Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased use of antidepressants at the end of life: population-based study among people aged 65 years and above.

BACKGROUND The new antidepressants are generally effective and safe for older people, but may have serious side-effects. The use has been rapidly increasing, but focus on upper age groups has been limited. The pattern of antidepressant use as death approaches has never been analysed. OBJECTIVE To analyse the use of antidepressants among individuals aged 65 years and above with respect to time trends, age and proximity to death. DESIGN Population-based prescription study. SETTING The County of Funen, Denmark, 1992-2004 (approximately 470,000 inhabitants). RESULTS The 1-year prevalence of antidepressants increases steadily over time in all age groups. Among the 65+ year-olds it also increases with age and differs substantially between the youngest and the oldest. Very high prevalences are observed: 26.8% among females 85-89 years old and 17.5% among males 85 years and above in 2004. In all age groups the use of antidepressants increases substantially with proximity to death in the last 3 years of life. In the last phase of life the use is independent of whether the patient dies at age 65 or 90 about 33% of females and 25% of males receive antidepressants in the last 6 months. CONCLUSIONS The use of antidepressants among 65+ year-olds increases with age and proximity to death to very high levels. Future studies may clarify the problems and diagnoses giving rise to the use of antidepressants for such a large proportion of older people, and especially the problems giving rise to treatment as death approaches.
Effect of training on the dose-response relationship for insulin action in men.

Seven endurance-trained subjects [maximal O2 consumption (VO2max) 64 +/- 1 (SE) ml.min-1.kg-1] were subjected to three sequential hyperinsulinemic euglycemic clamps 15 h after having performed their last training session (T). Results were compared with findings in seven untrained subjects (VO2max 44 +/- 2 ml.min-1.kg-1) studied both at rest (UT) and after 60 min of bicycle exercise at 150 W (UT-ex). In T and UT-ex compared with UT, sensitivity for insulin-mediated whole-body glucose uptake was higher [insulin concentrations eliciting half-maximal glucose uptake being 44 +/- 2 (T) and 43 +/- 4 (UT-ex) vs. 52 +/- 3 microU/ml (UT), P less than 0.05] and responsiveness was higher [13.4 +/- 1.2 (T) and 10.9 +/- 0.7 (UT-ex) vs. 9.5 +/- 0.7 mg.min-1.kg-1 (UT), P less than 0.05]. Furthermore, responsiveness was higher (P less than 0.05) in T than in UT-ex. Insulin-stimulated O2 uptake and maximal glucose oxidation rate were higher in T than in UT and UT-ex. Insulin-stimulated conversion or glucose to glycogen and muscle glycogen synthase was higher in T than in UT and UT-ex. However, glycogen storage in vastus lateralis muscle was found only in UT-ex. No change in any glucoregulatory hormone or metabolite could explain the increased insulin action in trained subjects. It is concluded that physical training induces an adaptive increase in insulin responsiveness of whole-body glucose uptake, which does not reflect increased glycogen deposition in muscle. (ABSTRACT TRUNCATED AT 250 WORDS)
Comparison between propidium iodide and 7‐amino‐actinomycin‐D for viability assessment during flow cytometric analyses of the human sperm acrosome

Evaluation of the acrosome reaction can shed light on the fertilising competence of spermatozoa. To eliminate false‐positive results when evaluating the acrosome status of human sperm cells, two viability probes propidium iodide (PI) and 7‐amino‐actinomycin D (7‐AAD) were compared for their ability to stain nonviable cells post‐fixation and permeabilisation. Both the mean fluorescence and % dead cells differed significantly with time (P < 0.0001). Unlike PI, 7‐AAD did not leach from cells and fluorescence remained stable for up to 4 h. Furthermore, 7‐AAD proved to be a proficient marker to exclude dead sperm cells during flow cytometric evaluation of ionophore‐induced acrosome reaction.
l-Galactose Metabolism in Bacteroides vulgatus from the Human Gut Microbiota

