Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterizing aquatic ecological risks from pesticides using a diquat dibromide case study III. Ecological process models

The purpose of this study was to add to the set of risk characterization approaches developed in an earlier study beyond simple comparisons of exposure and effects (e.g., quotients, overlapping frequency distributions) through use of ecological models. These models were used to evaluate the ecological risks from diquat dibromide for individual Daphnia using an individual‐oriented model, a population of bluegill sunfish (Lepomis macrochirus) using a demographic model, and ecological communities within a generic lake in Central Florida, USA, using the Comprehensive Aquatic Systems Model. The ecological models presented in this study more realistically address the potential risks posed by pesticides to individual organisms, populations, communities, and ecosystems than risk assessment methods based on simple comparisons of exposure and effects. The ecological impacts calculated by these models support the inference of minimal risks being posed by diquat dibromide to aquatic systems as concluded from previous empirical comparisons of exposure and toxicity data.
Surgical performance for specialties undertaking temporal artery biopsies: who should perform them?

We read with interest the paper by Galloway and colleagues which suggests that ophthalmologists are best suited to perform temporal artery biopsies.1 We recently completed a retrospective study of all the temporal artery biopsies performed at four teaching hospitals (Hammersmith Hospital, Charing Cross Hospital, St Mary’s Hospital and The Western Eye Hospital) in north London between January 1998 and January 2002. Ninety one patients underwent 92 biopsies. Of these, 15 were positive for temporal arteritis implying a 16% positive biopsy rate which …
Using microsatellite and MHC variation to identify species, ESUs, and MUs in the endangered Sonoran topminnow

Highly variable loci can provide insight into the recognition of species, evolutionarily significant units (ESUs) and management units (MUs). In general, the ESU and MU categories are thought to be reflective of adaptive differences between them. Here we examine this premise by presenting a comprehensive examination of genetic variation for both microsatellite loci and a major histocompatibility complex (MHC) locus, thought to be of adaptive significance, in the endangered Sonoran topminnow. The extent of variation for the microsatellite loci and the MHC gene within the 13 populations of the Gila topminnow is highly correlated, suggesting that nonselective factors have played an important role in influencing variation within and between populations for the MHC locus. Therefore, using all of these loci, we found that the eight natural populations of the Gila topminnow fell into two different ESUs, one of which had four different MUs. The source of the Boyce Thompson sample, a population that was used extensively for restocking, appeared to be Monkey Spring. The source of the Watson Wash population also appeared to be Monkey Spring (or Boyce Thompson). The newly colonized Santa Cruz River population, which had the most genetic variation of any Gila topminnow population, appeared to descend primarily from Sonoita Creek populations. The Yaqui topminnow, presently considered another subspecies of the Sonoran topminnow, was very distinct for both microsatellite (only two of 25 alleles found in the Yaqui were in any of the Gila topminnow samples) and MHC alleles (nonoverlapping sets of alleles for the two groups). As a result, it appeared that the taxonomic status of the two subspecies should be re‐evaluated and that full species status for Gila and Yaqui topminnows was appropriate. There was evidence for the importance of long‐term selection at the MHC locus in the higher rate of nonsynonymous than synonymous substitution. In addition, there appeared to have been a duplication of the MHC locus that was present in most of the fish in six of the natural populations of the Gila topminnow.
MicroRNA-125b and chemokine CCL4 expression are associated with calcific aortic valve disease

Abstract Calcific aortic valve disease (CAVD) is a progressive pathological condition with no effective pharmacological therapy. To identify novel molecular pathways as potential targets for pharmacotherapy, we studied microRNA (miRNA) profiles of heavily stenotic aortic valves (AS). One of the most upregulated miRNAs in AS valves compared to control valves was miR-125b (1.4-fold; P < 0.05). To identify CAVD-related changes in gene expression, DNA microarray analysis was performed, including an intermediate fibro(sclero)tic stage of the disease. This revealed changes especially in genes related to inflammation and immune response, including chemokine (C-C motif) ligand 3 (CCL3) and 4 (CCL4). CCL3 mRNA level was increased 3.9-fold (P < 0.05) when AS valves were compared to control valves, and a 2.5-fold increase (P < 0.05) in CCL4 gene expression was observed when fibro(sclero)tic valves were compared to control valves. Both CCL3 and CCL4 localized to macrophages by immunofluorescence. To identify chemokine–miRNA target pairs, data from miRNA target prediction databases were combined with valvular miRNA and mRNA expression profiles. MiR-125b was computationally predicted to target CCL4, as confirmed experimentally in cultured human THP-1 macrophages. Collectively, miR-125b and CCL4 appear to be involved in the progression of CAVD and may offer novel therapeutic and diagnostic strategies related to this disease.
Impact of protracted venous infusion fluorouracil with or without interferon alfa-2b on tumor response, survival, and quality of life in advanced colorectal cancer.

