Miracle-dz/UniFAR-FTUs huggingface dataset:
Omega 3 polyunsaturated fatty acids and the treatment of depression

ABSTRACT Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.
Laser-generated broadband antireflection structures for freeform silicon lenses at terahertz frequencies

We present a new flexible technology to generate broadband antireflection structures for the THz frequency range on planar and curved surfaces of silicon optics. Ultrashort laser pulses are used to ablate the surface in order to form subwavelength structures. Such structures effectively provide a gradual transition of the refractive index from air to silicon. We demonstrate antireflection structures on convex silicon lenses of both photoconductive emitter and detector devices. Thus, the THz pulse amplitude can be increased by about 28% and the spectral amplitude of single frequencies up to 58% in the range from 0.1 to 1.5 THz.
Constitutive Release of ATP and Evidence for Major Contribution of Ecto-nucleotide Pyrophosphatase and Nucleoside Diphosphokinase to Extracellular Nucleotide Concentrations*

Nucleotides are important extracellular signaling molecules. At least five mammalian P2Y receptors exist that are specifically activated by ATP, UTP, ADP, or UDP. Although the existence of ectoenzymes that metabolize extracellular nucleotides is well established, the relative flux of ATP and UTP through their extracellular metabolic products remains undefined. Therefore, we have studied the kinetics of accumulation and metabolism of endogenous ATP in the extracellular medium of four different cell lines. ATP concentrations reached a maximum immediately after change of medium and decreased thereafter with a single exponential decay (t½;1 ∼;230–40 min). ATP levels did not fall to zero but attained a base-line concentration that was independent of the medium volume and of the initial ATP concentration. Although the base-line concentration of ATP remained stable for up to 12 h, [γ-32P]ATP added to resting cells as a radiotracer was completely degraded within 120 min, indicating that steady state reflected a basal rate of ATP release balanced by ATP hydrolysis (20–200 fmol × min− 1 × cell− 6). High performance liquid chromatography analysis revealed that the γ-phosphate of ATP was rapidly, although transiently, transferred during steady state to species subsequently identified as UTP and GTP, indicating the existence of both ecto-nucleoside diphosphokinase activity and the accumulation of endogenous UDP and GDP. Conversely, addition of [γ-32P]UTP to resting cells resulted in transient formation of [γ-32P]ATP, indicating phosphorylation of endogenous ADP by nucleoside diphosphokinase. The final32P-products of [γ-32P]ATP metabolism were [32P]orthophosphoric acid and a 32P-labeled species that was further purified and identified as [32P]inorganic pyrophosphate. In C6 cells, the formation of [32P]pyrophosphate from [γ-32P]ATP at steady state exceeded by 3-fold that of [32P]orthophosphate. These results illustrate for the first time a constitutive release of ATP and other nucleotides and reveal the existence of a complex extracellular metabolic pathway for released nucleotides. In addition to the existence of an ecto-ATPase activity, our results suggest a major scavenger role of ecto-ATP pyrophosphatase and a transphosphorylating activity of nucleoside diphosphokinase.
Functional Contrast-Enhanced CT for Evaluation of Acute Ischemic Stroke Does Not Increase the Risk of Contrast-Induced Nephropathy

