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To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. Retrospective cohort study. A large multi-site health system with hospitals across the United States. Patients: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. None. Between May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71–2.20) or multivariable analysis (OR 1.34, 95% CI 0.68–2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37–16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74–12.18, p < 0.001). There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is a neurologic emergency, requiring rapid recognition and treatment with intravenous thrombolysis. Since the publication of the 2019 American Heart Association/American Stroke Association Guidelines that recommend tenecteplase as an alternative agent, several centers across the United States are transitioning from alteplase to tenecteplase as the agent of choice for thrombolysis in acute ischemic stroke. Our health system transitioned to tenecteplase for the treatment of acute ischemic stroke in 2021 due to increasing evidence for efficacy and potential for improved door-to-needle time. Herein we describe our experience and provide guidance for other institutions to implement this change. Emergency nurses are vital to the care of acute ischemic stroke patients. There are several pharmacologic and logistical differences between alteplase and tenecteplase for this indication. This paper outlines these key differences. [ABSTRACT FROM AUTHOR]

Animals live in habitats fraught with a range of environmental challenges to their bodies and brains. Accordingly, cells and organ systems have evolved stress-responsive signaling pathways that enable them to not only withstand environmental challenges but also to prepare for future challenges and function more efficiently. These phylogenetically conserved processes are the foundation of the hormesis principle, in which single or repeated exposures to low levels of environmental challenges improve cellular and organismal fitness and raise the probability of survival. Hormetic principles have been most intensively studied in physical exercise but apply to numerous other challenges known to improve human health (e.g., intermittent fasting, cognitive stimulation, and dietary phytochemicals). Here we review the physiological mechanisms underlying hormesis-based neuroplasticity and neuroprotection. Approaching natural resilience from the lens of hormesis may reveal novel methods for optimizing brain function and lowering the burden of neurological disorders. In this review, Mattson and Leak discuss challenges that can improve brain function (e.g., exercise, fasting, and cognitive stimulation) and mechanisms that underlie hormesis-based neuroplasticity and neuroprotection. They consider how through the lens of hormesis, we may discover new ways to optimize brain health and lower the burden of neurological disorders. [ABSTRACT FROM AUTHOR]

Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018–2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study. [ABSTRACT FROM AUTHOR]

Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made. [ABSTRACT FROM AUTHOR]

We aimed to examine the concurrent associations of gender-affirming hormonal interventions (i.e., puberty blockers, testosterone, estrogen), as well as family and friend social support, on transgender and nonbinary (TNB) adolescents' reports of anxiety symptoms, depressive symptoms, nonsuicidal self-injury (NSSI), and suicidality. We hypothesized that gender-affirming hormonal interventions and greater social support would be associated with lower levels of mental health concerns. Participants (n = 75; aged 11–18; M age = 16.39 years) were recruited for this cross-sectional study from a gender-affirming multidisciplinary clinic. Fifty-two percent were receiving gender-affirming hormonal interventions. Surveys assessed anxiety and depressive symptoms, NSSI and suicidality in the past year, and social support from family, friends, and significant others. Hierarchical linear regression models examined associations between gender-affirming hormonal interventions and social support (i.e., family, friend) with mental health while accounting for nonbinary gender identity. Regression models explained 15%–23% of variance in TNB adolescents' mental health outcomes. Gender-affirming hormonal interventions were associated with fewer anxiety symptoms (β = −0.23; p <.05). Family support was associated with fewer depressive symptoms (β = −0.33; p =.003) and less NSSI (β = −0.27; p =.02). Friend support was associated with fewer anxiety symptoms (β = −0.32; p =.007) and less suicidality (β = −0.25; p =.03). TNB adolescents had better mental health outcomes in the context of receiving gender-affirming hormonal interventions and having greater support from family and friends. Findings highlight the important role of quality family and friend support for TNB mental health. Providers should aim to address both medical and social factors to optimize TNB mental health outcomes. [ABSTRACT FROM AUTHOR]

To examine the safety and effectiveness of benzodiazepines (BZD) as compared to antipsychotics for the management of acute agitation in older adults in the emergency department (ED). Retrospective observational cohort study of 21 EDs across four states in the US, including adults ≥60 years old who received either BZD or antipsychotics for acute agitation in the ED and subsequently were admitted to the hospital. Safety was measured as presence of adverse events: respiratory depression, cardiovascular effects, extrapyramidal side effects, or a fall during hospitalization. Effectiveness was measured as indicators of treatment failure: need for additional medication, one-to-one observation, or physical restraints following initial medication administration. Proportions and odds ratios with 95% confidence intervals (CI) were calculated. Univariable and multivariable logistic regression were used to assess the association between potential risk factors and for efficacy and safety endpoints. A total of 684 patients were included (63.9% received a BZD and 36.1% an antipsychotic). There was no difference in the incidence of adverse events between groups (20.6% vs 14.6%, difference 6.0%, 95% CI -0.2% to 11.8%), but there was a higher intubation rate in the BZD group (2.7% vs 0.4%, difference 2.3%). There were more treatment failures in the antipsychotic group for the composite primary efficacy endpoint (94.3% vs 87.6%, difference 6.7%, 95% CI 2.5% to 10.9%). This appears to have been driven by the need for 1:1 observation; sensitivity analysis excluding 1:1 observation in the composite outcome demonstrated no significant difference with a failure rate of 38.5% in the antipsychotic group and 35.2% in the benzodiazepine group. Overall there are high rates of treatment failure among agitated older adults receiving pharmacological treatment for agitation in the emergency department. The optimal selection of pharmacological treatment for agitation in older adults should be made considering patient-specific factors that could increase the risk of adverse effects or treatment failure. [ABSTRACT FROM AUTHOR]