PURPOSE The aim of this study was to investigate the effects of adding interferon alfa-2b (IFN) to protracted venous infusion fluorouracil (PVI 5-FU) from the start of treatment in patients with advanced colorectal cancer. PATIENTS AND METHODS Patients who attended our unit with histologically confirmed advanced colorectal cancer were randomized to receive either PVI 5-FU 300 mg/m2/d via Hickman line, and IFN 5 MU subcutaneously three times weekly, or PVI 5-FU alone. Treatment was given for a maximum of two 10-week blocks, with a 2-week gap for reassessment of all parameters. Quality of life (QL) was measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) pretreatment and every 6 weeks thereafter. RESULTS A total of 160 patients were randomized, with 155 eligible for assessment. Radiologic response was observed in 43 patients (28%): 17 of 77 (22%) in the 5-FU-plus-IFN arm (all partial responses [PRs]) and 26 of 78 (33%) in the 5-FU-alone group (complete responses [CRs] and 22 PRs) (difference not significant). Symptomatic improvement occurred in the majority of patients, and equally in both arms: 61% to 80% depending on the symptom. There was no significant difference between the two groups in failure-free survival (median, 161 v 193 days) or overall survival (median, 328 v 357 days). However, patients who received IFN did experience significantly more toxicity in the form of leukopenia (P = .001), neutropenia (P = .04), mucositis (P = .008), and alopecia (P = .0002). There were no toxic deaths and few notable differences in QL between the two arms. CONCLUSION This study confirms that PVI 5-FU is effective in treating the symptoms associated with metastatic colorectal carcinoma, with only mild to moderate toxicity and maintenance of QL. IFN 5 MU three times weekly does not enhance these palliative benefits.
Outcomes after treatment of high-energy tibial plafond fractures.

To The Editor: A review of the data presented in the “Supplementary Material” for the article “Outcomes After Treatment of High-Energy Tibial Plafond Fractures” (2003;85:1893-900), by Pollak et al., reveals several disturbing trends that were not reported in the published article. No data were listed to define the severity of the open injuries. Therefore, the ramifications of the severity of the soft-tissue wounds and the method of treatment chosen cannot be determined. The authors reported that eleven of the forty-two fractures managed with open reduction and internal fixation and twenty of the thirty-eight fractures managed with external fixation with or without limited internal fixation were open injuries. With an appropriate sample size, it could be predicted that the group that had external fixation with or without limited internal fixation would have a higher severity of soft-tissue injury compared with the group that had open reduction and internal fixation. Likewise, a comparison of the Type-B and Type-C fracture groups would reveal a trend that, with larger numbers, would indicate that the external fixation group had a substantial level of structural damage compared with … Corresponding author: Andrew N. Pollak, MD Department of Orthopaedics University of Maryland School of Medicine 22 South Greene Street, Suite T3R54 Baltimore, MD 21201 apollak{at}umoa.umm. edu
Effects of interleukin-6 and interleukin-1β on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes.

