Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of Acellular Mucin Pools in Rectal Carcinoma After Neoadjuvant Chemoradiotherapy

The presence of mucin pools lacking neoplastic epithelium (“acellular” mucin) in resection specimens of rectal carcinoma after neoadjuvant chemoradiotherapy (CRT) is a well-recognized phenomenon. The current recommendation by the College of American Pathologists is to regard acellular mucin as a type of treatment response and not as residual tumor. However, data-based evidence for or against such an approach is incomplete. In this study, we systematically analyzed the pattern and significance of mucin pools in 108 consecutive, prospectively collected resection specimens from patients who had uT3-4 and/or uN1 rectal cancer and were treated with preoperative long-course CRT. The 108 patients, 39 female and 69 male, had a median age of 58.5 years. With every tumor entirely examined in whole-mount sections, mucin pools were identified in 33 cases (33 of 108, 31%); in 16 (15%) they were all acellular. The mucin pools were focal (10% to 50% of the entire lesion) in 25 cases and extensive (>50%) in 8 cases. Mucin pools were also noted in the lymph nodes in 6 cases (6%); 3 of these were entirely acellular. Five cases had mucin pools in both the primary site and the lymph nodes. When acellular mucin was considered as “no residual tumor,” the complete pathologic response rate for the entire cohort was 22% (24 of 108). The pathologic stage of the residual tumor (ypT) was 0 or 1 for 27 cases (25%) and 2 to 4 for 81 cases. The pathologic stage of nodal disease (ypN) was 0 for 83 (77%) and 1 or 2 for 25 cases. When acellular mucin was considered as “residual tumor,” the complete pathologic response rate dropped to 17%; ypT was upstaged in 10 tumors and ypN was upstaged in 2 tumors. With a median follow-up of 31 months, the 3-year recurrence-free survival (RFS) was 73% for the entire group. Advanced pathologic response and low pathologic stage of the residual tumor (determined based on the depth of only viable tumor cells) correlated significantly with better RFS. However, the correlation between pathologic response and RFS became insignificant when acellular mucin pools were considered as residual tumor. Neither the presence of mucin pools nor their extent or cellularity had an impact on RFS. Furthermore, none of the 12 patients whose ypT or ypN was upstaged by acellular mucin had recurrent disease (3-y RFS of 100%). Thus, our results suggest that mucin pools in rectal carcinoma after neoadjuvant CRT do not have a significant impact on patient outcome, supporting the College of American Pathologists recommendation that only viable tumor cells, not acellular mucin, are to be interpreted as residual disease in the tumor pathologic staging.
Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related (GITR)-Fc Fusion Protein Inhibits GITR Triggering and Protects from the Inflammatory Response after Spinal Cord Injury

Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion protein can exert an anti-inflammatory effect. To investigate the mechanism by which GITR-Fc exerts its effects, we first used GITR knock-out (GITR-/-) mice to verify whether GITR ligand (GITRL)/GITR system played a pro-inflammatory role in the spinal cord injury (SCI) model. It is noteworthy that less pronounced disease was induced in GITR-/- compared with GITR+/+ mice. We then evaluated the effect of GITR-Fc fusion protein against SCI-induced injuries in GITR-/- and wild-type (GITR+/+) mice. Administration of GITR-Fc ameliorated SCI-induced inflammation in GITR+/+ mice as evaluated through: 1) histological damage and apoptosis, 2) modulation of apoptosis-related transduction factors (Bax and Bcl-2), 3) expression of inflammatory markers [nitrotyrosine, inducible nitric-oxide synthase, interleukin (IL)-2, IL-12, and tumor necrosis factor-α], and 4) T-lymphocyte infiltration. GITR-Fc was effective in GITR+/+ but not in GITR-/-, suggesting that in this experimental model, its anti-inflammatory action was due to inhibition of GITR triggering and not to GITRL activation. In conclusion, GITR plays a role in SCI, and administration of GITR-Fc results in amelioration of SCI severity, prompting further studies on the potential anti-inflammatory properties of GITR-Fc.
Use of ibuprofen and risk of Parkinson disease

