Search

Release of the ATP hydrolysis product ortophosphate (Pi) from the active site of myosin is central in chemo-mechanical energy transduction and closely associated with the main force-generating structural change, the power-stroke. Despite intense investigations, the relative timing between Pi-release and the power-stroke remains poorly understood. This hampers in depth understanding of force production by myosin in health and disease and our understanding of myosin-active drugs. Since the 1990s and up to today, models that incorporate the Pi-release either distinctly before or after the power-stroke, in unbranched kinetic schemes, have dominated the literature. However, in recent years, alternative models have emerged to explain apparently contradictory findings. Here, we first compare and critically analyze three influential alternative models proposed previously. These are either characterized by a branched kinetic scheme or by partial uncoupling of Pi-release and the power-stroke. Finally, we suggest critical tests of the models aiming for a unified picture., (© 2023 The Authors. BioEssays published by Wiley Periodicals LLC.)

Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America., Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury., Study Design: Prospective cohort study., Methods: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus ® RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period., Results: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1β, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFβ), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index., Main Limitations: Samples were collected as soon as possible postinjury (within 30 minutes)., Conclusions: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified., (© 2021 EVJ Ltd.)

Aims and Methods: To facilitate antigenic characterization of the influenza A 2009 pandemic H1N1 [A(H1N1)pdm09] hemagglutinin (HA), we generated a panel of murine monoclonal antibodies (mAbs) using as the immunogen mammalian-derived virus-like particles containing the HA of the A/California/04/2009 virus. The antibodies were specific for the A/California/04/2009 HA, and individual mAbs suitable for use in several practical applications including ELISA, immunofluorescence, and Western blot analysis were identified., Results and Conclusions: As the panel of mAbs included antibodies with hemagglutination inhibition (HI) and virus neutralizing activities, this allowed identification and characterization of potentially important antigenic and neutralizing epitopes of the A/California/04/2009 HA and comparison of those epitopes with the HAs of other influenza viruses including seasonal H1N1 viruses as well as the A/South Carolina/1918 and A/New Jersey/1976 H1N1 viruses. Three mAbs with the highest HI and neutralizing titers were able to provide passive protection against virus challenge. Two other mAbs without HI or neutralizing activities were able to provide partial protection against challenge. HA epitopes recognized by the strongest neutralizing mAbs in the panel were identified by isolation and selection of virus escape mutants in the presence of individual mAbs. Cloned viruses resistant to HI and antibody neutralization were sequenced to identify mutations, and two unique mutations (D127E and G155E) were identified, both near the antigenic site Sa. Using human post-vaccination sera, however, there were no differences in HI titer between A/California/04/2009 and either escape mutant, suggesting that these single mutations were not sufficient to abrogate a protective antibody response to the vaccine., (Published 2012. This article is a US Government work and is in the public domain in the USA.)

Wordom is a versatile, user-friendly, and efficient program for manipulation and analysis of molecular structures and dynamics. The following new analysis modules have been added since the publication of the original Wordom paper in 2007: assignment of secondary structure, calculation of solvent accessible surfaces, elastic network model, motion cross correlations, protein structure network, shortest intra-molecular and inter-molecular communication paths, kinetic grouping analysis, and calculation of mincut-based free energy profiles. In addition, an interface with the Python scripting language has been built and the overall performance and user accessibility enhanced. The source code of Wordom (in the C programming language) as well as documentation for usage and further development are available as an open source package under the GNU General Purpose License from http://wordom.sf.net., (Copyright © 2010 Wiley Periodicals, Inc.)

Objective: We sought to determine the incidence of injury to the cochlea or vestibular system from the use of ototopic antibiotic ear drops., Study Design: We conducted a MEDLINE search of the published literature from 1966 to the present using the search items of "ototopic antibiotics," "ototopic drops," "antibiotic resistance," and others to identify pertinent articles. These articles were reviewed and graded according to evidence quality. Forty-four articles were found; 27 articles were considered appropriate for review and 14 of these articles were thought to warrant further extensive review. The latter 14 articles dealt directly with the evaluation of either hearing loss or changes in vestibular function after the use of ototopic ear drops. We eliminated studies that did not consider hearing or vestibular function. We considered only articles in the English language, eliminating articles that not address the ototoxicity of ototopical ear drops., Results: Most of these articles were in the level 3 to 3b category. Two of the articles were in the 1b category, evaluating evidence-based studies. An article that reviewed case reports of ototopical ototoxicity and a survey article are included in this study, as case reports of ototopical ototoxicity and survey articles., Conclusion: We found a total of 54 cases of gentamicin vestibular toxicity and, in 24 of these patients, cochlear toxicity was also documented. Our review also found 11 cases of cochlear and 2 cases of vestibular toxicity in neomycin-based ear drops.