BACKGROUND AND PURPOSE: Concerns have recently grown regarding the safety of iodinated contrast agents used for CTA and CTP imaging. We tested whether the incidence of AN, defined by a ≥25% increase in the post−contrast scan creatinine level, was higher among patients with ischemic stroke who underwent a functional contrast-enhanced CT protocol compared with those who had no iodinated contrast administration. MATERIALS AND METHODS: The contrast-exposed group consisted of 575 patients with acute ischemic stroke who underwent CTA (n = 313), CTA/CTP (n = 224), or CTA/CTP followed by conventional angiography (n = 38) within 24 hours of stroke onset and were consecutively enrolled in a prospective cohort study. The nonexposed group consisted of 343 patients with ischemic stroke, consecutively admitted to the same institution, who did not receive iodinated contrast material. Patients were stratified by baseline eGFR. In the primary analysis, the Fisher exact test was used to compare the incidence of AN between the contrast-exposed and the nonexposed patients at 24, 48, and 72 hours and on a cumulative basis. A secondary analysis compared the incidence of AN in patients who underwent conventional angiography following CTA/CTP versus patients who underwent CTA/CTP only. RESULTS: The incidence of AN was 5% in the exposed and 10% in the nonexposed group (P = .003). Patients who underwent conventional angiography after contrast CT were at no greater risk of AN than patients who underwent CTA/CTP alone (26 patients, 5%; and 2 patients, 5%, respectively; P = .7). CONCLUSIONS: Administration of a contrast-enhanced CT protocol involving CTA/CTP and conventional angiography in selected patients does not appear to increase the incidence of CIN.
An Open-Label Extension Study to Evaluate Safety and Efficacy of Pazopanib in Patients with Advanced Renal Cell Carcinoma

Objectives: Evaluation of the safety and efficacy of pazopanib, a multikinase angiogenesis inhibitor, in a single-arm, open-label, extension study (VEG107769/NCT00387764) for placebo-treated patients with advanced renal cell carcinoma (RCC) from a randomized, double-blind, placebo-controlled phase III study (VEG105192/NCT00334282). Methods: Patients received pazopanib 800 mg/day. The primary endpoint was the safety and tolerability of pazopanib treatment. Secondary endpoints included response rate per Response Evaluation Criteria in Solid Tumors, progression-free survival (PFS), and overall survival (OS). Results: Seventy-nine placebo-treated patients from VEG105192/NCT00334282 who experienced disease progression and one pazopanib-treated patient (an exemption) were enrolled. Forty-one patients (51%) were treatment-naive; 39 (49%) were cytokine-pretreated. Median exposure to pazopanib was 9.7 months. All patients had discontinued pazopanib at the time of analysis. The most common reason for discontinuation was disease progression (61%). The most common adverse events were hypertension (45%), diarrhea (45%), hair color changes (44%), anorexia (30%), and nausea (25%). The response rate was 37.5% [95% confidence interval (CI): 26.9-48.1]; median PFS was 9.2 months (95% CI: 7.3-12.0); median OS was 23.5 months (95% CI: 16.3-28.0). Conclusions: Efficacy and safety profiles for pazopanib in this extension study of patients with RCC previously treated with placebo were very similar to those observed for pazopanib-treated patients in the pivotal phase III study.
Excellent long‐term graft survival in low risk, primary renal allografts treated with prednisolone‐avoidance immunosuppression

Primary avoidance of oral corticosteroids for renal transplant recipients is uncommon. The South Australian renal transplant service used a double therapy (DT) regimen of cyclosporin and azathioprine from August 1986 to July 1996 for low risk (first graft, PRA<50%) allografts. Oral corticosteroid, prednisolone (P), was reserved for severe rejection or two mild rejection episodes, but could be later withdrawn at the physician's discretion. This regimen is associated with more early acute rejection (Russ et al., Clin Transplant 1990: 4: 26). We have now analysed long‐term patient survival (PS) and graft survival (GS) for this group. Of 448 transplants in South Australia between August 1986 and July 1996, 295 commenced DT regimen. Ninety‐four (31.8%) never received P at any stage post‐transplantation (group 1), 96 (32.5%) were placed on P and later weaned (group 2), and 97 (33%) remained on long‐term P (group 3). Technical losses, eight (2.7%), within 30 d of transplantation, were excluded from sub‐group analysis. PS for the total DT cohort at 1, 5 and 9 yr post‐transplantation was 97, 88 and 74%, respectively. GS over the same time period was 88, 75 and 55%, respectively. There was no statistically significant difference in survival compared to other ‘low risk’ grafts in the rest of Australia during the same time period. Mean serum creatinine concentration (CrC) for the DT group at 3 and 6 months and 1, 3, 5 and 10 yr was not significantly different to the rest of the Australian ‘low risk’ grafts. In the DT cohort, there were 334 acute rejections (<90 d) in 206 patients (70%), but only 42 (12.5%) required anti‐lymphocyte antibody therapy (OKT3 or ATG) for rejection. PS at 9 yr was not statistically significantly different between groups 1 and 2, but both groups survived better than group 3 (p<0.0043). GS for group 1 at 1, 5 and 9 yr post‐transplantation was 90, 81 and 73%, respectively; for group 2, 98, 87 and 66%, respectively; and for group 3, 84, 63 and 29%, respectively. Statistical significance was reached in group 1 versus 3 (p<0.001) and group 2 versus 3 (p<0.001). In summary, a DT regimen in low risk, first renal allografts gives excellent long‐term patient and GS and minimises long‐term P, despite a high rate of early acute rejection.
Enhanced angiogenesis characteristic of SPARC‐null mice disappears with age