Background: Neuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to be related to lower PD risk in previous epidemiologic studies. Methods: We prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations. Results: We identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk [RR], adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval [CI] 0.42–0.93; p = 0.02). There was a dose–response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78–1.26), other NSAIDs (RR = 1.26; 95% CI 0.86–1.84), or acetaminophen (RR = 0.86; 95% CI 0.62–1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63–0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk. Conclusions: The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD.
Regulation of Gene Transcription by Voltage-gated L-type Calcium Channel, Cav1.3*

Background: Cav1.3 Ca2+ channel is highly expressed in atria and pacemaking cells in the heart. Results: The C terminus of the Cav1.3 Ca2+ channel can translocate into the nucleus. Conclusion: The C terminus of Cav1.3 can function as a transcriptional regulator to regulate Ca2+-activated K+ channels. Significance: New insights into the cross-talk between ion channels may have broad therapeutic ramifications beyond cardiac myocytes. Cav1.3 L-type Ca2+ channel is known to be highly expressed in neurons and neuroendocrine cells. However, we have previously demonstrated that the Cav1.3 channel is also expressed in atria and pacemaking cells in the heart. The significance of the tissue-specific expression of the channel is underpinned by our previous demonstration of atrial fibrillation in a Cav1.3 null mutant mouse model. Indeed, a recent study has confirmed the critical roles of Cav1.3 in the human heart (Baig, S. M., Koschak, A., Lieb, A., Gebhart, M., Dafinger, C., Nürnberg, G., Ali, A., Ahmad, I., Sinnegger-Brauns, M. J., Brandt, N., Engel, J., Mangoni, M. E., Farooq, M., Khan, H. U., Nürnberg, P., Striessnig, J., and Bolz, H. J. (2011) Nat. Neurosci. 14, 77–84). These studies suggest that detailed knowledge of Cav1.3 may have broad therapeutic ramifications in the treatment of cardiac arrhythmias. Here, we tested the hypothesis that there is a functional cross-talk between the Cav1.3 channel and a small conductance Ca2+-activated K+ channel (SK2), which we have documented to be highly expressed in human and mouse atrial myocytes. Specifically, we tested the hypothesis that the C terminus of Cav1.3 may translocate to the nucleus where it functions as a transcriptional factor. Here, we reported for the first time that the C terminus of Cav1.3 translocates to the nucleus where it functions as a transcriptional regulator to modulate the function of Ca2+-activated K+ channels in atrial myocytes. Nuclear translocation of the C-terminal domain of Cav1.3 is directly regulated by intracellular Ca2+. Utilizing a Cav1.3 null mutant mouse model, we demonstrate that ablation of Cav1.3 results in a decrease in the protein expression of myosin light chain 2, which interacts and increases the membrane localization of SK2 channels.
Effect of carmellose-based artificial tears on the ocular surface in eyes after laser in situ keratomileusis.

BACKGROUND Strategies to minimize intraoperative ocular surface disturbance and accelerate postoperative ocular surface recovery are an important consideration to the surgeon. METHODS Eighteen eyes of 10 patients were randomized to receive intraoperative and postoperative non-preserved balanced salt solution or non-preserved carboxymethylcellulose-based (carmellose) artificial tears. Presence and severity of McMonnies dry eye symptom survey score primary dry eye symptoms, fluorescein break-up time, and rose bengal staining were graded preoperatively and at 1 day, 1 week and 1 month postoperatively. Conjunctival impression cytology of the perilimbal conjunctiva was performed 1 month after surgery to determine goblet cell density. RESULTS McMonnies dry eye symptoms were reported more frequently for the balanced salt solution group at 1 day, 1 week, and 1 month after surgery. Fluorescein break-up time was significantly greater in the carmellose-based group at 1 day (P < .01), 1 week (P = .04), and 1 month (P < .01) after surgery. The rose bengal staining score was significantly greater at 1 day (P < .01) and 1 week (P < .01) postoperatively for the balanced salt solution group. Mean goblet cell density for the carmellose-based group at 1 month postoperatively was significantly greater than that for the balanced salt solution group (P < .01). CONCLUSIONS Postoperative and intraoperative use of carmellose-based artificial tears resulted in significantly more rapid recovery of the ocular surface after LASIK when compared to balanced salt solution.
Direct evidence for the role of LGL in the inhibition of experimental tumor metastases.