Objective: The objective of this study was to systematically review the literature on animal ototoxicity from ototopical medications. A secondary objective was to assess the relevance of animal data to the use of ototopical drops in clinical situations involving humans., Study Design: We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed, summarized, and tabulated., Results: One hundred seventy-three articles were reviewed; 61 articles were appropriate to the study question and were further analyzed., Conclusions: Virtually all studies demonstrate that aminoglycoside antibiotics, when applied topically into the middle ear space, are ototoxic in experimental animals.

Objective: There is growing concern over the use of systemic antibiotics and the development of bacterial resistance. The question remains as to whether ototopical medications may also promote antibiotic-resistant organisms, either on a local level (in the ear) or in other areas of the aerodigestive tract. We performed an evidence-based review to answer the following clinical question, "Do antibiotic ototopical medications induce antibiotic resistant organisms?", Study Design: We performed a MEDLINE search of the published literature from 1966 to the present. We used appropriate search terms such as "ototopical antibiotics," "ototopical drops," "antibiotic resistance," "topical antibiotics and otitis externa," "otitis externa and treatment," "otitis externa and antibiotic drops," "otitis externa and ototopical drops," "otitis media," "otitis media and treatment," "otitis media and antibiotic drops," "chronic suppurative otitis media," "chronic suppurative otitis media and treatment," "chronic suppurative otitis media and antibiotic drops," " otitis externa and resistant organisms," "otitis media and resistant organisms," "chronic suppurative otitis media and resistant organisms," "ophthalmic antibiotic drops," "draining ear," "P.E. tube otorrhea," "pressure equalizing tube otorrhea," "pressure equalizing tube otorrhea and treatment," and "pressure equalizing tube otorrhea and ototopical therapy" to identify pertinent articles. These articles were reviewed and graded according to the evidence quality., Results: After an initial screening of over 2,500 articles, 38 articles were analyzed further; of these, 11 were determined to warrant extensive review. Eight articles evaluated chronic suppurative otitis media; 2, otitis externa; and 1, post-tympanostomy tube otorrhea, whereas 3 others studied systemic absorption. Of the 8 chronic suppurative otitis media studies, there were thought to be 5 grade 2B studies, 1 grade 1B study, and 1 grade 2C study. These studies did not demonstrate a propensity for the development of resistant organisms. No study answered the question as to whether resistance to systemic antibiotics might occur in otitis externa., Conclusions: Overall grade B evidence seems to indicate that no significant antibiotic resistance develops from the use of ototopical antibiotic treatment.

Objective: We evaluated hearing outcomes in patients with sudden hearing loss and vestibular schwannoma who underwent a hearing preservation operation for tumor resection in an effort to determine whether a history of sudden sensorineural hearing loss has an impact on subsequent hearing preservation surgery., Methods: Retrospective chart review of 45 patients operated between 1990 and 1998. Patients were divided into "Recovery" (n = 22) and "No Recovery" (n = 23) groups based on preoperative hearing recovery. Hearing preservation was assessed using the AAO-HNS hearing classification system., Results: Measurable hearing was preserved in 73% of patients, with 47% having good postoperative hearing (AAO-HNS Classes A-B). There was no significant difference in hearing outcome from patients presenting with progressive hearing loss (45% Classes A-B). There was also no difference in postoperative hearing between the "Recovery" and "No Recovery" groups., Conclusions: Patients with sudden hearing loss and vestibular schwannoma have the same chance of hearing preservation after tumor removal as those with progressive loss. Preoperative recovery of hearing is not predictive of hearing preservation. Available data support the nerve compression theory as the mechanism of sudden hearing loss in patients with vestibular schwannoma.

