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This article discusses the use of ultrasound of the gastric antrum to aid in the decision of deep extubation for a patient with hypertrophic cardiomyopathy (HOCM) who is at risk for aspiration. The patient in the case study had multiple comorbidities and presented for dental restoration under general anesthesia. Prior to emergence, the patient's gastric volume was assessed using point-of-care ultrasound, and it was determined that the risk for aspiration was low. The patient underwent a deep extubation without complications. The article highlights the utility of gastric antrum ultrasound as an aspiration risk assessment tool in patients with HOCM. [Extracted from the article]

OBJECTIVES: To assess the effectiveness of a proactive provider intervention in prompting prior authorization (PA) submissions or provider response prior to PA expiration for medically complex Medicaid patients. STUDY DESIGN: Pre-post outreach study with data from pharmacy claims and provider outreach. METHODS: The intervention and historical comparison (control) groups included expired PAs from December 2019 to February 2020 and from December 2018 to February 2019, respectively. Provider outreach, including telephonic and fax attempts, was conducted over a 2-week period prior to PA expiration. Outcomes were classified as positive or negative based on provider conversation coupled with the result (eg, PA submission) for the intervention group and based solely on pharmacy claims for the control group. The primary end point was the percentage of positive outcomes between the groups, analyzed via χ² test. The time from PA expiration to the new PA submission was evaluated via t test. RESULTS: A total of 342 outreach attempts were conducted for 270 PAs representing 193 unique patients. Outreach was more likely to result in positive outcomes in the intervention group vs no outreach in the control group (87% vs 25%; P < .00001). On average, PAs were submitted 3.5 days prior to expiration in the intervention group vs 13.0 days after expiration in the control group (t = --7.50; P < .00001). CONCLUSIONS: Proactive outreach resulted in a greater percentage of PA submissions and a significantly reduced time to PA submission. These findings provide important information for payers in guiding clinical programs to enhance continuity of care among at-risk populations. [ABSTRACT FROM AUTHOR]

External sensory cues can reduce freezing of gait in people with Parkinson's disease (PD), yet the role of the basal ganglia in these movements is unclear. We used microelectrode recordings to examine modulations in single unit (SU) and oscillatory local field potentials (LFP) during auditory-cued rhythmic pedaling movements of the feet. We tested five blocks of increasing cue frequencies (1 Hz, 1.5 Hz, 2 Hz, 2.5 Hz, and 3 Hz) in 24 people with PD undergoing deep brain stimulation surgery of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Single unit firing and beta band LFPs (13–30 Hz) in response to movement onsets or cue onsets were examined. We found that the timing accuracy of foot pedaling decreased with faster cue frequencies. Increasing cue frequencies also attenuated firing rates in both STN and GPi neurons. Peak beta power in the GPi and STN showed different responses to the task. GPi beta power showed persistent suppression with fast cues and phasic modulation with slow cues. STN beta power showed enhanced beta synchronization following movement. STN beta power also correlated with rate of pedaling. Overall, we showed task-related responses in the GPi and STN during auditory-cued movements with differential roles in sensory and motor control. The results suggest a role for both input and output basal ganglia nuclei in auditory rhythmic pacing of gait-like movements in PD. • Single neurons in STN (72%) and GPi (52%) responded to auditory cued foot pedaling at rates from 1 to 3 Hz in awake PD persons OFF-drug • Accuracy of pedaling with respect to cues progressively decreased as cue frequencies increased, particularly above 1.5 Hz. • GPi showed decrease in tonic beta LFP power with fast auditory cues. STN showed tonic increases in beta power after onset of foot movement. • STN is involved in motor aspects of auditory cued pedaling while the GPi may play a role in sensory processing of the task. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer affects millions of women worldwide, and for many, therapy results in treatment-induced menopause. Menopausal symptoms in breast cancer survivors are often more severe, frequent, and of greater duration compared with natural menopause. Hot flushes and night sweats pose a significant burden for many women, with limited therapeutic options as menopausal hormone therapy is contraindicated. Guidelines recommend non-hormonal pharmacological agents including clonidine, gabapentin, and some antidepressants. However, some women may be reluctant to use medications due to concerns about side effects. The aim of this narrative review was to appraise recent evidence for nonpharmacological treatments for vasomotor symptoms in breast cancer survivors including cognitive behavioural therapy, hypnosis, yoga, mindfulness, acupuncture, and lifestyle changes. Methods: A literature search was conducted. Studies were included if they were randomised and involved breast cancer survivors and nonpharmacological treatments for menopausal vasomotor symptoms. Results: Twelve studies met the criteria, and three studies of exercise in healthy menopausal women were included. Cognitive behavioural therapy reduces menopausal symptoms and perceived impact of hot flushes and night sweats in breast cancer survivors and is cost effective. The efficacy of hypnosis as a treatment for menopausal vasomotor symptoms in women with breast cancer is supported by two randomised controlled trials. Yoga and acupuncture may reduce vasomotor symptom frequency and/or burden. Studies of exercise as an intervention for vasomotor symptoms in healthy menopausal women have not shown benefit. Conclusion: Evidence for nonpharmacological interventions supports cognitive behavioural therapy and hypnosis in the management of vasomotor symptoms in breast cancer survivors. [ABSTRACT FROM AUTHOR]

