Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms

1 Cardiac V3 myosin generates slower actin filament velocities and higher average isometric forces (in an in vitro motility assay) when compared with the V1 isoform. 2 To account for differences in V1 and V3 force and motion generation at the molecular level, we characterized the mechanics and kinetics of single V1 and V3 myosin molecules using a dual laser trap setup. 3 No differences in either unitary displacement (≈7 nm) or force (≈0.8 pN) were observed between isoforms; however, the duration of unitary displacement events was significantly longer for the V3 isoform at MgATP concentrations > 10 μm. 4 Our results were interpreted on the basis of a cross‐bridge model in which displacement event durations were determined by the rates of MgADP release from, and MgATP binding to, myosin. 5 We propose that the release rate of MgADP from V3 myosin is half that of V1 myosin without any difference in their rates of MgATP binding; thus, kinetic differences between the two cardiac myosin isoforms are sufficient to account for their functional diversity.
The Views of Older Malaysians on Advanced Directive and Advanced Care Planning: A Qualitative Study

The provision of optimum care for the ageing population is dependent on the understanding of their views and values on end of life issues. A qualitative descriptive study was conducted to describe views of elderly Malaysians on Advanced Care Planning (henceforth ACP) and Advanced Directives (henceforth AD), and explore factors influencing these views. Fifteen elderly subjects with ages ranging from 65 to 83 years, representing different ethnic and religious groups in Malaysia were selected for in-depth interviews guided by a questionnaire. Five core themes were extracted from the interviews:1) Considering the future 2) Contingency plans for future illnesses 3) Attitudes towards life prolonging treatment procedures 4) Doctor-patient relationships and 5) Influence of religion on decisions related to future illness. Despite the lack of knowledge on ACP and AD, older respondents were very receptive to their concept. Although the majority agreed on the importance of planning for future medical management and having open discussion on end of life issues with their doctor, they felt it unnecessary to make a formal written AD. Most felt that the future was best left to fate or God, and none had made any contingency plan for severe future illnesses citing religion as reason for this view. Cardiopulmonary resuscitation, mechanical ventilation and dialysis were considered by most to be invasive life prolonging treatments. We suggest that doctors initiate discussions on end of life care with every older patient and their family so as to promote awareness and introduce the concept of ACP/AD to a Malaysian setting. Asia Pac J Public Health 2007; 19(3): 58-67.
Acute kidney injury in children : incidence and prognostic factors in critically ill patients

Acute kidney injury (AKI) is characterized by a sudden and generally revertible renal function impairment, involving inability to maintain the homeostasis, and may or not be accompanied by reduced diuresis. (1-5) Usually, AKI may be categorized as pre-renal, related to reduced renal blood flow (RBF) for inappropriate cardiac output or intravascular volume; intrinsic renal disease, from an insult to the renal parenchyma including ischemic, vascular, tubular or glomerular disorders; and postrenal, due to urinary tract obstruction either in single kidney or both kidneys. (1,3,4,6) Kenia Machado Souza Freire1, Nilzete Liberato Bresolin2, Ana Camila Flores Farah3, Francisca Lígia Cirilo Carvalho3, José Eduardo Coutinho Góes3
Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men

We aimed to determine if any mechanistic differences exist between a single set (1SET) and multiple sets (i.e. 3 sets; 3SET) of resistance exercise by utilizing a primed constant infusion of [ring‐13C6]phenylalanine to determine myofibrillar protein synthesis (MPS) and Western blot analysis to examine anabolic signalling molecule phosphorylation following an acute bout of resistance exercise. Eight resistance‐trained men (24 ± 5 years, BMI = 25 ± 4 kg m−2) were randomly assigned to perform unilateral leg extension exercise at 70% concentric one repetition maximum (1RM) until volitional fatigue for 1SET or 3SET. Biopsies from the vastus lateralis were taken in the fasted state (Fast) and fed state (Fed; 20 g of whey protein isolate) at rest, 5 h Fed, 24 h Fast and 29 h Fed post‐exercise. Fed‐state MPS was transiently elevated above rest at 5 h for 1SET (2.3‐fold) and returned to resting levels by 29 h post‐exercise. However, the exercise induced increase in MPS following 3SET was superior in amplitude and duration as compared to 1SET at both 5 h (3.1‐fold above rest) and 29 h post‐exercise (2.3‐fold above rest). Phosphorylation of 70 kDa S6 protein kinase (p70S6K) demonstrated a coordinated increase with MPS at 5 h and 29 h post‐exercise such that the extent of p70S6K phosphorylation was related to the MPS response (r= 0.338, P= 0.033). Phosphorylation of 90 kDa ribosomal S6 protein kinase (p90RSK) and ribosomal protein S6 (rps6) was similar for 1SET and 3SET at 24 h Fast and 29 h Fed, respectively. However, 3SET induced a greater activation of eukaryotic translation initiation factor 2Bɛ (eIF2Bɛ) and rpS6 at 5 h Fed. These data suggest that 3SET of resistance exercise is more anabolic than 1SET and may lead to greater increases in myofibrillar protein accretion over time.
Evaluation of nonneoplastic findings on vaginal smears with comparison of intrauterine devices and oral contraceptive pill effects