Stretch of nerve has been reported to decrease the amplitude of the compound action potential (CAP) with a complete block appearing in approximately 30 minutes. But for the most part, those experiments were carried out in vivo, and it is generally accepted that the failure of responses was due to a closure of vessels supplying the nerve with a resulting ischemia and anoxia. These studies were undertaken to determine if stretch of nerve has effects that are independent of interference with its vascular supply. In the studies, lengths of rat sciatic and dog peroneal nerves were removed and placed in a chamber supplied with oxygen in which their CAPs were continuously elicited and recorded. This in vitro preparation obviated interference with the nerve's metabolism on stretching. We have previously shown that the form change termed 'beading,' appearing within 10 seconds and reversing as quickly on relaxation, can be elicited with tensions of only several grams. We wished to determine if stretch adequate to produce beading could alter CAPs with the same rapidity. Tensions below 2 g had little effect. On applying tensions of 10-100 g, levels well above those needed to bead the fibers, both increases and decreases of CAP amplitude were seen. The changes occurred within 10 seconds of stretch application, the time at which beading arises with stretch. Although the decreases of CAP amplitudes could be accounted for by beading, the degree of CAP change did not correspond to the amount of tension applied. We hypothesize that the constrictions in the beaded fibers increase axial resistivity and diminish local currents so as to block conduction. The lack of an increasing degree of decreased CAP amplitude with increases in tension is ascribed to the inhibition of elongation offered by the collagen fibrils present in nerve. Collagenase applied to nerves allowed a further increase in length, producing a 'hyperbeading,' showing much longer lengths of beading constrictions on stretch. This would further increase axial resistance and is taken to account for the greater decreases of CAP amplitudes seen following collagenase treatment. To account for those cases where increases of CAP amplitude were seen on stretch, we hypothesize that stretch can also cause an increase in the excitability of the nodes. The outcome of stretch in any given nerve would be the resultant of two opposing actions; beading of the internodes causes a decrease of local currents leading to block of CAPs, while an increased excitability of the nodes acts to augment the responses.

Background: This study examined the impact of secondary cytoreductive surgery on survival of patients with recurrent epithelial ovarian carcinoma., Methods: One hundred six patients with a disease free interval (DFI) > 6 months after primary treatment underwent secondary cytoreductive surgery. Multivariate analysis determined which variables influenced the cytoreductive outcome and survival., Results: Eighty-seven patients (82.1%) underwent removal of all visible tumor. The median and estimated 5-year survival for the entire cohort after recurrence was 35.9 months and 28%, respectively. The probability of complete cytoreduction was influenced by the largest size of recurrent tumor (< 10 cm ¿90.0% vs. > 10 cm ¿66.7%; P = 0.003), use of salvage chemotherapy before secondary surgery (chemotherapy given ¿64.3% vs. chemotherapy not given ¿93.8%; P = 0.001), and preoperative Gynecologic Oncology Group performance status (0 ¿100%, 1 ¿91.4%, 2 ¿82.4%, and 3 ¿47.4%; P = 0.001). Survival was influenced by the DFI after primary treatment (6-12 months ¿median, 25.0 months vs. 13-36 months ¿median, 44.4 months vs. > 36 months ¿median, 56.8 months; P = 0.005), the completeness of cytoreduction (visibly disease free ¿median, 44.4 months vs. any residual disease ¿median, 19.3 months; P = 0.007), the use of salvage chemotherapy before secondary surgery (chemotherapy given ¿median, 24.9 months vs. chemotherapy not given ¿median, 48.4 months; P = 0.005), and the largest size of recurrent tumor (< 10 cm ¿median, 37.3 months vs. > 10 cm ¿median, 35.6 months; P = 0.04)., Conclusions: Complete cytoreduction is possible for the majority of patients with recurrent epithelial ovarian carcinoma and maximizes survival if undertaken before salvage chemotherapy. The authors believe a randomized trial should be initiated to confirm these findings., (Copyright 2000 American Cancer Society.)

This study examines the effects of Aloe vera on neurotransmission processes in a well-established invertebrate neuromuscular junction preparation. We studied concentration-response relationships of an Aloe vera extract on excitatory junctional potentials (EJPs) at the opener muscle of the dactyl in the first and second walking limbs of crayfish (Procambarus clarkii and simulans). We observed concentration-dependent depolarizations of the muscle fibre membrane resting potential, depression of EJP amplitudes and an increase in latency to onset of the EJP following electrical stimulation of the isolated excitatory axon in the meropodite. These effects occurred with Aloe concentrations within the 1%-10% (wt-vol) range. Effects of lower concentrations, ranging to a minimum of 0.01% were equivocal. The effects of Aloe were at least partially, and in a majority of cases totally, reversible. EJPs reduced by Aloe could be restored by increasing the nerve stimulation amplitude. This, along with the latency increase, suggests a depression of action potential generation and conduction. The results provide a preliminary characterization of the effects of Aloe vera on the neurotransmission process and suggest that these effects may at least partially account for Aloe's analgesic and antiinflammatory effects. This study shows that the crayfish NMJ preparation should be useful for further elucidating the location(s) and mechanism(s) of action of Aloe on the nervous system., (Copyright 1999 John Wiley & Sons, Ltd.)

Trigeminal neuromas are slow-growing benign tumors representing approximately 10% of all intracranial neuromas and less than 0.5% of all intracranial tumors. Historically, excision of these tumors through traditional neurosurgical routes--including the frontotemporal transsylvian, subtemporal-intradural, subtemporal-transtentorial, or suboccipital approaches--has resulted in an unsatisfactorily high rate of recurrence. In this study we compare contemporary skull base/neurotologic approaches with conventional procedures for trigeminal neuroma extirpation.

