Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.

PURPOSE We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system. RESULTS TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS. CONCLUSION In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.
Elimination of Transfusions Through Induction of Fetal Hemoglobin Synthesis in Cooley's Anemia a

Pharmacological stimulation of fetal hemoglobin production is of considerable interest as an alternative approach to therapy for Cooley's anemia. While intravenous compounds have been effective in inducing short‐term increases in fetal hemoglobin in a few patients, long‐term elimination of transfusion requirement has not been reported. In patients with Cooley's anemia, treatment with oral sodium phenylbutyrate alone, sodium phenylbytyrate combined with hydroxyurea, and hydroxyurea alone, has augmented fetal hemoglobin production and increased total hemoglobin concentration as much as 5 g/dl over baseline eliminating transfusion requirement in two patients. Parallel declines in circulating nucleated red cell count, and concentrations of serum transform receptor and erythropoietin. are consistent with more effective erythropoiesis. Over extended periods of treatment, no induction of other fetal proteins and no adverse effects were observed. Particular disease mutations and other genetic factors may be of prime importanec in determining the response to agents that induce production of fetal hemoglobin.
Personal and social‐environmental correlates of objectively measured physical activity in Norwegian pre‐adolescent children

The aim of this study was to examine modifiable biological, psychological, behavioral and social‐environmental correlates of physical activity among 1129 Norwegian 11‐year‐old children within a cross‐sectional sample from the HEalth In Adolescents study. Physical activity was assessed by accelerometer, and weight and height were measured objectively. Age‐ and gender‐specific cut‐off points proposed by the International Obesity Task Force were used to define body mass index. Social‐environmental variables were self‐reported by questionnaire. Hierarchical regression (linear mixed models) revealed that normal weight children scored higher on percentage daily moderate‐to‐vigorous physical activity [% daily moderate to vigorous physical activity (MVPA)] than overweight/obese children (P<0.001). Self‐efficacy (P<0.01) and perceived social support from friends (P<0.01) were positively associated with children's % daily MVPA, and a negative association was found for computer/game‐use on weekends (P<0.01). A moderator effect of weight category (normal vs overweight/obese) in the relationship between computer/game‐use on weekends and % daily MVPA was detected (P<0.05), reflecting that higher computer/game‐use on weekends was associated with lower % MVPA among the overweight/obese, but not among the normal weight. Modifiable correlates from multiple domains accounted for 14% of the variance in % daily MVPA. Prospective and intervention studies are needed to examine whether these factors act as mediators for physical activity change in pre‐adolescent children.
LSD and DOB: interaction with 5‐HT2A receptors to inhibit NMDA receptor‐mediated transmission in the rat prefrontal cortex

Both the phenethylamine hallucinogen (–)‐1‐2,5‐dimethoxy‐4‐bromophenyl‐2‐aminopropane (DOB), a selective serotonin 5‐HT2A,2C receptor agonist, and the indoleamine hallucinogen d‐lysergic acid diethylamide (LSD, which binds to 5‐HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and α1 and α2 adrenergic receptors), but not their non‐hallucinogenic congeners, inhibited N‐methyl‐d‐aspartate (NMDA)‐induced inward current and NMDA receptor‐mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5‐HT in the presence of selective 5‐HT1A and 5‐HT3 receptor antagonists. The inhibitory action of DOB, LSD and 5‐HT on the NMDA transmission was blocked by the 5‐HT2A receptor antagonists r‐(+)‐α‐(2,3‐dimethoxyphenil)‐1‐[4‐fluorophenylethyl]‐4‐piperidinemethanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5‐HT, suggesting a partial agonist action. Whereas N‐(4‐aminobutyl)‐5‐chloro‐2‐naphthalenesulphonamide (W‐7, a calmodulin antagonist) and N‐[2‐[[[3‐(4′‐chlorophenyl)‐ 2‐propenyl]methylamino]methyl]phenyl]‐N‐(2‐hydroxyethyl)‐4′‐methoxy‐benzenesulphonamide phosphate (KN‐93, a Ca2+/CaM‐KII inhibitor), but not the negative control 2‐[N‐4′methoxybenzenesulphonyl]amino‐N‐(4′‐chlorophenyl)‐2‐propenyl‐N‐methylbenzylamine phosphate (KN‐92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5‐HT2A receptors via a Ca2+/CaM‐KII‐dependent signal transduction pathway as partial agonists and modulating the NMDA receptors‐mediated sensory, perceptual, affective and cognitive processes.
Protein Energy Malnutrition in India: The Plight of Our Under Five Children