• Loss-of-function mutations of PLAG1 causes Silver-Russell syndrome; PLAG1 is abundantly expressed in the murine brain. • Circadian activity levels and various other behaviours are not affected by PLAG1 deficiency in mice. • The responses of PLAG1 knockout mice in sound-based behavioural tests suggest a hearing impairment. The proto-oncogene pleomorphic adenoma gene 1 (Plag1) encodes a zinc finger transcription factor. PLAG1 is part of the high motility group AT hook-2 (HGMA2)–PLAG1–insulin-like growth factor 2 (IGF2) pathway that, when disrupted, leads to Silver–Russell syndrome, a severe form of intrauterine growth restriction. With little known about PLAG1's role in normal physiology, this study is the first to characterise the behavioural phenotype of PLAG1-deficient mice. Mice were tested for differences in circadian locomotor activity and body temperature, sleep-like behaviour, anxiety-like behaviour, cognition, social behaviour, and sensorimotor gating. Overall, the behavioural phenotype of the Plag1 knock-out (KO) mice was mild: no significant differences were seen in circadian activity levels, locomotion, object recognition, spatial memory or sociability compared to wild-type mice. However, the cued test of fear conditioning, prepulse inhibition of the startle response and Preyer's reflex test suggest that Plag1 KO mice may have a hearing impairment. This implies that PLAG1 plays an important role in proper functioning and/or development of the neural circuitry behind the auditory processes or interacts with genes involved in those processes. [ABSTRACT FROM AUTHOR]

Postural control requires effective sensory integration. People with Parkinson's disease (PD) are reported to have impaired visual and vestibular perception. While self-motion perception is a key aspect of locomotion, visual-vestibular integration has not been directly characterized in people with PD during gait. We compared the ability of people with PD and healthy older adults (OA) to integrate multi-sensory information during straight-line walking in response to visual and vestibular perturbations, using continuous translations of the visual surround and galvanic vestibular stimulation within a virtual reality environment. We measured their endpoint deviations from midline and changes in gait parameters. We found that people with PD deviated more than OA when walking in a dark environment but did not show differences in deviations when walking in a virtual room with visual information. With visual and vestibular perturbations, people with PD did not differ from OA in endpoint deviations nor variabilities. However, people with PD did not adopt a more cautious gait when GVS was applied in a virtual room, unlike OA. Overall, we showed that people with mild PD did not perform worse than OA but did show differences in gait patterns, suggesting that visual-vestibular integration is relatively preserved during gait in PD. • People with PD deviate more than older adults when walking with reduced visual information (i.e., in the dark). • People with PD do not deviate more than age-matched older adults with sensory perturbations. • Visual-vestibular sensory integration may be preserved in PD. [ABSTRACT FROM AUTHOR]