Patients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. This is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. Screening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). Cardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability. • Patients commonly experience peri-intubation hypotension. • There are various vasopressor strategies to obtain mean arterial pressure. • Vasopressor selection should be patient specific. • No difference in cardiovascular instability with various vasopressor strategies. [ABSTRACT FROM AUTHOR]

Policy aimed at transitioning from a linear to a circular economy by recycling has gained importance the last decade, with the waste management system being critical for this transition. This study provides a detailed model of resource use and environmental impacts, combining material flow analysis and life cycle assessment of the full waste management chain for household municipal solid waste in Norway, constructing 18 circular economy indicators. Results shows system improvements in terms of emissions due to an increase of recyclable material, residual waste diverted from landfills, and anaerobic digestion treatment of food waste. However, sustained waste generation with high shares of residual waste require incineration treatment. In 2009, 49 % of generated MSW was incinerated, in 2019 the incineration rate increased to 65 % when accounting for sorting and recycling loss in the waste treatment chain. The potential for increased recycling rates is considerable, however, there are also constraints within the waste management system that needs attention if circularity policies are to become more effective. The issue of low transparency is specifically highlighted in this study, as well as the importance of formulating and adopting meaningful circular economy indicators for the waste management system. [Display omitted] [ABSTRACT FROM AUTHOR]

Anthropogenic sources of total phosphorus (TP) and chloride (Cl−) to lakes and rivers have been issues of concern for many decades in the Great Lakes Basin with northern Boreal Shield headwater tributaries less well studied. In the Sturgeon River – Lake Nipissing – French River basin, a headwater basin of Georgian Bay, Lake Huron, water quality monitoring of major inflows to Lake Nipissing, the third largest inland lake located entirely within Ontario, is only available from the mid-1960s to the 1990s. During the period of 2015–2018, we conducted monthly water quality surveys of major and minor inflows for two water years and have generated the first chloride (Cl−) and total phosphorus (TP) elemental budgets for the lake. Review of available long-term concentration data indicate decreasing TP concentrations by decade in major inflows, but select inflows continue to exhibit concentrations above provincial objectives, including inflows from agricultural areas that are no longer part of provincial monitoring programs. Some inflows also show high average Cl− concentrations with potential influences (e.g., road salt, agricultural activities) to stream water quality throughout the year. Water and elemental budgets indicate that while specific runoff (l/s/km2) is quite similar across contributing catchments, yields of Cl− and TP (kg/ha/yr) are disproportionately higher in catchments with urban and agricultural activities. While uncertainties in the water balance and elemental yields remain, this first effort to quantify annual elemental budgets of Lake Nipissing highlights the need to develop community-based, spatially distributed water quality surveying for long-term ecosystem monitoring and future planning. [ABSTRACT FROM AUTHOR]

Objective: To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department.Methods: Prospective cohort study of patients aged ≥12 years of age who received low-dose droperidol (≤ 2.5 mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc ≥ 500 ms after droperidol, delta ≥ +60 ms, and incidence of clinical adverse events. Patients were monitored up to 30 min after IV bolus and up to 46 min after infusion.Results: A total of 68 patients were included (mean age 42.1 years, 66.2% females). The median dose of droperidol was 1.875 mg (range 0.625 mg, 2.5 mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n = 41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9 ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval ≥ 500 ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc ≥ +60 ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n = 9) had at least one non-serious adverse event including restlessness and/or anxiety.Conclusion: The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500 msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low. [ABSTRACT FROM AUTHOR]

The concept of bike sharing has existed around the world for several decades. However, the prevalence and popularity of bike share programs has increased rapidly, both in the United States and internationally, in the last decade. Initially implemented in larger cities, the programs' effectiveness and applicability is prompting smaller communities to launch their own programs. While bike share is expanding to many smaller cities, there is a need to better understand the impact of bike share programs on other travel modes such as automobile, public transportation, bicycling, and walking in smaller communities. To that end, this study analyzes the impact of bike share on mode share and transit usage in a smaller, university city of Fargo, North Dakota. This objective is achieved by surveying North Dakota State University (NDSU) students who are the primary users of the bike share program; surveys were conducted before and after the launch of the bike share program. A regression model was also developed, using daily transit ridership data, to estimate the impact of bike share use on bus ridership. Results showed that the bike share program did have some negative effect on bus ridership. [ABSTRACT FROM AUTHOR]

• Integrated primary care can improve evidence-based treatment access during COVID-19. • Low intensity, high yield resources can be quickly and easily disseminated. • Cognitive behavioral therapy can be adapted and employed as a higher level of care. The coronavirus disease 2019 (COVID-19) pandemic has consistently been described as an "unprecedented" global health crisis. While the focus has been primarily on the medical and economic impact of the pandemic, psychological sequelae are anticipated. Primary care is the main point of access for mental health care in the United States, making it the ideal locale to provide psychological services for a larger proportion of the population than traditional mental health care settings. The aim of this paper is to describe how our multi-state, multi-site integrated primary care program adapted and applied cognitive behavioral therapy in the context of COVID-19. Access to mental health care was disrupted despite burgeoning mental health concerns, necessitating novel approaches to providing care. A stepped-care approach was implemented within our primary care practice, which consisted of a combination of low-intensity, high-yield stress management and resiliency building resources and cognitive behavioral therapy that were delivered flexibly based on patient preference, technological capabilities, state ordinances, insurance coverage, and institutional policies. The lessons learned from this experience can inform other integrated primary care clinics in responding to the current and future pandemics. [ABSTRACT FROM AUTHOR]

