the suitability for automation, both immunoassays may represent a good choice as a screening test. However, the use of a confirmatory test, such as TPHA or WB, remains a must in order to avoid false‐positive results. J. Clin. Lab. Anal. 23:1–6, 2009. © 2009 Wiley‐Liss, Inc.
Maritime health emergencies.

BACKGROUND Commercial ships flying the US flag must conform to Coast Guard standards and have medical care available onboard. Consultation with a physician is required if medication is to be prescribed. AIM To evaluate the epidemiology of medical contacts for US ships at sea. METHOD Retrospective analysis of cases where shipboard caregivers made contact with US emergency medicine physicians for advice. RESULTS There were 866 cases and 1720 contacts in 48 consecutive months of study. Eighty-eight per cent of cases were men with a mean age of 43.7 years (SD 13.7). Eighty-four per cent of cases were medical, 14% were injuries and 2% were purely psychiatric. Fifty-eight per cent of medical cases, 50% of psychiatric cases and 42% of injury cases were handled with a single contact. Injuries and psychiatric cases required a higher number of contacts per case compared with medical cases (P < 0.01). Five categories of illness accounted for 43% of medical cases (respiratory infections, abdominal problems, genitourinary complaints, rashes and dental issues). Psychiatric cases required the most medication, with 12% requiring four medications. The most common categories of medication given were pain relievers (non-steroidal anti-inflammatory drugs, opiates, heartburn relief) and antibiotics. CONCLUSIONS Even with pre-screening of seafarers and the potential dangers of life at sea, the majority of cases requiring physician advice are not related to trauma. However, cases of injury or acute psychiatric problems required more physician interaction and medication than medical cases.
Inclusion of rehabilitation medicine concepts in school of medicine resources

Abstract Purpose: To perform a gap analysis of rehabilitation medicine learning objectives (RMLOs) coverage within school of medicine (SOM) curriculum and educational resources as a basis for development of educational resources to fill any identified gaps. Method: Following ethics approval, interviews were carried out with SOM academics and clinicians to assess the relevance of a set of RMLOs and the extent to which RMLOs were addressed in SOM resources. Interviewee opinion was quantified via Likert scales and additional free comments were subjected to thematic analysis. Results: Most RMLOs were perceived as relevant by more than half of the 18 participants. There was evidence of relevant material relating to each RMLO in SOM resources. Thematic analysis suggested that rehabilitation medicine was addressed at the SOM in less detail than outlined in the RMLOs, and that additional rehabilitation content could be included in SOM resources across a number of courses and year levels. Conclusions: Rehabilitation medicine is considered relevant by clinicians and academics at the SOM. The most effective way of filling identified gaps in coverage of rehabilitation medicine at the SOM will be via engagement across a number of medical and surgical disciplines. Implications for Rehabilitation Rehabilitation-related knowledge and skills are relevant to medical education. Many of these issues are already partially addressed in existing educational resources. The design and delivery of medical school curricula should include a trans-disciplinary and inter-year approach to the inclusion of rehabilitation concepts and aptitudes. This could be done by introducing relevant concepts early, making resources available online, and embedding rehabilitation items across different disciplines, courses and assessments.
Four-year visual outcomes after photorefractive keratectomy in pilots with low–moderate myopia