Highlights • Plant performance on identical green roofs differed in cities 1000 s of km apart. • Climate altered plant survival, growth and phenology. • Canopy density higher in three species polyculture compared with monocultures. Abstract Green rooftops are installed in many climates worldwide to support urban ecosystem services. Across North America, green roofs often make use of the same limited set of plant species, but the effects of regional climates on the survival and growth of a core set of plant species has seldom been investigated. To identify the impact of climate on green roof plant performance, we installed an identical green roof system in three Canadian cities that experience different climate conditions: Calgary, Alberta; London, Ontario; and Halifax, Nova Scotia. The green roofs were monitored across three growing seasons for plant survival, plant height, and canopy density of three species grown in monoculture: Aquilegia canadensis , Sporobolus heterolepis , and Sedum spurium , and a mixture planting with all three species. Green roof vegetation canopy density, plant height and growth rates differed by city, plant species, substrate depth and planting type (monoculture or mixture treatment). Between sites, plant species exhibited different growth phenologies. Mixture treatments performed slightly better than monoculture plantings at each site in canopy density measures but were not significantly greater in plant height measures. The growth rate between years two and three was greatest for the mixture treatment, indicating greater potential for long term survival and performance of mixture plantings. The London, Ontario site, with a relatively moderate climate, supported the best green roof growth and performance compared to the cooler and drier Calgary and the rainier Halifax. [ABSTRACT FROM AUTHOR]

Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil (liposomal doxorubicin) in 1995 to Onivyde (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale-up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical trials, and the challenges that may hinder development of the nanomedicines for cancer treatment. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 11 article‐registration‐date‐day 23 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_175.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil® (liposomal doxorubicin) in 1995 to Onivyde® (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale‐up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical trials, and the challenges that may hinder development of the nanomedicines for cancer treatment. [ABSTRACT FROM AUTHOR]

Bradykinesia is a disabling symptom of Parkinson's disease (PD) which presents with slowness of movement. Visual assessment using clinical rating scales is currently the gold standard to assess bradykinesia. Such assessments require multiple separate movements, are subjective, and rely on the ability of the rater to determine frequency and amplitude features of excursion of multiple joints simultaneously. The current study introduces the use of wearable inertial measurement units (IMUs) to characterize full-arm repetitive movements and provide a new index score for bradykinesia severity (BKI) in the upper limbs. The BKI provides an approach to measuring bradykinesia reliably and objectively. Importantly, this index is needed to demonstrate separability between healthy individuals and PD participants, and also between bradykinetic and non-bradykinetic PD participants. Thirteen PD participants and ten age-matched healthy control participants were studied. Using a single upper limb task that activated multiple joints and recordings from angular displacements from all joints, features relevant to demonstrating bradykinesia were extracted and systematically combined to create the total BKI. A strong correlation coefficient was obtained comparing BKI to upper limb UPDRS bradykinesia scores ( r s = − 0.626, p = 0.001). The BKI successfully identified differences between control and PD participants ( p = 0.018). The BKI was also sensitive enough to identify differences within the PD population, separating PD participants with and without bradykinesia ( p < 0.001). This study demonstrates the feasibility of using IMU-based motion capture systems and employing the new BKI for quantitative assessment of bradykinesia. This approach when generalized to lower extremity and truncal movements would be able to provide an objective and reproducible whole body bradykinesia index. [ABSTRACT FROM AUTHOR]

Plants make important contributions to the services provided by engineered ecosystems such as green roofs. Ecologists use plant species traits as generic predictors of geographical distribution, interactions with other species, and ecosystem functioning, but this approach has been little used to optimize engineered ecosystems. Four plant species traits (height, individual leaf area, specific leaf area, and leaf dry matter content) were evaluated as predictors of ecosystem properties and services in a modular green roof system planted with 21 species. Six indicators of ecosystem services, incorporating thermal, hydrological, water quality, and carbon sequestration functions, were predicted by the four plant traits directly or indirectly via their effects on aggregate ecosystem properties, including canopy density and albedo. Species average height and specific leaf area were the most useful traits, predicting several services via effects on canopy density or growth rate. This study demonstrates that easily measured plant traits can be used to select species to optimize green roof performance across multiple key services. [ABSTRACT FROM AUTHOR]

