Miracle-dz/UniFAR-FTUs huggingface dataset:
MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential

ABSTRACT During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption. Therefore, a pseudo-MMP (PMMP) was formed via maintenance of exogenous positive charges. Proton backflow was severely impaired, leading to a decrease in ATP production and an increase in AMP production. Excess AMP activates AMP kinase, which inhibits the MTOR (mechanistic target of rapamycin) pathway and induces macroautophagy/autophagy. Therefore, we conclude that MitoQ increases PMMP via proton displacement with exogenous positive charges. In addition, PMMP triggered autophagy in hepatocellular carcinoma HepG2 cells via modification of mitochondrial bioenergetics pathways.
Rapid transport of neural intermediate filament protein

Peripherin is a neural intermediate filament protein that is expressed in peripheral and enteric neurons, as well as in PC12 cells. A determination of the motile properties of peripherin has been undertaken in PC12 cells during different stages of neurite outgrowth. The results reveal that non-filamentous, non-membrane bound peripherin particles and short peripherin intermediate filaments, termed `squiggles', are transported at high speed throughout PC12 cell bodies, neurites and growth cones. These movements are bi-directional, and the majority require microtubules along with their associated molecular motors, conventional kinesin and cytoplasmic dynein. Our data demonstrate that peripherin particles and squiggles can move as components of a rapid transport system capable of delivering cytoskeletal subunits to the most distal regions of neurites over relatively short time periods.
Intramedullary Fixation of Unstable Intertrochanteric Hip Fractures: One or Two Lag Screws

Objective To compare the screw sliding characteristics and biomechanical stability of four-part intertrochanteric hip fractures stabilized with an intramedullary nail using either one large-diameter lag screw (intramedullary hip screw [IMHS]; Smith & Nephew, Memphis, TN) or two small-diameter lag screws (trochanteric antegrade nail [TAN]; Smith & Nephew, Memphis, TN). Design Laboratory investigation using eight matched pairs of cadaveric human femurs with simulated, unstable intertrochanteric hip fractures. Intervention One femur of each matched pair was stabilized with an IMHS intramedullary nail, and the other was stabilized with a TAN intramedullary nail. Femurs were statically, then cyclically loaded on a servohydraulic materials testing machine. Finally, all specimens were loaded to failure. Main Outcome Measures Screw sliding and inferior and lateral head displacements were measured for applied static loads from 500N to 1250N. The same measurements were obtained before and after cyclically loading the specimens at 1250N. Ultimate failure strength of the implant constructs also was determined. Results There was no significant difference between the TAN and IMHS in static or cyclical loading with respect to screw sliding or inferior and lateral head displacements. There was a statistically significant difference (P < 0.02) in failure strength, with the IMHS construct failing at an average of 2162N and the TAN construct failing at an average of 3238N. Conclusion The two constructs showed equivalent rigidity and stability in all parameters assessed in elastic and cyclical tests. The TAN had a greater ultimate failure load.
Comparison of serum immunofixation electrophoresis and free light chain assays in the detection of monoclonal gammopathies.

BACKGROUND Diagnosis of monoclonal gammopathies (MGs) is determined by demonstration of a monoclonal immunoglobulin molecule or chain in serum and/or urine. Previous results on immunofixation electrophoresis (IFE) and quantitative free light chain (FLC) measurements have been conflicting. PATIENTS AND METHODS The purpose of this study was to compare IFE with serum FLC assays in the detection of MG. Between November 2006 and November 2007, results on routinely ordered serum IFE specimens were compared with independently conducted FLC assays. RESULTS Monoclonal gammopathies were identified in 144 specimens by IFE; 73 patients (50.7%) had a normal kappa/lambda ratio in the FLC assay. Also, 44.6% of samples with IgG and IgA M-proteins had a normal kappa/lambda ratio. Of 357 sera that showed no M-protein by IFE, 95.8% exhibited a normal kappa/lambda ratio. Out of 11 patients with light chain disease, 9 had abnormal kappa/lambda ratios. It is unclear why half of the patients with MG by IFE had normal kappa/lambda ratios. Lower M-components in these patients suggested that some had monoclonal gammopathy of undetermined significance. CONCLUSION For screening purposes, serum IFE should be carried out in patients with suspected MG.
Stem and leaf anatomy of three taxa in Lamiaceae