A previously unknown metabolic pathway for the utilization of l-galactose was discovered in a prevalent gut bacterium, Bacteroides vulgatus. The new pathway consists of three previously uncharacterized enzymes that were found to be responsible for the conversion of l-galactose to d-tagaturonate. Bvu0219 (l-galactose dehydrogenase) was determined to oxidize l-galactose to l-galactono-1,5-lactone with kcat and kcat/Km values of 21 s–1 and 2.0 × 105 M–1 s–1, respectively. The kinetic product of Bvu0219 is rapidly converted nonenzymatically to the thermodynamically more stable l-galactono-1,4-lactone. Bvu0220 (l-galactono-1,5-lactonase) hydrolyzes both the kinetic and thermodynamic products of Bvu0219 to l-galactonate. However, l-galactono-1,5-lactone is estimated to be hydrolyzed 300-fold faster than its thermodynamically more stable counterpart, l-galactono-1,4-lactone. In the final step of this pathway, Bvu0222 (l-galactonate dehydrogenase) oxidizes l-galactonate to d-tagaturonate with kcat and kcat/Km values of 0.6 s–1 and 1.7 × 104 M–1 s–1, respectively. In the reverse direction, d-tagaturonate is reduced to l-galactonate with values of kcat and kcat/Km of 90 s–1 and 1.6 × 105 M–1 s–1, respectively. d-Tagaturonate is subsequently converted to d-glyceraldehyde and pyruvate through enzymes encoded within the degradation pathway for d-glucuronate and d-galacturonate.
Genetic control of antibody responses induced against an antigen delivered by recombinant attenuated Salmonella typhimurium

Recombinant derivatives of nonpathogenic bacteria such as attenuated Salmonella typhi have the potential to be used for delivery of heterologous antigens to the immune system. Genetic factors may modulate the immune responses to these live attenuated organisms and could therefore modify the immunogenicity of future human vaccines. In the present study, we compared the antibody responses of Ity or H-2 congenic strains of mice to a foreign antigen expressed by the murine attenuated aroA S. typhimurium strain. Our results demonstrate that the Ity gene may modulate the antibody responses to the foreign antigen but that the major genetic influence is exerted by H-2 genes, which control the capacity of mice to respond to the antigen expressed by recombinant attenuated Salmonella cells. This genetic control is related to differences in responsiveness of different strains of mice to low doses of antigen. Increasing the amount of foreign antigen expressed by recombinant Salmonella cells overcame the genetic restriction of these responses. These findings are potentially of great importance for the design of live vaccines for humans and show that care must be taken to optimize the amount of foreign antigen delivered to the immune system.
Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor α blockers can make sense

Objective: When one TNFα blocker (etanercept or infliximab) has failed, to determine whether it makes sense to treat patients with the other. Patients and methods: Since 1999 patients treated with etanercept or infliximab have been systematically followed up at our institution in the STURE database. We identified 31 patients who had received both agents. Results: Eighteen patients received etanercept first; discontinuation was mostly due to lack of efficacy. DAS28 values had improved only slightly with etanercept, with a mean (SEM) best DAS28 value of 4.8 (0.6). After switching to infliximab, the mean best DAS28 was 3.6 (0.6)—significantly better than the previous result (p<0.05). Similarly, the mean best ACR-N during etanercept treatment was 17.2 (6.65) and during subsequent infliximab treatment 40.4 (10.6) (p = 0.08). Thirteen patients received infliximab first; discontinuation was mainly due to adverse events. The best DAS28 value achieved during etanercept was 3.6 (0.4) compared with 4.1 (0.4) for infliximab (p<0.05), but the change in DAS28 was not different and ACR-N were similar for infliximab and etanercept in this group. Conclusion: For patients with insufficient efficacy from etanercept, treatment with infliximab provided better results, suggesting that a trial of infliximab is reasonable for such patients. For patients who discontinued infliximab owing to adverse events, treatment with etanercept gave at least similar clinical efficacy. Taken together, these data provide support for a trial of the reciprocal TNFα blocker in patients when one such agent has failed.
Human immunodeficiency virus type 1 tat activates non—N‐methyl‐D‐aspartate excitatory amino acid receptors and causes neurotoxicity

