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Introduction Greater late-life brain volumes are associated with resilience against dementia. We examined relationships between birthweight, life-long socioeconomic status and health with late-life brain volumes. We hypothesised that early-life factors directly affect late-life brain volumes. Methods Adults aged 59-67y underwent MRI and brain volumes were measured. Birthweight and lifelong health, and socioeconomic status were quantified and the principle components of each extracted. Relationships were examined using regression and structural equation analysis. Results Birthweight (β=0.095, p=0.017) and childhood socioeconomic status (β=0.091, p=0.033, n=280) were directly associated with brain volume. Childhood socioeconomic status was further associated with grey matter volume (β=0.04, p=0.047). Adult health was linked to increased brain volume (β=0.15, p=0.003). Conclusion Birthweight and childhood socioeconomic status are associated with whole and regional brain volume through direct mechanisms. Optimal fetal development, reduced childhood poverty and good adult health could reduce brain atrophy and delay dementia onset in late-life., (The Author(s). Published by S. Karger AG, Basel.)

Corticospinal excitability (CSE) increases prior to a voluntary contraction; however, the relative contributions of premotor cortical and spinal mechanisms are poorly understood. It is unknown whether the intended voluntary contractile rate affects CSE. Eighteen young, healthy participants (nine females) completed isometric elbow flexion contractions targeting 50% maximal voluntary contraction (MVC) torque, at either fast (fast as possible) or slow (25% MVC/s) contractile rates. Participants were cued to contract with warning (red) and "GO" (green) visual signals. Magnetic and electric stimulations were applied to elicit motor evoked potentials (MEPs), cervicomedullary evoked potentials (CMEPs), and M-waves, in the surface electromyogram (EMG) recorded over the biceps brachii. MEPs and CMEPs were collected at 0, 25, 50 and 75% premotor reaction time (RT - defined as the time between the "GO" cue and onset of biceps brachii EMG) and compared to a resting baseline. MEP amplitude was greater than baseline at 75% RT (p=0.009), and CMEP amplitude was significantly increased at all RT points relative to baseline (p≤0.001). However, there were no differences in MEP and CMEP amplitudes when compared between fast and slow conditions (p≥0.097). Normalized to the CMEP, there was no difference in MEP amplitude from baseline in either contractile condition (p≥0.264). These results indicate that increased premotor CSE is a spinally-mediated response. Furthermore, premotor CSE is not influenced by the intended voluntary contractile rate. CMEP amplitudes were larger for females than males within the premotor RT period (p=0.038), demonstrating that premotor spinal excitability responses may be influenced by sex.

Whole-body vestibular-evoked balance responses decrease following ~ 55 min of normobaric hypoxia. It is unclear how longer durations of hypoxia affect the vestibular control of balance at the muscle and whole-body levels. This study examined how four hours of normobaric hypoxia influenced the vestibular control of balance. Fifteen participants (4 females; 11 males) stood on a force plate with vision occluded and head rotated rightward while subjected to three blocks of binaural, bipolar stochastic electrical vestibular stimulation (EVS; 0-25 Hz, root mean square amplitude = 1.1 mA) consisting of two, 90-s trials. The relationship between EVS and anteroposterior (AP) forces or medial gastrocnemius (MG) electromyography (EMG) was estimated in the time and frequency domains at baseline (BL; 0.21 fraction of inspired oxygen-F I O 2 ) and following two (H2) and four (H4) hours of normobaric hypoxia (0.11 F I O 2 ). The EVS-MG EMG short-latency peak and peak-to-peak amplitudes were smaller than BL at H2 and H4, but the medium-latency peak amplitude was only lower at H4. The EVS-AP force medium-latency peak amplitude was lower than BL at H4, but the short-latency peak and peak-to-amplitudes were unchanged. The EVS-MG EMG coherence and gain were reduced compared to BL at H2 and H4 across multiple frequencies ≥ 7 Hz, whereas EVS-AP force coherence was blunted at H4 (≤ 4 Hz), but gain was unaffected. Overall, the central nervous system's response to vestibular-driven signals during quiet standing was decreased for up to four hours of normobaric hypoxia, and vestibular-evoked responses recorded within postural muscles may be more sensitive than the whole-body response., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Low fractions of inspired oxygen (FI O2 ; i.e., hypoxia) affect aspects of skeletal muscle contractility in humans, but it remains unclear if post-activation potentiation (PAP) and the torque-frequency (T-F) relationship are altered. We investigated the effects of two (H2) and four hours (H4) of normobaric hypoxia (FI O2 =0.11±0.47) on the magnitude of PAP of the knee extensors (KE) and the T-F relationship of the dorsiflexors (DF) in 13 and 12 healthy participants, respectively. To assess PAP, a resting twitch was evoked via femoral nerve stimulation before, and 2-300 s following a 10-s maximal voluntary contraction (MVC). A T-F relationship was obtained by stimulating the common fibular nerve with a single pulse and 1-s trains between 5-100 Hz. During hypoxia, peripheral oxygen saturation decreased by ~18% from 98.0±0.8% at baseline (P<0.001). MVC force and voluntary activation (VA) of the KE were lower than baseline throughout hypoxia (e.g., ~8 and ~5%, respectively at H2; P≤0.027); however, the magnitude of PAP was not altered by hypoxia (P≥0.711). Surprisingly, PAP did increase with time across the control day (P≤0.012). MVC torque and VA of the DF were unaffected by hypoxia (P≥0.127), but the estimated frequency required to evoke 50 % of 100-Hz torque increased by ~1.2 Hz at H2 (P≤0.021). These results imply that two hours of normobaric hypoxia were sufficient to: i) impair neural drive to the KE but not the mechanism(s) responsible for PAP, and ii) lead to a rightward shift of the T-F relationship for the DF.