Pelvic radiation disease (PRD) occurs in 2-11% of patients undergoing pelvic radiation for urologic and gynecologic malignancies. Hyperbaric oxygen therapy (HBOT) has previously been described as a noninvasive therapeutic option for the treatment of PRD. the purpose of study was to analyze prospectively the results of HBOT in 44 consecutive patients with PRD who were resistant to conventional oral or topical treatments. Material and Methods. The median age of the cohort was 65.7 years (39-85). Twenty-seven percent of patients required blood transfusion (n = 12). The median of delay between radiotherapy and HBOT was 26 months (3-175). We evaluated the results of HBOT, using SOMA-LENT Scale. Results. SOMA-LENT score was decreased in 59% of patient. The median of SOMA-LENT score before HBOT was significantly higher, being equal to 14 (0-36), than after HBOT with the SOMA-LENT score of 12 (0-38) (P = 0.003). Tenesmus (P = 0.02), bleeding (P = 0.0001), and ulceration (P = 0.001) significantly decreased after HBOT. Regarding patients with colostomy, 33% (n = 4) benefited from colostomies closure. HBOT was generally well tolerated. Only one patient stopped precociously due to transient myopia. Conclusion. This study is in favor of the interest of HBOT in pelvic radiation disease treatment(PRD). [ABSTRACT FROM AUTHOR]

Mpox, monkeypox, air travel, infection transmission, commercial flights While these long international flights may pose a risk of infection transmission, our analysis identified no secondary cases of mpox amongst flight contacts of 15 infectious returned travellers to Australia. Keywords: Mpox; monkeypox; air travel; commercial flights; infection transmission EN Mpox monkeypox air travel commercial flights infection transmission 1 3 3 09/13/23 20230701 NES 230701 Although difficult to assess accurately, there is a risk of infectious disease transmission during commercial air travel.[1] During flight, the aircraft cabin is a ventilated, enclosed environment that exposes passengers to hypobaric hypoxia, dry humidity and close proximity to fellow passengers.[1] Aside from infections transmitted via food or water, conditions that have historically been transmitted on commercial aircraft include tuberculosis,[2] norovirus,[3] measles, SARS,[4] COVID-19[5] and influenza.[1] During the global mpox outbreak of 2022, the first cases in Australia were amongst returned travellers from Europe. [Extracted from the article]

A letter to the editor is presented regarding the use of several risk models including Gail model, Breast Cancer Surveillance Consortium (BCSC), and Tyrer-Cuzick model in implementing breast cancer risk assessment program in a multiethnic patient population.

A letter to the editor is presented about a child suffering from long QT syndrome.

Purpose: This study aimed to measure the prevalence of menopausal symptoms in patients attending a multidisciplinary model of care clinic at their initial clinic visit and their subsequent follow-up consultation using a validated patient-reported outcome measure to assess whether menopausal symptoms after cancer had improved. Methods: A retrospective review was conducted of patients attending the clinic in a 12-month period in 2017 (n = 189). Recorded variables included patient demographics, details of index cancer, previous treatments, and menopausal symptom management strategies. Severity of menopausal symptoms was evaluated using the Greene Climacteric Scale. The extent to which patients were bothered by symptoms was combined into two categories and dichotomized (present/absent). Differences in symptom prevalence between the initial consultation and first follow-up visit were examined using McNemar's test. Results: The majority of patients attending the clinic had a history of breast cancer (72%). Fifty-five percent of patients were prescribed a non-hormonal therapy at their initial visit, most commonly gabapentin. Significantly fewer patients reported being bothered by hot flushes, fatigue, sleep difficulties, and loss of interest in sex, anxiety, or troubles concentrating at the first follow-up visit compared to their initial consultation (p < 0.01). Conclusion: In this study, there was an improvement in self-reported menopausal symptoms in a significant proportion of cancer survivors attending a multidisciplinary menopause clinic between their initial and first subsequent follow-up consultations. [ABSTRACT FROM AUTHOR]

