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Several experimental proposals expect to confirm the recent measurement of the coherent elastic neutrino-nucleus scattering (CEvNS). Motivated in particular by the next generation experiments of the COHERENT collaboration, we study their sensitivity to different tests of the Standard Model and beyond. We analyze the resolution that can be achieved by each future proposed detector in the measurement of the weak mixing angle; we also perform a similar analysis in the context of Nonstandard Interaction (NSI) and in the case of oscillations into a sterile neutrino state. We show that future perspectives are interesting for these types of new physics searches. [ABSTRACT FROM AUTHOR]

In the article titled "Coherent Elastic Neutrino-Nucleus Scattering as a Precision Test for the Standard Model and Beyond: The COHERENT Proposal Case" [[1]], there was an error in Figure 6 due to a minor error in the code. REFERENCES 1 Miranda O. G., Sanchez Garcia G., Sanders O. Coherent Elastic Neutrino-Nucleus Scattering as a Precision Test for the Standard Model and Beyond: The COHERENT Proposal Case. Again, the different curves are for the ideal case of =0% with 100% efficiency and a background error of =0% (solid), for =5% with 50% efficiency and a background error of =10% (dotted), for =15% with 100% efficiency and a background error of =10% (dashed-dotted), and =30% with 100% efficiency and a background error of =10% (dashed); see text for details. [Extracted from the article]

Background: The rise in prevalence of atopic dermatitis (AD) has been correlated with numerous elements of the exposome, modern-day lifestyle, and familial history. The combined analysis of familial history and other risk elements may allow us to understand the driving factors behind the development of AD., Objective: To develop prediction models to assess the risk of developing AD using a large and diverse cohort (N = 77,525) and easily assessed risk factors., Methods: We analyzed electronic medical record data from Leumit Health System. Documented predictive factors include sex, season of birth, environment (urban/rural), socioeconomic status, household smoking, diagnosed skin conditions, number of siblings, a paternal, maternal, or sibling history of an atopic condition, and antibiotic prescriptions during pregnancy or after birth. Predictive models were trained and validated on the data set., Results: Medium (odds ratio [OR] 2.04, CI 1.92-2.17, P < .001) and high (OR 2.13, CI 1.95-2.34, P < .001) socioeconomic status, a previous diagnosis of contact dermatitis (OR 2.57, CI 2.37-2.78, P < .001), presence of siblings with an AD diagnosis (OR 2.21, CI 2.04-2.40, P < .001), and the percentage of siblings with any atopic condition (OR 2.58, CI 2.09-3.17, P < .001) drove risk for AD in a logistic regression model. A random forest prediction model with a sensitivity of 61% and a specificity of 84% was developed. Generalized mixed models accounting for the random effect of familial relationships boasted an area under the curve of 0.98., Conclusion: Predictive modeling using noninvasive and accessible inputs is a powerful tool to stratify risk for developing AD., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Technologies that capture and analyze movement patterns for diagnostic or therapeutic purposes are a major locus of innovation in the United States. Several studies have evaluated their measurement properties in different conditions with variable findings. To date, the authors are not aware of any systematic review of studies conducted to assess the concurrent validity of pressure-sensing walkway technologies. The results of such an analysis could establish the body of evidence needed to confidently use these systems as reference or gold-standard systems when validating novel tools or measures. A comprehensive search of electronic databases including MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed. The initial search yielded 7670 papers. After removing duplicates and applying study inclusion/exclusion criteria, 11 papers were included in the systematic review with 10 included in a meta-analysis. There were 25 spatial and temporal gait parameters extracted from the included studies. The results showed there was not a significant bias for nearly all spatiotemporal gait parameters when the walkway system was compared to the reference systems. The findings from this analysis should provide confidence in using the walkway systems as reference systems in future studies to support the evaluation and validation of novel technologies deriving gait parameters.