OBJECTIVE To determine the effects of interleukin (IL)-6 and IL-1β stimulation on expression of growth differentiation factor (GDF)-5 and Wnt signaling pathway genes in equine chondrocytes. SAMPLE Macroscopically normal articular cartilage samples from 6 horses and osteochondral fragments (OCFs) from 3 horses. PROCEDURES Chondrocyte pellets were prepared and cultured without stimulation or following stimulation with IL-6 or IL-1β for 1, 2, 12, and 48 hours; expression of GDF-5 was determined with a quantitative real-time PCR assay. Expression of genes in various signaling pathways was determined with microarrays for pellets stimulated for 1 and 2 hours. Immunohistochemical analysis was used to detect GDF-5, glycogen synthase kinase 3β (GSK-3β), and β-catenin proteins in macroscopically normal cartilage samples and OCFs. RESULTS Chondrocytes stimulated with IL-6 had significantly higher GDF-5 expression within 2 hours versus unstimulated chondrocytes. Microarray analysis of Wnt signaling pathway genes indicated expression of GSK-3β and coiled-coil domain containing 88C increased after 1 hour and expression of β-catenin decreased after 2 hours of IL-6 stimulation. Results of immunohistochemical detection of proteins were similar to microarray analysis results. Chondrocytes in macroscopically normal articular cartilage and OCFs had immunostaining for GDF-5. CONCLUSION AND CLINICAL RELEVANCE Results indicated IL-6 stimulation decreased chondrocyte expression of the canonical Wnt signaling pathway transactivator β-catenin, induced expression of inhibitors of the Wnt pathway, and increased expression of GDF-5. This suggested IL-6 may inhibit the Wnt signaling pathway with subsequent upregulation of GDF-5 expression. Anabolic extracellular matrix metabolism in OCFs may be attributable to GDF-5 expression. This information could be useful for development of cartilage repair methods.
PH‐Domain‐driven targeting of collybistin but not Cdc42 activation is required for synaptic gephyrin clustering

Collybistin (Cb) is a brain‐specific guanine nucleotide exchange factor (GEF) that is essential for the synaptic clustering of gephyrin and GABAA receptors in selected regions of the mammalian central nervous system. It has been previously proposed that Cb regulates gephyrin clustering by activating Cdc42, and thus acts as a signal transducer in a membrane activation process which labels postsynaptic membrane domains for inhibitory synapse formation. Here, we dissected the functional roles of the Dbl‐homology (DH) and pleckstrin homology (PH) domains of the constitutively active splice variant Cb II by substituting conserved amino acid residues that are required for GEF activity towards Cdc42 and phosphoinositide binding, respectively. A Cb II mutant lacking any detectable GEF activity towards Cdc42 was still fully active in inducing gephyrin scaffold formation, both in transfected NIH‐3T3 cells and in cultured hippocampal neurons. Furthermore, mice with a forebrain‐specific inactivation of the Cdc42 gene displayed normal densities of gephyrin and GABAA receptor clusters in the hippocampus. In contrast, substitution of Cb II PH‐domain residues essential for phosphoinositide binding abolished gephyrin recruitment to synaptic sites. Our results provide evidence that the formation of gephyrin scaffolds at inhibitory synapses requires an intact Cb II PH‐domain but is Cdc42‐independent.
Genetic regulation of the kinetics of glucose‐induced insulin release in man Studies in families with diabetic and non‐diabetic probands

Insulin release and sensitivity were estimated from glucose and insulin curves obtained at a glucose infusion test performed on altogether 601 subjects belonging to 155 nuclear families. Ascertainment was through one of the parents, and 96 of the probands had diabetes with clinical onset after the age of 30 years, while 59 were healthy subjects. Three variables obtained by a computer model were analysed, i.e. the glucose regulation of insulin release by a direct stimulatory event (KI) and time‐dependent modulatory events (KP) as well as insulin sensitivity (KG). Complex segregation analysis revealed that the variables are genetically regulated, but there was no evidence for a major locus. The children of the diabetics did not differ from those of the non‐diabetics as far as insulin release is concerned.
A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