Protein energy malnutrition (PEM) is a major public health problem in India. This affects the child at the most crucial period of time of development, which can lead to permanent impairment in later life. PEM is measured in terms of underweight (low weight for age), stunting (low height for age) and wasting (low weight for height). The prevalence of stunting among under five is 48% and wasting is 19.8% and with an underweight prevalence of 42.5%, it is the highest in the world. Undernutrition predisposes the child to infection and complements its effect in contributing to child mortality. Lalonde model (1974) is used to look into the various determinants of PEM in under five children and its interrelation in causation of PEM. The determinants of PEM are broadly classified under four distinct categories: Environmental factors including the physical and social environment, behavioral factors, health-care service related and biological factors. The socio-cultural factors play an important role wherein, it affects the attitude of the care giver in feeding and care practices. Faulty feeding practice in addition to poor nutritional status of the mother further worsens the situation. The vicious cycle of poor nutritional status of the mother leading to low birth weight child further exposes the child to susceptibility to infections which aggravates the situation. However, it is seen that percapita income of the family did not have much bearing on the poor nutritional status of the child rather lack of proper health-care services adversely contributed to poor nutritional status of the child. PEM is a critical problem with many determinants playing a role in causing this vicious cycle of undernutrition. With almost half of under five children undernourished in India, the Millennium Development Goal (MDG) of halving the prevalence of underweight by 2015 seems a distant dream.
Agomelatine for the Treatment of Patients with Fibromyalgia and Depressive Symptomatology: An Uncontrolled, 12-Week, Pilot Study

Abstract Introduction: Agomelatine, a melatonin agonist and selective 5-HT2C antagonist, is a novel antidepressant with sleep-enhancing properties. The purpose of this study was to assess the efficacy and tolerability of agomelatine among patients with fibromyalgia and depression. Methods: 23 patients with fibromyalgia and depressive symptomatology received 25–50 mg of agomelatine daily for 12 weeks. The primary outcome measure was the change of the Beck depression inventory score. Secondary outcome measures included the hospital anxiety and depression scale, Pittsburgh sleep quality index, Fibromyalgia Impact Questionnaire, short-form health survey, brief pain inventory and patient’s global impression scale. Results: Agomelatine significantly improved depression, global fibromyalgia severity and pain intensity but effect sizes were small. No improvement was seen in sleep quality. Patients categorized as responders to treatment had milder disease severity than non-responders. Agomelatine therapy was well tolerated and patients only reported mild and transient side effects. Discussion: Agomelatine slightly improved depressive and fibromyalgia symptomatology but did not improve sleep quality. Our data do not support agomelatine as a first-line treatment option for the treatment of fibromyalgia and depression.
Autoimmune hepatitis in men: examining the gender gap

thermore, similarly high mortality rates were observed in the cohort of cirrhotic patients with non-HRS renal failure, reemphasizing the poor prognosis in concomitant liver and renal failure. In summary, this study by Watt and colleagues has highlighted important concepts regarding the diagnosis, management and prognosis of HRS. In light of the extremely poor prognosis of HRS, it is imperative that physicians are fully aware of the diagnostic criteria, predictive and precipitating factors of this syndrome. A better understanding of the pathophysiology of this syndrome has led to novel approaches in therapy, including splanchnic vasoconstrictors, renal vasodilators, and plasma expanders (3). However, these treatments are in their initial stages of development, and liver transplantation is still the best treatment. In the present era of organ scarcity, and therefore prolonged waiting times for transplantation, the prevention and pretransplant management of HRS will assume increasing importance and pose a continuing challenge.
Trauma-Induced Coagulopathy Is Associated with a Complex Inflammatory Response in the Rat

