Miracle-dz/UniFAR-FTUs huggingface dataset:
Pancreatic cancer: gene therapy approaches and gene delivery systems

Importance of the field: Due to the absence of early diagnosis, the highly invasive and metastatic features and the lack of effective therapeutic modalities, the prognosis of patients with pancreatic cancer is poor. Gene therapy is currently regarded as a potential and promising therapeutic modality for pancreatic cancer. Areas covered in this review: This article summarizes an update of gene therapy approaches and reviews the latest progress in gene delivery systems that have been tested on pancreatic cancer. What the reader will gain: The treatment effectiveness of gene combination therapy is better than that of the regulation of single-gene or single gene therapy approaches. Naked DNA is limited because of degradation by intracellular and extracellular nucleases. Virus vectors show high transfection efficiency but are limited due to immunogenicity, inflammatory response and potential carcinogenicity. Non-viral vectors, such as cationic polymers or inorganic nanoparticles, show an important feature that they can be easily modified, and the progress of materials science will provide more and better non-viral vectors, accordingly improving the efficiency and safety of gene therapy, which will make them the most promising vectors for pancreatic cancer.
The diagnostic value of repetitive preoperative analyses of C-reactive protein and total leucocyte count in patients with suspected acute appendicitis.

BACKGROUND Studies have shown that C-reactive protein (CRP) and total leucocyte count (WBC) in suspected acute appendicitis analysed only on admission gave valuable information to guide the surgeon. The aim of this study was to investigate the usefulness of CRP and WBC measured repetitively before operation. METHODS During a 1-year period 227 patients were studied before emergency appendicectomy. CRP and WBC were analysed every 4th h. The upper limits of the reference intervals used were 9.0 x 10(9)/l for WBC and 10 mg/l for CRP. RESULTS Of the 227 appendicectomized patients, 170 (75%) had acute appendicitis. Sixty-six of the patients were tested on two or more occasions every 4th h. Forty-six of these patients had appendicitis; repetitive tests showed a continuing rise in CRP values but a continuing decrease in WBC. The negative appendicectomy rate among these 66 patients was 30%, which theoretically would have fallen to 19% if patients with normal results had not been subjected to surgery. CONCLUSIONS Repeated laboratory tests for CRP and WBC should be performed in patients with suspected acute appendicitis requested to stay for further observation. If these test results are normal, the surgeon should preferably refrain from operating but consider other differential diagnoses.
Comparison of Spatio-Temporal, Metabolic, and Psychometric Responses in Recreational and Highly Trained Swimmers during and after a 400-m Freestyle Swim

Spatio-temporal, metabolic and psychometric responses during and after a 400-m freestyle swim trial were investigated for gender and skill-level effects. Thirty-four men and women, 18 national and international competitors and 16 recreational swimmers, were compared. Mean speed, stroke rate (SR), and stroke length (SL) were obtained from video recordings. Peak heart rate (HR) and the lactate value (Hla) were determined, as were the recovery kinetics, i.e., the recovery time index (RTI) for heart rate and %Hla (r) for the lactate values. Well-being was assessed with the Profile of Mood States questionnaire (POMS). Subjective workload was assessed with the NASA-TLX questionnaire. The experts showed less variation in their swim speed than the recreational swimmers. The male experts showed greater SL and the female experts showed greater SL and SR. No significant difference was noted between the experts and recreational swimmers for peaks of HR and Hla, POMS (157.3 +/- 15.1 vs. 163.1 +/- 21.5), or subjective workload (32.4 +/- 6.7 vs. 31.6 +/- 6.1). The experts exhibited higher RTI (- 38.5 +/- 5.5 % vs. - 31.1 +/- 5.4 %) and %Hla (r) (8.6 +/- 7.18 % vs. 1.65 +/- 8.2 %). They also showed an improvement of 7.8 +/- 2.6 % for men and 6.02 +/- 1.6 % for women between the performance time for the trial and the best competitive time of the season. Last, our results suggest that the 400-m freestyle trial is a valid field test to evaluate the maximal aerobic speed (MAS) of swimmers with different training status. The systemic analysis herein described can be used to set the end-of-season target time for expert competitors. Attention should focus on SL, race management, and the physiological recovery for training prescription.
Accumulation of silver nanoparticles by cultured primary brain astrocytes

Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO3 already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.
Topological analysis of a plant vacuolar Na+/H+ antiporter reveals a luminal C terminus that regulates antiporter cation selectivity

