Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclic Loading of Olecranon Fracture Fixation Constructs

Background: Despite the good results that are usually reported after fixation at the sites of olecranon fractures and osteotomies, problems such as loss of fixation, nonunion, and the need for revision surgery are still encountered. Various types of fixation have been recommended, but few have been evaluated with use of clinically relevant cyclic load testing at appropriate levels of stress. The purpose of the present study was to test multiple olecranon fixation techniques under physiologic cyclic loads. Methods: We studied ten cadaveric elbows with use of cyclic loading that simulated (1) active range of motion and (2) pushing up from a chair. Each specimen underwent fixation of a simulated 50% transverse olecranon fracture with use of intramedullary and cortically fixed tension band constructs (in randomized order) followed by fixation with a 7.3-mm-diameter cancellous screw with and without a tension band. Displacement transducers were placed posteriorly on the tension side and anteriorly near the articular surface. Results: Both configurations involving the 7.3-mm-diameter cancellous screw provided the most stable fixation—nearly five times better than that provided by the Kirschner-wire techniques. Use of the tension band in conjunction with the intramedullary screw improved the stability of fixation. In none of the constructs did the AO tension band result in compression across the osteotomy gap. Conclusions and Clinical Relevance: The use of a 7.3-mm screw in conjunction with a tension band provided better fixation of simulated displaced transverse fractures than did the use of Kirschner wires in conjunction with a tension band or the use of a screw only. The AO principle of converting posterior tensile forces to articular compressive forces was not demonstrated in this study. We therefore question the validity of the tension band concept in olecranon fracture fixation and recommend passive rather than active range of motion in the immediate postoperative period to limit fracture distraction.
Oscillations in ciliary beat frequency and intracellular calcium concentration in rabbit tracheal epithelial cells induced by ATP

To investigate how Ca2+ regulates airway ciliary activity, changes in ciliary beat frequency (CBF) and intracellular calcium concentration ([Ca2+]i) of rabbit tracheal ciliated cells, in response to ATP, were simultaneously quantified with high‐speed phase‐contrast and fast fluorescence imaging. [ATP]⩽ 1 μm induced an increase in [Ca2+]i and CBF that declined to the initial basal levels and was followed by irregular brief increases in [Ca2+]i and CBF. [ATP] > 1 but < 16 μm induced a similar increase in [Ca2+]i and CBF but this was followed by oscillations in CBF and [Ca2+]i. The minimum CBF of the oscillations in CBF remained elevated above the basal rate while the minimum concentration of the [Ca2+]i oscillations returned to the basal level. The minimum and maximum CBF of the oscillations in CBF were independent of the [ATP], whereas the frequency of the oscillations in CBF was dependent on the [ATP]. Similar oscillations in CBF and [Ca2+]i were induced by ATP‐ γ ‐S. Although ADP, AMP and adenosine induced a Ca2+‐independent increase in CBF, neither ATP nor ATP‐ γ ‐S induced an increase in CBF when the Ca2+ increases were abolished by 20 μm BAPTA AM, a result suggesting that ATP hydrolysis was minimal. [ATP]≥16 μm induced a sustained elevation in CBF and only a temporary, non‐oscillating increase in [Ca2+]i. A similar response was induced by thapsigargin (2 μm). Flash photolysis of caged Ca2+ (NP‐EGTA) produced both transient and prolonged increases in [Ca2+]i which were accompanied by transient and sustained increases in CBF, respectively. From these results, we propose that CBF can be increased by a direct Ca2+ ‐dependent mechanism that generates the rapid increases in CBF associated with the oscillations or by an indirect Ca2+‐dependent mechanism that is responsible for the sustained minimum increase in CBF.
Choosing the degree of formalisation of activities: deciding with stakeholders

Abstract The main objective of this research is to articulate how the informal entrepreneur decides on the degree of formalisation of his activities. Indeed, it would be naïve to believe that the proliferation of the informal is solely due to the discretion entrepreneurs. The study uses qualitative approach, mainly case studies analysis to retrace the choices of activity development trajectories of entrepreneurs. Exploratory results of life-story with 12 entrepreneurs in Cameroon suggest that some stakeholders play a central role in the choice of the degree of formalisation of activities. These are the partners involved in commercial relations (strategic or tactical) with entrepreneurs such, bankers, advisory and support organisations (accountants and tax consultants), and civil servants in charge of control and State legislators. The public authorities must, therefore, consider cooperating with these actors to develop effective political solutions to support the formalisation of entrepreneurial activities.
Heterogeneity of Monetary Policy Spillovers to Monetary Responsiveness in Emerging Market Economies