Adenosine, an important signaling molecule in asthma, produces bronchoconstriction in asthmatics. Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating A1 adenosine receptors (ARs). Effects of L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxyethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione] a water-soluble, small molecule A1 AR antagonist were investigated on early and late phase allergic responses (EAR and LAR) in a hyper-responsive rabbit model of asthma. Rabbits were made allergic by intraperitoneal injections of house dust mite [HDM; 312 allergen units (AU)] extract within 24 h of their birth. Booster HDM injections were given weekly for 1 month, biweekly for 4 months, and continued monthly thereafter. Hyperresponsiveness was monitored by measuring lung dynamic compliance (Cdyn), after histamine or adenosine aerosol challenge in allergic rabbits. Hyper-responsive rabbits were subjected to aerosol of HDM (2500 AU), 1 h after intragastric administration of L-97-1 (10 mg/kg) solution or an equivalent volume of saline. Cdyn was significantly higher after treatment with L-97-1 compared with untreated controls (p < 0.05 n = 5). Histamine PC30 was significantly higher (p < 0.05; n = 5) after L-97-1 at 24 h compared with histamine PC30 at 24 h after HDM. Adenosine PC30 was significantly higher at 15 min and 6 h after L-97-1 compared with control (p < 0.05; n = 5). L-97-1 showed strong affinity for human A1 ARs in radioligand binding studies and no inhibition toward human phosphodiesterase II, III, IV, and V enzymes. These data suggest that L-97-1 produces a significant reduction of histamine or adenosine-induced hyper-responsiveness and HDM-induced EAR and LAR in allergic rabbits by blocking A1 ARs and may be beneficial as an oral therapy for human asthma.
Risk of obstructive sleep apnea in patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVES Type 2 diabetes mellitus (DM) and obstructive sleep apnea (OSA) share several clinical findings: obesity, hypertension, and impaired glucose tolerance. OSA may be an under-recognized comorbidity of DM. The purpose of this study is to estimate the proportion of patients with type 2 DM at risk for OSA and describe factors associated with that risk. METHODS This cross-sectional study enrolled 297 adults, ages 18 years and older, with type 2 DM from a university-based Family Medicine Center. Participants completed a research questionnaire recording sociodemographic information, medical history, and clinical data including medications and hemoglobin A1C. OSA risk was determined using the Berlin Questionnaire. Relationships between risk of OSA and sociodemographic and clinical variables were evaluated using bivariate analyses and covariate adjusted logistic regression models. RESULTS Thirty-seven participants (12.5%) had a prior diagnosis of OSA. Based on the Berlin Questionnaire, 124 (48.6%) of the remaining patients were classified as high risk for OSA. Patients less than age 60 years were at increased risk for OSA, adjusted OR=2.67 (1.57, 4.54; 95% CI). Non-Hispanic whites, adjusted OR=1.76 (1.01, 3.06; 95% CI), and patients with symptoms of depression, adjusted OR=2.64 (1.60, 4.52; 95% CI), were also at higher risk. Gender and hemoglobin A1C were not associated with increased risk of OSA. CONCLUSIONS Nearly half of adults with type 2 DM may be at high risk for OSA, and many may be undiagnosed. In a primary care setting, the Berlin Questionnaire is an easily applied screening instrument that identifies patients at increased risk of OSA who may benefit from further diagnostic studies and treatment of OSA.
Effectiveness of Steroid Injection in Treating Patients With Moderate and Severe Degree of Carpal Tunnel Syndrome Measured by Clinical and Electrodiagnostic Assessment

ObjectivesThis study is to assess the effectiveness of steroid injections to improve the clinical and electrodiagnostic (EDX) parameters associated with moderate and severe carpal tunnel syndrome (CTS). The study will also evaluate the correlation between EDX and clinical assessment scores. MethodsPatients with moderate or severe CTS identified by EDX were recruited. A visual analog scale, the Boston Carpal Tunnel Syndrome Questionnaire, and EDX procedures were all used during patients' pretreatment. These tests were repeated at 4 and 8 weeks after patients received a 20 mg injection of triamcinolone in the carpal tunnel to evaluate the changes and the correlation between the clinical and EDX parameters. ResultsAlthough moderate and severe CTS showed significant improvement in clinical parameters at 4 weeks and 2 months, EDX parameters of moderate CTS were significantly improved at 4 weeks, but diminished at 8 weeks. Those with severe CTS were not significantly improved at either 4 or 8 weeks. There was no correlation between clinical and EDX results for both groups. DiscussionSteroid injection is an effective method to improve clinical scales but has limited ability to restore nerve conduction in moderate or severe CTS. Because there is no correlation between clinical and EDX parameters, we should consider both clinical and neurophysiologic tests to assess CTS.
Structure of Vps26B and Mapping of its Interaction with the Retromer Protein Complex