Background The photorefractive keratectomy (PRK) is approved for Air Force pilots in several nations. The occupational environments of pilots in the Air Force are unique, including extremely high altitude, low oxygen tension, high ultraviolet light exposure and high G-force load. The short-term efficacy and safety of PRK for pilots are documented. However, the study for long-term visual and refractive outcomes of PRK in pilots is limited. Objective To investigate the long-term visual and refractive outcomes in a 4-year follow-up period after PRK in pilots with low to moderate myopia. Methods Thirty-eight eyes of 20 subjects that underwent PRK and recruited to Air Force pilot were evaluated preoperatively and at 3, 6, 12, 24, and 48 months postoperatively. Results The mean patient age was 21.42±0.75 years. The mean preoperative manifest refraction spherical equivalent (SE) was −1.51±1.15 diopters (D). At 4 years postoperatively, the mean SE was −0.29±0.51, 89.5% of eyes achieved 20/20 or better Snellen uncorrected visual acuity, 71.1% of eyes were within ±0.50 D of emmetropia. The refraction stabilised by 6 months and was maintained up to the 4-year follow-up stage. Conclusions PRK for pilots with low to moderate myopia is safe and effective in the long term. High-altitude environmental stress exposure has no effect on the refractive stability after PRK. Trial registration number ROKAF-ASMC-2015-IRB-002.
Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and prevailing known genetic basis of autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP). FMRP binds to and controls translation of mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent work shows that FMRP interacts with the transcript encoding striatal‐enriched protein tyrosine phosphatase (STEP; Ptpn5). STEP opposes synaptic strengthening and promotes synaptic weakening by dephosphorylating its substrates, including ERK1/2, p38, Fyn and Pyk2, and subunits of N‐methyl‐d‐aspartate (NMDA) and AMPA receptors. Here, we show that basal levels of STEP are elevated and mGluR‐dependent STEP synthesis is absent in Fmr1KO mice. We hypothesized that the weakened synaptic strength and behavioral abnormalities reported in FXS may be linked to excess levels of STEP. To test this hypothesis, we reduced or eliminated STEP genetically in Fmr1KO mice and assessed mice in a battery of behavioral tests. In addition to attenuating audiogenic seizures and seizure‐induced c‐Fos activation in the periaqueductal gray, genetically reducing STEP in Fmr1KO mice reversed characteristic social abnormalities, including approach, investigation and anxiety. Loss of STEP also corrected select nonsocial anxiety‐related behaviors in Fmr1KO mice, such as light‐side exploration in the light/dark box. Our findings indicate that genetically reducing STEP significantly diminishes seizures and restores select social and nonsocial anxiety‐related behaviors in Fmr1KO mice, suggesting that strategies to inhibit STEP activity may be effective for treating patients with FXS.
Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment.

OBJECTIVES This study examined the relationships of measures of cognitive functioning and psychiatric symptoms with work outcomes and use of vocational services for clients with schizophrenia in a supported employment program. METHODS Thirty clients who were newly enrolled in a supported employment program were evaluated with cognitive and symptom measures at program entry and two years later. The clients' amounts of competitive work, wages earned, on-job support, and contact with employment specialists during the two-year follow-up period were documented. RESULTS Predictors of clients' work outcomes included previous work history, amount of government entitlement income received, severity of negative symptoms, involvement in sheltered work activity at baseline, and level of cognitive functioning, including scores on measures of executive functioning and verbal learning and memory. The amounts of on-job support and contact with employment specialists were predicted by the cognitive domains of executive functioning, verbal learning, attention, and psychomotor speed as well as by the severity of psychotic symptoms. CONCLUSIONS Clients with schizophrenia who have higher levels of cognitive impairment may require greater amounts of vocational support than those with lower levels of impairment. A variety of rehabilitation strategies may be required to improve vocational outcomes and reduce the amount of supported employment services needed by clients with schizophrenia.
Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease

Background: To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding α-synuclein in familial parkinsonism and the accumulation of α-synuclein in the PD brain suggested a critical role for this protein in PD etiology. Methods: We investigated total and α-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory. Results: The levels of α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF α-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-α-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF α-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05). Conclusion: Our results demonstrate that levels of α-synuclein oligomers in CSF and the oligomers/total-α-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD.
Ectodomains 3 and 4 of Human Polymeric Immunoglobulin Receptor (hpIgR) Mediate Invasion of Streptococcus pneumoniae into the Epithelium*

Streptococcus pneumoniae binds to the ectodomain of the human polymeric Ig receptor (pIgR), also known as secretory component (SC), via a hexapeptide motif in the choline-binding protein SpsA. The SpsA-pIgR interaction mediates adherence and internalization of the human pathogen into epithelial cells. In this study the results of SpsA binding to human, mouse, and chimeric SC strongly supported the human specificity of this unique interaction and suggested that binding sites in the third and fourth Ig-like domain of human SC (D3 and D4, respectively) are involved in SpsA-pIgR complex formation. Binding of SpsA to SC-derived synthetic peptides indicated surface-located potential binding motifs in D3 and D4. Adherence and uptake of pneumococci or SpsA-coated latex beads depended on the SpsA hexapeptide motif as well as SpsA-binding sites in D3 and D4 of human pIgR. The involvement of D3 and D4 in adherence and invasion was demonstrated by the lack of binding of SpsA-coated latex beads to transfected epithelial cells expressing mutated pIgR. Finally, blocking experiments with chimeric human-mouse SC as well as synthetic peptides indicated the participation of D3 and a key role of D4 in pneumococcal invasion.
Pharmacokinetics, endocrine and antitumour effects of leuprolide depot (TAP-144-SR) in advanced prostatic cancer: a dose-response evaluation.