We conducted an analysis of the topology of AtNHX1, an Arabidopsis thaliana vacuolar Na+/H+ antiporter. Several hydrophilic regions of the antiporter were tagged with a hemagglutinin epitope, and protease protection assays were conducted to determine the membrane topology of the antiporter by using yeast as a heterologous expression system. The overall structure of AtNHX1 is distinct from the human Na+/H+ antiporter NHE1 or any known Na+/H+ antiporter. It is comprised of nine transmembrane domains and a hydrophilic C-terminal domain. Three hydrophobic regions do not appear to span the tonoplast membrane, yet appear to be membrane associated. Our results also indicate that, whereas the N terminus of AtNHX1 is facing the cytosol, almost the entire C-terminal hydrophilic region resides in the vacuolar lumen. Deletion of the hydrophilic C terminus resulted in a dramatic increase in the relative rate of Na+/H+ transport. The ratio of Na+/K+ transport was twice that of the unmodified AtNHX1. This altered ratio resulted from a relatively small decrease in K+/H+ transport with a large increase in Na+/H+ transport. The vacuolar localization of the C terminus of the AtNHX1, taken together with the regulation of the antiporter selectivity by its C terminus, demonstrates the existence of luminal vacuolar regulatory mechanisms of the antiporter activity.
The Efficacy of Minimal Contact Interventions for Acute Tinnitus: A Randomised Controlled Study

Acute tinnitus can lead to substantial distress and eventually result in long-lasting impairment. The aim of this study was to compare the efficacy of a cognitive-behavioural intervention (delivered as Internet self-management, bibliotherapy or group training) to the information-only control condition. Applicants suffered from subjective tinnitus for up to six months, were between 18 and 75 years old and received no other tinnitus-related psychological treatment. A total of 304 participants were randomly assigned to one of the four study arms. Tinnitus distress, depressive symptoms, psychosomatic discomfort and treatment satisfaction were assessed. At the post-assessment tinnitus distress was significantly lower in the Internet and the group training conditions compared to the control condition. Inter-group effect sizes were moderate to large. At follow-up, all active training conditions showed significantly reduced tinnitus distress compared to the control condition (intention-to-treat analysis). An additional completer analysis showed a significant reduction in tinnitus distress only for the group condition. All effect sizes were moderate. There were no differences regarding psychosomatic discomfort, but depressive symptoms were reduced in the group condition at the post-assessment (intention-to-treat analysis). Treatment satisfaction was significantly higher in the training conditions. The dropout rate was 39%. The present study shows that distress can be reduced as early as the acute stadium and that minimal-contact interventions are a promising way to do this. In particular, the Internet and group conditions led to a large, immediate decrease in distress, and the participants were highly satisfied with the training.
Predominance of CD8+ T lymphocytes in psoriatic arthritis.

OBJECTIVE To characterize the synovial fluid (SF) derived T cell populations in psoriatic arthritis (PsA) and compare with similar populations from rheumatoid arthritis (RA). METHODS Paired peripheral blood (PB) and SF samples were analyzed by 3 color flow cytometry using monoclonal antibodies to CD3, CD4, CD8, HLA-DR, CD25, CD45RA, and CD45RO. RESULTS There was a significantly increased CD8+ T cell population in PsA SF compared to RA: PsA mean 61% (range 35-93), RA mean 46% (range 6-72) (p < 0.005). This resulted in a reversal of the CD4:CD8 ratio in PsA SF compared to RA SF (p < 0.001). Patients with oligoarticular PsA had the most pronounced differences in SF derived T cell populations compared to RA (p < 0.0005) but these results were not significantly different from PsA patients with a polyarticular disease pattern. PB PsA T cell populations were not different from controls, in contrast to RA, where the CD4+ T cell population was increased (p < 0.0026), giving an exaggerated PB CD4:CD8 ratio. The majority of PsA SF CD8+ T cells expressed CD45RO, mean 73% (range 58-95), and HLA-DR antigen: mean 72% (range 38-94). Low levels of CD25 were detectable in this population, indicating a nonclassical activation pattern: mean 2% (range 0.3-4.4). CONCLUSION In PsA, activated (HLA-DR+) and mature (CD45RO+) CD8+ T cells predominate in SE Analysis of this population may uncover clues to pathogenesis in this HLA class I mediated disease.
Off-ice performance and draft status of elite ice hockey players.