Stem and leaf anatomy of Origanum rotundifolium Boiss. , O. vulgare L. ssp. viride (Boiss.) Hayek, Teucrium hircanum L. , belonging to Lamiaceae were characterized and compared. Some important differences were determined in the taxa. In addition, trichome diversity was investigated by light microscopy and three main types of trichomes (peltate, capitate glandular and non-glandular) were observed in three taxa. DOI: http://dx.doi. org/10.3329/bjb.v43i3. 21612 Bangladesh J. Bot. 43 (3): 345-352, 2014 (December)
Health Care-Based Interventions for Women Who Have Experienced Sexual Violence

Thirty publications that evaluated health care-based interventions for women who experienced sexual violence were reviewed. The findings highlight that clinicians often need training in the provision sexual assault care, and that not all emergency departments have sexual assault care protocols. Studies examining effectiveness found that Sexual Assault Nurse Examiner programs are very helpful, that health care-based sexual assault treatment settings attract more women than do forensic-based settings, that sexual assault survivors often prefer a combination of medication and counseling treatment, and that preexam administration of a video explaining the collection of forensic evidence may reduce women's stress during the procedure. Studies on postexposure HIV prophylaxis found that many women did not complete the treatment regimen, often because of side effects. Emergency contraception to prevent postrape pregnancy is not consistently offered to women. Only one study reported on abortion as part of the range of sexual assault services.
Efficacy of High Doses of Levofloxacin in Experimental Foreign-Body Infection by Methicillin-Susceptible Staphylococcus aureus

ABSTRACT Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of experimental foreign-body infection by Staphylococcus aureus. The antimicrobial efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves) for logarithmic- and stationary-phase bacteria was compared with the in vivo efficacy. In vitro bactericidal activity at clinically relevant concentrations was reached by all drugs except rifampin and linezolid in the log-phase studies but only by levofloxacin in the stationary-phase studies. The bacterial count decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100 mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls, respectively, were: −1.24, −2.26, −2.1, −1.56, −1.47, −1.15, and 0.33 (all groups versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the concentration-time curve/MIC ratio, 234) was the most active therapy (P = 0.03 versus linezolid). Overall, in vivo efficacy was better predicted by stationary-phase studies, in which it reached a high correlation coefficient even if the rifampin group was excluded (r = 0.96; P < 0.05). Our results, including in vitro studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial efficacy in experimental infection, provide good evidence to support the use of levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for treating patients with orthopedic prosthesis infections.
Prevention of Perioperative Myocardial Infarction

Perioperative myocardial infarction (PMI) remains a significant clinical problem in modern medical practice. In the current decade, it is estimated that of the 27 million patients undergoing anesthesia annually in the United States, approximately 50,000 will suffer PMI. In addition, because the prevalence of cardiovascular disease increases with age and because the number of noncardiac surgical procedures performed in older patients is projected to increase from the current 6 million to nearly 12 million per year over the next 30 years, the incidence of PMI is likely to increase in future decades. Moreover, it is estimated that as many as 50% of PMIs are clinically unrecognized. The consequences of PMI are significant: patients experiencing a myocardial infarction (MI) have a hospital mortality rate of 15% to 25%, and nonfatal PMI is an independent risk factor for cardiovascular death in the 6 months after surgery. Although these statistics are daunting, accumulating evidence indicates that the risk-adjusted incidence of PMI can be reduced. The recent inclusion of cardiovascular complications as one of the ‘‘preventable complications’’ modules in the Surgical Care Improvement Project provides an additional mandate for healthcare institutions to find solutions to this problem. In this article, we provide a
The incidence of non‐melanocytic skin cancers in an Australian population: results of a five‐year prospective study