Twenty-two patients with advanced prostatic cancer and one with benign prostatic hypertrophy were given the GnRH analogue leuprolide in the form of a slow-release depot formulation by subcutaneous injection at doses of 3.75, 7.5, 15 or 30 mg. Following the first dose, drug levels were measured by a double-antibody RIA over an observation period of 5 weeks. Thereafter patients continued long-term subcutaneous treatment at the same dose every 4 weeks. Serum levels of leuprolide showed a rapid increase immediately after injection, reaching a peak proportional to dose within 3 h (range of mean values 13.1-54.5 ng/ml). Subsequently, mean drug levels declined to a plateau proportional to dose (0.49-1.99 ng/ml at 5 weeks). A significant dose-dependent increase in the area under the serum concentration-time curve from zero to 35 days (AUC0-35 days) from 541.7 to 1653.9 ng/ml.h was also noted (p less than 0.01). With all doses there was an initial rise in serum LH and FSH, followed by a rise in testosterone and dihydrotestosterone, then a sharp decrease within 3 weeks. FSH inhibition was achieved in all the 20 evaluable patients and was maintained in 17 of them (85%) over 5 weeks. Fifteen subjects (75%) had marked suppression of LH levels. In 13 of them (65%) this condition continued for the entire observation time. Castration levels of serum testosterone and dihydrotestosterone, however, were maintained in all patients for up to 5 weeks. Two of the 21 evaluable patients (10%) had a complete response; 15 a partial response (71%) and 3 stable disease (14%). No significant differences were observed in relation to dose. Clinical improvement and serum hormonal changes support this as a new and superior method of administration of leuprolide at a dose as low as 3.75 mg.
Evidence for Two Sites of Superoxide Production by Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex I)*

Complex I (NADH-ubiquinone oxidoreductase) can form superoxide during forward electron flow (NADH-oxidizing) or, at sufficiently high protonmotive force, during reverse electron transport from the ubiquinone (Q) pool (NAD+-reducing). We designed an assay system to allow titration of the redox state of the superoxide-generating site during reverse electron transport in rat skeletal muscle mitochondria: a protonmotive force generated by ATP hydrolysis, succinate:malonate to alter electron supply and modulate the redox state of the Q pool, and inhibition of complex III to prevent QH2 oxidation via the Q cycle. Stepwise oxidation of the QH2/Q pool by increasing malonate concentration slowed the rates of both reverse electron transport and rotenone-sensitive superoxide production by complex I. However, the superoxide production rate was not uniquely related to the resultant potential of the NADH/NAD+ redox couple. Thus, there is a superoxide producer during reverse electron transport at complex I that responds to Q pool redox state and is not in equilibrium with the NAD reduction state. In contrast, superoxide production during forward electron transport in the presence of rotenone was uniquely related to NAD redox state. These results support a two-site model of complex I superoxide production; one site in equilibrium with the NAD pool, presumably the flavin of the FMN moiety (site IF) and the other dependent not only on NAD redox state, but also on protonmotive force and the reduction state of the Q pool, presumably a semiquinone in the Q-binding site (site IQ).
Determining the antiviral activity of tenofovir disoproxil fumarate in treatment-naive chronically HIV-1-infected individuals

Objective: To assess the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy by following the initial rate of decline in plasma viral load, which is a measure of the efficacy of therapy in blocking viral replication. Design: An open-label, single-site study of TDF monotherapy in 10 antiretroviral drug-naive chronically HIV-1-infected individuals. Methods: Antiviral responses were assessed at baseline and during 21 days of monotherapy with TDF by measuring plasma HIV-1 RNA levels. The rate of change in HIV-1 RNA from baseline was determined both by linear regression and by fitting to a published model. Slopes were compared with those previously determined for ritonavir monotherapy. Results: Over 21 days, mean plasma HIV-1 RNA levels in the TDF-treated patients fell 1.5 log10 copies/ml (range, 0.7–2.0). The initial rates of decline in plasma HIV-1 RNA in the 10 TDF-treated patients and in 25 protease inhibitor-naive subjects treated with ritonavir monotherapy were nearly identical. Conclusions: The reduction in plasma HIV-1 RNA with TDF montherapy was comparable with the decline observed in previous studies of protease inhibitor monotherapy. TDF is a potent antiretroviral agent and has comparable inherent antiviral activity with that of ritonavir, a potent protease inhibitor. These data support further study of TDF-based regimens in simplified combinations of antiviral agents as initial treatment for chronic HIV-1 infection.