Introduction: Despite being a primary impairment in individuals with cerebral palsy (CP), selective motor control (SMC) is not routinely measured. Personalized treatment approaches in CP will be unattainable without the ability to precisely characterize the types and degrees of impairments in motor control. The objective of this study is to report the development and feasibility of a new methodological approach measuring muscle activation patterns during single-joint tasks to characterize obligatory muscle co-activation patterns that may underly impaired SMC., Methods: Muscle activation patterns were recorded during sub-maximal voluntary isometric contraction (sub-MVIC) tasks at the hip, knee, and ankle with an interactive feedback game to standardize effort across participants. We calculated indices of co-activation, synergistic movement, mirror movement, and overflow (indices range 0-2, greater scores equal to greater impairment in SMC) for each isolated joint task in 15 children - 8 with typical development (TD) (mean age 4.7 ± 1.0 SD years) and 7 with CP (mean age 5.8 ± 0.7 SD years). Indices were compared with Mann-Whitney tests. The relationships between the indices and gross motor function (GMFM-66) were examined with Pearson's r ., Results: Mean indices were higher in the CP vs. the TD group for each of the six tasks, with mean differences ranging from 0.05 (abduction and plantarflexion) to 0.44 (dorsiflexion). There was great inter-subject variability in the CP group such that significant group differences were detected for knee flexion mirroring ( p  = 0.029), dorsiflexion coactivation ( p  = 0.021), and dorsiflexion overflow ( p  = 0.014). Significant negative linear relations to gross motor function were found in all four indices for knee extension ( r  = -0.56 to -0.75), three of the indices for ankle dorsiflexion ( r  = -0.68 to -0.78) and in two of the indices for knee flexion ( r  = -0.66 to -0.67), and ankle plantarflexion ( r  = -0.53 to -0.60)., Discussion: Indices of coactivation, mirror movement, synergy, and overflow during single-joint lower limb tasks may quantify the type and degree of impairment in SMC. Preliminary concurrent validity between several of the indices of SMC and gross motor function was observed. Our findings established the feasibility of a new methodological approach that quantifies muscle activation patterns using electromyography paired with biofeedback during single-joint movement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Graci, O’Neill, Bloss, Akkem, Paremski, Sanders and Prosser.)

Aims: To examine the impact of intensive management of type 1 diabetes (T1D) from diagnosis on HbA1c 12 months from diagnosis., Methods: HbA1c measured 12 months after diagnosis for 70 consecutively newly diagnosed children with T1D following implementation of an intensive management protocol was compared with 70 children consecutively diagnosed immediately pre-implementation. Intensive management involved carbohydrate counting and flexible insulin dosing from first meal with subcutaneous insulin, targeted blood glucose levels from 4-8mmol/L irrespective of time of day, avoidance of twice daily insulin regimen and promotion of continuous glucose monitoring (CGM). HbA1c, diabetes technology use and insulin regimen at 12 months post-diagnosis were compared., Results: The post-intensive management implementation cohort had an improved mean HbA1c of 58.2±15.3mmol/mol vs 63.7±10.7mmol/mol at 12 months (p=0.014). The proportion of young people with diabetes meeting a target HbA1c of <53mmol/mol at 12 months improved from 11% to 40% (p=<0.001). There was a reduction of twice daily insulin regimen from 66% to 11% (p=<0.001), and increased CGM use from 57% to 76% (p=0.02)., Conclusion: Intensive management when implemented with consistent messaging from the multi-disciplinary team resulted in clinic-wide improvements in HbA1c and the proportion meeting HbA1c targets., Competing Interests: None to declare., (© PMA.)

Competing Interests: The authors have no conflicts to report.

