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Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest [...]

Historically, clavicle fracture repairs have been performed with patients under general anesthesia. However, in the past few years, the combination of an interscalene brachial plexus block and a modified superficial cervical plexus block has been described to provide adequate anesthesia for clavicle fracture surgery, with the added benefit of postoperative analgesia. In March 2013, members of our anesthesiology department began using this block with sedation for a subset of patients undergoing clavicle fracture fixation. This study was a retrospective review of patients who underwent clavicle fracture repair at a single institution between June 2014 and November 2017. The decision on the type of anesthesia (regional vs. general) was made jointly by the patient, anesthesiologist, and surgeon. Demographic data, relevant perioperative times, and intraoperative pain medication consumption were recorded, and comparisons of these variables were made between the regional and general anesthesia groups. A total of 110 patients with 110 fractures were included. Of these patients, 52 received only regional anesthesia with the combined block whereas 58 received general anesthesia with an interscalene brachial plexus block. No major anesthetic-related complications were noted in any patients, and there were no cases in which regional anesthesia had to be converted to general anesthesia because of block failure. The anesthesia start time was significantly longer in the general anesthesia group (29 minutes vs. 20 minutes, P =.022), as was the total case time (164 minutes vs. 131 minutes, P <.001). Patients in the general anesthesia group required significantly more intraoperative fentanyl to be administered (207 μg vs. 141 μg, P =.002). Regional anesthesia using a combined brachial plexus and modified superficial cervical plexus block is a reliable, efficacious technique. The combined block appears to be a reasonable alternative to general anesthesia with an interscalene brachial plexus block, and it may have benefits regarding the anesthesia start time and total case time. [ABSTRACT FROM AUTHOR]

Operating room (OR) efficiency has an impact on surgeon productivity and patient experience. Accuracy of case duration estimation is important to optimize OR efficiency. The purpose of this study was to identify factors associated with inaccurate case time estimates in outpatient hand surgery. A better understanding of these findings may help to improve OR efficiency and scheduling. All outpatient hand surgical cases from 2018 to 2019 were reviewed. Poorly-estimated cases (i.e., poor scheduling accuracy) were defined as those cases where the actual operative time differed from the predicted time by >50% (either quicker by >50% or slower by >50% than the predicted time). The percentages of poorly-estimated cases were analyzed, categorized, and compared by surgeon, procedure type, and scheduled case length. A total of 6,620 cases were identified. Of 1,107 (16.7%) cases with poorly estimated case durations, 75.2% were underestimated. There was no difference in the likelihood of poor estimation related to start time. Well-estimated cases tended to have longer scheduled case duration, but shorter realized case duration and surgical time. Our systems analysis identified specific surgeons and procedures as predictable outliers. Cases scheduled for 15–30 minutes frequently were inaccurate, whereas cases scheduled for 30–45 and 106–120 minutes had accurate estimates. The accuracy of case time estimations in a standard outpatient hand surgery practice is highly variable. Nearly one-fifth of outpatient hand surgery case durations are poorly estimated, and inaccurate case time estimation can be predicted based on surgeon, procedure type, and case time. Maximizing OR efficiency should be a priority for surgeons and hospital systems. With multiple surgeries done per day, the efficiency of the OR has an impact on surgeon productivity and patient experience. [ABSTRACT FROM AUTHOR]

Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice. [ABSTRACT FROM AUTHOR]

Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in everyother- day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice. [ABSTRACT FROM AUTHOR]

Background Total shoulder arthroplasty (TSA) may be associated with substantial blood loss, and some patients require perioperative blood transfusion. Possible blood transfusion methods include predonated autologous blood transfusion, perioperative autologous blood transfusion, and allogeneic blood transfusion (ALBT). The purposes of the present study were to assess the incidence and recent trends over time of blood transfusion in TSA and analyze patient and hospital characteristics that affect the risk of ALBT. Methods This study used national hospital discharge data from the National Inpatient Sample between 2000 and 2009. The data were used to generate the overall blood transfusion rate, and linear regression was used to assess trends in transfusion patterns over time. Logistic regression analysis was performed to analyze which patient and hospital characteristics independently influence the likelihood that a given patient undergoes ALBT. Results The overall blood transfusion rate (ie, the proportion of patients who received at least 1 transfusion of any kind) was 6.7%. This rate increased over time, from 4.9% in 2000 to 7.1% in 2009 ( P < .001). Risk factors associated with ALBT included age, gender, race, insurance status, hospital region, and hospital annual caseload. Conclusions The increase in overall blood transfusion rate in TSA found in the present study may be related to factors specific to TSA, such as the introduction of reverse total shoulder arthroplasty during the study period. A variety of patient and hospital characteristics contribute to the risk of undergoing ALBT. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2α (eIF2α) at serine 51. Increased phosphorylation of eIF2α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an eIF2αS51A knock-in line that expresses the nonphosphorylatable eIF2α variant eIF2αS51A. Behavioral assessment of the resulting mice revealed motor and cognitive deficits in 5xFAD mice that were, with the possible exception of locomotor hyperactivity, not restored by the eIF2αS51A allele. Telemetric intracranial EEG recordings revealed no measurable effects of the eIF2αS51A allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the eIF2αS51A allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2α to emerge; they also show that heterozygosity for the nonphosphorylatable eIF2αS51A allele has limited effects on 5xFAD-related disease manifestations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2α (eIF2α) at serine 51. Increased phosphorylation of eIF2α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an eIF2α(S51A) knock-in line that expresses the nonphosphorylatable eIF2α variant eIF2α(S51A). Behavioral assessment of the resulting mice revealed motor and cognitive deficits in 5xFAD mice that were, with the possible exception of locomotor hyperactivity, not restored by the eIF2α(S51A) allele. Telemetric intracranial EEG recordings revealed no measurable effects of the eIF2α(S51A) allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the eIF2α(S51A) allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2α to emerge; they also show that heterozygosity for the nonphosphorylatable eIF2α(S51A) allele has limited effects on 5xFAD-related disease manifestations.