Miracle-dz/UniFAR-FTUs huggingface dataset:
High-dose (2.0 mg) Intravitreal Ranibizumab for Recalcitrant Radiation Retinopathy

Purpose To evaluate the safety and tolerability and treatment efficacy of high-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Methods A phase I to II open-label, nonrandomized prospective clinical trial was performed on 10 eyes of 10 patients with recalcitrant radiation retinopathy who were failing standard dose anti–vascular endothelial growth factor (VEGF) therapy. External beam or plaque brachytherapy–associated retinopathy was characterized by persistent macular edema or leakage on optical coherence tomography or fluorescein angiography. Intravitreal 2.0 mg ranibizumab was given monthly up to 12 months and monitored for tolerability and change in best-corrected visual acuity (BCVA), central foveal thickness, and clinical signs of radiation retinopathy. Results Seven patients completed the 1-year study and received all 12 injections; 3 withdrew from the study due to worsening retinopathy (1 after external beam, 2 following plaque). Treatment was well-tolerated with no severe adverse reactions. A total of 70% had stable (n = 3) or improved (n = 4) BCVA. Mean change in BCVA was +3.3 letters at 6 months and +0.7 letters at 1 year. Mean improvement in central foveal thickness (CFT) was −19.3% (range −57 to +15%) at 1 year. Initial mean CFT was 428 μm (range 192–776); final mean CFT was 333 μm (range 190–532). A total of 80% demonstrated a statistically significant (p<0.05) reduction in CFT. Conclusions Regardless of radiation source, intravitreal injections of 2.0 ranibizumab induced significant reductions in macular edema and maintained or improved BCVA in most patients who were failing standard dose anti-VEGF therapy.
Biomarkers of inflammation and endothelial dysfunction and risk of hypertension among Inner Mongolians in China

Objective We examined the association between plasma concentrations of high-sensitivity C-reactive protein, soluble intercellular adhesion molecule 1, soluble E-selectin, angiotensin II, renin activity and the risk of hypertension among 2589 study participants aged 20 years and older from Inner Mongolia, China. Methods Three blood pressure measurements were obtained using a standard mercury sphygmomanometer and hypertension was defined as blood pressure of at least 140/90 mmHg or use of antihypertensive medications. Overnight fasting blood samples were obtained to measure the biomarkers of endothelial dysfunction and inflammation. Results The average levels of high-sensitivity C-reactive protein (7.5 vs. 5.4 mg/l), soluble intercellular adhesion molecule 1 (339.4 vs. 322.6 ng/ml), soluble E-selectin (19.1 vs. 18.2 ng/ml), and angiotensin II (52.0 vs. 47.0 pg/ml) were significantly higher, whereas renin activity (1.3 vs. 1.5 mg/ml.h) was lower in hypertensive compared to normotensive participants (all P value <0.001). Compared to the lowest quartile, the multivariable-adjusted odds ratios (95% confidence interval) of hypertension for the highest quartile were 1.41 (1.06, 1.86) for high-sensitivity C-reactive protein, 1.93 (1.48, 2.53) for angiotensin II, and 0.70 (0.54, 0.91) for renin activity. Conclusion Our study indicated that elevated plasma levels of high-sensitivity C-reactive protein and angiotensin II were positively and renin activity inversely associated with the risk of hypertension. These data suggest that inflammation and endothelial dysfunction may play a role in the cause of hypertension.
Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media

Otitis media, a common and often recurrent bacterial infection of childhood, is a major reason for physician visits and the prescription of antimicrobials. Haemophilus influenzae is the cause of ≈20% of episodes of bacterial otitis media, but most strains lack the capsule, a factor known to play a critical role in the virulence of strains causing invasive H. influenzae disease. Here we show that in capsule-deficient (nontypeable) strains, sialic acid, a terminal residue of the core sugars of H. influenzae lipopolysaccharide (LPS), is a critical virulence factor in the pathogenesis of experimental otitis media in chinchillas. We used five epidemiologically distinct H. influenzae isolates, representative of the genetic diversity of strains causing otitis media, to inoculate the middle ear of chinchillas. All animals developed acute bacterial otitis media that persisted for up to 3 wk, whereas isogenic sialic acid-deficient mutants (disrupted sialyltransferase or CMP-acetylneuraminic acid synthetase genes) were profoundly attenuated. MS analysis indicated that WT bacteria used to inoculate animals lacked any sialylated LPS glycoforms. In contrast, LPS of ex vivo organisms recovered from chinchilla middle ear exudates was sialylated. We conclude that sialylated LPS glycoforms play a key role in pathogenicity of nontypeable H. influenzae and depend on scavenging the essential precursors from the host during the infection.
Diminished Akt phosphorylation in neurons lacking glutathione peroxidase‐1 (Gpx1) leads to increased susceptibility to oxidative stress‐induced cell death