Background: Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma that most often develops in children. Chemoradiation therapy is a standard treatment modality; however, the detrimental long-term skeletal muscle consequences of this therapy in juvenile cancer survivors include muscle atrophy and fibrosis resulting in decreased physical performance. Using a novel model of murine resistance and endurance exercise training, we investigate its role in preventing the long-term effects of juvenile RMS plus therapy., Methods: Four-week-old male (n = 10) and female (n = 10) C57Bl/6J mice were injected with M3-9-M RMS cell into the left gastrocnemius with the right limb serving as an internal control (CON). Mice received a systemic vincristine injection and then five doses of 4.8 Gy of gamma radiation localized to the left hindlimb (RMS + Tx). Mice were then randomly divided into either sedentary (SED) or resistance and endurance exercise training (RET) groups. Changes in exercise performance, body composition, myocellular adaptations and the inflammatory/fibrotic transcriptome were assessed., Results: RET improved endurance performance (P < 0.0001) and body composition (P = 0.0004) compared to SED. RMS + Tx resulted in significantly lower muscle weight (P = 0.015) and significantly smaller myofibre cross-sectional area (CSA) (P = 0.014). Conversely, RET resulted in significantly higher muscle weight (P = 0.030) and significantly larger Type IIA (P = 0.014) and IIB (P = 0.015) fibre CSA. RMS + Tx resulted in significantly more muscle fibrosis (P = 0.028), which was not prevented by RET. RMS + Tx resulted in significantly fewer mononuclear cells (P < 0.05) and muscle satellite (stem) cells (MuSCs) (P < 0.05) and significantly more immune cells (P < 0.05) than CON. RET resulted in significantly more fibro-adipogenic progenitors (P < 0.05), a trend for more MuSCs (P = 0.076) than SED and significantly more endothelial cells specifically in the RMS + Tx limb. Transcriptomic changes revealed significantly higher expression of inflammatory and fibrotic genes in RMS + Tx, which was prevented by RET. In the RMS + Tx model, RET also significantly altered expression of genes involved in extracellular matrix turnover., Conclusions: Our study suggests that RET preserves muscle mass and performance in a model of juvenile RMS survivorship while partially restoring cellular dynamics and the inflammatory and fibrotic transcriptome., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: Open-source automated insulin delivery (AID) is used by thousands of people with type 1 diabetes (T1D), but has unknown generalisability to marginalised ethnic groups. This study explored experiences of Indigenous Māori participants in the CREATE trial with use of an open-source AID system to identify enablers/barriers to health equity., Methods: The CREATE randomised trial compared open-source AID (OpenAPS algorithm on an Android phone with a Bluetooth-connected pump) to sensor-augmented pump therapy. Kaupapa Māori Research methodology was used in this sub-study. Ten semi-structured interviews with Māori participants (5 children, 5 adults) and whānau (extended family) were completed. Interviews were recorded and transcribed, and data were analysed thematically. NVivo was used for descriptive and pattern coding., Results: Enablers/barriers to equity aligned with four themes: access (to diabetes technologies), training/support, operation (of open-source AID), and outcomes. Participants described a sense of empowerment, and improved quality of life, wellbeing, and glycaemia. Parents felt reassured by the system's ability to control glucose, and children were granted greater independence. Participants were able to use the open-source AID system with ease to suit whānau needs, and technical problems were manageable with healthcare professional support. All participants identified structures in the health system precluding equitable utilisation of diabetes technologies for Māori., Conclusion: Māori experienced open-source AID positively, and aspired to use this therapy; however, structural and socio-economic barriers to equity were identified. This research proposes strength-based solutions which should be considered in the redesign of diabetes services to improve health outcomes for Māori with T1D. Trial Registration: The CREATE trial, encompassing this qualitative sub-study, was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000034932p) on the 20 th January 2020., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01215-3., Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article. The authors have no financial or proprietary interests in any material discussed in this article. Author MB acquired the APEG grant for this study, and has no conflicts of interest to declare. Authors TH, HC, DL, RM, OS, CJ, AF, CL, SP, CF, SJ, TG, SP, and CL declare they have no conflicts of interest. RP has received educational honoraria from Eli Lilly, Boehringer Ingelheim, Novo Nordisk, Astra Zeneca, Sanofi, Novartis, and Blue Horizons. BW has received research grants and equipment from Medtronic, Dexcom, and iSENS. MdB has received research grants from Dexcom and Medtronic, and research equipment from Dexcom, Medtronic, and Ypsomed. MdB has received honoraria from Medtronic, Ypsomed, and Dexcom.Conflicts of InterestNone., (© The Author(s) 2023.)