Diet may promote brain health in metabolically impaired older individuals. In an 8-week randomized clinical trial involving 40 cognitively intact older adults with insulin resistance, we examined the effects of 5:2 intermittent fasting and the healthy living diet on brain health. Although intermittent fasting induced greater weight loss, the two diets had comparable effects in improving insulin signaling biomarkers in neuron-derived extracellular vesicles, decreasing the brain-age-gap estimate (reflecting the pace of biological aging of the brain) on magnetic resonance imaging, reducing brain glucose on magnetic resonance spectroscopy, and improving blood biomarkers of carbohydrate and lipid metabolism, with minimal changes in cerebrospinal fluid biomarkers for Alzheimer's disease. Intermittent fasting and healthy living improved executive function and memory, with intermittent fasting benefiting more certain cognitive measures. In exploratory analyses, sex, body mass index, and apolipoprotein E and SLC16A7 genotypes modulated diet effects. The study provides a blueprint for assessing brain effects of dietary interventions and motivates further research on intermittent fasting and continuous diets for brain health optimization. For further information, please see ClinicalTrials.gov registration: NCT02460783. [Display omitted] • 8 weeks of 5:2 intermittent fasting caused more weight loss than healthy living diet • Both diets reduced neuronal insulin resistance and the pace of brain aging • Both diets improved memory and executive function, with 5:2 intermittent fasting more so • Biomarkers of Alzheimer's disease did not change with either diet In this randomized clinical trial, Kapogiannis et al. examined the effects of 5:2 intermittent fasting and healthy living diet on brain health of adults with overweight and insulin resistance. The two diets decreased weight, reduced neuronal insulin resistance and the pace of brain aging, and improved executive function and memory. [ABSTRACT FROM AUTHOR]

Background: Permanent His-bundle pacing (HBP) is an attractive, perhaps more physiological, alternative to traditional right ventricular pacing.Objective: The purpose of this study was to utilize direct visualization to more comprehensively understand the anatomy central to HBP, correlating electrical lead performance to implant locations along the His-bundle (HB) pathway.Methods: Canine hearts (n = 5) were isolated and reanimated using Visible Heart methodologies. Medtronic 3830 SelectSecure leads were fixated where His potentials were present. The location of each implant was mapped/binned into 4 regions approximately analogous to the proximal, penetrating, and distal HB. Locational differences in HBP capture and resultant QRS morphology were assessed.Results: Average HBP capture thresholds did not significantly vary with respect to implant location (1.0-ms pulse width; P = .48). The resulting QRS morphologies from HB-paced beats varied in relation to implant location. As leads were placed further distally along the HB, the ratio of paced to native QRS complex duration increased (ΔQRSpaced/ΔQRSnative ratios-region 2: 0.84 ± 0.16; region 3: 1.04 ± 0.42; region 4: 1.74 ± 0.86).Conclusion: We demonstrated correlation between the anatomic locations of HBP lead placement and resultant QRS morphologies in a reanimated canine heart model. Proximal placement along the HB pathway resulted in more favorable QRS morphologies, suggesting improved selective HBP capture, with no significant increase in HBP capture thresholds. Pacing the HB in more proximal pathway locations improved the selectivity of HBP and may confer electrical and anatomic benefits relative to distal HBP. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a disorder of pregnancy, which is categorized by hypertension and proteinuria or signs of end-organ damage. Though PE is the leading cause of maternal and fetal morbidity and mortality, the mechanisms leading to PE remain unclear. The present study examined the contribution of dietary protein source (casein versus wheat gluten) to the risk of developing maternal syndrome utilizing two colonies of Dahl salt-sensitive (SS/JrHsdMcwi) rats. While the only difference between the colonies is the diet, the colonies exhibit profound differences in the pregnancy phenotypes. The SS rats maintained on the wheat gluten (SSWG) chow are protected from developing maternal syndrome; however, approximately half of the SS rats fed a casein-based diet (SSC) exhibit maternal syndrome. Those SSC rats that develop pregnancy-specific increases in blood pressure and proteinuria have no observable differences in renal or placental immune profiles compared to the protected SS rats. A gene profile array of placental tissue revealed a downregulation in Nos3 and Cyp26a1 in the SSC rats that develop maternal syndrome accompanied with increases in uterine artery resistance index suggesting the source of this phenotype could be linked to inadequate remodeling within the placenta. Investigations into the effects of multiple pregnancies on maternal health replicated similar findings. The SSC colony displayed an exacerbation in proteinuria, renal hypertrophy and renal immune cell infiltration associated with an increased mortality rate while the SSWG colony were protected highlighting how dietary protein source could have beneficial effects in PE. [ABSTRACT FROM AUTHOR]