Discussions about monetary policy spillovers increased as major advanced economies move to policy normalization. In this paper, I investigate the differences in policy spillovers on monetary policy setting of emerging market economies. In particular, I investigated how interest differentials from major advanced economies, US, ECB and Japan, influence the movements of interest rates in emerging market economies. Using panel fixed effects regression, the results of this study show heterogeneity in the significance of policy spillover from US, ECB and Japan to emerging market economies. The results support previous findings that international monetary policy spillovers influence movements in short term interest rates, which is not explained by policy factors.
Effects of YC-1 on Hypoxia-Inducible Factor 1-Driven Transcription Activity, Cell Proliferative Vitality, and Apoptosis in Hypoxic Human Pancreatic Cancer Cells

Objectives: To investigate the effects of 3-(5&vprime;-hydroxymethyl-2&vprime;-furyl)-1-benzyl indazole (YC-1) on HIF-1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells. Methods: Human pancreatic cancer PC-3 cells were incubated under normoxic or hypoxic conditions. YC-1 was added to the media with different concentrations. The HIF-1&agr; protein expression was detected by means of immunocytochemical staining and Western blotting. Semiquantitative reverse transcriptase polymerase chain reaction was used to determine the mRNA expression of HIF-1&agr;, vascular endothelial growth factor (VEGF), and glucose phosphate isomerase (GPI). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect the cells' proliferative vitality and apoptosis. Results: Hypoxic PC-3 cells expressed a higher level of HIF-&agr; protein in nucleus compared with the normoxic controls. When the dose of YC-1 was at 100 &mgr;mol/L, the expression location of HIF-&agr; shifted from nucleus to cytoplasm. Western blotting revealed that YC-1 reduced the level of HIF-1&agr; protein expression, and the inhibitory effect was dose dependent. Moreover, YC-1 dose dependently inhibited mRNA expression levels of VEGF and GPI in hypoxic cells. YC-1 inhibited proliferative vitality and induced apoptosis of hypoxic PC-3 cells in a dose-dependent manner. Conclusions: YC-1 inhibits HIF-1&agr; expression in hypoxic pancreatic cancer cells, which is accompanied by the translocation of HIF-1&agr; from nucleus to cytoplasm, decreased mRNA expression of VEGF and GPI, reduced cell proliferative vitality, and increased apoptosis. These results suggest that HIF-1 is a potential therapeutic target for pancreatic cancer.
Circumvention of Immunity to the Adenovirus Major Coat Protein Hexon

ABSTRACT Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon sequences from a different adenovirus serotype (Ad12). We successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The vector was also capable of transducing the livers of C57BL/6 mice previously immunized with Ad5.
Panitumumab safety for treating colorectal cancer

Introduction: Panitumumab is a human IgG2 mAb against the EGFR, inhibiting tumor cell proliferation, survival and angiogenesis. It has demonstrated clinical efficacy in metastatic colorectal cancer (CRC) in combination with chemotherapy in first- and second-line settings and as monotherapy in third-line setting. Recently, mutations in the RAS genes have been shown to be predictive of lack of efficacy, panitumumab should be restricted to patients with RAS wild-type (wt) tumors. Areas covered: This review focuses on main efficacy results of panitumumab in metastatic CRC in first-, second- and third-line settings in combination with chemotherapy or as monotherapy. Additionally, we have covered safety aspects of this agent in these indications, especially in K-RAS and all RAS wt patients. These safety aspects refer to the most common toxicities (i.e., acne-like skin rash, diarrhea and hypomagnesaemia). Expert opinion: Panitumumab adds to the armamentarium of effective agents in the treatment of metastatic CRC. Due to its human origin, panitumumab is a well-tolerated agent with low rates of infusional reactions. Skin toxicity is frequent and should be pre-emptively treated. Other common toxicities related to panitumumab treatment, such as diarrhea and hypomagnesaemia, should be closely monitored to ensure early treatment or substitution.
[Problems of a physician-patient interaction and control of arterial hypertension in Russia. Main results of scientific-practical program ARGUS-2].