Two thousand, six hundred and sixty‐nine persons who were aged 40 years and older attended for examination of the light‐exposed areas of the head and neck, forearms and dorsa of the hands during a skin‐cancer survey of the population of Maryborough, which was conducted annually for five years from 1982‐1986 inclusive. Sixty (2.25%) persons —12 persons each with a squamous‐cell carcinoma and 48 persons with a total of 51 basal‐cell carcinomas — had at least one non‐melanocytic skin cancer at the first examination. One thousand, nine hundred and eighty‐one (74% of the study population) persons were seen on more than one occasion, which allowed for 6288 person‐years of follow‐up for the determination of the incidence of new cancers. The findings showed a calculated minimal age‐standardized incidence rate of 873 non‐melanocytic skin cancers/100 000 population each year. The minimal incidence rate for basal‐cell carcinomas was 672 cases/100 000 population each year and for squamous‐cell carcinomas was 201 cases/100 000 population each year. The rate ratio of the incidence of basal‐cell carcinomas to that of squamous‐cell carcinomas was 3.34 to one. Age, sex, skin reaction to sunlight and occupation all were significant factors in the determination of the risk of developing non‐melanocytic skin cancers. The enormous costs that are involved in the treatment of non‐melanocytic skin cancers and related lesions suggest that more time, effort and money need to be spent to reduce what has become a major public‐health problem in Australia. (Med J Aust 1989; 150: 475‐478)
Structural Aspects of Congo Red as an Inhibitor of Protease‐Resistant Prion Protein Formation

Abstract: Congo red (CR) has been shown to inhibit the accumulation in scrapie‐infected cells of prion protein (PrP) in the abnormal protease‐resistant form (PrP‐res). However, it was not clear if this effect was due to a direct interaction of CR with either PrP‐res or its protease‐sensitive precursor (PrP‐sen) or to a less direct effect on living cells. Here we show that CR inhibits PrP‐res formation in a simple cell‐free reaction composed predominantly of purified PrP‐res and PrP‐sen. Structurally modified CR analogues were also compared in both the cell‐free conversion reaction and scrapie‐infected neuroblastoma cells. Methylation of the central phenyl groups at the 2,2′ positions diminished the inhibitory potency by ≥10‐fold. In contrast, there was little effect of 3,3′ methylation of the phenyls, deletion of one phenyl, or addition of an amido group between the phenyls. The relative activities of these compounds were well correlated in both cellular and acellular systems. Molecular modeling indicated that CR and 3,3′‐methyl‐CR have little rotational restriction about the biphenyl bond and can readily adopt a planar conformation, as can phenyl‐CR and amido‐CR. In contrast, 2,2′‐methyl‐CR is restricted to a nonplanar conformation of the biphenyl group. Thus, planarity and/or torsional mobility of the central phenyl rings of CR and its analogues is probably important for inhibition of PrP‐res formation. On the other hand, variations in the intersulfonate distance in these molecules had little effect on PrP‐res inhibition. These results indicated a high degree of structural specificity in the inhibition of PrP‐res formation by CR and related compounds.
Downregulation of protease‐activated receptor‐1 in human lung fibroblasts is specifically mediated by the prostaglandin E2 receptor EP2 through cAMP elevation and protein kinase A