Although the Pap smear is a common screening test for cervical cancer and its precursors, it can detect some benign conditions as well. In this study, the aim was to evaluate smear results with regard to nonneoplastic findings and to compare them to the detectable effects of intrauterine devices (IUDs) and oral contraceptive pills (OPs). Materials and methods: In this retrospective study, the hospital records and cytopathology reports of 4248 patients were recorded. Smear results were evaluated according to the 2001 Bethesda System and were evaluated according to age groups, menopausal/menstrual status, physical examination findings, and contraceptive method usage. Results: Of the 4248 patients, 75% were menstruating and 25% were menopausal. The most common smear result was nonspecific inflammation (NSI). In comparing the IUD (n = 730) and OP (n = 322) groups, we found Candida species, Actinomyces, and bacterial vaginosis to be significantly higher in the IUD-using group, while NSI, discharge, and erosion were found to be significantly higher in the OP group. Conclusion: Pap smears can provide information about infectious diseases that can occur in the cervicovaginal region. These results reflect the fact that the IUDs disrupt vaginal flora more than OPs do.
Patient and family caregiver dyadic adherence to the allogeneic hematopoietic cell transplantation medical regimen

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for hematologic disease. To minimize infection risk and poor outcomes post hospital discharge, patients are required to identify a family caregiver to work with them to adhere to the multicomponent post‐HCT medical regimen. In addition to medical surveillance and taking medication as prescribed, the National Marrow Donor Program's recommendations for the first 100 days after HCT include proper catheter care; avoidance of crowds; and reliance on a caregiver for transportation, shopping, and cooking. Frequent, thorough hand washing is also strongly recommended to reduce the risk of bacterial, viral, and fungal infections, and patients typically must monitor their temperature daily to quickly recognize signs of infection. Further, patients who are neutropenic must generally follow a diet that avoids bacteria found in foods, such as fresh fruits and vegetables, salad bars, and fresh deli meats. Despite the importance of adherence, little research has examined levels of adherence or how patients and caregivers manage task requirements. Adherence is particularly critical over the initial period post hospital discharge, when patients are at highest risk for complications and mortality. Studies of adherence to medical regimens in other clinical contexts have focused primarily on the patient's role, although family caregivers are often involved. The present study is among the first to describe adherence levels across post‐HCT medical regimen tasks and explore the contribution of dyadic factors to successful adherence in HCT. An additional goal was to describe how post‐HCT
Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell Immunosurveillance of Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs). Based on plasma and tumor samples of 44 HNSCC patients, we found that despite compositional heterogeneity the total plasma level of NKG2DLs correlates with NK cell inhibition and disease progression. Strikingly, based on tumor spheroids and primary tumors of HNSCC patients, we found that NK cells failed to infiltrate HNSCC tumors in the presence of high levels of NKG2DLs, demonstrating a novel mechanism of NKG2DL-dependent tumor immune escape. Therefore, the diagnostic acquisition of the plasma level of all NKG2DLs might be instrumental for prognosis and to decipher a patient cohort, which could benefit from restoration of NKG2D-dependent tumor immunosurveillance. Along these lines, we could show that removal of shed NKG2DLs (sNKG2DLs) from HNSCC patients’ plasma restored NK cell function in vitro and in individual patients following surgical removal of the primary tumor. In order to translate these findings into a therapeutic setting, we performed a proof-of-concept study to test the efficacy of adsorption apheresis of sNKG2DLs from plasma after infusion of human MICA in rhesus monkeys. Complete removal of MICA was achieved after three plasma volume exchanges. Therefore, we propose adsorption apheresis of sNKG2DLs as a future preconditioning strategy to improve the efficacy of autologous and adoptively transferred immune cells in cellular cancer immunotherapy.
Effect of anisomycin, a protein synthesis inhibitor, on the in vitro developmental potential, ploidy and embryo quality of bovine ICSI embryos

