Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been ...linked to the inheritable, or familial, form of ALS, much less is known about the cause(s) of sporadic ALS, which accounts for ~90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1) protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a "toxic conformation" that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.
Chicken meat is rich in unsaturated fatty acids. Therefore, it is more susceptible to lipid oxidation and production of volatile organic compounds (VOC). In this study, we evaluated the fatty acids, ...antioxidants, and VOC profiles of raw and cooked meat samples derived from 4 strains of chicken differing in their growth rates, which were as follows: slow-growing (SG, Leghorn), medium-growing (MG, Hubbard and Naked Neck), and fast-growing (FG, Ross). The VOC profile of meat was measured using proton-transfer reaction–mass spectrometry (PTR–MS). The VOC were identified using PTR–time of flight-MS (PTR-ToF-MS). The data were analyzed using both univariate and multivariate models. Twenty main VOC were identified, which were classified into the following chemical categories: aldehydes, alkadienes, alkenes, furans, amides, alcohols, and other compounds. Our results revealed that the chicken genotype and the method of cooking strongly influenced the VOC profile of the meat. Identifying the relationships between these traits allowed us to highlight the trade-off of the main substrates such as n-3 and n-6 polyunsaturated fatty acids (PUFA), protective substances (antioxidants), and degradation products (VOC) of the poultry meat produced during cooking. The extent of VOC production and n-3 loss was found to be higher for the SG genotype. Reduction of n-6 was higher in MG, whereas small losses in antioxidants and PUFA were observed in the FG genotype, consequently, resulting in the lowest production of VOC. The SG and MG are genotypes more active from a kinetic point of view respect to the FG ones. For this reason, in the FG genotypes, the antioxidants are less involved in the oxidative stress induced by the movement; thus, they were available to protect the lipid of the meat during the cooking process. These results suggested that the use of SG and MG genotypes requires a specific dietary protocol (i.e., increasing the antioxidants content) to counteract the lipid oxidations in all the phases: in vivo, postmortem, and during/after cooking.
Summary
The natural fecundity of suids, great ability to adapt to new habitats and desire for local hunting opportunities leading to translocation of feral pigs to regions where they are not yet ...established have all been instrumental in the home range expansion of feral swine. Feral swine populations in the United States continue to expand, wreaking havoc on agricultural lands, further compromising threatened and endangered species, and posing a microbiological threat to humans, domestic livestock and companion animals. This manuscript thoroughly reviews zoonotic diseases of concern including brucellosis, bovine tuberculosis, leptospirosis, enteric pathogens, both Salmonella spp. and shiga toxin‐producing Escherichia coli, and hepatitis E. These pathogens are not a comprehensive list of microbes that are capable of infecting both humans and feral swine, but rather have been selected as they are known to infect US feral swine, direct transmission between wild suids and humans has previously been documented, or they have been shown to be readily transmitted during processing or consumption of feral swine pork. Humans that interact directly or indirectly with feral swine are at much higher risk for the development of a number of zoonotic pathogens. Numerous case reports document transmission events from feral swine and wild boar to humans, and the resulting diseases may be mild and self‐limiting, chronic or fatal. Individuals that interact with feral swine should take preventative measures to minimize the risk of disease transmission and all meat should be thoroughly cooked. Additionally, public health campaigns to increase knowledge of the risks associated with feral swine are imperative.
Abstract Background In 2011 Medicare initiated a Bundled Payment for Care Improvement (BPCI) program with the goal of introducing a payment model that would “lead to higher quality, more coordinated ...care at a lower cost to Medicare.” Methods A Model 2 bundled payment initiative for Total Joint Replacement (TJR) was implemented at a large, tertiary, urban academic medical center. The episode of care includes all costs through 90 days following discharge. After one year, data on 721 Medicare primary TJR patients were available for analysis. Results Average length of stay (LOS) was decreased from 4.27 days to 3.58 days (Median LOS 3 days). Discharges to inpatient facilities decreased from 71% to 44%. Readmissions occurred in 80 patients (11%), which is slightly lower than before implementation. The hospital has seen cost reduction in the inpatient component over baseline. Conclusion Early results from the implementation of a Medicare BPCI Model 2 primary TJR program at this medical center demonstrate cost-savings. Level of Evidence IV economic and decision analyses—developing an economic or decision model
Retrospective review of medical records.
We reviewed all early readmissions after elective spine surgery at a single orthopedic specialty hospital to analyze the causes of unplanned readmissions.
...Recent advances in techniques and instrumentation have made more complex spinal surgeries possible, although sometimes with more complications. Early readmission rate is being used as a marker to evaluate quality of care. There is little data available regarding the causes of early readmissions after spine surgery.
Using the hospital's administrative database of patient records from 2007 to 2009, all patients who underwent spine surgery and were readmitted to the hospital within 30 days were identified and broadly categorized as planned (a staged or rescheduled procedure or a direct transfer) or unplanned. Unplanned readmissions were defined to have occurred as a result of either a surgical or a nonsurgical complication. Analysis was focused on 12 common spine procedures based on the principle procedure International Classification of Diseases, Ninth Revision, Clinical Modification code for the patient's initial admission. The readmission rate was calculated for each procedure.
