Miracle-dz/UniFAR-FTUs huggingface dataset:
Colonic treatments and targets: issues and opportunities

The colon provides a plethora of therapeutic opportunities. There are multiple disease targets, drug molecules, and colon-specific delivery systems to be explored. Clinical studies highlight the potential for systemic delivery via the colon, and the emerging data on the levels of cell membrane transporters and metabolic enzymes along the gut could prove advantageous for this. Often efflux transporters and metabolic enzyme levels are lower in the colon, suggesting a potential for improved bioavailability of drug substrates at this site. The locoregional distribution of multiple metabolic enzymes (including cytochromes), efflux transporters (including P-glycoprotein and breast cancer resistance proteins), and influx transporters (including the solute carrier family) along the intestine is summarized. Local delivery to the colonic mucosa remains a valuable therapeutic option. New therapies that target inflammatory mediators could improve the treatment of inflammatory bowel disease, and old and new anticancer molecules could, when delivered topically, prove to be beneficial adjuncts to the current systemic or surgical treatments. New issues such as pharmacogenomics, chronotherapeutics, and the delivery of prebiotics and probiotics are also discussed in this review. Targeting drugs to the colon utilizes various strategies, each with their advantages and flaws. The most promising systems are considered in the light of the physiological data which influence their in vivo behavior.
Accuracy of various techniques in the measurement of the duration of the q wave: A possible source of error in diagnosing myocardial infarction by electrocardiography

The method of measuring the width of the Q wave on electrocardiogram is one of the variables contributing to conflicting findings regarding the accuracy of the ECG in the diagnosis of myocardial infarction. This study assesses the accuracy of a variety of methods of measuring the width of the Q wave recorded by direct‐writing electrocardiographic instruments. The assessment was made by comparing the width of the Q wave as inscribed by thermal direct‐writing electrocardiographs to the width of the Q wave as measured from an oscilloscopic display, the latter representing the “true” width of the Q wave. The measurement of the width as obtained from the upper edge of the tracing obtained with direct‐writing electrocardiographs underestimated the true width of the Q wave, while the opposite was the case by measuring the width along the lower edge of the tracing. The most reliable ways to obtain the true width of the Q wave are: (1) to average the measurements as obtained along the upper and lower edge, (2) to measure the width along an ideal line in the middle of the tracing, or (3) to measure the width along the trailing edge of the deflection.
Cognitive domains associated with performance on the Telephone Interview for Cognitive Status—modified

Global cognitive screening tests are increasingly used in clinical and research settings. However, many have not been developed following systematic psychometric principles; thus, construct validity is not clearly defined. It is the aim of this study to identify the cognitive domains that are associated with the total score from the Telephone Interview for Cognitive Status-modified (TICS-m). Data came from 104 women (75 years of age and older) who were participants in a longitudinal study of dementia and had been given the TICS-m and a battery of standardized neuropsychological tests. Factor analysis of all these neuropsychological tests yielded six interpretable factors: episodic memory for words, episodic memory for contextual information, working memory, episodic memory for nonverbal information, attention, and visuospatial processing efficiency. The TICS-m score showed modest associations with several distinct cognitive domains, including episodic memory for words and nonverbal information and attention.
Mind and heart: Heart rate variability in major depressive disorder and coronary heart disease - a review and recommendations

Objective: There is a reciprocal association between major depressive disorder (MDD) and coronary heart disease (CHD). These conditions are linked by a causal network of mechanisms. This causal network should be quantitatively studied and it is hypothesised that the investigation of vagal function represents a promising starting point. Heart rate variability (HRV) has been used to investigate cardiac vagal control in the context of MDD and CHD. This review aims to examine the relationship of HRV to both MDD and CHD in the context of vagal function and to make recommendations for clinical practice and research. Methods: The search terms ‘heart rate variability’, ‘depression’ and ‘heart disease’ were entered into an electronic multiple database search engine. Abstracts were screened for their relevance and articles were individually selected and collated. Results: Decreased HRV is found in both MDD and CHD. Both diseases are theorised to disrupt autonomic control feedback loops on the heart and are linked to vagal function. Existing theories link vagal function to both mood and emotion as well as cardiac function. However, several factors can potentially confound HRV measures and would thus impact on a complete understanding of vagal mechanisms in the link between MDD and CHD. Conclusions: The quantitative investigation of vagal function using HRV represents a reasonable starting point in the study of the relationship between MDD and CHD. Many psychotropic and cardiac medications have effects on HRV, which may have clinical importance. Future studies of HRV in MDD and CHD should consider antidepressant medication, as well as anxiety, as potential confounders.
Systemic CD14 Inhibition Attenuates Organ Inflammation in Porcine Escherichia coli Sepsis