Theta‐burst transcranial ultrasound stimulation (tbTUS) increases primary motor cortex (M1) excitability for at least 30 min. However, the remote effects of focal M1 tbTUS on the excitability of other cortical areas are unknown. Here, we examined the effects of left M1 tbTUS on right M1 excitability. An 80 s train of active or sham tbTUS was delivered to the left M1 in 20 healthy subjects. Before and after the tbTUS, we measured: (1) corticospinal excitability using motor‐evoked potential (MEP) amplitudes from single‐pulse transcranial magnetic stimulation (TMS) of left and right M1; (2) interhemispheric inhibition (IHI) from left to right M1 and from right to left M1 using a dual‐site paired‐pulse TMS paradigm; and (3) intracortical circuits of the right M1 with short‐interval intracortical inhibition and intracortical facilitation (ICF) using paired‐pulse TMS. Left M1 tbTUS decreased right M1 excitability as shown by decreased MEP amplitudes, increased right M1 ICF and decreased short‐interval IHI from left to right hemisphere at interstimulus interval (ISI) of 10 ms but not long‐interval IHI at interstimulus interval of 40 ms. The study showed that left M1 tbTUS can change the excitability of remote cortical areas with decreased right M1 excitability and interhemispheric inhibition. The remote effects of tbTUS should be considered when it is used in neuroscience research and as a potential neuromodulation treatment for brain disorders. Key points: Transcranial ultrasound stimulation (TUS) is a novel non‐invasive brain stimulation technique for neuromodulation with the advantages of being able to achieve high spatial resolution and target deep brain structures.A repetitive TUS protocol, with an 80 s train of theta burst patterned TUS (tbTUS), has been shown to increase primary motor cortex (M1) excitability, as well as increase alpha and beta movement‐related spectral power in distinct brain regions.In this study, we examined on the effects of the motor cortical tbTUS on the excitability of contralateral M1 measured with MEPs elicited by transcranial magnetic stimulation.We showed that left M1 tbTUS decreased right M1 excitability and left‐to‐right M1 interhemispheric inhibition, and increased intracortical facilitation of right M1.These results lead to better understand the effects of tbTUS and can help the development of tbTUS for the treatment of neurological and psychiatric disorders and in neuroscience research. [ABSTRACT FROM AUTHOR]

Botticelli et al. proposed the activity of indoleamine-2,3-dioxygenase 1 (IDO) as a potential mechanism and predictive marker for primary resistance against anti-PD-1 treatment in the context of non-small cell lung cancer. However, there are a few points for the authors to address in order to strengthen their claims. First, there are many enzymes that modulate the kynurenine to tryptophan ratio, thereby calling into question their use of the ratio as a proxy for IDO activity. Second, the authors could compare IDO to other proposed markers in the literature, providing a better understanding of its predictive value. [ABSTRACT FROM AUTHOR]

Positive frequency-dependent selection should theoretically lead to monomorphic warning coloration. Instead, numerous examples of polymorphic warning signals exist. Biases – for example, in human perception – hinder our appreciation and research of understanding warning signal diversity. We propose strategies to counter such biases and objectively move our field forward. Positive frequency-dependent selection should theoretically lead to monomorphic warning coloration. Instead, numerous examples of polymorphic warning signals exist. Biases – for example, in human perception – hinder our appreciation and research in understanding warning signal diversity. We propose strategies to counter such biases and objectively move our field forward. [ABSTRACT FROM AUTHOR]

• JYNNEOS vaccination produces robust anti-orthopoxvirus antibody response. • Naive vaccinees generate OPXV-specific IgM early after vaccination. • IgG responses peak around 2 weeks after second vaccine dose. • Titers wane at 2 years, and more rapidly in naïve vaccinees. • Antibodies neutralize VACV and MPXV differently, but had similar rise from baseline. The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation. [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG. We tested 19 patients with PD who had been assessed for FOG (n =14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest. EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n =14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n =5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas. Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG. • Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD). • EEG source activity localized to right frontal and parietal areas in PD-FOG. • Alpha rhythms in these areas increased with severity of lower limb motor blocks. • Dopaminergic medications improved FOG and led to fewer alpha rhythms. • These brain signals may be useful for neurorehabilitation of PD-FOG. [ABSTRACT FROM AUTHOR]

Green roof ecosystems are constructed to provide services such as stormwater retention and urban temperature reductions. Green roofs with shallow growing media represent stressful conditions for plant survival, thus plants that survive and grow are important for maximizing economic and ecological benefits. While field trials are essential for selecting appropriate green roof plants, we wanted to determine whether plant leaf traits could predict changes in abundance (growth) to provide a more general framework for plant selection. We quantified leaf traits and derived life-history traits (Grime’s C-S-R strategies) for 13 species used in a four-year green roof experiment involving five plant life forms. Changes in canopy density in monocultures and mixtures containing one to five life forms were determined and related to plant traits using multiple regression. We expected traits related to stress-tolerance would characterize the species that best grew in this relatively harsh setting. While all species survived to the end of the experiment, canopy species diversity in mixture treatments was usually much lower than originally planted. Most species grew slower in mixture compared to monoculture, suggesting that interspecific competition reduced canopy diversity. Species dominant in mixture treatments tended to be fast-growing ruderals and included both native and non-native species. Specific leaf area was a consistently strong predictor of final biomass and the change in abundance in both monoculture and mixture treatments. Some species in contrasting life-form groups showed compensatory dynamics, suggesting that life-form mixtures can maximize resilience of cover and biomass in the face of environmental fluctuations. This study confirms that plant traits can be used to predict growth performance in green roof ecosystems. While rapid canopy growth is desirable for green roofs, maintenance of species diversity may require engineering of conditions that favor less aggressive species. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear.Objective: To investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies.Methods: In 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings.Results: There was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here.Conclusions: Premotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway. [ABSTRACT FROM AUTHOR]