The role of NK cells in the control of the metastatic spread of tumor cells was studied. Rats pretreated with rabbit anti-asialo GM1 (anti-asGM1) serum exhibited a diminished ability to destroy circulating MADB106 mammary adenocarcinoma cells, which in turn caused an increased incidence of experimental pulmonary metastasis. The anti-asGM1 treatment caused a selective inhibition of NK activity without detectable effect on T cell-mediated immunity, and overall had no effect on the cytotoxic activity or numbers of alveolar macrophages (alv.M phi) or monocytes. The suggestion of a role for NK cells in resistance to metastases from the MADB106 tumor cells was confirmed by the adoptive transfer of 5 X 10(6) highly purified large granular lymphocytes (LGL) into NK-depressed animals 2 hr before tumor challenge. This transfer of LGL, highly enriched in NK activity, partially or fully restored the ability of these rats to inhibit the development of pulmonary metastases. This ability to adoptively transfer resistance to metastases appeared to be confined to the LGL population, because transfer of the same number of mature peripheral blood T cells had no effect on tumor development. These results provide the first unequivocal evidence that LGL, with high NK activity, are involved in in vivo resistance to tumors, particularly in the elimination of potentially metastatic tumor cells from the circulation and capillary beds.
In Vitro Assessment of Cytotoxicity and Carcinogenic Potential of Chemicals: Evaluation of the Cytotoxicity Induced by 58 Metal Compounds in the Balb/3T3 Cell Line

A new, mechanistically based, in vitro strategy involving Balb/c 3T3 clone A31-1-1 mouse embryo fibroblasts has been proposed for the determination of the carcinogenic potential of inorganic chemicals, in order to establish priority of metal compounds to be tested and, whenever possible, to compare the in vitro results with the corresponding in vivo data. As a first step in this research, this study reports on the cytotoxic effects of 58 metal compounds in the Balb/3T3 cell line. After harmonisation and standardisation of the Balb/3T3 protocol, cells were exposed for 72 hours to a fixed dose (100μM) of 58 individual compounds. The cytotoxicity induced by some metal compounds was found to be related to their chemical form (for example, Cr(NO3)3 and Na2CrO4), suggesting that the Balb/3T3 cell line is a valuable cellular model in relation to this aspect of metal speciation. The results of the systematic study on the metal-induced cytotoxic effects in the Balb/3T3 cell line could be arbitrarily classified into three groups according to the degree of cytotoxicity. Group I includes 26 species that induced no observable effect or only a slight cytotoxic effect; Group II includes 13 metal compounds that exhibited an obvious degree of cytotoxicity; and Group III includes 19 metal species that displayed a strong cytotoxic response. Metal compounds of Groups II and III are considered to be of the highest priority for setting of dose–effect relationships for a subsequent in vitro study on metal-induced concurrent cytotoxicity and morphological transformation in the Balb/3T3 cell line.
Standard Morphologic Evaluation of the Heart in the Laboratory Dog and Monkey

The nonrodent species most commonly utilized in preclinical safety studies are the purpose-bred beagle dog and cynomolgus macaque (Macaca fascicularis). Potential effects of a new chemical entity (NCE) on the heart pose serious concerns; consequently in vivo testing is focused on detection of functional alterations as well as morphological changes. Macroscopic and microscopic evaluation of the heart is based on a standard survey of key structures to properly assess presence of spontaneous and potential drug-induced lesions. Evaluation of historical controls to determine type and frequency of background change is valuable, as studies with non-rodent species generally have a small sample size. Archived control dog and monkey data were retrospectively reviewed, including terminal body weight (BW), heart weight (HW), and archival glass slides of heart. Control dogs had minimal background changes that included myxomatous or cartilagenous change in the cardiac skeleton and a variable degree of vacuolation in Purkinje fibers. Control monkey hearts commonly contained inflammatory cell infiltrates, myocyte anisokaryosis, and handling artifacts, while myocyte degeneration, squamous plaques, pigment, and intimal plaques were occasionally observed. These findings highlight the utility of consistently recorded and readily accessible archived control data when attempting to discern background spontaneous changes and artifacts from test-article induced changes.
Drastic bottlenecks in the endangered crayfish species Austropotamobius pallipes in Spain and implications for its colonization history