The low cerebral metabolic rate of oxygen despite the relatively preserved perfusion in Alzheimer's disease (AD) patients' medial temporal lobes suggest histotoxic hypoxia due to mitochondrial dysfunction that is independent of, but could precede, insulin resistance. Neuropathological, metabolomic, and preclinical evidence are consistent with the notion that this mitochondrial dysfunction may be contributed to by oxidative stress and DNA damage, leading to poly-(ADP-ribose)-polymerase-1 (PARP1) activation and consequent AMP accumulation, clogging of mitochondrial adenine nucleotide transporters (ANTs), matrix ADP deprivation, and ATP synthase inhibition. Complementary mechanisms may include mitochondrial-protein poly-ADP-ribosylation and mitochondrial-biogenesis suppression via PARPs outcompeting Sirtuin-1 (SIRT1) for nicotinamide-adenine-dinucleotide (NAD + )., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Background: The conventional focus on discrete finger movements (i.e., index finger flexion or button-box key presses) has been an effective method to study neuromotor control using magnetoencephalography (MEG). However, this approach is challenging for young children and not possible for some people with physical disability., New Method: We have developed a novel, interactive MEG compatible reach-to-target task to investigate neuromotor function, specifically for use with young children. We used an infrared touch-screen frame to detect responses to targets presented using custom software. The game can be played using a conventional computer monitor or during MEG recordings via projector. We termed this game the Target-Touch Motor Task (TTMT)., Results: We demonstrate that the TTMT is a feasible motor task for use with young children including children with physical impairments. TTMT response-to-target trial counts are also comparable to conventional methods. Artifacts from the touch screen, while present &gt; 100 Hz, did not affect MEG source analysis in the beta band (14-30 Hz). MEG responses during TTMT game play reveal robust cortical activity from expected areas of motor cortex as typically observed following movements of the upper limb., Comparison With Existing Method(s): The TTMT paradigm allows participation by individuals with a broad range of motor abilities on a reach-to-target' functional task rather than conventional tasks focusing on discrete finger movements., Conclusions: The TTMT is well suited for young children and successfully activates expected motor cortical areas. The TTMT opens-up new opportunities for the assessment of motor function across the lifespan, including for children with physical limitations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Open-source automated insulin delivery (AID) is a user-driven treatment modality used by thousands globally. Healthcare professionals' (HCPs) ability to support users of this technology is limited by a lack of knowledge of these systems., Aims: To describe the challenges experienced by HCPs supporting participants' use of open-source automated insulin delivery in the Community deRivEd AuTomatEd insulin delivery (CREATE) study., Methods: Data were collected prospectively from the study team's fortnightly meetings and Slack Workspace (Slack Technologies, Ltd. 2018) during the first 4 months of the trial. Key topics were identified from minutes of meetings. Slack conversations were categorised by topic, with the number of posts per conversation, number of sites per conversation and involvement of experts in open-source AID being recorded., Results: In the first 4 months of the trial, there were 254 conversations in Slack with a mean of 5.2 (±4.25) posts per conversation. The most frequent learning challenge was insulin pump and cannula problems relating to the DANA-i TM insulin pump, which totalled 24.0% of all conversations. Experts on open-source AID use were involved in 83.3% of conversations., Conclusions: A significant proportion of challenges related to specific devices, rather than AID. Challenges relating to the functioning of open-source AID were more likely to involve input from experts in open-source AID. This is the first report of challenges experienced by a multidisciplinary team in a supported open-source environment that may inform expectations in routine clinical care., (© 2021 Diabetes UK.)

Objectives: To investigate the impact of SARS-CoV-2 on self-reported mood, coping and health behaviours of people living with existing health conditions in the UK to understand how to improve coping responses to the threat of SARS-CoV-2., Design: Quantitative design using a cross-sectional survey., Setting: Online survey in the UK., Participants: UK adults (18+ years) were eligible to participate. A total of 9110 people participated. Of these, 4377 (48%) reported at least one existing health condition, 874 (10%) reported having two or more existing conditions, and 715 (8%) reported having an existing mental health condition., Primary and Secondary Outcome Measures: Multivariable linear regression and sequential multiple mediation analysis were used to estimate differences in average scores for active and avoidant coping response scores due to pre-existing health conditions, and to investigate the extent to which these differences are explained by differences in perceptions, beliefs, concerns and mood., Results: People with pre-existing physical (+1.11 higher; 95% CI 0.88 to 1.34) and especially mental health conditions (3.06 higher; 95% CI 2.65 to 3.48) reported poorer health and used more avoidant coping compared with healthy participants. Under some strong untestable assumptions, we estimate that experiencing low mood or concern related to SARS-CoV-2 mostly explained the relationship between existing health conditions and avoidant coping., Conclusion: Psychological support and interventions including behaviour change are required to mitigate the psychological burden of the SARS-CoV-2 pandemic and increase autonomy in people with and without pre-existing conditions during this highly uncertain time. Psychologists are well placed to support clinicians and people with existing health conditions to minimise the psychological impact of SARS-CoV-2, in order to alleviate the subsequent strain on healthcare services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The LI-RADS M (LR-M) category describes hepatic lesions probably or definitely malignant, but not specific for hepatocellular carcinoma in at-risk patients. Differentiation among LR-M entities, particularly detecting cholangiocarcinoma-containing tumors (M-CCs), is essential for treatment and prognosis. Thus, we aimed to develop diagnostic models on gadoxetate disodium-enhanced MRI comprising serum tumor markers and LI-RADS imaging features for M-CC., Methods: Consecutive at-risk patients with LR-M lesions exclusively (no co-existing LR-4 and/or LR-5 lesions) were retrieved retrospectively from a prospectively collected database spanning 3 years. Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (c-HCC-CCA) were classified together as M-CC. LI-RADS features determined by three independent radiologists and clinically relevant serum tumor markers were used to generate M-CC diagnostic models through logistic regression analysis against histology. Per-patient performance was evaluated using area under the receiver operating curve (AUC), sensitivity, and specificity., Results: Forty-five patients were included, 42.2% (19/45) with hepatocellular carcinoma, 33.3% (15/45) with ICC, 13.3% (6/45) with c-HCC-CCA, and 11.1% (5/45) with other hepatic lesions. Carbohydrate antigen (CA)19-9 > 38 U/mL, α-fetoprotein (AFP) > 4.8 ng/mL, and absence of the LI-RADS feature "blood products in mass" were significant predictors of M-CC. Combining three predictors demonstrated AUC of 0.862, sensitivity of 76%, and specificity of 88%. The risk of M-CC with all three criteria fulfilled was 98% (AUC, 0.690; sensitivity, 38%; specificity, 100%)., Conclusions: In at-risk patients with LR-M lesions, integrating CA19-9, AFP, and the LI-RADS feature "blood products in mass" achieved high diagnostic performance for M-CC. When all three criteria were fulfilled, the specificity for M-CC was 100%., Key Points: • In at-risk patients who had LR-M lesions exclusively (no concomitant LR-4/5 lesions), a model with carbohydrate antigen > 38 U/mL, α-fetoprotein > 4.8 ng/mL, and absence of the LI-RADS feature "blood products in mass" achieved high accuracy for diagnosing cholangiocarcinoma-containing tumors. • In patients of whom all three criteria were fulfilled, the specificity for M-CC was 100%, which might reduce or eliminate the need for biopsy confirmation.