The human immunodeficiency virus type 1 (HIV‐1) protein Tat is known to be released from HIV‐1‐infected cells. We show that micromolar concentrations of Tat depolarized young rat and adult human neurons. In addition, Tat, at similar concentrations, was toxic to human fetal neurons in culture. Tat‐induced responses were insensitive to the Na+ channel blocker tetrodotoxin, suggesting a direct effect of Tat on neurons. Tat‐induced depolarizations and cytotoxicity were blocked by the excitatory amino acid antagonist kynurenate. The N‐methylvD‐aspartate receptor antagonist Dv2vaminov5‐phosphonovalerate had little effect on Tatvinduced depolarizations but did provide protection from Tat neurotoxicity. These results suggest that Tat, released from HIVv1vinfected cells, may be an important mediator of neurotoxicity observed in HIV1 encephalopathy.
Effect of transcranial magnetic stimulation on single‐unit activity in the cat primary visual cortex

Transcranial magnetic stimulation (TMS) has become a well established procedure for testing and modulating the neuronal excitability of human brain areas, but relatively little is known about the cellular processes induced by this rather coarse stimulus. In a first attempt, we performed extracellular single‐unit recordings in the primary visual cortex (area 17) of the anaesthetised and paralysed cat, with the stimulating magnetic field centred at the recording site (2 × 70 mm figure‐of‐eight coil). The effect of single biphasic TMS pulses, which induce a lateral‐to‐medial electric current within the occipital pole of the right hemisphere, was tested for spontaneous as well as visually evoked activity. For cat visual cortex we found that a single TMS pulse elicited distinct episodes of enhanced and suppressed activity: in general, a facilitation of activity was found during the first 500 ms, followed thereafter by a suppression of activity lasting up to a few seconds. Strong stimuli exceeding 50 % of maximal stimulator output could also lead to an early suppression of activity during the first 100–200 ms, followed by stronger (rebound) facilitation. Early suppression and facilitation of activity may be related to a more or less direct stimulation of inhibitory and excitatory interneurons, probably with different thresholds. The late, long‐lasting suppression is more likely to be related to metabotropic or metabolic processes, or even vascular responses. The time course of facilitation/inhibition may provide clues regarding the action of repetitive TMS application.
The aberrant retino‐retinal projection during optic nerve regeneration in the frog. III. Effects of crushing both nerves

Previous reports from this laboratory have shown that a substantial number of optic axons are misrouted after optic nerve regeneration in the adult frog, Rana pipiens. Regenerating axons from a crushed optic nerve are distributed throughout the opposite nerve. In this study, we report the effect of crushing both optic nerves (double crush) on the pattern and degree of axonal misrouting. In 28 frogs both optic nerves were crushed at the same time (simultaneous double crush) and animals survived for varying periods before the right eye was injected with 3H‐proline and the brain processed for autoradiography 24 hours later. In every frog with postoperative survivals longer than 2 weeks, labeled axons from the right eye were found in the left optic nerve. However, when compared to the amount of label seen in frogs in which only the right optic nerve was crushed (single crush) there was substantially less label within the left nerve of frogs after crushing both nerves. Label was also found only at the edge of the left nerve in material from double crush frogs, unlike that found after single crush. In four of six frogs where the left nerve was crushed 1 week after the right nerve (delayed double crush), the proximal end of the left nerve was completely filled with label, but more distally, label was found only along the edge of this nerve. Although fewer optic axons were labeled in the opposite optic nerve of double crush frogs, label did extend to the optic disc of that eye. However, label was not apparent in the ganglion cell fiber layer of the opposite eye. Instead, it was confined to the edge of the optic disc in a space apparently associated with papilledema resulting from crushing the optic nerve of that eye. In six frogs the retina of the left eye was removed at the same time the right optic nerve was crushed. Labeled axons of the right eye filled the left optic nerve to the retina‐less shell of the left eye. Thus, these data show that the amount and distribution of axonal misrouting into the opposite optic nerve during optic nerve regeneration is affected by intact or regenerating optic axons from the other eye.
Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States

