Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes

Abstract Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS.
MRI Findings in Throwing Shoulders: Abnormalities in Professional Handball Players

Shoulders of throwing athletes are highly stressed joints and likely to have more structural abnormalities seen on magnetic resonance imaging scans. Prevalence and type of structural abnormalities, especially abnormalities of the rotator cuff tendons and the superolateral humeral head, and correlation of magnetic resonance imaging findings with symptoms and clinical tests, are not well known. Throwing and nonthrowing (symptomatic and asymptomatic) shoulders of 30 fully competitive professional handball players and 20 dominant shoulders of randomly selected volunteers were evaluated for comparison clinically and with magnetic resonance imaging. An average of seven abnormal magnetic resonance imaging findings was observed in the throwing shoulders; more than in the nonthrowing and the control shoulders. Although 93% of the throwing shoulders had abnormal magnetic resonance imaging findings, only 37% were symptomatic. Partial rotator cuff tears and mainly superolateral osteochondral defects of the humeral head were identified as typical throwing lesions. Symptoms correlated poorly with abnormalities seen on magnetic resonance imaging scans and findings from clinical tests. This suggests that the evaluation of an athlete’s throwing shoulder should be done very thoroughly and should not be based mainly on abnormalities seen on magnetic resonance imaging scans. Level of Evidence: Diagnostic study, Level III-1 (study of nonconsecutive patients—no consistently applied reference “gold” standard)
Accumulation of 7S SNARE complexes in hippocampal synaptosomes from chronically kindled rats

Kindling is a model of complex partial epilepsy wherein periodic application of an initially subconvulsive stimulus leads to first limbic and then generalized tonic‐clonic seizures. Several laboratories have reported that augmented neurotransmitter release of l‐glutamate is associated with the chronically kindled state. Neurotransmitter release requires membrane proteins called SNAREs, which form transmembrane complexes that participate in vesicle docking and are required for membrane fusion. We show here that kindling by entorhinal stimulation is associated with an accumulation of 7S SNARE complexes in the ipsilateral hippocampus. This increase of 7S SNARE complexes appears to begin early in the kindling process, achieves a peak with full kindling, and remains at this level for at least a month following cessation of further kindling stimuli. The increase is focal and permanently limited to the ipsilateral hippocampus despite progression to generalized electrographic and behavioral seizures. It is not seen in animals that receive electroconvulsive seizures, suggesting it is related to the kindling process itself. The duration and focality of increased 7S SNARE complexes with entorhinal kindling suggest that this is an altered molecular process associated with epileptogenesis.
Continuous Photo-Oxidation in a Vortex Reactor: Efficient Operations Using Air Drawn from the Laboratory

We report the construction and use of a vortex reactor which uses a rapidly rotating cylinder to generate Taylor vortices for continuous flow thermal and photochemical reactions. The reactor is designed to operate under conditions required for vortex generation. The flow pattern of the vortices has been represented using computational fluid dynamics, and the presence of the vortices can be easily visualized by observing streams of bubbles within the reactor. This approach presents certain advantages for reactions with added gases. For reactions with oxygen, the reactor offers an alternative to traditional setups as it efficiently draws in air from the lab without the need specifically to pressurize with oxygen. The rapid mixing generated by the vortices enables rapid mass transfer between the gas and the liquid phases allowing for a high efficiency dissolution of gases. The reactor has been applied to several photochemical reactions involving singlet oxygen (1O2) including the photo-oxidations of α-terpinene and furfuryl alcohol and the photodeborylation of phenyl boronic acid. The rotation speed of the cylinder proved to be key for reaction efficiency, and in the operation we found that the uptake of air was highest at 4000 rpm. The reactor has also been successfully applied to the synthesis of artemisinin, a potent antimalarial compound; and this three-step synthesis involving a Schenk-ene reaction with 1O2, Hock cleavage with H+, and an oxidative cyclization cascade with triplet oxygen (3O2), from dihydroartemisinic acid was carried out as a single process in the vortex reactor.
Evaluation of a successful vancomycin-resistant Enterococcus prevention intervention in a community of health care facilities.