A total of 156 early readmissions were identified, of which 141 were unplanned. Of the unplanned readmissions, the most common causes were infection or a concern for an infection (45 patients, 32% of unplanned readmissions), nonsurgical complications (31 patients, 22% of readmissions), complications requiring surgical revision (21 patients, 15% of readmissions), and wound drainage (12 patients, 9% of readmissions). Fifty-seven percent of unplanned readmissions required a return to the operating room (76% of infections or concern for infection). The average length of stay for the unplanned readmissions was 6.5 days. When using the 12 most common procedures based on the International Classification of Diseases, Ninth Revision, Clinical Modification, the early readmission rate was 3.8% (141 early readmissions in 3673 procedures).
Infection, medical complications after surgery, and surgical complications requiring revision of implants are the primary causes of unplanned early readmissions and spine surgery. Further studies are necessary to identify patients and procedures most associated with readmission.
Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable ...modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties similar to familial ALS-linked mutant SOD1, perhaps through posttranslational modifications. Using patients’ lymphoblasts, we show here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates mutant SOD1-like properties and damages mitochondria by forming a toxic complex with mitochondrial Bcl-2. This study conclusively demonstrates the existence of an iper-oxidized SOD1 with toxic properties in patient-derived cells and identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers to subclassify ALS and devise SOD1-based therapies that go beyond the small group of patients with mutant SOD1.
Abstract The Centers for Medicare and Medicaid Services has proposed bundling of payments for acute care episodes for certain procedures, including total joint arthroplasty. The purpose of this study ...is to quantify the readmission burden of TJA as a function of readmission rate and reimbursement for the bundled payment. Using the hospital’s administrative database, we identified all unplanned 30-day readmissions following index admissions for total hip and total knee arthroplasty, and revision hip and knee arthroplasty among Medicare beneficiaries from 2009 to 2012. For each group, we determined 30-day readmission rates and direct costs of each readmission. The hospital cost margins for Medicare TJAs are small and any decrease in these margins can potentially make performing these procedures economically unfeasible potentially decreasing Medicare patient access.
The kinematic parameters of reach-to-grasp movements are modulated by action intentions. However, when an unexpected change in visual target goal during reaching execution occurs, it is still unknown ...whether the action intention changes with target goal modification and which is the temporal structure of the target goal prediction. We recorded the kinematics of the pointing finger and wrist during the execution of reaching movements in 23 naïve volunteers where the targets could be located at different directions and depths with respect to the body. During the movement execution, the targets could remain static for the entire duration of movement or shifted, with different timings, to another position. We performed temporal decoding of the final goals and of the intermediate trajectory from the past kinematics exploiting a recurrent neural network. We observed a progressive increase of the classification performance from the onset to the end of movement in both horizontal and sagittal dimensions, as well as in decoding shifted targets. The classification accuracy in decoding horizontal targets was higher than the classification accuracy of sagittal targets. These results are useful for establishing how human and artificial agents could take advantage from the observed kinematics to optimize their cooperation in three-dimensional space.
Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a ...conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To compare the respiratory syncytial virus (RSV)-related hospitalization rate, hospital length of stay (LOS), and need for assisted ventilation in children aged <2 years with Down syndrome and those ...without Down syndrome.
MEDLINE, Embase, and CINAHL databases were searched from inception up to December 2017. Studies that provided data on RSV-related hospitalization in children aged <2 years with Down syndrome and those without Down syndrome were included. Data were independently extracted in pairs by 2 reviewers and synthesized with random-effects meta-analysis.
In 10 studies including a total of 1 748 209 children, 12.6% of the children with Down syndrome (491 of 3882) were hospitalized with RSV infection. The presence of Down syndrome was associated with a significantly higher risk of RSV-related hospitalization (relative risk RR, 6.06; 95% CI, 4.93-7.45; I2 = 65%; Grading of Recommendations, Assessment, Development and Evaluation GRADE, moderate). RSV-related LOS (mean difference, 2.11 days; 95% CI, 1.47-2.75 days; I2 = 0%; GRADE, low), and the need for assisted ventilation (RR, 5.82; 95% CI, 1.81-18.69; I2 = 84%; GRADE, low). Children with Down syndrome without congenital heart disease (RR, 6.31; 95% CI, 4.83-8.23; GRADE, moderate) also had a significantly higher risk of RSV-related hospitalization. The risk of RSV-related hospitalization remained significant in the subgroup of children aged <1 year (RR, 6.25; 95% CI, 4.71-8.28; GRADE, high).
RSV-related hospitalization, hospital LOS, and the need for assisted ventilation are significantly higher in children with Down syndrome aged <2 years compared with those without Down syndrome. The results should prompt reconsideration of the need for routine RSV prophylaxis in children with Down syndrome up to 2 years of age.
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