ABSTRACT Sepsis is an infection-induced systemic inflammatory response syndrome. Upstream recognition molecules, like CD14, play key roles in the pathogenesis. The aim of the present study was to investigate the effect of systemic CD14 inhibition on local inflammatory responses in organs from septic pigs. Pigs (n = 34) receiving Escherichia coli-bacteria or E. coli-lipopolysaccharide (LPS) were treated with an anti-CD14 monoclonal antibody or an isotype-matched control. Lungs, liver, spleen, and kidneys were examined for bacteria and inflammatory biomarkers. E. coli and LPS were found in large amounts in the lungs compared to the liver, spleen, and kidneys. Notably, the bacterial load did not predict the respective organ inflammatory response. There was a marked variation in biomarker induction in the organs and in the effect of anti-CD14. Generally, the spleen produced the most cytokines per weight unit, whereas the liver contributed the most to the total load. All cytokines were significantly inhibited in the spleen. Interleukin-6 (IL-6) was significantly inhibited in all organs, IL-1β and IP-10 were significantly inhibited in liver, spleen, and kidneys, and tumor necrosis factor, IL-8, and PAI-1 were inhibited only in the spleen. ICAM-1 and VCAM-1 was significantly inhibited in the kidneys. Systemic CD14-inhibition efficiently, though organ dependent, attenuated local inflammatory responses. Detailed knowledge on how the different organs respond to systemic inflammation in vivo, beyond the information gained by blood examination, is important for our understanding of the nature of systemic inflammation and is required for future mediator-directed therapy in sepsis. Inhibition of CD14 seems to be a good candidate for such treatment.
Pressor Responsiveness to Intravenous Quinpirole is Blunted in Malnourished, Conscious Rats: Central vs. Peripheral and Spinal Mechanisms

In conscious rats, intravenous treatment with the dopamine D2-like receptor agonist quinpirole, elicited a pressor effect, which is attributed to central dopamine D2 receptor-mediated activation of sympathetic outflow associated with arginine vasopressin release. This prominent central effect is opposed to peripheral sympathoinhibitory and spinal depressor effects. The present study investigated the effects of pre- and postnatal undernutrition on the central pressor responsiveness to quinpirole. Malnourished (MalN) rats were obtained by feeding dams a multideficient diet (providing 8% protein) during pregnancy and nursing. At 90 days of age, MalN rats weighed significantly less than control (CNT) rats born to dams fed standard commercially diet (23% protein) during pregnancy and nursing. Baseline mean arterial pressure and heart rate in MalN rats were comparable to those of CNT. Intravenous treatment with quinpirole (0.3 mg/kg) in MalN conscious rats induced a pressor effect, which was significantly reduced in both magnitude and duration, when compared with CNT rats. In both groups studied, pressor response to quinpirole was fully abolished by the peripheral and central dopamine D2 receptor antagonist, metoclopramide (5 mg/kg, i.v.) whereas was significantly enhanced after pretreatment with either intravenous (0.5 mg/kg) or intrathecal (40 μg per rat at T9–T10 level) domperidone, a dopamine D2 receptor antagonist that does not cross the blood-brain barrier. However, even under peripheral and spinal dopamine D2 receptor blockade, maximum pressor effect of quinpirole remained significantly reduced in MalN when compared with CNT rats. Neither the maximum pressor nor the bradycardiac responses to intravenous phenylephrine or arginine vasopressin differed between CNT and MalN rats. This study shows that undernutrition imposed during fetal life and suckling blunted the pressor response to quinpirole in conscious rats. This blunted response appears mainly related to desensitization of brain dopamine D2 receptors rather than enhanced peripheral and/or spinal dopamine D2 receptor-mediated depressor effect or vascular hyporesponsiveness to &agr;1-adrenoceptor and vasopressin receptor stimulation.
Survey of knowledge, attitudes and practices for tuberculosis among general practitioners in Delhi, India.