Importance Among adults with diabetes in the United States, severe forms of diabetic retinopathy (DR) are significantly associated with a greater vision-related functional burden. Objective To assess the functional burden of DR across severity levels in the United States. Design, Setting, and Participants This cross-sectional study was based on 1004 participants 40 years or older with diabetes and valid ocular and sociodemographic outcomes in the National Health and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic retinopathy was based on fundus photograph grading, using the Early Treatment Diabetic Retinopathy Study severity scale. The analysis was performed from October 15, 2016, to June 15, 2017. Main Outcomes and Measures Functional difficulties secondary to vision were assessed during a household questionnaire in which participants self-reported difficulty with reading, visuospatial tasks (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking down steps, stairs, or curbs), and driving. The main outcome measure was vision-related functional burden, which was defined as present for individuals reporting moderate or greater difficulty in any of the aforementioned tasks. Results Of the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95% CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI, 44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR or proliferative diabetic retinopathy (PDR). The prevalence of vision-related functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy, 20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95% CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable analysis, the odds of vision-related functional burden were significantly greater among those with severe NPDR or PDR relative to those with no retinopathy (adjusted odds ratio [aOR], 3.59; 95% CI, 1.29-10.05; P = .02). Those with severe NPDR or PDR did not have a statistically significant greater odds of vision-related functional burden than did those with mild or moderate NPDR (aOR, 2.70; 95% CI, 0.93-7.78; P = .07). Conclusions and Relevance Among US adults with diabetes, approximately half of those with severe NPDR or PDR had difficulty with at least one visual function task. Moreover, vision-related functional burden was significantly greater among those with severe NPDR or PDR than among those with no retinopathy. These data suggest the importance of preventing severe forms of DR to mitigate the vision-related functional burden among US adults with diabetes. Future studies should complement our study by assessing the association of worsening retinopathy with objectively measured functional outcomes.
Clinical and angiographic outcomes, with treatment data, for patients with cerebral aneurysms treated with Guglielmi detachable coils: a single-center experience.

OBJECTIVE The purpose of this report is to provide the most detailed treatment and outcome data currently available in the literature, to allow for the further evaluation of Guglielmi detachable coils (GDC) as an appropriate treatment option for patients with cerebral aneurysms. METHODS During a period of 4.5 years, 74 patients with intracerebral aneurysms were treated with GDC in the Department of Neurosurgery at Oregon Health Sciences University. A comprehensive retrospective and prospective analysis of these patients was performed, to assess the overall angiographic and clinical outcomes for these patients. RESULTS Seventy-seven aneurysms were treated, with an average angiographic follow-up period of 1.4 years. Initially, 40% of aneurysms exhibited complete (100%) occlusion, 52% near complete (90-99%) occlusion, and 8% incomplete (<90%) occlusion. The average clinical follow-up period was 2.2 years. For unruptured aneurysms, 85% of patients returned to independent status. Of patients of Hunt and Hess Grade I/II status, 81% were independent; of patients of Grade III status, 100% were independent; and, of patients of Grade IV/V status, 50% were independent. The procedure-related morbidity rate was 9.1%, with a 7.8% risk of death from aneurysm perforation, stroke, or delayed hemorrhage. No completely occluded aneurysm hemorrhaged after GDC treatment (follow-up period, 1.9 yr). Of near complete occlusions, 2.6% hemorrhaged after embolization, at a rate of 1.4%/yr (follow-up period, 1.9 yr). CONCLUSION This study details long-term clinical outcomes after GDC treatment and describes factors affecting the need for retreatment. Although complete anatomic cure was not obtained in all cases and the long-term protection from subarachnoid hemorrhage remains to be determined, these data indicate that GDC are a safe and efficacious treatment for cerebral aneurysms.
Changes in size and compliance of the calf after 30 days of simulated microgravity.