OBJECTIVE To study the problems of physician-patient cooperation, patient- and physician related barrieres to target blood pressure (BP) achievement and to demonstrate improvement of BP control with indapamide SR 1.5 mg, when given to patients remaining uncontrolled while receiving antihypertensive therapy without thiazide diuretics (TD). METHODS The trial Improvement of Arterial Hypertension Control in High-Risk Hypertensive Patients (ARGUS-2) run in 15 Russian centres during the year 2006. Retrospective analysis of medical notes of 684 outpatients and 575 inpatients with arterial hypertension. Validated questionnaires were used for interview of 373 physicians and 1298 patients. The study of Arifon retard efficacy was carried out in 1438 outpatients with difficult-to-control hypertension. RESULTS BP was above the goal level in 97.1% pts at the first analyzed visit to an outpatient department. Antihypertensive therapy was unchanged in 20.5% cases, the drug dose was increased in 46,6%, additional medication was administered in 36,8%. In 30.8% pts antihypertensive agent was substituted by another class drug. At the last analyzed visit target BP was found in 24.4% pts. BP control was poorer in pts with BP goal <130/80 mmHg (20.1%) than in those with higher target BP (25.9%). Achievement of BP goal was associated with combination therapy, higher rate of TD administration and with more frequent visits to physician. During hospitalization target BP <140/<90 mmHg was achieved in 87.1%,<130/<80 mmHg in. 76.2%. Arifon retard administration resulted in target BO achievement in 84.5% patients. Physicians percept low adherence to antihypertensive treatment, lack of patients knowledge about risk related to arterial hypertension, economical problems as main barriers to improvement of arterial hypertension management. Patients considered economical problems related to antihypertensive treatment more much less important than physicians did. CONCLUSION The study results suggest the importance of therapeutic inertia overcome to improve arterial hypertension management in Russia. Low rate of multiple combination therapy and TD prescription are important features of therapeutic inertia. Polar perception of problems related to arterial hypertension by physicians and patients should be considered as influencing factors for educational programs development.
Onset of disability in depressed and non-depressed primary care patients

Background. While cross-sectional and longitudinal studies have consistently found depressive illness and disability to be related, understanding whether depression leads to subsequent onset of disability is limited. Methods. In the context of the multi-centre international WHO Collaborative Study on Psychological Problems in General Health Care, we followed prospectively consulting non-elderly primary care patients who were essentially disability free at baseline but who differed in baseline depression status, comprising 1051 patients free of physical disability at baseline including 14% depression; 914 free of social disability including 9% depression. Depression status was assessed with the CIDI; patient-reported physical disability with the MOS physical functioning scale and social disability with the BDQ role functioning and number of disability days measures; investigator-rated social disability with the Occupational section of Groningen Social Disability schedule; and the treating physicians rated the severity of physical illness. Results. In patients essentially disability free at baseline, depressive illness resulted in a 1·5-fold (at 3 months) and a 1·8-fold (at 12 months) increase in risk of onset of physical disability, after controlling for physical disease severity. Depressive illness also resulted in a 2·2-fold (at 3 months) and a 2·3-fold (at 12 months) increase in risk of onset of social disability, after controlling for physical disease severity, physical disability and onset of physical disability. Conclusions. Among non-elderly primary care patients, depressive illness is associated with onset of physical disability and shows an even stronger association with onset of social disability.
Calcification or dedifferentiation: Requirement to lock mesenchymal stem cells in a desired differentiation stage

A current challenge in mesenchymal stem cell (MSC)‐based cartilage repair is to solve donor and tissue‐dependent variability of MSC cultures and to prevent chondrogenic cells from terminal differentiation like in the growth plate. The aim of this study was to select the best source for MSC which could promise stable cartilage formation in the absence of hypertrophy and ectopic in vivo mineralization. We hypothesized that MSC from synovium are superior to bone marrow‐ and adipose tissue‐derived MSC since they are derived from a joint tissue. MSC were characterized by flow cytometry. MSC pellets were cultured under chondrogenic conditions and differentiation was evaluated by histology, gene expression analysis, and determination of alkaline phosphatase activity (ALP). After chondrogenic induction, pellets were transplanted subcutaneously into SCID mice. MSC from bone marrow, adipose tissue, and synovium revealed similar COL2A1/COL10A1 mRNA levels after chondrogenic induction and were positive for collagen‐type‐X. Bone marrow‐derived and adipose tissue‐derived MSC showed significantly higher ALP activity than MSC from synovium. Low ALP‐activity before transplantation of pellets correlated with marginal calcification of explants. Surprisingly, non‐mineralizing transplants specifically lost their collagen‐type II, but not collagen‐type I deposition in vivo, or were fully degraded. In conclusion, the lower donor‐dependent ALP activation and reduced mineralization of synovium‐derived heterotopic transplants did not lead to stable ectopic cartilage as known from articular chondrocytes, but correlated with fibrous dedifferentation or complete degeneration of MSC pellets. This emphasizes that beside appropriate induction of differentiation, locking of MSC in the desired differentiation state is a major challenge for MSC‐based repair strategies. J. Cell. Physiol. 219: 219–226, 2009. © 2008 Wiley‐Liss, Inc.
Incidences of Selected Lesions in Control Female Harlan Sprague–Dawley Rats from Two-Year Studies Performed by the National Toxicology Program

The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague–Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats (Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats.
Structure-activity studies of conantokins as human N-methyl-D-aspartate receptor modulators.