The impairment of angiogenesis in aging has been attributed, in part, to alterations in proteins associated with the extracellular matrix (ECM). SPARC (secreted protein acidic and rich in cysteine/osteonectin/BM‐40) is a matricellular protein that regulates endothelial cell function as well as cell–ECM interactions. We have previously shown that angiogenesis, as reflected by fibrovascular invasion into subcutaneously implanted polyvinyl alcohol (PVA) sponges, is increased in SPARC‐null mice (6–9 months of age) relative to their wild‐type (WT) counterparts. In this study, we define the influence of aging on (a) the expression of SPARC and (b) fibrovascular invasion into sponge implants in SPARC‐null and WT mice. The expression of SPARC in fibroblasts and endothelial cells derived from young donors (humans mean age less than 30 years and mice 4–6 months of age) and old donors (humans mean age over 65 years and mice 22–27 months of age) decreased 1.6 to 2.3‐fold with age. Analysis of fibrovascular invasion into sponges implanted into old (22–27 months) SPARC‐null and WT mice showed no differences in percent area of invasion or collagenous ECM. Moreover, sponges from old SPARC‐null and WT mice contained similar levels of VEGF that were significantly lower than those from young (4–6 months) mice. In contrast to fibroblasts from young SPARC‐null mice, dermal fibroblasts from old SPARC‐null mice did not migrate farther, proliferate faster, or produce greater amounts of VEGF relative to their old WT counterparts. However, when stimulated with TGF‐β1, primary cells isolated from the sponge implants, and dermal fibroblasts from both old SPARC‐null and WT mice, showed marked increases in VEGF secretion. These data indicate that aging results in a loss of enhanced angiogenesis in SPARC‐null mice, as a result of the detrimental impact of age on cellular functions, collagen deposition, and VEGF synthesis. However, the influence of aging on these processes may be reversed, in part, by growth factor stimulation. © 2005 Wiley‐Liss, Inc.
Metabolic Origin of Carbon Isotope Composition of Leaf Dark-Respired CO2 in French Bean1

The carbon isotope composition (δ13C) of CO2 produced in darkness by intact French bean (Phaseolus vulgaris) leaves was investigated for different leaf temperatures and during dark periods of increasing length. The δ13C of CO2 linearly decreased when temperature increased, from −19‰ at 10°C to −24‰ at 35°C. It also progressively decreased from −21‰ to −30‰ when leaves were maintained in continuous darkness for several days. Under normal conditions (temperature not exceeding 30°C and normal dark period), the evolved CO2 was enriched in 13C compared with carbohydrates, the most 13C-enriched metabolites. However, at the end of a long dark period (carbohydrate starvation), CO2 was depleted in 13C even when compared with the composition of total organic matter. In the two types of experiment, the variations of δ13C were linearly related to those of the respiratory quotient. This strongly suggests that the variation of δ13C is the direct consequence of a substrate switch that may occur to feed respiration; carbohydrate oxidation producing 13C-enriched CO2 and β-oxidation of fatty acids producing 13C-depleted CO2 when compared with total organic matter (−27.5‰). These results are consistent with the assumption that the δ13C of dark respired CO2 is determined by the relative contributions of the two major decarboxylation processes that occur in darkness: pyruvate dehydrogenase activity and the Krebs cycle.
Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups.