PURPOSE The primary purpose of this study was to determine whether tests performed at the National Hockey League (NHL) Combine could distinguish draft status (ie, the round selected). A secondary aim was to provide performance ranges and percentiles for each of the dependent variables. METHODS A retrospective, cross-sectional study design was used with performance data and draft order from 2001, 2002, and 2003 Combine participants. Draft round was divided into 5 classifications (rounds 1, 2, 3, 4, and 5 through 9), and performances on 12 physical tests served as dependent variables. Three multiple analyses of covariance (MANCOVAs) were used to determine the significance of performance scores at the NHL Combine on draft selection. Age (years), body mass (kg), height (cm), and percentage body fat were treated as covariates. RESULTS Overall, MANCOVA results indicated no significant effect of performance on draft selection for 2001, 2002, or 2003. Subsequent univariate tests revealed that no single dependent variable was able to distinguish between draft rounds for any of the 3 years sampled. CONCLUSIONS Using draft status as an indicator of ice hockey performance, it appears that off-ice tests cannot accurately predict ice hockey playing ability in an elite group of athletes. This might stem from homogeneity of the Combine participants, a lack of validity of the tests, or other factors (eg, on-ice hockey skills, psychological variables, etc) that play a role in draft selection.
Single-Port Laparoscopic Appendectomy Versus Conventional Laparoscopic Appendectomy: A Prospective Randomized Controlled Study

Objective: To compare surgical outcomes and quality of life between single-port laparoscopic appendectomy (SPLA) and conventional laparoscopic appendectomy (CLA) in patients with acute appendicitis. Background: A prospective randomized single center study was performed to compare the outcome of SPLA and CLA in patients with acute appendicitis. Methods: A total of 248 patients were randomized, but because of 18 withdrawals, the outcome of 224 is analyzed, 116 in CLA and 114 in SPLA. Results: There was no significant difference in the overall complication rate (P = 0.470). There were no significant differences in infectious complications between the SPLA group and the CLA group (10.2% and 12.4%, respectively). The wound complication rate between the 2 groups was not significant (5.1% and 10.6%, respectively; P = 0.207). Cosmetic satisfaction score, 36-item short-form health survey, and postoperative pain scores were not significantly different between 2 groups. Conclusions: SPLA failed to show any advantages over CLA relative to pain and cosmesis. However, SPLA is as safe as CLA (RCT number 01348464).
Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia.

BACKGROUND Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. MATERIALS AND METHODS We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. RESULTS FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374). CONCLUSIONS The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.
Caring for a relative with dementia: family caregiver burden.

AIM This paper is a report of part of a study to investigate the burden experienced by families giving care to a relative with dementia, the consequences of care for the mental health of the primary caregiver and the strategies families use to cope with the care giving stressors. BACKGROUND The cost of caring for people with dementia is enormous, both monetary and psychological. Partners, relatives and friends who take care of patients experience emotional, physical and financial stress, and care giving demands are central to decisions on patient institutionalization. METHOD A volunteer sample of 172 caregiver/care recipient dyads participated in the study in Cyprus in 2004-2005. All patients were suffering from probable Alzheimer's type dementia and were recruited from neurology clinics. Data were collected using the Memory and Behaviour Problem Checklist, Burden Interview, Center for Epidemiological Studies-Depression scale and Ways of Coping Questionnaire. FINDINGS The results showed that 68.02% of caregivers were highly burdened and 65% exhibited depressive symptoms. Burden was related to patient psychopathology and caregiver sex, income and level of education. There was no statistically significant difference in level of burden or depression when patients lived in the community or in institutions. High scores in the burden scale were associated with use of emotional-focused coping strategies, while less burdened relatives used more problem-solving approaches to care-giving demands. CONCLUSION Caregivers, especially women, need individualized, specific training in how to understand and manage the behaviour of relatives with dementia and how to cope with their own feelings.
Lymph Node Metastasis Is Associated with Allelic Loss on Chromosome 13 q 12 – 13 in Esophageal Squamous Cell Carcinoma 1