The activities of conantokin-G (con-G), conantokin-T (con-T), and several novel analogues have been studied using polyamine enhancement of [3H]MK-801 binding to human glutamate-N-methyl-D-aspartate (NMDA) receptors, and their structures have been examined using CD and 1H NMR spectroscopy. The potencies of con-G[A7], con-G, and con-T as noncompetitive inhibitors of spermine-enhanced [3H]MK-801 binding to NMDA receptor obtained from human brain tissue are similar to those obtained using rat brain tissue. The secondary structure and activity of con-G are found to be highly sensitive to amino acid substitution and modification. NMR chemical shift data indicate that con-G, con-G[D8, D17], and con-G[A7] have similar conformations in the presence of Ca2+. This consists of a helix for residues 2-16, which is kinked in the vicinity of Gla10. This is confirmed by 3D structure calculations on con-G[A7]. Restraining this helix in a linear form (i.e., con-G[A7,E10-K13]) results in a minor reduction in potency. Incorporation of a 7-10 salt-bridge replacement (con-G[K7-E10]) prevents helix formation in aqueous solution and produces a peptide with low potency. Peptides with the Leu5-Tyr5 substitution also have low potencies (con-G[Y5,A7] and con-G[Y5,K7]) indicating that Leu5 in con-G is important for full antagonist behavior. We have also shown that the Gla-Ala7 substitution increases potency, whereas the Gla-Lys7 substitution has no effect. Con-G and con-G[K7] both exhibit selectivity between NMDA subtypes from mid-frontal and superior temporal gyri, but not between sensorimotor and mid-frontal gyri. Asn8 and/or Asn17 appear to be important for the ability of con-G to function as an inhibitor of polyamine-stimulated [3H]MK-801 binding, but not in maintaining secondary structure. The presence of Ca2+ does not increase the potencies of con-G and con-T for NMDA receptors but does stabilize the helical structures of con-G, con-G[D8,D17], and, to a lesser extent, con-G[A7]. The NMR data support the existence of at least two independent Ca2+-chelating sites in con-G, one involving Gla7 and possibly Gla3 and the other likely to involve Gla10 and/or Gla14.
Compliance after 17 years of breast cancer screening - Factors associated with reattendance for periodic breast screening

The motives and reasons for regular attendance, irregular attendance and drop-out were studied in women who were enrolled in a biennial breast screening programme in 1975 and who were invited to each subsequent screening round until 1992. Three compliance groups were compared: 'attended all rounds' (group A, n=79), 'missed 1 or 2 rounds' (group B, n=73) and 'missed more than 2 rounds' (group C, n=64). The groups did not differ with respect to background variables such as sociodemographic characteristics, actual health problems or preventive health orientations, but significant differences were found in general attitudes to breast screening and to the organizational aspects of screening procedures. The results suggest that during the course of a screening programme, for a substantial group of not strongly motivated women, the recurring negative aspects of mammography (pain and anxiety) are increasingly becoming a burden. 'Circumstantial factors' like waiting for one's turn, the distance to the screening centre and incidental dissatisfaction with handling by screening staff, appear to trigger the decision to skip screening rounds or to drop out of the programme. From the perspective of maintaining a regular attendance throughout the programme this is an important group. Special efforts must be made to encourage these women to stay in the programme.
Transplantation of BMSCs expressing hVEGF165/hBD3 promotes wound healing in rats with combined radiation‐wound injury

The combined radiation‐wound injury is a refractory wound with decreased number or dysfunction of repairing cells and growth factors. This remains a challenge in clinical practice. The object of this study is to evaluate the therapeutic efficacy of a combination of human vascular endothelial growth factor 165 (hVEGF165) and human beta‐defensin 3 (hBD3) in the treatment of such wounds. A plasmid‐carrying hVEGF165 gene and hBD3 gene was used to transfect rat bone‐marrow‐derived mesenchymal stem cells (BMSCs). The supernatant from the modified BMSCs significantly promoted the proliferation and cell migration of human endothelial cells and it also inhibited the growth of bacteria and fungus, demonstrating the successful expression of the transfected genes. The hVEGF165/hBD3‐modified BMSCs were then injected into the sites of combined radiation‐wound injury on rats. It demonstrated that wound‐healing time was shortened significantly in the treated rats. The granulation tissue formation/maturation, skin appendage regeneration and collagen deposition were also improved significantly. Strong expression of hVEGF165 and hBD3 was detected in the wound surface at early stage of the healing. The results indicate that topical transplantation of hVEGF165/hBD3‐modified BMSCs promoted wound healing, and this gene therapy strategy presents a promising approach in the treatment of refractory wounds such as the combined radiation‐wound injury.