We have previously identified an increased susceptibility of glutathione peroxidase‐1 (Gpx1)–/– mice to neuronal apoptosis following mid‐cerebral artery (MCA) occlusion. This study was designed to elucidate the mechanisms involved in elevated neuronal cell death arising from an altered endogenous oxidant state. This was addressed in both an in vitro and in vivo model of oxidative stress in the form of exogenous H2O2 and cerebral ischaemia, respectively. Increased levels of cell death were detected in primary neurons lacking Gpx1 following the addition of exogenous H2O2. This increased apoptosis correlated with a down‐regulation in the activation of the phospho‐inositide 3‐kinase [PI(3)K]–Akt survival pathway. The importance of this pathway in protecting against H2O2‐induced cell death was highlighted by the increased susceptibility of wildtype neurons to apoptosis when treated with the PI(3)K inhibitor, LY294002. The Gpx1–/– mice also demonstrated elevated neuronal cell death following MCA occlusion. Although Akt phosphorylation was detected in the Gpx1–/– brains, activation was not seen in later reperfusion events, as demonstrated in wildtype brains. Previous studies have highlighted the importance of Akt phosphorylation in protecting against neuronal cell death following cerebral ischaemia–reperfusion. Our results suggest that the increased susceptibility of Gpx1–/– neurons to H2O2‐induced apoptosis and neuronal cell death in vivo following cerebral ischaemia–reperfusion injury can be attributed in part to diminished activation of Akt. Perturbations in key anti‐apoptotic mechanisms as a result of an altered redox state may have implications in the study of oxidative stress‐mediated neuropathologies.
Association of suicide and antidepressant prescription rates in Japan, 1999-2003.

OBJECTIVE We examined the relationship of increasing prescription volume of newer antidepressants, introduced in Japan in 1999, to national rates of suicide. METHOD The relationship between annual changes in rates of suicide (obtained from the Japanese Ministry of Health, Labor, and Welfare Vital Statistics Database) and prescription volume of the newer antidepressants paroxetine, fluvoxamine, and milnacipran (obtained from the database of IMS Japan K.K.), stratified by gender and age groups, was modeled statistically for the years 1999 through 2003. Effects of unemployment and alcohol consumption and the interaction of gender and age with antidepressant prescribing were assessed. RESULTS From 1999 through 2003 in Japan, total antidepressant prescriptions increased 57% among males and 50% among females. Approximately 80% of this increase involved the selective serotonin reuptake inhibitors (SSRIs). To reduce a limitation of ecological analysis, we compared annual change in prescription and suicide rates, which eliminates the effect of long-term (secular) linear trends. We found an inverse association between year-to-year changes in the suicide rate and prescription volume of newer antidepressants (fluvoxamine, paroxetine, and milnacipran) (beta = -1.34, p = .008) and SSRIs specifically (fluvoxamine, paroxetine) (beta = -1.41, p = .019). An increase of 1 defined daily dose of SSRI use/1000 population/day was associated with a 6% decrease in suicide rate. Exploratory analysis suggested a stronger association in males, who experienced a greater increase in antidepressant use. Changes in unemployment and alcohol consumption rates did not explain the association. CONCLUSION In Japan during 1999 through 2003, absent long-term linear trend effects, annual increases in prescribing of newer antidepressant medications, mainly SSRIs, were associated with annual decreases in suicide rates, particularly among males.
Issue Information–ISSN page

Cover The upper part of the cover depicts the locations of missense mutations in SCN8A encephalopathy. The dots show the thirty-one published de novo mutations that were identified in 50 unrelated patients. Pathogenic mutations are concentrated in transmembrane segments and in the Nand C-terminal domains. The lower part of the figure shows the functional consequences of gain-of-function mutations in SCN8A in patients with epileptic encephalopathy. Different mutations can cause (1) a hyperpolarizing shift in the voltage-dependence of activation, resulting in premature channel opening (left panel), (2) the removal of a critical positive charge resulting in delayed channel inactivation (middle panel) or (3) an increase in persistent sodium current that facilitates repetitive firing (right panel). For more details see Meisler et al in this issue (pp. 1027 1035).
Couple counselling and testing for HIV at antenatal clinics: Views from men, women and counsellors