Summary Increasing the efficiency of intracytoplasmic sperm injection (ICSI) in domestic animals has been attempted by many researchers, however embryonic development to the blastocyst stage remains low compared with that of in vitro fertilization (IVF) embryos. One of the main problems observed in cattle is inadequate oocyte activation after ICSI. The present study compared the effect of cycloheximide (CHX), 6-dimethylaminopurine (DMAP), and anisomycin (ANY) on the fertilization rate, development, ploidy and quality of bovine embryos generated by ICSI. Although no differences were observed between treatments in terms of cleavage, higher blastocyst rates were observed for ANY (37.3%) compared with CHX (21.8%, P < 0.05) and DMAP (28.6%, P > 0.05) treatments. No differences were observed in the quality of embryos as assessed by the total number of cells, their distribution to the different embryo compartments [inner cell mass (ICM) and trophectoderm (TE)], the proportion of ICM cells to the total cell numbers and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive cells. Similarly, no differences were observed in the normal ploidy of embryos (56, 67, and 55%) for ANY, CHX and DMAP, respectively. However, higher fertilization rates were observed for ANY (75%) and CHX (87%) treatments compared with DMAP (35%). In conclusion, ANY showed a superior developmental rate compared with CHX treatment. Although no significant differences were observed compared with an improved protocol of DMAP (2Io-DMAP), the lower fertilization rate recorded with DMAP strongly suggests that ANY could be a better alternative for oocyte activation than traditional chemical compounds used currently in ICSI.
Comparative efficacy of liquid enrichment medium for isolation of Campylobacter jejuni

Isolation of Campylobacter jejuni from 1,249 human fecal specimens by direct inoculation on selective Columbia agar and liquid enrichment medium was compared. The use of liquid enrichment medium provided a 30% higher isolation rate of C. jejuni. The overall isolation rate achieved by using direct plating and enrichment together was 8.2%.
Effect of autologous platelet gel on early and late graft fusion in anterior cervical spine surgery.

OBJECT In a double-blind randomized study, platelet concentrate was used to treat 50 patients who underwent anterior cervical fusion with allograft bone and internal fixation, predominantly for degenerative disc disease or soft herniated cervical disc. The goal in this study was to compare the outcomes in patients treated with and without the platelet gel. METHODS Patients were assessed radiographically at 6, 12, and 52 weeks and at 2 years if needed. Clinically, patients were evaluated with the visual analog scale, Neck Disability Index, Short Form-36, and a modified Prolo Scale. RESULTS Follow-up included 90% of the patients at 1 year and 84% at 2 years. The overall fusion rate was 84%. CONCLUSIONS Whereas patients with degenerative discs treated with platelet gel demonstrated early fusion at the 12-week follow-up interval, no consistent early fusion was obtained with the use of the platelet gel preparation in patients with a soft disc herniation.
Zinc in wound healing: Theoretical, experimental, and clinical aspects

Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc‐dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine‐rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc‐deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri‐ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound‐healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti‐infective action, and promotion of epithelialization.
Ovarian cancer after successful ovulation induction: a case report.

BACKGROUND Questions have been raised regarding the potential association of ovulation-inducing drugs and ovarian cancer. Worldwide there have been 13 cases of ovarian carcinoma reported to occur in women previously treated with ovulation-inducing drugs (clomiphene citrate and/or gonadotropins). CASE A 40-year-old woman complained of secondary infertility. She conceived after five cycles of human menopausal gonadotropins with intrauterine insemination. Eight months after cesarean delivery, she presented with right lower quadrant pain and a right adnexal mass. At exploratory laparotomy the patient was found to have a poorly differentiated papillary serous carcinoma of the ovary. CONCLUSION Ovarian carcinoma developed within 18 months of exposure to ovulation-inducing agents, human menopausal gonadotropins. It would be prudent to gather a registry of cases to assess the risk associated with human menopausal gonadotropins with or without gonadotropin-releasing hormone analogs.
An attempt to physiologically discriminate imagined withdrawal and high states in narcotic addicts under treatment.

Pupil size was continuously monitored during responses to a set of taped instructions which asked a group of 20 addicts under treatment, in a counterbalanced design, to think about withdrawal, and to think about a drug-high. The results indicated that there were no differences in responses to the two imagined states. A number of possible interpretations of the results are offered. One of the more promising of these suggests that addicts may not be able to reconstruct the affective components of their drug experience to the same extent that nonad-dicts are able to recreate their life experiences. Suggestions for the direction of further research are made.
Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease

Risk factors associated with pathologic gambling include male sex, age (25 to 29 years), comorbid psychiatric disorders, suicide, and lower socioeconomic status.1 In addition, some authors report significant increases in both casino gambling and single-day money losses within a year after the introduction of readily available casinos.2 The prevalence of this condition is unknown in patients with Parkinson disease (PD). 3 Some authors suggest that these symptoms may be related to high dose dopaminergic therapy, especially in subjects prone to poorly regulated, self-medicating behaviors.4-7⇓⇓⇓ We report nine patients with pathologic gambling associated with chronic high dose dopamine agonist (DA) therapy. A retrospective database review of all patients with PD seen at the Muhammad Ali Parkinson Research Center (MAPRC) from May 1, 1999, to April 30, 2000, was performed for pathologic gambling. Specific data collected included subject age, sex, race, duration of disease, Hoehn and Yahr stage (H&Y), Unified …
Specific In Vivo Labeling of Cell Surface-Exposed Protein Loops: Reactive Cysteines in the Predicted Gating Loop Mark a Ferrichrome Binding Site and a Ligand-Induced Conformational Change of theEscherichia coli FhuA Protein