ABSTRACT Severe trauma can lead to a coagulopathy in patients, which is associated with increased mortality. We developed a rat polytrauma model that demonstrates a similar progression of coagulopathy. Because coagulation is influenced by changes in inflammation, and this interrelationship is poorly understood, we have studied the progression of inflammation, and its correlation with coagulation, in this rat model of severe polytrauma. Sprague–Dawley rats were anesthetized with isoflurane. Polytrauma was induced by damaging 10 cm of small intestines, right and medial liver lobes, right leg skeletal muscle, femur fracture, and hemorrhaging 40% of blood volume. No resuscitation was given. Polytrauma and hemorrhage resulted in a significant decrease in the number of lymphocytes and an increase in monocytes and granulocytes. There was an increase in plasma proinflammatory cytokines: tumor necrosis factor &agr; (40×), interleukin (IL)-6 (20×), IL-1&bgr; (16×), IL-17 (15×), interferon &ggr; (10×), IL-1&agr; (8×) and IL-12p70 (5×); anti-inflammatory cytokines: IL-10 (100×), IL-13 (16×), and IL-4 (5×); chemokines: growth-regulated protein/keratinocyte chemoattractant (30×), macrophage inflammatory protein 3&agr; (10×), regulated and normal T-cell expressed and secreted (3×); and growth factors: vascular endothelial growth factor (5×), granulocyte macrophage colony-stimulating factor (6×), macrophage colony-stimulating factor (3×), granulocyte colony-stimulating factor (2×), and IL-5 (3×). There was a strong and significant correlation between prothrombin time, activated partial thromboplastin time, fibrinogen, and fibrin monomer concentration, and many cytokines. Polytrauma with hemorrhage is associated with a coagulopathy and a complex inflammatory response consisting of a concurrent rise in both proinflammatory and anti-inflammatory cytokines. The rise in plasma concentrations of chemokines and growth factors likely contribute to the mobilization of monocytes and granulocytes. There is strong correlation between prothrombin time, activated partial thromboplastin time, and IL-10 and IL-1&bgr;. This relationship could be exploited for the development of resuscitation strategies that attenuate these cytokines and allow for better outcomes in patients with trauma through concomitant modulation of inflammation and coagulopathy.
Neuropsychological Outcome from Blast versus Non-blast: Mild Traumatic Brain Injury in U.S. Military Service Members

Abstract The purpose of this study was to compare the neuropsychological outcome from blast-related versus non-blast related mild traumatic brain injury (MTBI). Participants were 56 U.S. military service members who sustained an MTBI, divided into two groups based on mechanism of injury: (a) non-blast related (Non-blast; n = 21), and (b) blast plus secondary blunt trauma (Blast Plus; n = 35). All participants had sustained their injury in theatre whilst deployed during Operation Iraqi Freedom or Operation Enduring Freedom. Patients had been seen for neuropsychological evaluation at Walter Reed Army Medical Center on average 4.4 months (SD = 4.1) post-injury. Measures included 14 clinical scales from the Personality Assessment Inventory (PAI) and 12 common neurocognitive measures. For the PAI, there were no significant differences between groups on all scales (p > .05). However, medium effect sizes were found for the Depression (d = .49) and Stress (d = .47) scales (i.e., Blast Plus > Non-blast). On the neurocognitive measures, after controlling for the influence of psychological distress (i.e., Depression, Stress), there were no differences between the Non-blast and Blast Plus groups on all measures. These findings provide little evidence to suggest that blast exposure plus secondary blunt trauma results in worse cognitive or psychological recovery than blunt trauma alone. (JINS, 2012, 18, 595–605)
An Excretory Function for the Escherichia coli Outer Membrane Pore TolC: Upregulation of marA and soxS Transcription and Rob Activity Due to Metabolites Accumulated in tolC Mutants