Abstract The purpose of this study was to gain insight from views of Tanzanian men and women on couple voluntary counselling and testing (CVCT) for HIV at antenatal clinics (ANC) in Tanzania. Data collection was through focus group discussions with women aged 25–48 years (n=8), women 18–24 years (n=10), HIV counsellors (n=11), men aged 20–34 (n=8) and men aged 35–75 years (n=8) and in-depth interviews (IDI) with five men and eight women. Participants were asked their views concerning men volunteering for CVCT for HIV, motivation of couples to receive results together and effective ways of counselling sero-discordant couples. Many participants agreed on the importance of incorporating CVCT at ANC, while others expressed reservations due to the cultural belief that ANC is for women. The importance of love, care and respect between sero-discordant couples was stressed; nonetheless, many anticipated that disclosure of HIV-positive status to an HIV-negative spouse could result in abandonment, divorce or violence against the woman whether she was sero-negative or -positive. Couple counselling and testing at ANC incorporating the suggestions made by study participants could become an important intervention for the prevention of HIV transmission and maintenance of good relations between sero-discordant partners.
Predictors of persistent sleep problems among older disaster survivors: a natural experiment from the 2011 Great East Japan earthquake and tsunami

Study Objectives To examine prospectively the associations of disaster experiences and social support with sleep problems in older adults. Methods Data came from a natural experiment caused by the 2011 Great East Japan earthquake and tsunami. Participants in an ongoing prospective cohort (3547 Japanese individuals aged 65 years or older) were inadvertently exposed to the disaster due to their residential location (Iwanuma city) after the 2010 baseline survey. We conducted a follow-up survey in 2013 to inquire about disaster-related experiences and short sleep duration, sleep insufficiency, poor sleep quality, insomnia symptoms, and sleep medication use. Poisson regression models adjusted for baseline socio-demographic and lifestyle covariates. Results Financial hardship predicted increased risks of short sleep duration (relative risk [RR] = 1.40; 95% confidence interval [CI] [1.03, 1.90]), sleep insufficiency (RR = 1.29; 95% CI [1.01, 1.66]), poor sleep quality (RR = 1.47; 95% CI [1.26, 1.70]), and insomnia symptoms (RR = 1.13; 95% CI [1.01, 1.28]). Home destruction predicted sleep medication use while health care disruption predicted poor sleep quality. Loss of close relatives or friends did not predict any sustained sleep problems. Additionally, having instrumental support reduced risks of all sleep problems while having emotional support reduced risk of poor sleep quality. Conclusions Approximately 2.5 years after the disaster, older survivors' sleep problems were more durably linked to material aspects of disaster damage than to loss of loved ones. Findings could inform targeted recovery efforts for groups with greatest need to promote older survivors' sleep health and overall well-being.
Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis.

BACKGROUND Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506). OBSERVATIONS All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage. CONCLUSIONS Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.
The development and enhancement of the collateral circulation in an animal model of lower limb ischaemia.

In an animal model of hind limb ischemia we documented the levels of endogenous basic fibroblast growth factor (bFGF) in control and ischaemic hind limbs, and evaluated the response to the administration of exogenous recombinant bFGF and heparin. Variations in this model were tested for their ability to alter the development of the collateral circulation. Recovery after acute arterial occlusion was significantly delayed by immediate bilateral mirror-image arterial ligations, when compared with either unilateral arterial ligation or delayed contralateral ligations performed after 2 months. If the major veins were also occluded all limbs developed gangrene, tissue loss and a marked delay in the recovery of blood flow, while none of the animals with unilateral arterial ligations developed gangrene. This indicates that the recovery in blood flow during the acute phase in this model is dependent on collateral vessels from the contralateral iliac artery and that major venous occlusion impedes the development of collateral vessels. Lumbar sympathectomy did not alter the recovery of blood flow after arterial occlusion, suggesting that collateral blood flow is not significantly influenced by autonomic neural supply. Following arterial occlusion there was a ten-fold increase in the levels of endogenous bFGF in all ischaemic muscle groups. Intramuscular implantation of bFGF in heparin-sepharose pellets at the time of arterial ligation markedly enhanced the blood flow for 3 weeks compared with untreated ischaemic limbs. A further increment in blood flow occurred if an additional dose of bFGF was administered 4 weeks after ligation. (ABSTRACT TRUNCATED AT 250 WORDS)
Drone Assisted Vehicular Networks: Architecture, Challenges and Opportunities

This article introduces the DAVN, which provides ubiquitous connections for vehicles by efficiently integrating the communication and networking technologies of drones and connected vehicles. Specifically, we first propose a comprehensive architecture of the DAVN and outline its potential services. By cooperating with vehicles and infrastructures, drones can improve vehicle-to-vehicle connectivity, infrastructure coverage, network information collection ability, and network interworking efficiency. We then present the challenges and research opportunities of DAVNs. In addition, a case study is provided to demonstrate the effectiveness of DAVNs by leveraging our designed simulation platform. Simulation results demonstrate that the performance of vehicular networks can be significantly enhanced with the proposed DAVN architecture.
A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa.