Falls contribute to injuries and reduced level of physical activity in older adults. During falls, the abrupt sensation of moving downward triggers a startle-like reaction that may interfere with protective response movements necessary to maintain balance. Startle reaction could be dampened by sensory pre-stimulation delivered immediately before a startling stimulus. This study investigated the neuromodulatory effects of pre-stimulation on postural/startle responses to drop perturbations of the standing support surface in relation to age. Ten younger and 10 older adults stood quietly on an elevated computer-controlled moveable platform. At an unpredictable time, participants were dropped vertically to elicit a startle-like response. Reactive drop perturbation trials without a pre-stimulus (control) were alternated with trials with acoustic pre-stimulus tone (PSI). A two-way mixed design analysis of variance comparing condition (control vs. PSI) X group (younger vs. older) was performed to analyze changes in muscle activation patterns, ground reaction force, and joint angular displacements. Compared to younger adults, older adults showed lower neck muscle electromyography amplitude reduction rate and incidence of response. Peak muscle activation in neck, upper arm, and hamstring muscles were reduced during PSI trials compared to control trials in both groups (p < 0.05). In addition, knee and hip joint flexion prior to ground contact was reduced in PSI trials compared to control (p < 0.05). During post-landing balance recovery, increased knee and hip flexion displacement and time to peak impact force were observed in PSI trials compared to control condition (p < 0.05). PSI reduced startle-induced muscle activation at proximal body segments and likely decreased joint flexion during abrupt downward vertical displacement perturbations of the body. Older adults retained the ability to modulate startle and postural responses but their neuromodulatory capacity was reduced compared with younger adults. Further research on the potential of applying PSI as a possible therapeutic tool to reduce the risk of fall-related injury is needed., (Copyright © 2020. Published by Elsevier B.V.)

Background: Preclinical studies, clinical trials, and reviews suggest increasing 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) with phosphodiesterase inhibitors is disease-modifying in Alzheimer's disease (AD). cAMP/protein kinase A (PKA) and cGMP/protein kinase G (PKG) signaling are disrupted in AD. cAMP/PKA and cGMP/PKG activate cAMP response element binding protein (CREB). CREB binds mitochondrial and nuclear DNA, inducing synaptogenesis, memory, and neuronal survival gene (e.g., brain-derived neurotrophic factor) and peroxisome proliferator-activated receptor- γ coactivator-1 α (PGC1 α ). cAMP/PKA and cGMP/PKG activate Sirtuin-1, which activates PGC1 α . PGC1 α induces mitochondrial biogenesis and antioxidant genes (e.g.,Nrf2) and represses BACE1. cAMP and cGMP inhibit BACE1-inducing NF κ B and tau-phosphorylating GSK3β., Objective and Methods: We review efficacy-testing clinical trials, epidemiology, and meta-analyses to critically investigate whether phosphodiesteraseinhibitors prevent or treat AD., Results: Caffeine and cilostazol may lower AD risk. Denbufylline and sildenafil clinical trials are promising but preliminary and inconclusive. PF-04447943 and BI 409,306 are ineffective. Vinpocetine, cilostazol, and nicergoline trials are mixed. Deprenyl/selegiline trials show only short-term benefits. Broad-spectrum phosphodiesterase inhibitor propentofylline has been shown in five phase III trials to improve cognition, dementia severity, activities of daily living, and global assessment in mild-to-moderate AD patients on multiple scales, including the ADAS-Cogand the CIBIC-Plus in an 18-month phase III clinical trial. However, two books claimed based on a MedScape article an 18-month phase III trial failed, so propentofylline was discontinued. Now, propentofylline is used to treat canine cognitive dysfunction, which, like AD, involves age-associated wild-type Aβ deposition., Conclusion: Phosphodiesterase inhibitors may prevent and treat AD., Competing Interests: The authors have no conflict of interest to report., (© 2020 – IOS Press and the authors. All rights reserved.)

Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is upregulated. Sildenafil inhibits PDE5 and increases cGMP levels. Integrating previous findings, we determine that most doses of sildenafil (especially low doses) likely activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) via protein kinase G-mediated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) phosphorylation and/or Sirtuin-1 activation and PGC1α deacetylation. Via PGC1α signaling, low-dose sildenafil likely suppresses β-secretase 1 expression and amyloid-β (Aβ) generation, upregulates antioxidant enzymes, and induces mitochondrial biogenesis. Plus, sildenafil should increase brain perfusion, insulin sensitivity, long-term potentiation, and neurogenesis while suppressing neural apoptosis and inflammation. A systematic review of sildenafil in AD was undertaken. In vitro, sildenafil protected neural mitochondria from Aβ and advanced glycation end products. In transgenic AD mice, sildenafil was found to rescue deficits in CREB phosphorylation and memory, upregulate brain-derived neurotrophic factor, reduce reactive astrocytes and microglia, decrease interleukin-1β, interleukin-6, and tumor necrosis factor-α, decrease neural apoptosis, increase neurogenesis, and reduce tau hyperphosphorylation. All studies that tested Aβ levels reported significant improvements except the two that used the highest dosage, consistent with the dose-limiting effect of cGMP-induced phosphodiesterase 2 (PDE2) activation and cAMP depletion on PGC1α signaling. In AD patients, a single dose of sildenafil decreased spontaneous neural activity, increased cerebral blood flow, and increased the cerebral metabolic rate of oxygen. A randomized control trial of sildenafil (ideally with a PDE2 inhibitor) in AD patients is warranted., Competing Interests: The authors have no conflict of interest to report., (© 2020 – IOS Press and the authors. All rights reserved.)

This study investigated aging changes in protective balance and startle responses to sudden drop perturbations and their effect on landing impact forces (vertical ground reaction forces, vGRF) and balance stability. Twelve healthy older (6 men; mean age = 72.5 ± 2.32 yr, mean ± SE) and 12 younger adults (7 men; mean age = 28.09 ± 1.03 yr) stood atop a moveable platform and received externally triggered drop perturbations of the support surface. Electromyographic activity was recorded bilaterally over the sternocleidomastoid (SCM), middle deltoid, biceps brachii, vastus lateralis (VL), biceps femoris (BF), medial gastrocnemius (MG), and tibialis anterior (TA). Whole body kinematics were recorded with motion analysis. Stability in the anteroposterior direction was quantified using the margin of stability (MoS). Incidence of early onset of bilateral SCM activation within 120 ms after drop onset was present during the first-trial response (FTR) for all participants. Co-contraction indexes during FTRs between VL and BF as well as TA and MG were significantly greater in the older group (VL/BF by 26%, P < 0.05; TA/MG by 37%, P < 0.05). Reduced shoulder abduction between FTR and last-trial responses, indicative of habituation, was present across both groups. Significant age-related differences in landing strategy were present between groups, because older adults had greater trunk flexion ( P < 0.05) and less knee flexion ( P < 0.05) that resulted in greater peak vGRFs and decreased MoS compared with younger adults. These findings suggest age-associated abnormalities of delayed, exaggerated, and poorly habituated startle/postural FTRs are linked with greater landing impact force and diminished balance stabilization. NEW & NOTEWORTHY This study investigated the role of startle as a pathophysiological mechanism contributing to balance impairment in aging. We measured neuromotor responses as younger and older adults stood on a platform that dropped unexpectedly. Group differences in landing strategies indicated age-associated abnormalities of delayed, exaggerated, and poorly habituated startle/postural responses linked with a higher magnitude of impact force and decreased balance stabilization. The findings have implications for determining mechanisms contributing to falls and related injuries.