SETTING Random survey of knowledge, attitudes and practices (KAP) for tuberculosis among private practitioners (PPs) in Delhi, India, in 1995. OBJECTIVE To investigate the KAP of private practitioners for tuberculosis in Delhi where the Revised National Tuberculosis Programme (RNTP) is being field tested. DESIGN A pre-tested questionnaire survey was performed among 204 doctors attending updates/seminars on tuberculosis in various parts of Delhi. RESULTS In a suspected case of tuberculosis, sputum examination was advised by only 12% of the PPs, while 89.5% would recommend chest X-ray. For treating tuberculosis 187 PPs were using 102 different regimens, and only 29.4% PPs were using the regimen recommended by the RNTP; 51.3% PPs were over-treating their patients. Only 23.5% of PPs requested sputum examination before the end of treatment, while 35.5% depended on X-ray clearance with clinical improvement. Only 19.5% of PPs emphasized the importance of regular treatment for their patients. CONCLUSION Among PPs there is marked reliance on X-ray; sputum examination is being neglected for initial diagnosis, treatment monitoring and as a criterion for stopping treatment. The majority of PPs are not aware of, or are not prescribing, the treatment regimen recommended by the RNTP, and the majority of patients are being over-treated. There is a lack of emphasis on proper health education. PPs need more training, and more collaborative efforts are required between public health facilities and practising doctors for national control of tuberculosis.
Evidence for the role of aberrant DNA methylation in the pathogenesis of Lynch syndrome adenomas

Colorectal cancer (CRC) forms through a series of histologic steps that are accompanied by mutations and epigenetic alterations, which is called the polyp‐cancer sequence. The role of epigenetic alterations, such as aberrant DNA methylation, in the polyp‐cancer sequence in sporadic CRC and particularly in hereditary colon cancer is not well understood. Consequently, we assessed the methylation status of CDKN2A/p16, MGMT, MLH1 and p14ARF in adenomas arising in the Lynch syndrome, a familial colon cancer syndrome caused by MLH1 and MSH2 mutations, to determine if DNA methylation is a “second hit” mechanism in CRC and to characterize the role of DNA methylation in the polyp phase of the Lynch syndrome. We found MLH1 and p14ARF are methylated in 53 and 60% of the Lynch syndrome adenomas and in 4 and 20% of sporadic adenomas, whereas CDKN2A/p16 and MGMT are methylated in 6 and 14% of the Lynch syndrome adenomas versus 50 and 64% of sporadic adenomas. Therefore, the frequency and pattern of gene methylation varies between the Lynch syndrome and sporadic colon adenomas, implying differences in the molecular pathogenesis of the tumors. MLH1 methylation in the Lynch syndrome adenomas suggests gene methylation might have a role in the initiation of these neoplasms. © 2007 Wiley‐Liss, Inc.
Heart Healthy Omega-3 s for Food — Stearidonic Acid ( SDA ) as a Sustainable Choice Stearidonic Acid Raises Red Blood Cell Membrane Eicosapentaenoic Acid 1 , 2

The consumption of EPA and DHA has been associated with reduced risk for cardiovascular disease morbidity andmortality. Mean intakes of EPA and DHA in the United States and elsewhere are below levels recommended by health authorities. The main non-marine source of dietary (n-3) fatty acids (a-linolenic acid) is poorly converted to EPA in humans. Stearidonic acid (SDA) is a non-marine fatty acid that appears to be more readily converted to EPA in humans. Results from previous studies suggested that SDA, relative to EPA, increases RBC EPA, with reported efficiencies ranging from ;16 to 30%. A recently published, randomized, single-blind, controlled, parallel group study in healthy men and women characterized the relationships between intakes of SDA and EPA and EPA enrichment of RBCmembranes over a 12-wk period. %EPA in RBC membraneswas greater after EPA (0.44, 1.3, or 2.7 g/d, respectively) and SDA (1.3, 2.6, or 5.2 g/d, respectively) consumption compared to a safflower control (all P , 0.02). Based on quadratic response surface models, for EPA intakes of 0.25, 0.50, and 0.89 g/d, SDA intakes of 0.61, 1.89, and 5.32 g/d, respectively, would be required to produce equivalent values for RBC% EPA, translating to relative efficiencies of 41.0, 26.5, and 16.7%. Thus, dietary SDA over a range of intakes increases RBC% EPA, with declining relative efficiency as SDA intake increases. J. Nutr. 142: 626S–629S, 2012.
BCG algorithm for unobtrusive heart rate monitoring