BACKGROUND Previous research has identified multiple risk and protective factors for late onset Alzheimer's disease (LOAD). However, it is not known whether these risk and protective factors differ for individuals who are cognitively stable versus those already experiencing declines. OBJECTIVE This study examined how dementia risk factors differ across subgroups of older adults defined by memory trajectory. This line of research may lead to more individualized risk profiles. METHODS Risk factors for incident LOAD were compared across previously-validated groups of older adults exhibiting different memory trajectories ("Stable-High," "Stable-Low," "Decliner," "Rapid Decliner") using stratified Cox regressions. Participants included 2,593 racially/ethnically diverse older adults (mean age of 76 at study entry) in the Washington Heights-Inwood Columbia Aging Project. RESULTS Predictors of incident dementia differed across trajectory groups: older age only incurred independent risk in stable groups, education did not incur independent protection in the rapidly declining group, depression only incurred independent risk in the stable-low group, stroke incurred independent risk in the two extreme groups, and APOE-ɛ4 only incurred independent risk in the rapidly declining group. CONCLUSION The finding that different risk factors for LOAD were associated with specific memory trajectories may reflect the existence of resilience or vulnerability factors that modify the individual influences of risk/protective factors. This study highlights the utility of considering interactions between dementia risk factors and a patient's unique cognitive history.
Electromyographic responses evoked in muscles of the forelimb by intracortical stimulation in the cat.

Chronically implanted microwires were used to deliver brief trains of electrical stimuli (11 cathodal pulses at 330 Hz and intensity 5‐35 microA) to sixty‐two locations in the grey matter of the pericruciate cortex in cats. Electromyographic (e.m.g.) responses in the contralateral forelimb were recorded from a total of ten muscles (four to eight in each animal) acting about the shoulder, elbow and wrist and on the digits. The animals were relaxed with little background e.m. g. in the muscles and as a result only excitatory effects could be described. Five muscles which are flexors in the locomotor context were excited from more electrodes, distributed more widely across the motor cortex, than another five muscles which are extensors during locomotion; this difference in 'accessibility' was present both at 35 microA stimulus intensity and at 15 microA. At a stimulus intensity of 15 microA, effective cortical electrodes tended to cluster either in the most lateral part of the anterior sigmoid gyrus (rostromedial focus) or in the coronal gyrus just caudal to a line prolonged beyond the lateral end of the cruciate sulcus (caudolateral focus). This is consistent with the existence of a double motor representation within the forelimb motor cortex (Pappas & Strick, 1981). The two foci were similar in that both gave rise to more flexor than extensor responses and to fewer responses in digit or wrist muscles than in muscles acting about more proximal joints (elbow and shoulder). At stimulus intensity 35 microA the latency of the earliest e.m. g. responses ranged from 11 to 14 ms in different muscles. For some muscles and electrodes the amplitude of the e.m. g. responses was substantially altered by a quite small postural change. After pyramidectomy the cortical thresholds and the e.m. g. latencies were both greatly increased.
Does the use of Nintendo Wii SportsTM improve arm function? Trial of WiiTM in Stroke: a randomized controlled trial and economics analysis

Objective: The Trial of Wii™ in Stroke investigated the efficacy of using the Nintendo Wii Sports™ (WiiTM) to improve affected arm function after stroke. Design: Multicentre, pragmatic, parallel group, randomized controlled trial. Setting: Home-based rehabilitation. Subjects: A total of 240 participants aged 24–90 years with arm weakness following a stroke within the previous six months. Intervention: Participants were randomly assigned to exercise daily for six weeks using the WiiTM or arm exercises at home. Main measures: Primary outcome was change in the affected arm function at six weeks follow-up using the Action Research Arm Test. Secondary outcomes included occupational performance, quality of life, arm function at six months and a cost effectiveness analysis. Results: The study was completed by 209 participants (87.1%). There was no significant difference in the primary outcome of affected arm function at six weeks follow-up (mean difference −1.7, 95% CI −3.9 to 0.5, p = 0.12) and no significant difference in secondary outcomes, including occupational performance, quality of life or arm function at six months, between the two groups. No serious adverse events related to the study treatment were reported. The cost effectiveness analysis showed that the WiiTM was more expensive than arm exercises £1106 (SD 1656) vs. £730 (SD 829) (probability 0.866). Conclusion: The trial showed that the WiiTM was not superior to arm exercises in home-based rehabilitation for stroke survivors with arm weakness. The WiiTM was well tolerated but more expensive than arm exercises.
Microarray Analysis of Quorum-Sensing-Regulated Genes in Porphyromonas gingivalis