BACKGROUND In April 1997, vancomycin-resistant enterococci (VRE) emerged in several health care facilities in the Siouxland region and a VRE Task Force was formed. From 1997 through 1999, an evaluation of VRE prevalence at 30 facilities was performed. METHODS In 1999, we conducted a survey and focus groups of health care workers to address initial reactions to VRE, feasibility of the Task Force recommendations, and lessons learned. RESULTS Personnel at 29 (97%) facilities surveyed completed the questionnaire, and 15 health care workers from 11 facilities participated in 5 focus groups. The outcomes of expanded education and improved awareness of VRE for patients and health care workers were ranked the No. 1 priority overall and by long-term care facility personnel. Respondents agreed that Task Force recommendation adherence had significantly improved infection control (83%) and that the Task Force was an appropriate mechanism to coordinate infection control efforts (90%). Focus groups commented that it was most difficult to educate family members about VRE; they expressed concern about variation between VRE policies, especially between acute care and long-term care facilities, and about the quality of life of isolated patients. CONCLUSIONS Our data illustrate that this intervention has been far-reaching and include the development of a health care infrastructure that may be used as a model to address additional health care issues (eg, emerging pathogens or biological threats).
Immunohistochemical analyses of DNA topoisomerase II isoforms in developing rat cerebellum

In mammalian cells, two isoforms of DNA topoisomerase II (topo IIα and topo IIβ) have been identified. Topo IIα is essential in mitotic cells, whereas the function of topo IIβ remains unclear. In the present study, we investigated the developmental control of topo II isoforms in two different neuronal lineages, cerebellar Purkinje cells and granule cells, by immunohistochemical analysis with isoform‐specific monoclonal antibodies. As expected, proliferating cells in the neuroepithelium and in the external germinal layer (EGL) were topo IIα immunopositive. The migrating as well as differentiating Purkinje cells and granule cells showed an enhanced topo IIβ immunoreactivity. The postmitotic granule cells in the postnatal EGL showed an abrupt transition of expressed topo II isoforms from IIα to IIβ. The transition was clearly coincident with the completion of final cell division and the initiation of terminal differentiation because no increase of the topo IIβ immunoreactivity was observed in the spreading EGL cells that are still in the cell division cycle. The topo IIβ signal was detected in both nucleoplasm and nucleolus of differentiating cells. However, the nucleoplasmic signal decreased significantly as the cells reached terminal differentiation. The residual topo IIβ in nucleoli was shown to occupy an unique location with respect to other nucleolar proteins, nucleolin and DNA topoisomerase I. Our findings indicate that both Purkinje cells and granule cells express the topo II isoforms in a similar timing during the cerebellar development and also suggest that topo IIβ localized in nucleoplasm is the functional entity involved in neuronal differentiation. J. Comp. Neurol. 431:228–239, 2001. © 2001 Wiley‐Liss, Inc.
[Body structure and ABO and Rh blood groups in patients with advanced coronary heart disease after aorto-coronary by-pass surgery].

A clinical analysis of the anthropometric traits related to body structure, ABO and rhesus blood groups was performed in 200 male individuals coming mainly from Warsaw and its territorial district. All patients were aged from thirty-one to sixty-eight years (X = 42.3) and total duration of coronary heart disease was from 1 to 12 years. The number of 54 patients (21%) was subjected to surgery because of coronary insufficiency, but without myocardial infarction (M.I.). One or three single cases of M.I. were reported in the remaining number of 146 patients (73%). A degree of extension of arteriosclerotic lesions either in two or three coronary arteries was larger determined upon coronarography. The control group for blood--groups in 200 patients was made of 11,820 healthy male--blood from District Blood Donor Station in Warsaw, but for the anthropometric tracts (height, body weight and Rohrer's index) the control group was made of 283 men aged 35-80 years (average 43.2) coming mainly from Warsaw and its district. Patients after aorto-coronary by-pas surgery with highly advanced arteriosclerosis of the coronary arteries featured indicated significantly higher number of cases with group AB (p < 0.01) due to deficiency in group O (p < 0.05). It has also been found that the occurrence of rhesus blood group lack in patients having undergone by-pass surgery is significantly common (p < 0.01). No significant difference in anthropological traits between the patients after aorto-coronary by-pass surgery and the control group from the same geographical region was reported. (ABSTRACT TRUNCATED AT 250 WORDS)
Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications.