Objective: Transcranial ultrasound stimulation (TUS) is a promising noninvasive brain stimulation technique with advantages of high spatial precision and ability to target deep brain regions. This study aimed to develop a TUS protocol to effectively induce brain plasticity in human subjects. Methods: An 80‐second train of theta burst patterned TUS (tbTUS), regularly patterned TUS (rTUS) with the same sonication duration, and sham tbTUS was delivered to the motor cortex in healthy subjects. Transcranial magnetic stimulation (TMS) was used to examine changes in corticospinal excitability, intracortical inhibition and facilitation, and the site of plasticity induction. The effects of motor cortical tbTUS on a visuomotor task and the effects of occipital cortex tbTUS on motor cortical excitability were also tested. Results: The tbTUS produced consistent increase in corticospinal excitability for at least 30 minutes, whereas rTUS and sham tbTUS produced no significant change. tbTUS decreased short‐interval intracortical inhibition and increased intracortical facilitation. The effects of TMS in different current directions suggested that the site of the plastic changes was within the motor cortex. tbTUS to the occipital cortex did not change motor cortical excitability. Motor cortical tbTUS shortened movement time in a visuomotor task. Interpretation: tbTUS is a novel and efficient paradigm to induce cortical plasticity in humans. It has the potential to be developed for neuromodulation treatment for neurological and psychiatric disorders, and to advance neuroscience research. ANN NEUROL 2022;91:238–252 [ABSTRACT FROM AUTHOR]

Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. We find the ssDNA-binding complexes canonical replication protein A (RPA1, RPA2, and RPA3) and Alternative-RPA (RPA1, RPA3, and primate-specific RPA4) are upregulated in Huntington disease and spinocerebellar ataxia type 1 (SCA1) patient brains. Protein interactomes of RPA and Alt-RPA reveal unique and shared partners, including modifiers of CAG instability and disease presentation. RPA enhances in vitro melting, FAN1 excision, and repair of slipped-CAGs and protects against CAG expansions in human cells. RPA overexpression in SCA1 mouse brains ablates expansions, coincident with decreased ATXN1 aggregation, reduced brain DNA damage, improved neuron morphology, and rescued motor phenotypes. In contrast, Alt-RPA inhibits melting, FAN1 excision, and repair of slipped-CAGs and promotes CAG expansions. These findings suggest a functional interplay between the two RPAs where Alt-RPA may antagonistically offset RPA's suppression of disease-associated repeat expansions, which may extend to other DNA processes. [Display omitted] • RPA and primate-specific Alt-RPA are upregulated in HD and SCA1 patient brains • RPA/Alt-RPA differentially interact with CAG instability and disease modifiers • RPA enhances and Alt-RPA inhibits correct repair of slipped-CAG intermediates • RPA prevents and Alt-RPA promotes disease-worsening somatic repeat expansions A balance between expression, function, and protein-protein interactions of single-stranded DNA-binding proteins canonical RPA and primate-specific Alternative-RPA regulates somatic trinucleotide CAG repeat expansions associated with neurodegeneration in Huntington Disease and Spinocerebellar Ataxia Type 1. [ABSTRACT FROM AUTHOR]