Variation in mitochondrial DNA (mtDNA) was surveyed, using restriction endonucleases, in the white-clawed crayfish, Austropotamobius pallipes lusitanicus, from 14 populations sampled in Spain. Four additional samples from France (1), Slovenia (1) and Italy (2) were also analysed. Among the 11 haplotypes listed, only one was detected from the 154 animals sampled from Spanish populations. This haplotype was also recorded in the Fosso di Ferfereta population (Italy). Estimates of nucleotide sequence divergence among haplotypes ranged from 0.45% to 17.4%. Interpopulational genetic relationships showed that Spanish populations were closely related to those of Fosso di Ferfereta with a small genetic distance (0.0003) found between them. AMOVA revealed that most of the genetic variance (71.97%) was attributed to variation between European regions. These results are in accordance with a drastic bottleneck event during the history of the Spanish populations. Four suggestions, based on human introduction, selection and recent or ancient historical events are discussed in relation to the lack of genetic variation in the Spanish crayfish stock.
Efficacy and safety of the inject and cut technique for endoscopic colonic polypectomy

Colonic polypectomy is the most important tool for stopping adenoma-cancer, and the inject and cut technique has demonstrated efficacy and safety in studies conducted in other countries. Since in our country there are no reported data on performance of this technique, it is necessary to describe the experience of a gastroenterology unit of a university. Objectives: The objectives of this study were to describe operational characteristics of en- doscopic colonic polypectomy using the inject and cut technique and to describe demographic characteristics of patients undergoing this procedure. Materials and Methods: We included all patients who underwent endosco- pic colonic polypectomies in the gastroenterology unit of the Clinica Fundadores in Bogota from January 2003 to September 2011. Data were processed using SPSS version 18 18.8 (SPSS-IBM) statistical package. Results: 420 patients underwent polypectomies which resected a total of 548 polyps. Mean patient age was 56.3 years (range 14 to 93), 201 patients were male, and 219 were female. Polyps were most commonly located in the left colon (238/64.4%). Average size was 1.6 cm. 83.8% were pedunculated, 13.3% were sessile, and 2.85% were flat. Intraoperative bleeding occurred in 36 cases (8.6%). There was no relationship between this complication and the size of polyps ( 20 mm), OR: 0.44 (CI 0.19-1.01), nor with the number of resected polyps (1Vs> 1) OR: 1.44, (95%:0.65-3 .2). All cases of bleeding were controlled endoscopically without further complications. There was no need for surgery. There were no local recurrences during follow-up. Conclusions: This study showed that the inject and cut technique is a practical, effective, economical and easy to perform technique for removal of colonic polyps. To date this is the largest series published in our country on the subject.
Progesterone production by human granulosa cells cultured in serum free medium: effects of gonadotrophins and insulin-like growth factor I (IGF-I).