Background: Droperidol is a dopamine receptor antagonist that functions as an analgesic, sedative, and antiemetic. In 2001, the U.S. Food and Drug Administration required a black box warning in response to case reports of QT prolongation and potential fatal arrhythmias. The aim of this study was to evaluate the effectiveness and safety of droperidol in patients presenting to a United States Emergency Department (ED).Methods: Observational cohort study of all droperidol administrations from 1/1/2012 through 4/19/2018 at an academic ED. The primary endpoint was mortality within 24 h of droperidol administration. Secondary endpoint included use of rescue analgesics.Results: A total of 6,881 visits by 5,784 patients received droperidol of whom 6,353 visits authorized use of their records for research, including 5.4% administrations in children and 8.2% in older adults (≥65). Droperidol was used as an analgesic for pain (N = 1,387, 21.8%) and headache (N = 3,622, 57.0%), as a sedative (N = 550, 8.7%), and as an antiemetic (N = 794, 12.5%). No deaths secondary to droperidol administration were recorded within 24 h. Need for rescue analgesia occurred in 5.2% of patients with headache (N = 188) and 7.4% of patients with pain (N = 102); 1.1% of patients with headache received rescue opioids (N = 38) after droperidol, as did 5.4% of patients with pain other than headache (N = 75). No patients had fatal arrhythmias. Akathisia occurred in 2.9%.Conclusion: No fatalities were seen among this large cohort of patients who received droperidol in the ED. Our findings suggest droperidol's effectiveness and safety when used as an analgesic, antiemetic and/or sedative. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety of a single dose of parenteral ketorolac for analgesia management in geriatric emergency department (ED) patients.Methods: This was a retrospective study of all administrations of parenteral ketorolac to adults ≥65 years of age and matched controls. The primary outcome was the occurrence of any of the following adverse events within 30 days of the ED visit: gastrointestinal bleeding, intracranial bleeding, acute decompensated heart failure, acute coronary syndrome, dialysis, transfusion, and death. The secondary outcome was the occurrence of an increase in serum creatinine of ≥1.5 times baseline within 7 and 30 days of the ED visit.Results: There were 480 patients included in the final analysis, of which 120 received ketorolac (3: 1 matching). The primary outcome occurred in 14 of 360 patients who did not receive ketorolac and 2 of 120 ketorolac patients (3.9% vs 1.7%, p = 0.38; OR 2.39, 95% CI 0.54-10.66). There was no occurrence of dialysis or death in either group. The secondary outcome occurred in 1 of 13 and 1 of 23 ketorolac patients with both a baseline serum creatinine and a measure within 7 and 30 days, respectively, but did not occur in patients who did not receive ketorolac (7 days: 7.7% vs 0.0%, p = 0.29; 30 days: 4.4% vs 0.0%, p = 0.22).Conclusion: The use of single doses of parenteral ketorolac for analgesia management was not associated with an increased incidence of adverse cardiovascular, gastrointestinal, or renal adverse outcomes in a select group of older adults. [ABSTRACT FROM AUTHOR]