Many cellular functions of lung fibroblasts are controlled by protease‐activated receptors (PARs). In fibrotic diseases, PAR‐1 plays a major role in controlling fibroproliferative and inflammatory responses. Therefore, in these diseases, regulation of PAR‐1 expression plays an important role. Using the selective prostaglandin EP2 receptor agonist butaprost and cAMP‐elevating agents, we show here that prostaglandin (PG)E2, via the prostanoid receptor EP2 and subsequent cAMP elevation, downregulates mRNA and protein levels of PAR‐1 in human lung fibroblasts. Under these conditions, the functional response of PAR‐1 in fibroblasts is reduced. These effects are specific for PGE2. Activation of other receptors coupled to cAMP elevation, such as β‐adrenergic and adenosine receptors, does not reproduce the effects of PGE2. PGE2‐mediated downregulation of PAR‐1 depends mainly on protein kinase A activity, but does not depend on another cAMP effector, the exchange protein activated by cAMP. PGE2‐induced reduction of PAR‐1 level is not due to a decrease of PAR‐1 mRNA stability, but rather to transcriptional regulation. The present results provide further insights into the therapeutic potential of PGE2 to specifically control fibroblast function in fibrotic diseases.
Design and Evaluation of Recirculating Water Systems for Maintenance and Propagation of Freshwater Mussels

Abstract A complete system for culturing, rearing, and holding juvenile and adult freshwater mussels (Unionidae) was designed and evaluated for use at hatcheries and research facilities. The system includes air delivery, water conditioning and delivery, algal culturing and automated algal feed delivery, and air-driven water-recirculating units. These systems are appropriate for holding and conditioning adult mussels for spawning, as well as for the grow-out phase of juvenile rearing. In a 41-d trial without water changes in 350-L water-recirculating units, we used 200 adult eastern elliptios Elliptio complanata (average biomass = 1.36 g dry weight/L); mean values (mg/L) during the trial were 0.02 for NH3, 0.01 for NO2, and 2.7 for NO3. An 8-L minirecirculating water unit (MRU) also was designed and evaluated for initial culturing of newly metamorphosed juvenile mussels. Survival of juvenile wavy-rayed lampmussels Lampsilis fasciola cultured in the MRU was 27.2% at 2 weeks, but this survival was negatively.
Comparison of postoperative pain management using two patient-controlled analgesia methods: nursing perspective.

AIM To compare the effect of fentanyl iontophoretic transdermal system and morphine intravenous patient-controlled analgesia on the time-efficiency and convenience of postoperative patient care. BACKGROUND Intravenous patient-controlled analgesia with morphine is effectively used to manage postoperative pain; however, it takes time to set up and administer. METHODS Nurses evaluated patient-care tasks with fentanyl iontophoretic transdermal system and/or morphine intravenous patient-controlled analgesia in two phase IIIb studies (n = 1305) using a nurse ease-of-care questionnaire. A responder for time-efficiency and convenience responded with one of the top three positive choices on all items; for satisfaction, a responder chose one of the top two positive choices on both items. Data were collected between March 2004 and April 2005. FINDINGS In both studies, greater proportions of nurses were responders for fentanyl iontophoretic transdermal system than for morphine intravenous patient-controlled analgesia, respectively, for time-efficiency [total hip replacement surgery, 80.9% (250/309) vs. 57.7% (172/298), P < 0.001; abdominal/pelvic surgery, 84.8% (162/191) vs. 57.7% (113/196), P < 0.001], convenience [total hip replacement surgery, 85.5% (271/317) vs. 64.1% (191/298), P < 0.001; abdominal/pelvic surgery, 89.2% (166/186) vs. 62.8% (123/196), P < 0.001], and satisfaction [total hip replacement surgery, 66.6% (247/371) vs. 33.3% (108/324), P < 0.001; abdominal/pelvic surgery, 67.4% (155/230) vs. 38.2% (84/220), P < 0.001]. Higher proportions of nurses favoured fentanyl iontophoretic transdermal system than morphine intravenous patient-controlled analgesia in both studies (P < 0.001). CONCLUSION The fentanyl iontophoretic transdermal system appears to be simpler, easier to use, and more satisfactory for nurses than morphine intravenous patient-controlled analgesia.
The Use of Outpatient Parenteral Antimicrobial Therapy in the Management of Osteomyelitis: Data from the Outpatient Parenteral Antimicrobial Therapy Outcomes Registries