Ballistocardiogram (BCG) has been revisited in the last years as an unobtrusive method to detect heart beats. New electromechanical film (EMFi) sensors are now able to detect minimal oscillations in its surface, allowing to detect the mechanical action of the heart as it beats. This has allowed to develop unobtrusive systems for heart rate monitoring to be used as Point-of-Care devices, and to deploy them in waiting rooms, assisted living facilities or at home. In this work, an EMFi sensor is used to measure BCG via the pressure changes on the seat produced by the beating heart. In a lab environment, 34 healthy volunteers are measured under two conditions: at rest and after exercise, simultaneously with ECG. Also, in a clinical environment, 24 volunteers are also measured while waiting. The algorithm looks for the variability of the length transform at different scales or windows to determine a search window to detect beats from the BCG. A second correlation filter helps eliminate false peaks detected due to noise in the signal. Results show that in resting conditions, the mean error between the BCG HR and the reference ECG is only 0.4 beats per minute, with a standard deviation of 1.88. The noise rejection accuracy is 93%. The proposed algorithm can be used to identify beats and issue alarms under abnormal rhythms, providing timely alerts for at-risk population.
Tissue and serum prolidase activity in patients with nasal polyposis

We a i med to eluc i date the role of prol i dase i n NP pathogenes i s by compar i ng serum and t i ssue prol i dase act i v i ty (PA) i n pat i ents w i th and w i thout NP. Pat i ents w i th NP enrolled to the study group and w i despread of NP evaluated us i ng the scor i ng system of Lund-Mackay (LMS) accord i ng to the computer tomography records preoperat i vely. Pat i ents w i thout NP and who underwent i nfer i or turb i nate reduct i on operat i on were i ncluded to the control group i n th i s study. All pat i ents serum and t i ssue PA were analyzed. The levels of serum PA were s i gn i f i cantly h i gher i n the control group compared w i th the polyp group, whereas the levels of t i ssue PA were s i gn i f i cantly h i gher i n the polyp group than the controls. There was a s i gn i f i cant negat i ve correlat i on between serum PA and LMS. There was no s i gn i f i cant correlat i on between t i ssue PA and serum PA, ne i ther t i ssue PA and LMS i n study group. We th i nk that t i ssue and serum PA play an i mportant role NP development.
Experimental repair of subglottic stenosis in piglets. "Trapdoor" thyrochondroplasty flap.

IN 1921 JACKSON 1-4 condemned the "high" tracheostomy because of the production of subglottic stenosis and pointed out, in 1943, the increasing incidence of crush injury to the larynx with the rising number of motorists on the highways. Severe fracture and collapse of the cricoid cartilage following trauma inevitably causes similar stenosis. The chondritis of the cricoid cartilage, chondromalacia, and eventual fibrosis which occurs following the above insults produces a crippling condition in the patient who then becomes dependent on a tracheostomy for an adequate airway. Murphy et al 5 cite four cases of stenosis in the trachea following the use of a 36-mm cuff on a metal tracheotomy tube which was utilized for respirator treatment for periods of time varying between 6 and 24 days. In 1953, Conley 6 comprehensively described six techniques for repair of the stenotic subglottic air passage which should be noted. "Dilatation" for the
Determination of aflatoxins B1, B2, G1, G2 and ochratoxin A in animal feed by ultra high-performance liquid chromatography-tandem mass spectrometry.