This study aimed to quantitatively summarise risk factors associated with surgical site infection (SSI) following surgically managed tibial fractures. We searched the Embase/Medline, Cochrane Library, and Scopus databases for relevant studies in October 2023. We included original studies investigating risk factors for SSI following surgically managed traumatic tibial fractures that included ≥10 adult patients with SSIs. Meta-analysis was performed when >5 studies investigated the same risk factor. The risk of bias was assessed using the critical appraisal checklist from Joanna Briggs Institute for cohort studies. This study included 42 studies comprising 24,610 patients with surgically managed tibial fractures and 2,418 SSI cases. The following were identified as significant risk factors for SSI (p < 0.05): compartment syndrome (odds ratio [OR] = 3.8, 95% confidence interval [CI]: 2.4–6.0), blood transfusion (OR = 3.8, 95% CI: 2.1–6.6), open fracture (OR = 3.6, 95% CI: 2.5–5.1), Gustilo–Anderson classification >2 (OR = 3.1, 95% CI: 2.1–4.6), external fixation (OR = 2.9, 95% CI: 2.3–3.8), American Society of Anesthesiologists classification >2 (OR = 2.5, 95% CI: 1.5–4.1), polytrauma (OR = 2.4, 95% CI: 1.5–4.0), dual incision approach (OR = 2.1, 95% CI: 1.5–3.0), smoking (OR = 1.8, 95% CI: 1.5–2.1), male sex (OR = 1.6, 95% CI: 1.3–1.8), high energy trauma (OR = 1.5, 95% CI: 1.1–2.1), and prolonged surgery time (OR = 0.62, 0.43–0.82). Other factors, including diabetes, hypertension, and time to surgery, were not identified as risk factors for SSI. However, the included studies were generally of poor quality and at risk of bias. The review provides a basis for preoperatively assessing a patient's risk of developing an SSI, which could be used to initiate adjusted antibiotic regimes and more frequent postoperative controls. Furthermore, it indicates the risk factors future research should include when adjusting for confounding factors. • Patient related risk factors for infection are male sex, ASA classification>2 and smoking. • Fracture related risk factors are open fracture, Gustilo Anderson type, compartment syndrome, high energy- and polytrauma. • Surgery related risk factors are external fixation, blood transfusions, prolonged operative time, and dual incision. • This review provides basis for preoperative assessment of a patient's risk for developing SSI. • This review indicates which risk factors future research should include when assessing for confounding factors. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study is to compare surgical margins, reoperation rates and local recurrences after breast conserving surgery (BCS) using radioguided occult lesion localization (ROLL) or radioactive seed localization (RSL). We reviewed 744 consecutive patients with impalpable primary invasive breast cancer who underwent BCS at Helsinki University Hospital between 2010 and 2012. ROLL was used in our unit until October 31st, 2011; from November 1st we changed localization method to RSL. 318 patients underwent ROLL and 426 RSL. Patients in the RSL group had more often multifocal (p = 0.013) tumours. No statistically significant differences were found regarding tumour size, specimen weight, histology or grade of tumours or lymph node status. 42 (5.6%) patients were reoperated because of insufficient margins, 13 (4.1%) in the ROLL group and 29 (6.8%) in the RSL group. The reoperation rate was not different between the groups either in the univariable analysis (p = 0.112) or in the multivariable binary logistic regression analysis (p = 0.204). Risk factors for reoperations were multifocality of the tumour (p < 0.001), extensive intraductal component (p < 0.001), larger tumour size (p = 0.011), and smaller specimen weight (p = 0.014). The median follow-up time in the ROLL group was 81 (8–94) months and 64 (3–73) months in the RSL group. The five-year local recurrence-free survival (LRFS) estimates for ROLL and RSL groups were 98.0% and 99.4%, respectively (log-rank test, p = 0.323). Reoperation rates and LRFS were comparable for ROLL and RSL in patients with impalpable breast cancer treated with BCS. • Radioguided occult lesion localization and radioactive seed localization provided similar surgical outcomes. • Local recurrence-free survival was also comparable for these two localization methods. • Radioactive seed localization provides more flexible scheduling and logistics. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine multiple ways youth may access firearms among a sample of urban, mountain west youth, and explore whether youth reporting various types of violence involvement and other behavioral or mental health factors have differential access to firearms compared with youth who do not report these issues. A cross-sectional community-based survey was conducted among adolescents aged 10–17 years and one of their parents. The main outcomes were youth firearm access and possession and associated violence and behavioral and mental health factors. Bivariate and binomial logistic regression, controlling for demographic factors, was used to determine associations and predictors. One thousand one hundred youth and 730 parents participated. Nearly half of youth were male; 58.2% were Hispanic, 24.7% non-Hispanic black, 10.5% multiracial, 3.9% other, and 2.5% white. About 20% were categorized as having potential access to firearms (i.e., youth knows how and/or where to access firearms); 1.9% possessed a firearm. Analyses revealed that being physically aggressive (odds ratio [OR] 2.7), risk for future violence perpetration (OR 2.6), using alcohol (OR 2.0), having internalizing symptoms (OR 1.9), peer problems (OR 1.9), and older age (OR 1.26) predicted youth's possible access to firearms. Marijuana use (OR 9.9), parental gun ownership (OR 6.5), and reported delinquency (OR 8.3) predicted youth's firearm possession. Youth with potential firearm access demonstrate more violence risk and involvement, and other behavioral or mental health issues than youth without potential firearm access. Parental firearm ownership predicts youth firearm possession. It is important for both health-care providers and parents to recognize these potentially lethal associations to provide appropriate counseling. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aims to compare surgical margins, reoperations and local recurrences after conventional or oncoplastic breast conservation surgery (BCS). Furthermore, we aim to investigate differences between various oncoplastic techniques. We reviewed 1800 consecutive patients with primary invasive breast cancer (N = 1707) or ductal carcinoma in situ (N = 93) who underwent BCS at Helsinki University Hospital between 2010 and 2012. Conventional BCS was performed in 1189 (66.1%) patients, oncoplastic BCS in 611 (33.9%). Various oncoplastic techniques were used. Patients with oncoplastic BCS had more often multifocal (p < 0.001), larger (p < 0.001), palpable tumours (p < 0.001) with larger resection specimens (p < 0.001). The amount of resected tissue varied substantially depending on the oncoplastic technique. Patients treated with oncoplastic BCS were younger (p < 0.001) and their tumours were more aggressive according to histological grade (p < 0.001), T-stage (p < 0.001), Ki-67 (p < 0.001) and lymph node status (p < 0.001). There was no difference, however, in surgical margins (p = 0.578) or reoperation rates (p = 0.430) between the groups. A total of 152 (8.4%) patients were reoperated because of insufficient margins, 96 (8.1%) in the conventional, 56 (9.2%) in the oncoplastic BCS group. The median follow-up time was 75 (2–94) months. There was no difference in local recurrence-free survival between the conventional and oncoplastic BCS groups (log-rank test, p = 0.172). Oncoplastic BCS was used for larger, multifocal and more aggressive tumours. Nevertheless, no difference in reoperation rate or local recurrences were found. Oncoplastic BCS is as safe as conventional BCS enabling breast conserving for patients who otherwise were candidates for mastectomy. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate outcome of treatment in patients over 80 years of age with early breast cancer at the time of the diagnosis with special interest in surgical treatment. Breast cancer patients older than 80 years of age, treated at the Breast Surgery Unit of Helsinki University Hospital in 2005–2010 were identified from electronic patient records. Patients were followed-up until the end of 2014. Patient and tumour characteristics, recurrences, co-morbidities and reasons for omission of surgery were collected from electronic patient records. Survival data was obtained from Finnish Cancer Registry. 446 patients were eligible for the study: 401 (90%) received surgery. The median follow-up time was 52 months. In the entire study population, local and regional recurrences/disease progression were diagnosed in 16 (3.6%) and 6 (1.3%) patients, respectively. The five-year overall survival was 50.6% in the surgical treatment and only 15.2% in non-surgical treatment group, p < 0.001. Also, the five-year breast cancer specific survival was significantly better in the patients with surgery, 82.0%, but 56.0% in the patients without surgery, p < 0.001. There was no mortality related to the surgery, but 122 (30%) patients died within three years from surgery. Surgical treatment rate was high. OS and BCSS were better in surgically treated elderly patients. Local and regional disease control was excellent, probably due to high rate of surgical treatment. Surgical treatment also seemed safe in this elderly patient population. However, surgical overtreatment was obvious in some patients. [ABSTRACT FROM AUTHOR]

Abstract Compared to conventional energy technologies, hydropower has the lowest carbon emissions per kWh. Therefore, hydropower electricity production can contribute to combat climate change challenges. However, hydropower electricity production may at the same time contribute to environmental impacts and has been characterized as a large water consumer with impacts on aquatic biodiversity. Life Cycle Assessment is not yet able to assess the biodiversity impact of water consumption from hydropower electricity production on a global scale. The first step to assess these biodiversity impacts in Life Cycle Assessment is to quantify the water consumption per kWh energy produced. We calculated catchment-specific net water consumption values for Norway ranging between 0 and 0.012 m3/kWh. Further, we developed the first characterization factors for quantifying the aquatic biodiversity impacts of water consumption in a post-glaciated region. We apply our approach to quantify the biodiversity impact per kWh Norwegian hydropower electricity. Our results vary over six orders of magnitude and highlight the importance of a spatial explicit approach. This study contributes to assessing the biodiversity impacts of water consumption globally in Life Cycle Assessment. Highlights • net water consumption values of Norwegian hydropower reservoirs. • Species-Discharge Relationships considering postglacial freshwater fish immigration. • Characterization Factors for biodiversity impacts of water consumption in Norway. • Quantified biodiversity impact of water consumption from hydropower reservoirs. [ABSTRACT FROM AUTHOR]