CONTEXT Recent developments indicate that pathophysiological mechanisms leading to beta-cell damage, insulin resistance, and the vascular complications of diabetes include an activation of the inflammation cascade, endothelial dysfunction, and procoagulant imbalance. Their circulating biomarkers may therefore provide opportunities for early diagnosis and targets for novel treatments. EVIDENCE Circulating biomarkers of these pathways such as TNFalpha, IL-6, C-reactive protein (CRP) (inflammation), vascular cellular adhesion molecule-1, interstitial cellular adhesion molecule-1, E-selectin, von Willebrand factor (endothelial dysfunction), plasminogen activator inhibitor-1, fibrinogen, P-selectin (procoagulant state), and adiponectin (antiinflammation) may be associated with development of both type 1 and type 2 diabetes and some studies, particularly in type 2 diabetes, have demonstrated that certain biomarkers may have independent predictive value. Similarly studies have shown that these biomarkers may be associated with development of diabetic nephropathy and retinopathy, and again, particularly in type 2 diabetes, with cardiovascular events as well. Finally, the comorbidities of diabetes, namely obesity, insulin resistance, hyperglycemia, hypertension and dyslipidemia collectively aggravate these processes while antihyperglycemic interventions tend to ameliorate them. CONCLUSIONS Increased CRP, IL-6, and TNFalpha, and especially interstitial cellular adhesion molecule-1, vascular cellular adhesion molecule-1, and E-selectin are associated with nephropathy, retinopathy, and cardiovascular disease in both type 1 and type 2 diabetes. Whereas further work is needed, it seems clear that these biomarkers are predictors of increasing morbidity in prediabetic and diabetic subjects and should be the focus of work testing their clinical utility to identify high-risk individuals as well as perhaps to target interventions.
Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production

Subversion of host organism cAMP signaling is an efficient and widespread mechanism of microbial pathogenesis. Bartonella effector protein A (BepA) of vasculotumorigenic Bartonella henselae protects the infected human endothelial cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet unknown mechanism. Here, adenylyl cyclase (AC) and the α-subunit of the AC-stimulating G protein (Gαs) were identified as potential cellular target proteins for BepA by gel-free proteomics. Results of the proteomics screen were evaluated for physical and functional interaction by: (i) a heterologous in vivo coexpression system, where human AC activity was reconstituted under the regulation of Gαs and BepA in Escherichia coli; (ii) in vitro AC assays with membrane-anchored full-length human AC and recombinant BepA and Gαs; (iii) surface plasmon resonance experiments; and (iv) an in vivo fluorescence bimolecular complementation-analysis. The data demonstrate that BepA directly binds host cell AC to potentiate the Gαs-dependent cAMP production. As opposed to the known microbial mechanisms, such as ADP ribosylation of G protein α-subunits by cholera and pertussis toxins, the fundamentally different BepA-mediated elevation of host cell cAMP concentration appears subtle and is dependent on the stimulus of a G protein-coupled receptor-released Gαs. We propose that this mechanism contributes to the persistence of Bartonella henselae in the chronically infected vascular endothelium.
Risk of fractures in celiac disease patients: a cross-sectional, case-control study

OBJECTIVES:Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients.METHODS:We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis.RESULTS:Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8–7.2; p < 0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7–11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p < 0.06) and remained undiagnosed for more prolonged periods (p < 0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures.CONCLUSIONS:This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.
Activity‐Based Probes for HECT E3 Ubiquitin Ligases

Activity‐based probes (ABPs) have been used to dissect the biochemical/structural properties and cellular functions of deubiquitinases. However, their utility in studying cysteine‐based E3 ubiquitin ligases has been limited. In this study, we evaluate the use of ubiquitin‐ABPs (Ub‐VME and Ub‐PA) and a novel set of E2–Ub‐ABPs on a panel of HECT E3 ubiquitin ligases. Our in vitro data show that ubiquitin‐ABPs can label HECT domains. We also provide the first evidence that, in addition to the RBR E3 ubiquitin ligase Parkin, E2–Ub‐ABPs can also label the catalytic HECT domains of NEDD4, UBE3C, and HECTD1. Importantly, the endogenous proteasomal E3 ligase UBE3C was also successfully labelled by Ub‐PA and His‐UBE2D2–Ub‐ABP in lysate of cells grown under basal conditions. Our findings provide novel insights into the use of ABPs for the study of HECT E3 ubiquitin ligases.
Early Diagnosis of Alzheimer Disease With Positron Emission Tomography