Retromer is a heteromeric protein complex with important roles in endosomal membrane trafficking, most notably in the retrograde transport of lysosomal hydrolase receptors from endosomes to the Golgi. The core of retromer is composed of three subunits vacuolar protein sorting (Vps)35, Vps26 and Vps29, and in mammals, there are two paralogues of the medium subunit Vps26A and Vps26B. We find that both Vps26A and Vps26B bind to Vps35/Vps29 with nanomolar affinity and compete for a single‐binding site to define distinct retromer complexes in vitro and in vivo. We have determined the crystal structure of mouse Vps26B and compare this structure with that of Vps26A. Vps26 proteins have a striking similarity to the arrestin family of proteins that regulate the signalling and endocytosis of G‐protein‐coupled receptors, although we observe that surface residues involved in arrestin function are not conserved in Vps26. Using structure‐based mutagenesis, we show that both Vps26A and Vps26B are incorporated into retromer complexes through binding of Vps35 to a highly conserved surface patch within the C‐terminal subdomain and that this interaction is required for endosomal recruitment of the proteins.
Modality of Postural Movement in Men and Women with Both Arms Flexed during Standing

We investigated postural movement associated with bilateral arm flexion in response to a light signal during standing in 179 healthy men and women to assess whether individual and sex differences are evident in the postural movement pattern. The following results were obtained, (a) A correlation of −. 87 was noted between movement angles of the foot-leg and leg trunk, (b) Individual differences in movement angle were approximately twice as large in the hip joint as in the ankle and knee joints, and the movement angle of the leg trunk showed approximately half the number of extension as flexion movements, (c) The postural movement pattern was categorized on the basis of the movement angle of the foot-leg and leg-trunk into the following three patterns: hip flexion, backward leaning, and hip extension. The percentages of subjects showing these patterns were 59.2%, 33.5%, and 7.3%, respectively. (d) The inclination angle reflecting the righting response showed a gradual increase in size in the order of trunk, head, and neck. However, the righting response was not controlled precisely enough to enable subjects to maintain the inclination angle in a quiet standing posture, (e) We identified a significant sex difference in the relative frequency of subjects in the postural movement pattern.
Symptoms of Psychoses

Background The literature on the statistical analysis of symptoms of psychoses was limited to positive and negative symptoms in schizophrenia. The present study explored the relationship between positive and negative symptoms as well as affective symptoms in a wider category of psychotic disorders. Method The symptoms of 584 psychiatric patients, consecutively admitted to any of the 95 mental hospitals in Japan, were studied. They manifested at least one of the following: (a) delusions, (b) hallucinations, (c) formal thought disorder, (d) catatonic symptoms, or (e) negative (defect) symptoms. Results Factor analysis yielded five factors interpretable as (a) manic symptoms, (b) depressive symptoms, (c) negative (defect) symptoms and formal thought disorders, (d) positive (psychotic) symptoms, and (e) catatonic symptoms. Conclusion These results suggest that although major symptoms seen among psychotic patients can be categorised into positive, negative, manic, and depressive groups, corresponding to current knowledge of phenomenology, catatonic symptoms constitute a discrete syndrome, while formal thought disorders merge into the negative syndrome.
Basic patterns in annual variations in fertility, nuptiality, mortality, and prices in pre-industrial Europe.

Examination of the responses of vital rates to variations in grain prices in nine pre-industrial European countries confirms the existence of the short-term Malthusian preventive and positive checks. The structure and magnitude of the preventive check are strikingly similar in all countries and all periods. On the other hand, the strength of the positive check varies widely and in remarkable accord with measures of economic development. The size of the positive relative to the preventive check diminishes as economic development increases. Among the countries examined, differences in the response of population growth rates to price fluctuations can be attributed primarily to differences in the strength of the positive check.
Truth in the Garden of Forking Paths

“This network of times which approached one another, forked, broke off, or were unaware of one another for centuries, embraces all possibilities of time. In the present one, which a favorable fate has granted me, you have arrived at my house; in another, while crossing the garden, you found me dead; in still another, I utter these same words, but I am a mistake, a ghost. Time forks perpetually toward innumerable futures. ”