Abstract Purpose Previous studies indicate that there is an axial gradient of collagen lamellar branching and anastomosing leading to regional differences in corneal tissue stiffness that may control corneal shape. To further test this hypothesis we have measured the axial material stiffness and quantified the collagen lamellar complexity in ectatic and mechanically weakened keratoconus corneas (KC). Methods Acoustic radiation force elastic microscopy (ARFEM) was used to probe the axial mechanical properties of the cone region of three donor KC buttons. 3 Dimensional second harmonic generation microscopy (3D-SHG) was used to qualitatively evaluate lamellar organization in 3 kC buttons and quantitatively measure lamellar branching point density (BPD) in a separate KC button that had been treated with epikeratophakia (Epi-KP). Results The mean elastic modulus for the KC corneas was 1.67 ± 0.44 kPa anteriorly and 0.970 ± 0.30 kPa posteriorly, substantially below that previously measured for normal human cornea. 3D-SHG of KC buttons showed a simplified collagen lamellar structure lacking noticeable angled lamellae in the region of the cone. BPD in the anterior, posterior, central and paracentral regions of the KC cornea were significantly lower than in the overlying Epi-KP lenticule. Additionally, BPD in the cone region was significantly lower than the adjacent paracentral region in the KC button. Conclusions The KC cornea exhibits an axial gradient of mechanical stiffness and a BPD that appears substantially lower in the cone region compared to normal cornea. The findings reinforce the hypothesis that collagen architecture may control corneal mechanical stiffness and hence corneal shape. Highlights • The anterior is stiffer than the posterior in the keratoconus cornea cone. • The keratoconus cornea cone is significantly less stiff than the healthy cornea. • Collagen complexity in the anterior keratoconus cone is greater than the posterior. • Collagen complexity in the keratoconus cone is less than in the healthy cornea. • Collagen complexity outside of the keratoconus cone is greater than within. [ABSTRACT FROM AUTHOR]

The primary purpose of this study was to examine whether the self-reported number of health care visits over a 1-year period was associated with engagement in health promoting behaviors (i.e., healthy eating and physical activity) and perceived health status among a cross-sectional sample of African American women who were pre-hypertensive/hypertensive and/or overweight or obese (N= 180). The study participants were recruited in predominantly African American churches and had their data collected in April and May of 2009. Age, income, and education were also examined as moderators in the aforementioned relationships. Results revealed that the self-reported number of health care visits was significantly positively associated with healthy eating and perceived health status. Income moderated the relationship between self-reported number of health care visits and engagement in healthy eating. These results provide support for health promotion programs for African American women with program components that explain the relationships among routine care from a health care provider, engagement in health promoting behaviors, and prevention of chronic health conditions. [ABSTRACT FROM PUBLISHER]

Potential health hazards from waste anesthetic gases (WAGs) have been a concern since the introduction of inhalational anesthetics into clinical practice. The potential to exceed recommended exposure levels (RELs) in the postanesthesia care unit (PACU) exists. The aim of this pilot study was to assess sevoflurane WAG levels while accounting for factors that affect inhalational anesthetic elimination. In this pilot study, 20 adult day surgery patients were enrolled with anesthesia maintained with sevoflurane. Following extubation, exhaled WAG from the patient breathing zone was measured 8 inches from the patient’s mouth in the PACU. Maximum sevoflurane WAG levels in the patient breathing zone exceeded National Institute for Occupational Safety and Health (NIOSH) RELs for every 5-minute time interval measured during PACU Phase I. Observed WAGs in our study were explained by inhalational anesthetic pharmacokinetics. Further analysis suggests that the rate of washout of sevoflurane was dependent on the duration of anesthetic exposure. This study demonstrated that clinically relevant inhalational anesthetic concentrations result in sevoflurane WAG levels that exceed current RELs. Evaluating peak and cumulative sevoflurane WAG levels in the breathing zone of PACU Phase I and Phase II providers is warranted to quantify the extent and duration of exposure. [ABSTRACT FROM AUTHOR]

arising from N. C. Derecki et al. 484, 105-109 (2012); doi:10.1038/nature10907 [ABSTRACT FROM AUTHOR]

Compulsive behavior is a debilitating clinical feature of many forms of neuropsychiatric disease, including Tourette syndrome, obsessive-compulsive spectrum disorders, eating disorders, and autism. Although several studies link striatal dysfunction to compulsivity, the pathophysiology remains poorly understood. Here, we show that both constitutive and induced genetic deletion of the gene encoding the melanocortin 4 receptor (MC4R), as well as pharmacologic inhibition of MC4R signaling, normalize compulsive grooming and striatal electrophysiologic impairments in synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3)-null mice, a model of human obsessive-compulsive disorder. Unexpectedly, genetic deletion of SAPAP3 restores normal weight and metabolic features of MC4R-null mice, a model of human obesity. Our findings offer insights into the pathophysiology and treatment of both compulsive behavior and eating disorders. [ABSTRACT FROM AUTHOR]