Abstract Extracellular matrix (ECM) plays critical roles in establishing tissue structure-function relationships and controlling cell fate. However, the mechanisms by which ECM mechanics influence cell and tissue behavior remain to be elucidated since the events associated with this process span length scales from the tissue to molecular level. Entirely new methods are needed in order to better understand the multiscale mechanics of ECM. In this study, a multiscale experimental approach was established by integrating Optical Magnetic Twisting Cytometry (OMTC) with a biaxial tensile tester to study the microscopic (local) ECM mechanical properties under controlled tissue-level (global) loading. Adventitial layer of porcine thoracic artery was used as a collagen-based ECM. Multiphoton microscopy imaging was performed to capture the changes in ECM fiber structure during biaxial deformation. As visualized from multiphoton microscopy images, biaxial stretch induces gradual fiber straightening and the fiber families become evident at higher stretch levels. The OMTC measurements show that the local apparent storage and loss modulus increases with the global biaxial stretch, however there exists a complex interplay among local ECM mechanical properties, ECM structural heterogeneity, and fiber distribution and engagement. The phase lag does not change significantly with global biaxial stretch. Our results also show a much faster increase in global tissue tangent modulus compared to the local apparent complex modulus with biaxial stretch, indicating the scale dependency of ECM mechanics. [ABSTRACT FROM AUTHOR]

Highlights • We examined salvage logging effects on surface fuels and understory vegetation. • Fine woody surface fuels were greater in salvaged sites than untreated controls. • Salvage logging altered understory plant community composition and cover. Abstract Recent, widespread spruce beetle (Dendroctonus rufipennis) outbreaks have driven extensive tree mortality across western North America. Post-disturbance forest management often includes salvage logging to capture economic value of dead timber, reduce fire hazard, and meet other social or ecological objectives. Little is known about effects of salvage logging on surface fuel loads or plant understory communities in Engelmann spruce (Picea engelmannii)-dominated forests. We sampled fine and coarse woody debris, ground cover, and plant species composition along transects in spruce-beetle impacted stands in southwestern Colorado, USA. Twenty stands had been subject to clearcut 1–2 years prior to sampling; 32 stands were unlogged controls. Salvage logged stands exhibited altered surface fuels, ground cover, plant species cover, and community composition. Salvage increased 1-, 10-, and 100-hr fuels, and cover by bare ground and woody debris; cover by litter and cryptogams was reduced. Understory plant cover was reduced in salvaged stands, primarily due to losses of shrub cover. We found no difference in species diversity or richness between treated stands and controls. Salvage logging also drove shifts in plant community composition. Mean cover by non-native species was low, and not different, between control and salvage stands. Our study characterizes short-term effects that will undoubtedly change substantially over longer periods, in particular due to anticipated tree seedling growth and movement of standing dead wood from the canopy to the surface. In the near term, abundant fine woody surface fuels at salvage sites could influence the likelihood and rate of spread of surface fires, though over time we expect surface fuels in untreated stands to increase to comparable or greater levels than in salvaged stands. Differences in vascular plant cover and composition imparted by salvage harvests is also expected to change over time, though whether treated and untreated communities diverge or converge is not known. As such, we recommend that salvage harvest effects be monitored over extended time frames in order to detect longer-term trends. [ABSTRACT FROM AUTHOR]

The article presents the discussion on professional healthcare teams while respecting the institutional restriction. Topics include University of Chicago's Pediatric Hospital Medicine (PHM) rotation traditionally been among the most highly rated in the residency program; and infection control issues not arising since the technology not coming in contact with any patients.

• Long-term transferability of clinical judgment is understudied. • Using in-class simulations may improve transferability of clinical judgment. • Nurses retained long-term memory of in-class simulation in nursing practice. The transferability of clinical judgment developed through in-class simulations to clinical practice is understudied. This qualitative descriptive study utilized semi-structured interviews to determine to what extent new-to-practice nurses transfer active learning that occurred during observation of in-class simulations during their traditional pre-licensure nursing program to their nursing practice three years later. Three major themes emerged: cue recognition through visual recall, increased confidence in decision-making, and new cognitive frameworks for nursing practice. Using in-class simulations may improve transferability of clinical judgment through contextualizing student learning and promoting long-term retention as learners transition to practice. [ABSTRACT FROM AUTHOR]

Abstract The objective of this research is to develop an intercity mode choice model that can be incorporated into a travel demand model to estimate demand for rural intercity bus services. Four intercity transportation modes are considered in the study: automobile, bus, rail, and air. A stated preference survey was conducted of individuals across the state of North Dakota, and a mixed logit model was developed to estimate a mode choice model. Results from the mode choice model show the significant impacts of individual, trip, and mode characteristics on choice of mode. Gender, age, income, disability, trip purpose, party size, travel time, travel cost, and access distance were all found to have significant impacts on mode choice. This study was conducted in the largely rural state of North Dakota, but results could be transferable to other areas with similar geographic characteristics. [ABSTRACT FROM AUTHOR]

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: −2.4, −4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: −3.6 kg [IQR: −3.0, −4.1] vs. intermittent CR: −3.0 kg [IQR: −1.95, −4.1]; P  = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR ( P  = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health. [ABSTRACT FROM AUTHOR]