We sought to investigate the functional integrity of the auditory nerve in patients with postoperative hearing loss after middle cranial fossa acoustic-tumor removal in a case-series descriptive study. The study setting was a tertiary referral center, a private otologic practice. The study population comprised seven patients who underwent a middle-cranial-fossa approach for unilateral acoustic-tumor resection and sustained postoperative anacusis with an anatomically intact auditory nerve. Four were men and three women; they ranged in age from 30 to 60 years; all underwent surgery between 1990 and 1994 and agreed to return to the center to participate in the study during 1995. Diagnostic electrical promontory stimulation was used to determine the functional integrity of the auditory nerve. Our main outcome measures were the presence or absence of discrete tone perception, electrical threshold, maximum acceptable level and dynamic range, gap detection and temporal difference limen during electrical promontory stimulation. Three of the seven patients demonstrated positive responses to electrical promontory testing (e.g., discrete tone perception). All three were able to perform the gap-detection and temporal difference limen tests. None of the preoperative characteristics was related to performance on promontory stimulation testing. We conclude that the middle cranial fossa approach permits anatomic--and, in some cases, functional auditory-nerve preservation. These data suggest that auditory rehabilitation in some patients who sustain anacusis after the middle cranial fossa approach to acoustic tumors, as in neurofibromatosis 2, may be provided with cochlear implantation.

Many studies have shown enhanced bone apposition to implants coated with hydroxyapatite, but the optimum implant texture, especially in abnormal trabecular bone, is unclear. The purpose of this project was to evaluate the histological and mechanical properties of cylindrical implants with three different surface textures that were placed in the cancellous bone of the distal femur of the rabbit after the production of an inflammatory knee arthritis. The three implant surfaces included a beaded surface (Group A), a beaded surface coated with hydroxyapatite (Group B), and a smooth surface coated with hydroxyapatite (Group C). The right knees of 36 rabbits were injected with carrageenan twice a week for 2 weeks. Then bilateral implantations were performed, with 12 rabbits in each group receiving identical implants in the right and left knees. The rabbits were killed 6 weeks after surgery. Mechanical (push-out test) and histomorphometric analyses were performed to determine the quality and quantity of bone ingrowth. In Group A, there was virtually no direct contact (a 20-60-microm clearance) between the bone and the beaded surfaces. Direct contact between the bone and the implant surfaces was seen in Groups B and C. The thickness and number of trabeculae were smaller on the arthritic side than on the control side for all groups but were not different between groups for either the control or the arthritic side. Mechanical testing showed that the shear strength of the interface was weaker on the arthritic side in all groups. The results suggest that inflammatory arthritis induced by carrageenan may influence the quality of local bone (osteopenic changes) and hence compromise the bone apposition and mechanical stability of the interface between the implant and bone.

This article reviews the mechanisms of bacterial adhesion to biomaterial surfaces and the factors affecting the adhesion. The process of bacterial adhesion includes an initial physicochemical interaction phase (phase one) and a late molecular and cellular interaction phase (phase two), which is a complicated process affected by many factors, including the characteristics of the bacteria themselves, the target material surface, and the environmental factors, such as the presence of serum proteins or bactericidal substances.

Titanium surfaces were coated with bovine serum albumin using carbodiimide, a crosslinking agent. The durability of the coated surfaces and the inhibitory effect of the albumin coating on bacterial adherence were tested in vitro for 20 consecutive days at 37 degrees C in phosphate buffered saline, with intermittent agitation. The results showed that only 10% of the coated bovine serum albumin decayed off the surface during the 20-day incubation period. The inhibition rate of the albumin coating on bacterial adherence remained high (greater than 8.5%) throughout the experiment. The results suggested potential use of this crosslinked albumin coating to reduce bacterial adherence and thus the subsequent possibility of prosthetic or implant infection in vivo.

Using a 1-year prospective design, this study examined the influence of family status variables (family income, parental education, family structure), parenting variables (maternal support and restrictive control), peer support, and neighborhood risk on the school performance of 120 African American junior high school students. In addition to main effects of these variables, neighborhood risk was examined as a moderator of the effects of parenting and peer support. Family status variables were not predictive of adolescent school performance as indexed by self-reported grade point average. Maternal support at Time 1 was prospectively related to adolescent grades at Time 2. Neighborhood risk was related to lower grades, while peer support predicted better grades in the prospective analyses. Neighborhood risk also moderated the effects of maternal restrictive control and peer support on adolescent grades in prospective analyses. These findings highlight the importance of an ecological approach to the problem of academic underachievement within the African American Community.