We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the hippocampal dentate gyrus. We have further found that chemicals having efficacy in this in vivo screening assay also protect dopaminergic neurons of the substantia nigra following exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a mouse model of Parkinson disease. Here, we provide evidence that an active analog of P7C3, known as P7C3A20, protects ventral horn spinal cord motor neurons from cell death in the G93A-SOD1 mutant mouse model of amyotrophic lateral sclerosis (ALS). P7C3A20 is efficacious in this model when administered at disease onset, and protection from cell death correlates with preservation of motor function in assays of walking gait and in the accelerating rotarod test. The prototypical member of this series, P7C3, delays disease progression in G93A-SOD1 mice when administration is initiated substantially earlier than the expected time of symptom onset. Dimebon, an antihistaminergic drug with significantly weaker proneurogenic and neuroprotective efficacy than P7C3, confers no protection in this ALS model. We propose that the chemical scaffold represented by P7C3 and P7C3A20 may provide a basis for the discovery and optimization of pharmacologic agents for the treatment of ALS. [ABSTRACT FROM AUTHOR]

We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the dentate gyrus. Here, we provide evidence that P7C3 also protects mature neurons in brain regions outside of the hippocampus. P7C3 blocks 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated cell death of dopaminergic neurons in the substantia nigra of adult mice, a model of Parkinson disease (PD). Dose-response studies show that the P7C3 analog P7C3A20 blocks cell death with even greater potency and efficacy, which parallels the relative potency and efficacy of these agents in blocking apoptosis of newborn neural precursor cells of the dentate gyrus. P7C3 and P7C3A20 display similar relative effects in blocking 1-methyl-4-phenylpyridinium (MPP+)-mediated death of dopaminergic neurons in Caenorhabditis elegans, as well as in preserving C. elegans mobility following MPP+ exposure. Dimebon, an antihistaminergic drug that is weakly proneurogenic and neuroprotective in the dentate gyrus, confers no protection in either the mouse or the worm models of PD. We further demonstrate that the hippocampal proneurogenic efficacy of eight additional analogs of P7C3 correlates with their protective efficacy in MPTP-mediated neurotoxicity. In vivo screening of P7C3 analogs for proneurogenic efficacy in the hippocampus may thus provide a reliable means of predicting neuroprotective efficacy. We propose that the chemical scaffold represented by P7C3 and P7C3A20 provides a basis for optimizing and advancing pharmacologic agents for the treatment of patients with PD. [ABSTRACT FROM AUTHOR]

Hsp70s comprise a deeply conserved chaperone family that has a central role in maintaining protein homeostasis. In humans, Hsp70 client specificity is provided by 49 different co-factors known as J domain proteins (JDPs). However, the cellular function and client specificity of JDPs have largely remained elusive. We have combined affinity purification-mass spectrometry (AP-MS) and proximity-dependent biotinylation (BioID) to characterize the interactome of all human JDPs and Hsp70s. The resulting network suggests specific functions for many uncharacterized JDPs, and we establish a role of conserved JDPs DNAJC9 and DNAJC27 in histone chaperoning and ciliogenesis, respectively. Unexpectedly, we find that the J domain of DNAJC27 but not of other JDPs can fully replace the function of endogenous DNAJC27, suggesting a previously unappreciated role for J domains themselves in JDP specificity. More broadly, our work expands the role of the Hsp70-regulated proteostasis network and provides a platform for further discovery of JDP-dependent functions. [Display omitted] • Protein-protein and proximity interaction networks of all human JDPs and Hsp70s • DNAJC9 is a histone H3/H4-specific chaperone essential for cell proliferation • DNAJC27 is a novel regulator of ciliogenesis together with its interactor FAM184A • J domains are not interchangeable; they can have unique roles beyond binding Hsp70 Piette and colleagues used AP-MS and BioID to systematically characterize the interaction network of all human J domain proteins (JDPs) and Hsp70s. They discovered roles for specific JDPs in RNA splicing, histone chaperoning, and ciliogenesis. They also uncovered an unexpected role for the J domain itself in determining JDP functional specificity. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Wild-type microglia do not reverse pathology in mouse models of Rett syndrome," which was published in a previous issue of the journal.