Objectives Cortical abnormalities in prenatal alcohol exposure (PAE) are known, including in gyrification (LGI), thickness (CT), volume (CV), and surface area (CS). This study provides longitudinal and developmental context to the PAE cortical development literature. Experimental design Included: 58 children with PAE and 52 controls, ages 6–17 at enrollment, from four Collaborative Initiative on FASD (CIFASD) sites. Participants underwent a formal evaluation of physical anomalies and dysmorphic facial features associated with PAE. MRI data were collected on three platforms (Siemens, GE, and Philips) at four sites. Scans were spaced two years apart. Change in LGI, CT, CS, and CV were examined. Principal observations Several significant regional age-by-diagnosis linear and quadratic interaction effects in LGI, CT, and CV were found, indicating atypical developmental trajectories in PAE. No significant correlations were observed between cortical measures and IQ. Conclusions Regional differences were seen longitudinally in CT, CV, and LGI in those with PAE. The findings represent important insights into developmental trajectories and may have implications for the timing of assessments and interventions in this population. It is noteworthy that cortical metrics did not correlate with IQ, suggesting that more specific aspects of cognitive development may need to be explored to provide further context. [ABSTRACT FROM AUTHOR]

This paper investigates the nexus of transit and rural livability as demonstrated by case studies in the North Dakota communities of Valley City and Dickinson. While there are many factors that influence the livability of a rural community, transit is believed to be an important contributor. For each of the two North Dakota communities considered, public/resident surveys, local transit rider surveys, and stakeholder interviews were conducted to understand differing opinions on livability and how transit contributes to livability. In both Valley City and Dickinson, surveys of residents showed that they believe affordable housing, low crime, quality healthcare, overall cost of living, quality public schools, and available jobs are the most important factors contributing to the livability of a small community. While transit was not among the top factors, survey respondents expressed considerable support for providing transit services and funding transit through various sources. Residents in both cities expressed the opinion that transit should be provided in their community as a transportation option for seniors, people with disabilities, those who choose not to drive, and those who cannot afford to drive. Transit riders in both cities indicated that transit is important to their quality of life, and stakeholders from both communities expressed the sentiment that transit is a critical lifeline for people who are elderly and/or have a disability, individuals with no vehicle, and those who cannot drive. [ABSTRACT FROM AUTHOR]

The growing popularity of bike share programs in the United States has prompted many cities to implement bike share systems to enhance mobility and health in their communities. While many of these programs have been introduced in large cities, and existing research has tended to focus on these large systems, bike share programs are becoming increasingly popular in smaller cities as well. Great Rides Bike Share launched with 11 stations and 101 bikes in 2015 in Fargo, North Dakota. This is one of the smaller systems in the United States, but it has been very successful. This study examines the ridership data for Great Rides Bike Share during its first two years of operations, investigates it keys to success, and estimates impacts of weather, temporal, and spatial variables on bike share use. In terms of trips per bike per day, bike share usage in Fargo surpasses that of the largest programs in the country. Keys to its success were the presence of a college campus and the reduced barriers to use for college students. The ridership model showed that temperatures, wind, precipitation, and the location of stations on a college campus all have significant impacts on bikes share use. [ABSTRACT FROM AUTHOR]

With several different imaging options available, it is not surprising that health care providers are unsure which imaging study is most appropriate for evaluating patients who present to the emergency department with abdominal pain. The American College of Radiology, currently, has appropriateness criteria for patients presenting with right upper, right lower, and left lower quadrant pain, and there are different variants for each of these quadrants. Clinicians should be aware of the American College of Radiology appropriateness criteria and, whenever possible, should be using criteria as guide to help them order the most appropriate imaging study. [ABSTRACT FROM AUTHOR]

Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task. [ABSTRACT FROM AUTHOR]

Collagen crosslinking, an important contributor to the stiffness of soft tissues, was found to increase with aging in the aortic wall. Here we investigated the mechanical properties of human descending thoracic aorta with aging and the role of collagen crosslinking through a combined experimental and modeling approach. A total of 32 samples from 17 donors were collected and divided into three age groups: <40, 40–60 and > 60 years. Planar biaxial tensile tests were performed to characterize the anisotropic mechanical behavior of the aortic samples. A recently developed constitutive model incorporating collagen crosslinking into the two-fiber family model (Holzapfel and Ogden, 2020) was modified to accommodate biaxial deformation of the aorta, in which the extension and rotation kinematics of bonded fibers and crosslinks were decoupled. The mechanical testing results show that the aorta stiffens with aging with a more drastic change in the longitudinal direction, which results in altered aortic anisotropy. Our results demonstrate a good fitting capability of the constitutive model considering crosslinking for the biaxial aortic mechanics of all age groups. Furthermore, constitutive modeling results suggest an increased contribution of crosslinking and strain energy density to the biaxial stress-stretch behaviors with aging and point to excessive crosslinking as a prominent contributor to aortic stiffening. [ABSTRACT FROM AUTHOR]

Our study examined the relationship between habitual high levels of vigorous physical activity on large and small artery compliance via radial artery pulse wave analysis. Eighty-three healthy men (n = 44) and women (n = 39), aged 18–78 years, were recruited as habitually less active (light-to-moderate exercise ≤3 times/wk) or habitually highly active (vigorous exercise ≥5 times/wk). A multivariate analysis of variance revealed a significant interaction of age and activity level; habitual vigorous activity was associated with greater compliance in large and small arteries in older adults (40–78 years) and younger adults (18–22 years). In the large and small arteries, we observed an age-associated decrease in arterial compliance (aged ≥ 40 years), though it appears to be less pronounced in the large artery among habitually highly active subjects. This study suggests that aging may be associated with declines in large and small artery compliance that can be attenuated by habitual vigorous activity. [ABSTRACT FROM AUTHOR]