ABSTRACT Efflux pumps function to rid bacteria of xenobiotics, including antibiotics, bile salts, and organic solvents. TolC, which forms an outer membrane channel, is an essential component of several efflux pumps in Escherichia coli. We asked whether TolC has a role during growth in the absence of xenobiotics. Because tolC transcription is activated by three paralogous activators, MarA, SoxS, and Rob, we examined the regulation of these activators in tolC mutants. Using transcriptional fusions, we detected significant upregulation of marRAB and soxS transcription and Rob protein activity in tolC mutants. Three mechanisms could be distinguished: (i) activation of marRAB transcription was independent of marRAB, soxR, and rob functions; (ii) activation of soxS transcription required SoxR, a sensor of oxidants; and (iii) Rob protein was activated posttranscriptionally. This mechanism is similar to the mechanisms of upregulation of marRAB, soxS, and Rob by treatment with certain phenolics, superoxides, and bile salts, respectively. The transcription of other marA/soxS/rob regulon promoters, including tolC itself, was also elevated in tolC mutants. We propose that TolC is involved in the efflux of certain cellular metabolites, not only xenobiotics. As these metabolites accumulate during growth, they trigger the upregulation of MarA, SoxS, and Rob, which in turn upregulate tolC and help rid the bacteria of these metabolites, thereby restoring homeostasis.
PTSD following terrorist attacks: a prospective evaluation.

OBJECTIVE This study evaluated the prevalence of posttraumatic stress disorder (PTSD) and the longitudinal course of early PTSD symptoms in survivors of terrorist attacks. It additionally assessed the effect of continuous terrorism on the course of early symptoms of PTSD. METHOD Thirty-nine survivors of terrorist attacks and 354 survivors of motor vehicle accidents were evaluated upon admission to a general hospital emergency room and 1 week and 4 months later. Heart rate was measured upon admission to the emergency room. Peritraumatic dissociation was assessed at 1 week. PTSD symptoms, anxiety, and depression were measured at 1 week and 4 months. The Clinician-Administered PTSD Scale conferred a diagnosis of PTSD at 4 months. Additionally, the course of early PTSD symptoms during an era of frequent terrorist attacks (N=137) was compared with that seen during years of relative calm (N=256). RESULTS Survivors of terrorist attacks had higher rates of PTSD than motor vehicle accident survivors (37.8% versus 18.7%). The type of traumatic event, however, did not add to the prediction of PTSD from the emergency room heart rate, peritraumatic dissociation symptoms, and early PTSD symptoms. The longitudinal course of early PTSD symptoms was not affected by the greater frequency of terrorist attacks. CONCLUSIONS Early symptoms are reliable risk indicators of PTSD across events and circumstances. Converging effects of terror-induced fear, adjustment, and resiliency might explain the lack of effect of intense terrorism on the course of PTSD symptoms.
Role of the central autonomic nervous system in the hypotension and bradycardia induced by (‐)‐Δ9‐trans‐tetrahydrocannabinol