ABSTRACT The FhuA protein of Escherichia coli K-12 transports ferrichrome, the antibiotic albomycin, colicin M, and microcin 25 across the outer membrane and serves as a receptor for the phages T1, T5, φ80, and UC-1. FhuA is activated by the electrochemical potential of the cytoplasmic membrane, which probably opens a channel in FhuA. It is thought that the proteins TonB, ExbB, and ExbD function as a coupling device between the cytoplasmic membrane and the outer membrane. Excision of 34 residues from FhuA, tentatively designated the gating loop, converts FhuA into a permanently open channel. FhuA contains two disulfide bridges, one in the gating loop and one close to the C-terminal end. Reduction of the disulfide bridges results in a low in vivo reaction of the cysteines in the gating loop and no reaction of the C-terminal cysteines with biotin-maleimide, as determined by streptavidin-β-galactosidase bound to biotin. In this study we show that a cysteine residue introduced into the gating loop by replacement of Asp-336 displayed a rather high reactivity and was used to monitor structural changes in FhuA upon binding of ferrichrome. Flow cytometric analysis revealed fluorescence quenching by ferrichrome and albomycin of fluorescein-maleimide bound to FhuA. Ferrichrome did not inhibit Cys-336 labeling. In contrast, labeling of Cys-347, obtained by replacing Val-347 in the gating loop, was inhibited by ferrichrome, but ferrichrome quenching was negligible. It is concluded that binding of ferrichrome causes a conformational change of the gating loop and that Cys-347 is part of or close to the ferrichrome binding site. Fluorescence quenching was independent of the TonB activity. The newly introduced cysteines and the replacement of the existing cysteines by serine did not alter sensitivity of cells to the FhuA ligands tested (T5, φ80, T1, colicin M, and albomycin) and fully supported growth on ferrichrome as the sole iron source. Since cells of E. coliK-12 display no reactivity to thiol reagents, newly introduced cysteines can be used to determine surface-exposed regions of outer membrane proteins and to monitor conformational changes during their function.
Assessing Nutrition Education Wants and Needs of Older Adults Through Focus Groups

Abstract Five focus groups assessed the nutrition education wants and needs of 37 non-institutionalized older adults ages 60 and older. Discussions were tape-recorded, transcribed and coded to facilitate data analysis. Findings cited most frequently included; doctors were influential, nutrition contributed to good health, basic nutrition topics were wanted/ needed, written materials were used most often, demonstration and discussion methods were prevalently used/wanted, and service providers were primarily informed directly about wants/needs. Older adults wanted/needed nutrition education to improve their health and make informed decisions, and because the topic interested them. Information obtained could be used to develop more focused nutrition education programs for older adults.
Impact of Field Release of Genetically Modified Pseudomonas fluorescens on Indigenous Microbial Populations of Wheat

In a field release experiment, an isolate of Pseudomonas fluorescens, which was chromosomally modified with two reporter gene cassettes (lacZY and Kan(supr)-xylE), was applied to spring wheat as a seed coating and subsequently as a foliar spray. The wild-type strain was isolated from the phylloplane of sugar beet but was found to be a common colonizer of both the rizosphere and phylloplane of wheat as well. The impact on the indigenous microbial populations resulting from release of this genetically modified microorganism (GMM) was compared with the impact of the unmodified, wild-type strain and a nontreated control until 1 month after harvest of the crop. The release of the P. fluorescens GMM and the unmodified, wild-type strain resulted in significant but transient perturbations of some of the culturable components of the indigenous microbial communities that inhabited the rhizosphere and phylloplane of wheat, but no significant perturbations of the indigenous culturable microbial populations in nonrhizosphere soil were found. Fast-growing organisms that did not produce resting structures (for example, fluorescent pseudomonads and yeasts) seemed to be most sensitive to perturbation. In terms of hazard and risk to the environment, the observed microbial perturbations that resulted from this GMM release may be considered minor for several reasons. First, the recombinant P. fluorescens strain caused changes that were, in general, not significantly different from those caused by the unmodified wild-type strain; second, perturbations resulting from bacterial inoculations were mainly small; and third, the release of bacteria had no obvious effects on plant growth and plant health.