Allelotype analysis of whole chromosomes showed that loss of heterozygosity (LOH) on 13q was exclusively associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma (ESC). To identify a locus responsible for lymph node metastasis, we performed fine deletion mapping on 13q by analyzing 60 ESCs with 18 polymorphic markers. Allelic loss was observed with at least one marker in 34 tumors (56.7%), and lymph node metastasis was significantly correlated with LOH (P 5 0.0053). We found frequent loss at D13S260(43.7%), D13S171 (38.6%), andD13S267(43.6%) on 13q12–13. Among these markers, LOH at D13S171showed a significant correlation with lymph node metastasis (P 5 0.0441). Because these markers flank the BRCA2gene, we intensively examined a mutation of the gene through all coding exons and exon-intron junctions by PCR-single-strand conformational polymorphism analysis under two different assays. We found only seven nucleotide substitutions as normal polymorphic changes; tumor-specific mutations were not detected, and loss of expression was not observed, indicating that the BRCA2 gene might not be a target of allelic loss in this region. Relatively frequent LOH was also found at theRB1 locus (34.7%), but a significant correlation with lymph node metastasis was not observed ( P 5 0.7430). Protein expression ofRB1 was examined in 31 ESC cell lines, and loss of expression was infrequent (6.5%), indicating that inactivation of the RB1 gene might not be responsible for lymph node metastasis. Taken together, allelic loss at 13q12–13 of the primary ESC was closely associated with lymph node metastasis, and unidentified tumor suppressor gene(s) in this region might be involved.
Pilot Randomized Controlled Trial of LEAP: A Selective Preventive Intervention to Reduce Adolescents’ Perceived Burdensomeness

This research draws upon the interpersonal-psychological theory of suicide in the development of the LEAP intervention, a web-based selective preventive suicide intervention targeting cognitions of perceived burdensomeness toward others. The pilot randomized controlled trial consisted of 80 adolescents (68.8% female, 65.8% Hispanic) 13–19 of age years who were randomly assigned to either the LEAP intervention or a psychoeducational control condition. Participants completed baseline, posttreatment, and 6-week follow-up assessments. All participants reported high levels of satisfaction with the program. Findings on outcome variables differed across intent-to-treat analyses and treatment completer analyses. Intent-to-treat analysis yielded no significant between-condition differences in perceived burdensomeness at posttreatment or follow-up. Treatment completer analyses revealed significant between-condition differences on outcome variables such that participants who completed the LEAP intervention showed significantly lower perceived burdensomeness scores at postintervention and significantly lower perceived burdensomeness, thwarted belongingness, and depressive symptom scores at follow-up as compared to participants in the control condition. No significant differences in suicidal ideation were found between conditions. These findings support the promise of the LEAP intervention as a brief, web-based selective preventive intervention for reducing perceived burdensomeness among adolescents who complete the intervention. This study provides evidence that perceived burdensomeness can be modified via a psychosocial intervention. Future research is needed to identify ways to enhance adolescent engagement with and completion of the intervention.
[Effect of liuwei dihuang pill on erythrocyte aldose reductase activity in early diabetic nephropathy patients].

OBJECTIVE To observe the inhibitory effect of Liuwei Dihuang Pill (LDP) on erythrocyte aldose reductase (EAR) activity in early diabetic nephropathy (DN) patients and to explore the clinical significance of applying LDP in prevention and treatment of DN as an inhibitor of aldose reductase. METHODS Seventy-two patients diagnosed as early DN with TCM Syndrome of both Qi-yin deficiency were randomly divided into the control group (31 patients) treated by conventional therapy (orally taken Gliquidone or injection of insulin) and the treated group (41 patients) treated by conventional therapy plus LDP for 3 months as one therapeutic course. Changes of symptoms, physical signs, fasting blood glucose (FBG), blood glucose 2 hrs post breakfast (2hPBG), blood total cholesterol (TC), triglyceride (TG), EAR activity, urinary albumin excretion rate (UAER), blood and urinary beta2-microglobulin (beta2-MG) in patients before and after treatment were observed. RESULTS LDP could improve the symptoms and signs of patients with DN, it could significantly inhibit EAR activity, to make it significantly lower than that in the control group (P < 0.05), and the levels of UAER, beta2-MG in blood and urine in the treated group after treatment were obviously lower than those in the control group (P < 0.05), and LDP showed no apparent effect on blood glucose, lipids and mean arterial pressure (P < 0.05). CONCLUSION LDP could obviously inhibit the activity of EAR in patients with early DN, improve various indexes of DN, so as to be helpful for its treatment.
Analyst Expertise and the Value of Cash Holdings

This study investigates whether analyst expertise mitigates the value destruction associated with an increase in cash holdings. We find that analyst expertise increases the marginal value of cash holdings, and that this effect is more pronounced for firms in an environment where analysts’ forecasts are more dispersed and for firms with weaker monitoring from institutional shareholders. Overall, our results are consistent with our conjecture that analyst expertise enhances external monitoring, thereby preventing potential misuse of cash holdings and the associated destruction of cash value.