Because osteomyelitis requires lengthy parenteral antibiotic treatment in patients who are often otherwise healthy, it lends itself well to outpatient parenteral antibiotic therapy (OPAT). Four delivery models for OPAT are (1) self-administration at home, (2) administration by a visiting nurse in the home, (3) infusion center and (4) nursing home. Patient selection is critical to the success of any OPAT program. Clinical and microbiologic data were compiled for more than 500 osteomyelitis patients reported in a registry of OPAT cases in the United States. The most commonly isolated pathogen was Staphylococcus aureus. The antibiotics used most frequently were vancomycin and ceftriaxone. Of 255 patients assessed for bacteriologic outcome, 2 patients developed infection with a new organism and 2 failed to eliminate the causative organism by the end of OPAT therapy. Of 266 patients who were assessed for clinical outcome, 259 improved and 7 failed. Data collected by the OPAT Outcomes Registry confirms that osteomyelitis can be safely and effectively treated with intravenous antibiotics outside the hospital.
Management of Closed Diaphyseal Humerus Fractures in Patients With Injury Severity Score ≥17

Objectives: The management of closed diaphyseal humerus fractures in the polytrauma patient varies widely. The aim of this study was to compare outcomes of operative and nonoperative management in this patient population. Design: Single-center, retrospective cohort analysis. Setting: Urban, Level 1 trauma center. Patients: Seventy-one patients with closed diaphyseal humerus fractures, and Injury Severity Score (ISS) of ≥17, treated between 2006 and 2011 were identified. Intervention: Patients were treated operatively versus nonoperatively with a functional brace by surgeon preference. Main Outcomes: Primary outcome was union. Secondary outcomes included time to union, time to release to weightbearing, and complications other than nonunion. Results: There was no statistical difference between age, Injury Severity Score, or fracture type between the 2 cohorts. There was a statistically higher incidence of associated orthopaedic injury, and more specifically, lower extremity injury in the group treated with operative intervention. There was no difference in union rates (95% operative, 94% nonoperative), time to union (17 weeks operative, 15 weeks nonoperative), or complication rates between the 2 groups. Time to release to weightbearing was 3 weeks shorter in the operative group (9.3 weeks operative, 12.8 weeks nonoperative). Conclusions: Polytrauma patients with closed diaphyseal humerus fractures can be treated successfully with equivalent union rates, time to union, and complication rates when selected for conservative management techniques. The decision to undertake operative management of closed diaphyseal humerus fractures in the polytraumatized patient is multifaceted and should consider patient expectations, demographics, injury profile, and ambulatory status. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
eview volutionary functions of early social modulation of ypothalamic-pituitary-adrenal axis development in humans ark

The hypothalamic-pituitary-adrenal axis (HPAA) is highly responsive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Here we review the hypothesis that large brains, an extended childhood and intensive family care in humans are adaptations resulting from selective forces exerted by the increasingly complex and dynamic social and cultural environment that co-evolved with these traits. Variations in the modulation of stress responses mediated by specific HPAA characteristics (e.g., baseline cortisol levels, and changes in cortisol levels in response to challenges) are viewed as phenotypically plastic, ontogenetic responses to specific environmental signals. From this perspective, we discuss relations between physiological stress responses and life history trajectories, particularly the development of social competencies. We present brief summaries of data on hormones, indicators of morbidity and social environments from our long-term, naturalistic studies in both Guatemala and Dominica. Results indicate that difficult family environments and traumatic social events are associated with temporal elevations of cortisol, suppressed reproductive functioning and elevated morbidity. The long-term effects of traumatic early experiences on cortisol profiles are complex and indicate domain-specific effects, with normal recovery from physical stressors, but some heightened response to negative-affect social challenges. We consider these results to be consistent with the hypothesis that developmental programming of the HPAA and other neuroendocrine systems associated with stress responses may facilitate cognitive targeting of salient social challenges in specific environments. © 2011 Elsevier Ltd. All rights reserved.