ABSTRACT Quorum sensing is a phenomenon defined as gene regulation in response to cell density that regulates various functions in bacteria. The periodontopathogen Porphyromonas gingivalis possesses a luxS gene homologue that may encode a quorum-sensing system. In order to identify genes of P. gingivalis that are regulated by luxS, gene expression analysis was done using microarrays and RNA samples from the W83 wild-type strain and an isogenic luxS mutant, LY2001. The results indicated that 17 open reading frames (ORFs) in LY2001 are upregulated and two are downregulated. Real-time PCR was done to confirm the microarray results. Among the upregulated ORFs is a group of stress-related genes, including htrA, clpB, groEL, dnaK, and the F subunit of alkyl hydroperoxide reductase. This suggested that luxS is involved in stress gene regulation in P. gingivalis. Stress response experiments, including high-temperature survival, resistance to hydrogen peroxide (H2O2), and survival during exposure to low and high pH, were performed on the P. gingivalis wild-type and LY2001 strains. LY2001 had a significantly higher survival rate than did W83 when stressed at 50°C. No difference was found at pH 5, but LY2001 had increased survival compared to W83 at pH 9. LY2001 also survived better than W83 when stressed with 0.35 mM H2O2. These results suggest that luxS might be involved in promoting survival of P. gingivalis in the host by regulating its response to host-induced stresses such as temperature, H2O2, and pH.
Prognostic implications of white cell differential count and white cell morphology in Malaria.

BACKGROUND Malaria is of immense importance amongst the tropical diseases in India. There is a need to develop newer diagnostic aids and research is necessary to identify new prognostic markers for prediction of the course and complications. AIMS To evaluate the white cell differential count and morphology in Plasmodium vivax and Plasmodium falciparum malaria and study their prognostic utility. SUBJECTS AND METHODS Two hundred and sixty-four adult patients in the age range of 20 to 65 years presenting to the hospital over a period of 4 months with clinical features of malaria and a positive peripheral smear examination were studied. RESULTS No statistically significant difference was noted in the white blood cell (WBC) count and neutrophil count in P.vivax versus P. falciparum malaria. Band cells were more frequently noted in P. falciparum malaria than in P.vivax malaria (p < 0.0001). Toxic granulation of the neutrophils was noted in 9.5% of the patients and exclusively in P. falciparum malaria. Presence of toxic granulation of the polymorphs in subjects with P. falciparum malaria was significantly associated with anaemia (p=0.019), jaundice, cerebral involvement, adult respiratory distress syndromes, renal dysfunction and death (p < 0.0001 for all these parameters). CONCLUSION Band cells were seen in P. vivax and P. falciparum malaria, although in higher numbers in P. falciparum malaria. Toxic granulation of the neutrophils was noted only in the presence of P. falciparum malaria in this study and correlated with severity.
Minimising collateral damage: family peer support and other strategies

The impact on family members of mental illness in a young person is intensely distressing. Symptoms that they cannot understand, and the stigma surrounding mental illness may lead to families feeling isolated in their distress. Family carers are reassured by talking with other families who have experienced the same or similar situations. The “Families Helping Families” program at ORYGEN Youth Health trains family peer‐support workers, who are employed to provide information and support to families new to the service. Medical practitioners need to appreciate the importance of ensuring that families receive information and emotional support to help them cope effectively. Difficulties in helping family carers, often around perceived confidentiality restraints, need to be overcome so that collateral damage — family breakdown, persistence of symptoms, and behavioural maladjustments — can be reduced. Families who are supported can become advocates for improvements to mental health services for young people.