The emergence of drugs that may slow progression of Alzheimer disease, if administered early during its course, has necessitated early diagnosis of the disease itself. Among the functional imaging methods that could assist in early diagnosis, positron emission tomography has an important role in providing quantitative measures of various aspects of brain function affected by the disease. Positron emission tomography studies in patients with Alzheimer disease have revealed a typical pattern of metabolic deficits in the temporal and parietal lobes. Additionally, converging evidence from numerous studies indicates that a similar pattern of deficits can be observed in nondemented subjects who are at risk of developing the disease, such as those with recognized genetic traits such as familial Alzheimer disease with mutations in chromosomes 21 and 14, Down syndrome, subjects with the ε4 allele of the apolipoprotein E gene, and individuals with mild cognitive impairment. These findings might have implications for the selection of patients for clinical trials, defining the outcome measures and evaluation of treatment efficacy and responder characteristics, but should be confirmed by prospective studies comprising larger samples and include clinicopathologic correlations.
Mechanisms of heat damage in proteins

1. The preparation of a propionylated protein is described, and the effects of this treatment on amino acid composition and availability are compared with the effects of severe heat treatment (autoclaving) of a protein. 2. Using chemical analyses, changes exceeding 5% for total tyrosine, histidine, methionine and cystine contents were found after propionylation of the protein. Autoclaving of the protein resulted in changes in total serine, lysine, methionine, cystine and tryptophan contents. 3. Microbiological estimates of total amino acid contents were not in close agreement with the chemical estimates for the autoclaved protein. 4. Fluorodinitrobenzene-reactive lysine content was reduced to almost zero by propionylation, and by almost 40% by autoclaving. 5. Both propionylating and autoclaving protein reduced the amount of lysine available to the chick by about half. In contrast, the availabilities of methionine and tryptophan to the chick were unchanged by propionylation, but were reduced to 0.66 and 0.44 respectively, relative to the untreated protein, by autoclaving. 6. Because of the difficulties of obtaining reliable absolute estimates of amino acid availability using chick growth assays, our interpretation of results is mainly based on relative values. The merits of microbiological microbiological estimates of amino acid availability are assessed.
Should Continuous Hydralazine Infusions be Utilized in Severe Pregnancy-Induced Hypertension?

Intravenous hydralazine therapy in severe preeclampsia-eclampsia may be administered by either continuous intravenous infusion or intermittent bolus therapy. We studied the hemodynamic effects of continuous intravenous hydralazine infusion in seven patients with severe pregnancy-induced hypertension. The starting infusion dose was 5 mg/hr and was increased every 15 to 20 minutes by 1 to 2 mg/hr to obtain a 20% reduction in mean arterial blood pressure. The initial mean systolic and diastolic blood pressures were 208.3 +/- 24.8 and 124.3 +/- 11.6 mmHg, respectively. The comparable mean levels following hydralazine therapy was 144 +/- 13.6 and 87 +/- 11.6 mmHg. This decline was obtained at a mean hydralazine dose of 16.04 +/- 3.65 mg/hr. Despite an increase in cardiac output, the rapid uncontrolled decline in blood pressure resulted in five of the seven patients developing fetal distress requiring cesarean delivery. If hydralazine therapy is to be used in severe preeclampsia-eclampsia, we advocate avoidance of continuous intravenous therapy.
Just in Time Research: Data Breaches in Higher Education.

This “Just in Time” research is in response to recent discussions on the EDUCAUSE Higher Education Information Security Council (HEISC) discussion list about data breaches in higher education. Using data from the Privacy Rights Clearinghouse, this research analyzes data breaches attributed to higher education. The results from this review will be used to inform EDUCAUSE research, programs, products, and services.