Summary Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD + , and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD + reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD + also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background and objectives This study aims to clarify quality of breast cancer surgery in population-based setting. We aim to elucidate factors influencing waiting periods, and to evaluate the effect of hospital volume on surgical treatment policies. Special interest was given to diagnostic and surgical processes and their impact on waiting times. Methods All 1307 patients having primary breast cancer surgery at the Helsinki and Uusimaa Hospital District during 2010 were included in this retrospective study. Results Median waiting time for primary surgery was 24 days and significantly affected by additional imaging and diagnostic biopsies as well as hospital volume. Final rate of breast conserving surgery was surprisingly low, 51%, not affected by hospital volume, p = 0.781. Oncoplastic resection and immediate breast reconstruction (IBR) were performed more often in high volume units, p < 0.001. Quality of axillary surgery varied with unit size. Multiple operations, IBR and high volume unit were factors prolonging initiation of adjuvant treatment. Conclusion Quality of preoperative diagnostics play a crucial role in minimizing the need of repeated imaging and biopsies as well as multiple operations. Positive impact of high-volume hospitals becomes evident when analyzing procedures requiring advanced surgical techniques. High-volume hospitals achieved better quality in axillary surgery. [ABSTRACT FROM AUTHOR]

Changes in gonadal hormones during puberty are thought to potentiate adolescents' social re-orientation away from caregivers and towards peers. This study investigated the effect of testosterone on neural processing of emotional (vocal) stimuli by unfamiliar peers vs. parents, in transgender boys receiving exogenous testosterone as a gender-affirming hormone (GAH+) or not (GAH-). During fMRI, youth heard angry and happy vocal expressions spoken by their caregiver and an unfamiliar teenager. Youth also self-reported on closeness with friends and parents. Whole-brain analyses (controlling for age) revealed that GAH+ youth showed blunted neural response to caregivers' angry voices—and heightened response to unfamiliar teenage angry voices—in the anterior cingulate cortex. This pattern was reversed in GAH- youth, who also showed greater response to happy unfamiliar teenager vs. happy caregiver voices in this region. Blunted ACC response to angry caregiver voices—a pattern characteristic of GAH+ youth—was associated with greater relative closeness with friends over parents, which could index more "advanced" social re-orientation. Consistent with models of adolescent neurodevelopment, increases in testosterone during adolescence may shift the valuation of caregiver vs. peer emotional cues in a brain region associated with processing affective information. • Exogenous testosterone was linked to shifts in ACC response to peer/parent voices. • These neural patterns were related to increased closeness with peers over parents. • Findings were aligned with expected social re-orientation processes in adolescence. [ABSTRACT FROM AUTHOR]

Summary The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington’s disease and epilepsy, Sirt3 −/− mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration. [ABSTRACT FROM AUTHOR]

The analysis of graphs has become increasingly important to a wide range of applications. Graph analysis presents a number of unique challenges in the areas of (1) software complexity, (2) data complexity, (3) security, (4) mathematical complexity, (5) theoretical analysis, (6) serial performance, and (7) parallel performance. Implementing graph algorithms using matrix-based approaches provides a number of promising solutions to these challenges. The GraphBLAS standard ( istc-bigdata.org/GraphBlas ) is being developed to bring the potential of matrix based graph algorithms to the broadest possible audience. The GraphBLAS mathematically defines a core set of matrix-based graph operations that can be used to implement a wide class of graph algorithms in a wide range of programming environments. This paper provides an introduction to the GraphBLAS and describes how the GraphBLAS can be used to address many of the challenges associated with analysis of graphs. [ABSTRACT FROM AUTHOR]

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled “Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.” Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying “-omics” technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine. [ABSTRACT FROM AUTHOR]

Bar districts, agglomerations of drinking establishments, are important to urban economies by nurturing urban subcultures. Their vernacular nature presents important contrasts to planned urban entertainment districts (UEDs). Unlike UEDs, bar districts are not necessarily amenities for middle- and upper-class consumption and identity, but the subcultures they nurture can include potential gentrifiers. I present a case study of Polk Street in San Francisco, showing that it supported a uniquely diverse and countercultural LGBT street scene in 1999. By 2013 it had been displaced by a heterosexual nightclub scene that was first hailed for revitalization, and then regulated as a rowdy urban nuisance. These transformations show how bar districts provide two interrelated spatial resources in the gentrification process: (1) infrastructures of adult leisure and consumption and (2) sites of subcultural networking and creativity. This case study suggests the importance of distinguishing between creativity desired by potential gentrifiers from that which is not. If gentrifiers, as a subculture, benefit from creative nightlife networking opportunities, countercultural creativity is especially fragile because few outsiders recognize it as such. Bohemian creativity that can be commercialized, the target of creative cities promoters, is only one form of creative practice, and queer practices without commercial appeal are especially fragile. [ABSTRACT FROM AUTHOR]

Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant condition often caused by mutations in SCN1A that usually first manifests as childhood simple febrile seizures but may progress to a variety of afebrile generalized seizure types. Here, we describe the case of an 8-year-old boy with a novel SCN1A mutation who developed febrile seizures at 10 months of age which eventually advanced to frequent afebrile tonic-clonic seizures. His condition was unresponsive to several antiepileptic drugs and the ketogenic diet, and he experienced gradual cognitive decline. The patient’s father carries the same novel mutation, but he only experienced childhood simple febrile seizures. SCN1A mutations display incomplete penetrance and variable expressivity, and the resulting severity may depend on the location and type of mutation, whether the mutation was spontaneous or inherited, and the effect of modifying alleles. The identification of novel pathogenic SCN1A mutations may eventually advance therapeutic development and prognostic capabilities. [ABSTRACT FROM AUTHOR]