This pilot study investigated the effect of age on the ability of motor prediction during self-triggered drop perturbations (SLF) to modulate startle-like first trial response (FTR) magnitude during externally-triggered (EXT) drop perturbations. Ten healthy older (71.4 ± 1.44 years) and younger adults (26.2 ± 1.63 years) stood atop a moveable platform and received blocks of twelve consecutive EXT and SLF drop perturbations. Following the last SLF trial, participants received an additional EXT trial spaced 20 min apart to assess retention (EXT RTN) of any modulation effects. Electromyographic (EMG) activity was recorded bilaterally over the sternocleidomastoid (SCM), vastus lateralis (VL), biceps femoris (BF), medial gastrocnemius (MG), and tibialis anterior (TA). Whole-body kinematics and kinetic data were recorded. Stability in the antero-posterior direction was quantified using the margin of stability (MoS). Compared with EXT trials, both groups reduced SCM peak amplitude responses during SLF and EXT RTN trials. VL/BF and TA/MG coactivation were reduced during SLF FTR compared to EXT FTR (p < 0.05) with reduced peak vertical ground reaction forces (vGRF) in both younger and older adults (p < 0.05). Older adults increased their MoS during SLF FTR compared to EXT FTR (p < 0.05). Both groups performed more eccentric work during SLF trials compared to EXT (p < 0.05). These findings indicate that abnormal startle effects with aging may interfere with balance recovery and increase risk of injury with external balance perturbations. Motor prediction may be used to acutely mitigate abnormal startle/postural responses with aging., (Published by Elsevier Ltd.)

Background: Hip fractures in older adults often result from a fall in the lateral direction. While younger adults tend to recover balance from a lateral perturbation with a single lateral sidestep, older adults are prone to multistep responses which are associated with an increased fall risk. This study compared the stepping characteristics and stability of single and multistep responses to lateral perturbation in healthy older adults., Methods: Eighty-four older adults received lateral waist-pull perturbations to either side. Spatio-temporal stepping characteristics and balance stability were quantified., Findings: Fewer steps were taken to recover balance when the first step was a lateral sidestep. The stability margin of single lateral sidesteps was greater than medial sidesteps and cross-over steps to the back but not significantly different from single cross-over steps to the front at step termination. Single step responses were more stable than multistep responses at step termination and at step initiation for lateral sidesteps and cross-over steps to the front. The decreased stability of multistep responses was attributed to an increased center of mass velocity and a smaller distance between the center of mass and base-of-support at step termination., Interpretation: Although lateral sidesteps result in fewer steps than cross-over steps to the front, the stability margin was not significantly different at step termination. These results suggest difficulty terminating center of mass motion and/or inefficient center of mass control differentiates single and multistep responses. Future studies should investigate perturbation training and/or hip abductor muscle conditioning as a means of improving compensatory stepping reactions., (Copyright © 2019. Published by Elsevier Ltd.)

Background: There is only limited information available about the effect of age on course of cognitive decline in patients with onset of Alzheimer's disease (AD) over the age of 64 years., Objective: We compared the rate of, and factors affecting, cognitive decline in patients with AD aged < 65 years (young-onset AD), 65-74 years (middle-onset AD), and ≥75 years (late-onset AD)., Method: The study used longitudinal data from the Essex Memory Clinic which included a total of 305 participants; 56 had YOAD, 73 had MOAD, and 176 had LOAD. The rate of cognitive decline was measured using scores from the Mini-Mental State Examination (MMSE), and the data were examined using multilevel models analysis., Results: There was evidence of a difference in cognitive decline across the age groups with the YOAD group declining 2.8 MMSE points per year, those with MOAD declined 2.0 MMSE points per year, and the LOAD group declined 1.4 MMSE points per year., Conclusions: Patients with LOAD have a better prognosis than YOAD and MOAD. However, even between the MOAD and LOAD groups, age is a significant predictor of cognitive decline, with older patients having a more benign course.

Objective: To determine and compare gait speed during head-forward and side-to-side head-turn walking in individuals with lower versus greater lateral balance., Design: Cross-sectional study., Setting: University research laboratory., Participants: Older adults (N=93; 42 men, 51 women; mean age ± SD, 73 ± 6.08y) who could walk independently., Main Outcome Measures: (1) Balance tolerance limit (BTL), defined as the lowest perturbation intensity where a multistep balance recovery pattern was first evoked in response to randomized lateral waist-pull perturbations of standing balance to the left and right sides, at 6 different intensities (range from level 2: 4.5-cm displacement at 180cm/s 2 acceleration, to level 7: 22.5-cm displacement at 900cm/s 2 acceleration); (2) gait speed, determined using an instrumented gait mat; (3) balance, evaluated with the Activities-specific Balance Confidence Scale; and (4) mobility, determined with the Timed Up and Go (TUG)., Results: Individuals with low versus high BTL had a slower self-selected head-forward gait speed and head-turn gait speed (P=.002 and P<.001, respectively); the magnitude of difference was greater in head-turn gait speed than head-forward gait speed (Cohen's d=1.0 vs 0.6). Head-turn gait speed best predicted BTL. BTL was moderately and positively related (P=.003) to the ABC Scale and negatively related (P=.017) to TUG., Conclusions: Head-turn gait speed is affected to a greater extent than head-forward gait speed in older individuals with poorer lateral balance and at greater risk of falls. Moreover, head-turn gait speed can be used to assess the interactions of limitations in lateral balance function and gait speed in relation to fall risk in older adults., (Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Our patient attributed his back pain to a recent fall, but his lab work and a sagittal CT pointed us in another direction.