There is evidence that insulin-like growth factor I (IGF-I) is a potent regulator of oestradiol synthesis by human granulosa and luteal cells; however, the question of whether IGF-I regulates progesterone synthesis by these cell types has yet to be answered. As a first step towards this goal, we have compared the effects of IGF-I, follicle stimulating hormone (FSH), and human chorionic gonadotrophin (HCG) on progesterone production by human granulosa cells obtained from individual dominant and cohort follicles, and granulosa luteal cells from preovulatory follicles of patients undergoing in-vitro fertilization (IVF). Granulosa cells from normal, unstimulated follicles cultured in serum-free medium as controls (no additions) produced some progesterone spontaneously. In all cases, FSH stimulated basal progesterone levels (10-fold average increase) and the effect was dose-dependent (ED50 of FSH = 9.1 +/- 3.9 ng/ml). Similar effects were observed when granulosa cells from large follicles were incubated with HCG (ED50 of HCG = 6.9 +/- 2.8 ng/ml). By comparison, the effects of IGF-I on progesterone production were not marked, being absent in 80% of the follicles tested. However, granulosa cells from healthy follicles co-incubated with IGF-I and FSH or HCG produced more progesterone compared with cells treated with the gonadotrophins alone; this effect of IGF-I was dose dependent (ED50 of IGF-I = 10 ng/ml). When the effect of each agonist was tested on IVF granulosa luteal cells, HCG but not FSH or IGF-I stimulated basal progesterone levels but the HCG effect required a two-day lag phase. (ABSTRACT TRUNCATED AT 250 WORDS)
Physician perspectives on collaborative working relationships with team‐based hospital pharmacists in the inpatient medicine setting

Collaborative care between physicians and pharmacists has the potential to improve the process of care and patient outcomes. Our objective was to determine whether team‐based pharmacist care was associated with higher physician‐rated collaborative working relationship scores than usual ward‐based pharmacist care at the end of the COLLABORATE study, a 1 year, multicentre, controlled clinical trial, which associated pharmacist intervention with improved medication use and reduced hospital readmission rates.
Strokes in Thai children : etiology and outcome.

In Asian countries, specific etiology and outcome of stroke in children are rarely reported. During January 1979 to December 1997, 68 children with stroke, admitted to the Department of Pediatrics, Ramathibodi Hospital, Bangkok were reviewed for etiology and outcome; 38 patients (22 males) had ischemic stroke and 30 (20 males) had hemorrhagic stroke. Severe headache, vomiting, disturbance of consciousness and papilledema were prominent presentations of hemorrhagic stroke. Bleeding from vascular anomalies of the brain (AVM) was the most common etiology of hemorrhagic stroke while septic and non-septic emboli from congenital and acquired heart diseases were the most common cause of ischemic stroke. The mortality rate was 7% and 9% in hemorrhagic and ischemic strokes, respectively. Complete recovery was observed in 52% of cases of hemorrhagic stroke but in only 26% of ischemic stroke. Hemiparesis was the most common residual neurological deficit with higher occurrence in ischemic stroke.
Aerobic Performance by Children in Grades 4 to 8: A Repeated-Measures Study

Aerobic capacity reflects consumption of O2 by working muscles during vigorous physical activity and is an indicator of cardiovascular health. This study examined change in aerobic performance by children in Grades 4 to 8 (Ages= 9–14) over 14 mo. 105 healthy children in a small, rural, middle-class school participated. All were tested five times on the Progressive Aerobic Cardiovascular Endurance Run (PACER) at 8- or 9-wk. intervals during the 2004–2005 school year, with follow-up measurements the next September and December. Hierarchical Linear Modeling applied to analyze the data showed that overall improvement in aerobic performance from September to May was statistically significant as children increased their PACER scores from 26 to 49 laps. These gains were lost over the summer but returned to the original slope by the second follow-up measurement. Regardless of age, sex, Body Mass Index, or sports participation, children followed a similar pattern: steady improvement during the school year, loss of those gains over the summer, and return to the original slope the following year.
Look at Me, I’m Happy and Creative: The Effect of Impression Management on Behavior in Social Presence

The present research tested competing approaches to individual differences in impression management (as measured with social desirability scales) and their implication for behavior in social contexts. A defensiveness approach argues that impression management is a source of defensive self-presentation, which causes performance impairment in public social settings. The competing adjustment approach argues that impression management measures friendliness and self-control, which should bring about performance facilitation in public social settings. To decide between these approaches, two experiments utilized a social facilitation paradigm, whereby task performance was compared between an alone and a public condition. The results supported the predictions of the adjustment approach. Across different tasks, a high impression management score was associated with performance facilitation in social presence, expressed in greater creativity, positive implicit affect, and high self-control. The results reveal previously unnoticed constructive effects of impression management, supporting the reframing of the trait as reflecting interpersonally oriented self-control.