(‐)‐Δ9‐trans‐Tetrahydrocannabinol (Δ9‐THC), when given intravenously (2 mg kg−1) to cats, produced marked decreases in blood pressure and heart rate which developed gradually and were of prolonged duration. Cervical spinal transection (C1‐C2) abolished these effects whereas surgical removal of neurogenic tone to the myocardium selectively eliminated the bradycardia. Bilateral vagotomy alone did not modify the action of Δ9‐THC upon heart rate or blood pressure. Recordings of spontaneous sympathetic outflow in the inferior cardiac nerve indicated a rapid reduction in neural discharge rate after Δ9‐THC administration. These observations support the hypothesis that Δ9‐THC produces a cardiodecellerator and hypotensive effect by acting at some level within the sympathetic nervous system. Experiments conducted to investigate transmission in the superior cervical and stellate ganglia demonstrated that Δ9‐THC did not alter ganglionic function. Also, responses to intravenous isoprenaline and noradrenaline were unchanged which suggested that Δ9‐THC did not interact with α‐ or β‐ adrenoceptors. The possible action of Δ9‐THC on central sympathetic structures was investigated by perfusion of Δ9‐THC into the lateral cerebral ventricle. Δ9‐THC so administered produced a significant reduction in heart rate without a substantial lowering of blood pressure. Tritiated or 14C‐Δ9‐THC perfused into the lateral ventricle demonstrated that the amount of radioactive compound passing into the peripheral circulation was insignificant and could not account for the decrease in heart rate. The current data are in agreement with the proposal that Δ9‐THC produces cardiovascular alterations by an action on the central nervous system which results in a decrease in sympathetic tone.
Mechanical stimulation of skeletal muscle increases prostaglandin F2α production, cyclooxygenase activity, and cell growth by a pertussis toxin sensitive mechanism

Repetitive mechanical stimulation of differentiated skeletal muscle in tissue culture increased the long‐term production of prostaglandin F2α, an anabolic stimulator of myofiber growth. Within 4 h of initiating mechanical stimulation, the enzymatic activity of cyclooxygenase (prostaglandin GH synthase [PGHS]), a regulatory enzyme in prostaglandin synthesis, was increased 82% (P <.005), and this increase was maintained for at least 24 h. Kinetic analysis of stretch‐activated cyclooxygenase activity indicated a two to threefold decrease in the enzyme's Km, with little change in its Vmax. Immunocytochemical analysis of the cell cultures indicated the presence of high levels of the mitogen‐inducible isoform of cyclooxygenase (PGHS‐2) in the skeletal myofibers compared to the interstitial fibroblasts. While the stretch‐induced increase in cyclooxygenase enzymatic activity was not inhibited by tetrodotoxin and therefore was independent of cellular electrical activity, the G protein inhibitor pertussis toxin prevented stretch‐induced cyclooxygenase activation. Pertussis toxin also inhibited stretch‐induced increases in PGF2α production, phospholipase D activation, and cell growth. It is concluded that stretch of skeletal muscle increases muscle cell growth through a G protein‐dependent process involving the activation of cyclooxygenase, an immediate early gene product. © 1995 Wiley‐Liss, Inc.
On the Government of Rulers: De Regimine Principum

Ptolemy, considered a proto-Humanist by some, combined the principles of Northern Italian republicanism with Aristotelian theory in his De Regimine Principum, a book that influenced much of the political thought of the later Middle Ages, the Renaissance, and the early modern period. He was the first to attack kingship as despotism and to draw parallels between ancient Greek models of mixed constitution and the Roman Republic, biblical rule, the Church, and medieval government. In addition to his translation of this important and radical medieval political treatise, written around 1300, James M. Blythe includes a sixty-page introduction to the work and provides over 1200 footnotes that trace Ptolemy's sources, explain his references, and comment on the text, the translation, the context, and the significance.
MRI induced heating of pacemaker leads: effect of temperature probe positioning and pacemaker placement on lead tip heating and local SAR

The radio frequency field used in magnetic resonance imaging (MRI) procedures leads to temperature and local absorption rate (SAR) increase for patients with implanted pacemakers (PM). In this work a methodological approach for temperature and SAR measurements using fluoroptic probes is presented. Experimental measures show how the position of temperature probes affects the temperature and SAR value measured at the lead tip. The transversal contact between the active portion of the probe and the lead tip is the configuration associated with the highest values for temperature and SAR, whereas other configurations may lead to an underestimation close to 11% and 70% for temperature and SAR, respectively. In addition measurements were performed on a human-shaped phantom inside a real MRI system, in order to investigate the effect of the PM placement and of the lead geometry on heating and local SAR