In a search for genes responsible for the accumulation of antimonite in Escherichia coli, TnphoA was used to create a pool of random insertional mutants, from which one antimonite-resistant mutant was isolated. Sequence analysis showed that the TnphoA insertion was located in the glpF gene, coding for the glycerol facilitator GlpF. The mutant was shown to be defective in polyol transport by GlpF. These results suggest that in solution Sb(III) is recognized as a polyol by the glycerol facilitator.

The arsenical resistance (ars) operon of the conjugative R-factor R773 confers resistance to arsenical and antimonial compounds in Escherichia coli, where resistance results from active extrusion of arsenite catalyzed by the products of the arsA and arsB genes. Previous in vivo studies on the energetics of arsenite extrusion showed that expression of both genes produced an ATP-coupled arsenite extrusion system that was independent of the electrochemical proton gradient. In contrast, in cells expressing only the arsB gene, arsenite extrusion was coupled to electrochemical energy and independent of ATP, suggesting that the Ars transport system exhibits a dual mode of energy coupling depending on the subunit composition. In vitro the ArsA-ArsB complex has been shown to catalyze ATP-coupled uptake of 73AsO2(-1) in everted membrane vesicles. However, transport catalyzed by ArsB alone has not previously been observed in vitro. In this study we demonstrate everted membrane vesicles prepared from cells expressing only arsB exhibit uptake of 73AsO2(-1) coupled to electrochemical energy.

Forty adult male white-footed mice (Peromyscus leucopus) were divided into four equal groups and fed diets containing 0, 100, 200 or 400 p.p.m. of a polychlorinated biphenyl (PCB) for 2 weeks. PCB ingestion increased liver weights and reduced pentobarbital-induced sleeping times at all levels tested, indicating increased hepatic microsomal enzyme activity. Plasma corticoid levels, seminal vesicle weights and testicular spermatozoa numbers were reduced at the 400 p.p.m. level.

Cottage cheese whey protein concentrate prepared by heat precipitation and centrifugation was mixed with skimmilk, NaCl and xanthan gum and used as a dressing for cottage cheese curd. The resultant experimental cottage cheese contained more protein than a sample of commercial cottage cheese. The dressed curd particles of the experimental cheese tended to cling together and the flavor was somewhat flat. When evaluated by an 18-member sensory panel, it was given preference scores slightly below the commercial sample.

The autoperfused heart-lung preparation was developed as a method for extending the acceptable donor-to-recipient interval in clinical heart-lung transplantation. Metabolic substrate enhancement has been shown to be necessary for the survival and homeostasis of the functioning preparation. To define basic metabolic requirements and to determine the resting energy expenditure of the working canine heart-lung preparation, two groups were studied. Ten canine heart-lung blocks were placed in a normothermic autoperfusion circuit. In Group 1 (n = 5), a hyperalimentation solution of balanced substrate was infused (15% dextrose, 4.25% amino acids, 8 meq magnesium sulfate, 30 IU/dl insulin, and 10% lipids). In Group 2 (n = 5), no substrate was given. The preparations were ventilated with a mixture of room air and 5% CO2 at a rate of 4 breaths/min to maintain physiological pH. Myocardial function was assessed by cardiac output determinations and mixed venous gases. Pulmonary function was assessed with arterial blood gases. The oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured with a Metabolic Cart, and the resting energy expenditure was calculated. The mean survival time for Group 1 was 360 minutes, and all preparations were terminated electively. The mean survival time for Group 2 was 219 +/- 43 minutes (p less than 0.01) with congestive heart failure as the common terminal event. All parameters of cardiac function and blood gases remained within physiological limits without significant differences between groups. The resting energy expenditure, a measure of metabolic rate, was 2.5 +/- 0.3 kcal/hr in Group 1 and 1.0 +/- 0.2 in Group 2 at termination (mean +/- SD) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)