OBJECTIVE The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN. METHOD We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the dopamine-4 receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype. RESULTS In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups. CONCLUSION These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
Trophic Cascades Following the Disease‐Induced Decline of an Apex Predator, the Tasmanian Devil

As apex predators disappear worldwide, there is escalating evidence of their importance in maintaining the integrity and diversity of the ecosystems they inhabit. The largest extant marsupial carnivore, the Tasmanian devil (Sarcophilus harrisii) is threatened with extinction from a transmissible cancer, devil facial tumor disease (DFTD). The disease, first observed in 1996, has led to apparent population declines in excess of 95% in some areas and has spread to more than 80% of their range. We analyzed a long‐term Tasmania‐wide data set derived from wildlife spotlighting surveys to assess the effects of DFTD‐induced devil decline on populations of other mammals and to examine the relative strength of top–down and bottom–up control of mesopredators between 2 regions with different environmental conditions. Collection of the data began >10 years before DFTD was first observed. A decrease in devil populations was immediate across diseased regions following DFTD arrival, and there has been no indication of population recovery. Feral cats (Felis catus) increased in areas where the disease was present the longest, and feral cat occurrence was significantly and negatively associated with devils. The smallest mesopredator, the eastern quoll (Dasyurus viverrinus), declined rapidly following DFTD arrival. This result suggests the species was indirectly protected by devils through the suppression of larger predators. Rainfall deficiency was also a significant predictor of their decline. Environmental variables determined the relative importance of top–down control in the population regulation of mesopredators. In landscapes of low rainfall and relatively higher proportions of agriculture and human settlement, top–down forces were dampened and bottom–up forces had the most effect on mesopredators. For herbivore prey species, there was evidence of population differences after DFTD arrival, but undetected environmental factors had greater effects. The unique opportunity to assess population changes over extensive temporal and spatial scales following apex predator loss further demonstrated their role in structuring ecosystems and of productivity in determining the strength of top–down control.
The preparedness of UK graduates in acute care: a systematic literature review

Purpose of study The ability to recognise acutely unwell patients and to instigate generic resuscitation is essential for all newly qualified doctors. The aim of this review is to synthesise recent work examining the perceived preparedness of UK medical graduates in acute care, relative to the other outcomes detailed in Tomorrow's Doctors (2009). Study design A systematic literature search was performed using five databases. It sought literature related to preparedness in acute care and other Tomorrow's Doctors outcomes from the perspectives of the graduates themselves and their professional colleagues. Two researchers undertook data extraction and quality scoring, and preparedness ratings in each outcome were mapped to a generic rating scale to allow comparison between studies. Results 256 articles were recovered, with 10 included in the final analysis. The 10 articles suggested that graduates perceive themselves to be least well prepared in acute care and prescribing. Their professional colleagues perceive them to be less prepared in acute care than in any of the other outcomes and perceive preparedness in acute care to have declined since the first publication of Tomorrow's Doctors. Furthermore, there is evidence that preparedness in acute care is an area of concern for UK graduates. Conclusions The assimilation of evidence in this review suggests that recent changes in UK undergraduate training, while improving preparedness in some areas, may have neglected acute care. While not a good surrogate for actual preparedness, perceived preparedness is important in influencing the behaviour of new graduates and therefore warrants further consideration.
Application of the microbial community coalescence concept to riverine networks

Flows of water, soil, litter, and anthropogenic materials in and around rivers lead to the mixing of their resident microbial communities and subsequently to a resultant community distinct from its precursors. Consideration of these events through a new conceptual lens, namely, community coalescence, could provide a means of integrating physical, environmental, and ecological mechanisms to predict microbial community assembly patterns better in these habitats. Here, we review field studies of microbial communities in riverine habitats where environmental mixing regularly occurs, interpret some of these studies within the community coalescence framework and posit novel hypotheses and insights that may be gained in riverine microbial ecology through the application of this concept. Particularly in the face of a changing climate and rivers under increasing anthropogenic pressures, knowledge about the factors governing microbial community assembly is essential to forecast and/or respond to changes in ecosystem function. Additionally, there is the potential for microbial ecology studies in rivers to become a driver of theory development: riverine systems are ideal for coalescence studies because regular and predictable environmental mixing occurs. Data appropriate for testing community coalescence theory could be collected with minimal alteration to existing study designs.