A rapid and simple method was developed to determine aflatoxins B1, B2, G1, G2 and ochratoxin A in animal feed and pet foods by UHPLC-MS/MS. Because the complexity of the evaluated matrices, the proposed method is based on sonication extraction using an ACN/water mixture (80:20 v/v) followed by a clean-up step utilising C(18) as sorbent. Performance parameters of the method were evaluated, including linearity, trueness, precision and LOQ. Good linearity was found for all mycotoxins, with determination coefficients higher than 0.99 in the range considered, using matrix-matched calibration for quantification purposes. Recoveries ranged from 84 to 113%, with RSD lower than 20%, whereas LOQs were 5 microg/kg for the assayed mycotoxins. Finally, the method was successfully applied to the analysis of 19 real samples, detecting aflatoxin G2 in two samples at 13 and 17 microg/kg respectively, whereas the other mycotoxins were detected at trace levels (
Multilocus Sequence Typing of Historical Burkholderia pseudomallei Isolates Collected in Southeast Asia from 1964 to 1967 Provides Insight into the Epidemiology of Melioidosis

ABSTRACT A collection of 207 historically relevant Burkholderia pseudomallei isolates was analyzed by multilocus sequence typing (MLST). The strain collection contains environmental isolates obtained from a geographical distribution survey of B. pseudomallei isolates in Thailand (1964 to 1967), as well as stock cultures and colony variants from the U.S. Army Medical Research Unit (Malaysia), the Walter Reed Army Institute for Research, and the Pasteur Institute (Vietnam). The 207 isolates of the collection were resolved into 80 sequence types (STs); 56 of these were novel. eBURST diagrams predict that the historical-collection STs segregate into three complexes when analyzed separately. When added to the 760 isolates and 365 STs of the B. pseudomallei MLST database, the historical-collection STs cluster significantly within the main complex of the eBURST diagram in an ancestral pattern and alter the B. pseudomallei “population snapshot. ” Differences in colony morphology among reference isolates were found not to affect the STs assigned, which were consistent with the original isolates. Australian ST84 is likely characteristic of B. pseudomallei isolates of Southeast Asia rather than Australia, since multiple environmental isolates from Thailand and Malaysia share this ST with the single Australian clinical isolate in the MLST database. Phylogenetic evidence is also provided suggesting that Australian isolates may not be distinct from those of Thailand, since ST60 is common to environmental isolates from both countries. MLST and eBURST are useful tools for the study of population biology and epidemiology, since they provide methods to elucidate new genetic relationships among bacterial isolates.
Postmarketing analysis of aflibercept-related sterile intraocular inflammation.

IMPORTANCE Aflibercept-related sterile inflammation, an event that is poorly understood, has been the subject of ongoing postmarketing reports. OBJECTIVE To analyze cases of aflibercept-related sterile inflammation reported to the American Society of Retina Specialists (ASRS) Therapeutic Surveillance Committee (TSC), an independent task force formed to monitor drug- and device-related safety events. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of 56 cases in 55 patients was performed of all cases of sterile inflammation after aflibercept injection that were voluntarily reported by 12 practices throughout the United States to the ASRS TSC from December 1, 2011, through February 12, 2014. MAIN OUTCOMES AND MEASURES Cases of aflibercept-related sterile inflammation were analyzed for baseline and demographic information, presenting symptoms and findings, visual acuity changes, injection technique, and management details. RESULTS Among 56 reported cases of sterile inflammation, mean time to onset was 3.5 days (median, 2 days; range, 0-30 days). Most cases consisted of initial loss of vision and intraocular inflammation without prominent redness, severe pain, or hypopyon. Thirty-seven cases (66%) were treated with topical corticosteroids and/or observation alone. Mean time to resolution was 28.6 days (median, 28 days; range, 4-84 days). Although final vision was overall unchanged, some patients developed permanent vision loss, which may have resulted from inflammation and/or progression of the underlying disease. Age older than 80 years was associated with worse visual outcomes. No difference in visual outcome was detected in patients with sterile inflammation undergoing topical therapy alone vs invasive procedures (vitreous biopsy and/or intravitreal antibiotic administration and/or vitrectomy). CONCLUSIONS AND RELEVANCE With the largest number of reported cases of aflibercept-related sterile inflammation to our knowledge, this analysis suggests typical findings and an often favorable prognosis of this event. Analysis of real-world, postmarketing data has limitations, and these findings should be considered as hypothesis-generating assessments rather than a definitive reflection of this event or its typical course. Distinguishing sterile inflammation and infectious endophthalmitis at the time of presentation may often be difficult, and cautious evaluation and management of these patients are warranted. The ASRS TSC encourages active postmarketing surveillance by all physicians.