Increased leg venous compliance may contribute to postflight orthostatic intolerance in astronauts. We reported that leg compliance was inversely related to the size of the muscle compartment. The purpose of this study was to test the hypothesis that reduced muscle compartment after long-duration exposure to microgravity would cause increased leg compliance. Eight men, 31-45 yr old, were measured for vascular compliance of the calf and serial circumferences of the calf before and after 30 days of continuous 6 degrees head-down bed rest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the calf were determined before and after bed rest by computed tomography. From before to after bed rest, calculated calf volume (cm3) decreased (P less than 0.05) from 1,682 +/- 83 to 1,516 +/- 76. Calf muscle compartment CSA (cm2) also decreased (P less than 0.05) from 74.2 +/- 3.6 to 70.6 +/- 3.4; calf compliance (ml.100 ml-1.mmHg-1.100) increased (P less than 0.05) from 3.9 +/- . 7 to 4.9 +/- . 5. The percent change in calf compliance after bed rest was significantly correlated with changes in calf muscle compartment CSA (r = 0.72, P less than 0.05). The increased leg compliance observed after exposure to simulated microgravity can be partially explained by reduced muscle compartment. Countermeasures designed to minimize muscle atrophy in the lower extremities may be effective in ameliorating increased venous compliance and orthostatic intolerance after spaceflight.
Hepatitis B virus and human immunodeficiency virus co‐infection in sub‐Saharan Africa: a call for further investigation

Abstract: A growing body of evidence indicates that human immunodeficiency virus (HIV)‐positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV‐negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV‐positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co‐infected individuals, and there is an even greater risk of liver disease when HIV and HBV co‐infected patients are treated with highly active anti‐retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to ‘sero‐silent’ HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub‐Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co‐infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co‐infection in sub‐Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses.
Estrogen receptor-alpha agonists promote angiogenesis in human myometrial microvascular endothelial cells.

OBJECTIVE The relative role of the two estrogen receptors, ERalpha and ERbeta, in mediating angiogenic responses in adult human endothelium is unknown. The aim of this study was to determine whether novel ERalpha-selective agonists, propyl pyrazole triol (PPT) and the tetrahydrochrysene (R,R-THC), up-regulate the expression of vascular endothelial growth factor receptor-2 (VEGFR-2), and promote VEGF-stimulated endothelial cell proliferation in primary cultures of adult female microvascular endothelial cells co-expressing endogenous ERalpha and ERbeta. METHODS Confluent primary cultures of microvascular endothelial cells isolated from human myometrium were incubated with 17beta-estradiol (1 and 10 nM), PPT (10 nM to 3 microM), or R,R-THC (10 nM to 3 microM) for 18 hours and VEGFR-2 expression measured by biotin-VEGF165 binding and flow cytometry. Endothelial cell proliferation was assessed in microvascular endothelial cells after incubation with 17beta-estradiol (10 nM), PPT (100 nM), and R,R-THC (100 nM) for 6 days using a tetrazolium-based bioassay. RESULTS Both PPT and R,R-THC increased VEGFR-2 expression on myometrial microvascular endothelial cells in a dose-dependent manner, reaching a maximum at 1 microM. Approximately 40% of myometrial microvascular endothelial cell isolates only express ERbeta and do not express ERalpha, and in these neither PPT, R,R-THC, nor 17beta-estradiol increased VEGF binding. PPT- or R,R-THC-stimulated increase in VEGF binding was significantly different between ERalpha+ and ERalpha- microvascular endothelial cell samples (P < .001 and P < .05, respectively). PPT, R,R-THC, and 17beta-estradiol significantly augmented VEGF-stimulated microvascular endothelial cell proliferation in ERalpha+ (P < .05), but not in ERalpha- samples. CONCLUSIONS This angiogenic effect of 17beta-estradiol on adult female microvascular endothelial cells is mediated by ERalpha, rather than ERbeta.