Sleep deprivation alters cognitive and sensorimotor function, but its effects on the control of standing balance are inconclusive. The vestibular system is critical for standing balance, and is modified by sleep deprivation; however, how sleep deprivation affects vestibular-evoked balance responses is unknown. Thus, this study aimed to examine the effect of 24 h of sleep deprivation on the vestibular control of standing balance. During both a well-rested (i.e., control) and sleep deprivation condition, nine females completed two 90-s trials of bilateral, binaural stochastic electrical vestibular stimulation (EVS) and two 120-s trials of quiet stance on a force plate. Quiet stance performance was assessed by center of pressure displacement parameters. Mediolateral ground reaction force (ML force) and surface electromyography (EMG) of the right medial gastrocnemius (MG) were sampled simultaneously with the EVS signal to quantify vestibular control of balance within the frequency (gain and coherence) and time (cumulant density) domains. Twenty-four hours of sleep deprivation did not affect quiet stance performance. Sleep deprivation also had limited effect on EVS-MG EMG and EVS-ML Force coherence (less than control at 8-10.5 Hz, greater at ~ 16 Hz); however, gain of EVS-MG EMG (< 8, 11-24 Hz) and EVS-ML force (0.5-9 Hz) was greater for sleep deprivation than control. Sleep deprivation did not alter peak-to-peak amplitude of EVS-MG EMG (p = 0.51) or EVS-ML force (p = 0.06) cumulant density function responses. Despite no effect on quiet stance parameters, the observed increase in vestibular-evoked balance response gain suggests 24-h sleep deprivation may lead to greater sensitivity of the central nervous system when transforming vestibular-driven signals for standing balance control., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brain iron increases in several neurodegenerative diseases are associated with disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron, systemic iron and inflammatory status. Brain magnetic resonance imaging (MRI) scans and blood plasma samples were collected from cognitively healthy females (n = 176, mean age = 61.4 ± 4.5 years, age range = 28-72 years) and males (n = 152, mean age = 62.0 ± 5.1 years, age range = 32-74 years). Regional brain iron was quantified using quantitative susceptibility mapping. To assess systemic iron, haematocrit, ferritin and soluble transferrin receptor were measured, and total body iron index was calculated. To assess systemic inflammation, C-reactive protein (CRP), neutrophil:lymphocyte ratio (NLR), macrophage colony-stimulating factor 1 (MCSF), interleukin 6 (IL6) and interleukin 1β (IL1β) were measured. We demonstrated that iron levels in the right hippocampus were higher in males compared with females, while iron in the right caudate was higher in females compared with males. There were no significant associations observed between subcortical iron levels and blood markers of iron and inflammatory status indicating that such blood measures are not markers of brain iron. These results suggest that brain iron may be regulated independently of blood iron and so directly targeting global iron change in the treatment of neurodegenerative disease may have differential impacts on blood and brain iron., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Interlimb asymmetry (ILA) refers to an anatomical or physiological imbalance between contralateral limbs, which can influence neuromuscular function. Investigating the influence of neuromuscular fatigue on ILA may be critical for optimizing training programs, injury rehabilitation, and sport-specific performance. The purpose of this study was to determine if a single bout of ice hockey-specific exercise creates or exacerbates lower-limb ILA. Before and after an on-ice training session, 33 youth ice-hockey athletes (14.9 [1.7] y; 11 females) performed 3 repetitions of a maximal vertical countermovement jump (CMJ), an eccentric hamstring contraction, and maximal isometric hip adduction and abduction contractions. Force- and power-related variables were analyzed to determine limb-specific neuromuscular function. The on-ice session reduced maximal isometric hip adduction (left: 7.3% [10.3%]; right: 9.5% [9.6%]) and abduction (left: 4.9% [6.9%]; right: 5.0% [8.1%]) force, but did not impair (P ≥ .10) CMJ performance (jump height, relative peak power, braking duration, and total duration). After the on-ice session, ILA was greater for CMJ propulsive impulse (6.3% [2.9%] vs 5.1% [2.6%]), CMJ braking rate of force development (19.3% [7.6%] vs 15.2% [6.4%]), and peak isometric hip adduction force (6.7% [5.5%] vs 6.1% [4.1%]). In conclusion, hockey-specific exercise leads to increased ILA for multiple force-related metrics, which may be a compensatory mechanism to maintain bilateral task performance when fatigued.

Introduction: When an isometric contraction is sustained at a submaximal torque, activation of the motoneuron pool increases, making it difficult to interpret neural excitability alterations. Thus, more recently, isometric contractions with maintained electromyographic (EMG) activity (matched-EMG) are being used to induce fatigue; however, little is known about the neurophysiological adjustments that occur to satisfy the requirements of the task., Methods: For our study, 16 participants performed a 10-min sustained isometric elbow flexion contraction at 20% maximal voluntary contraction (MVC) torque or the level of integrated biceps brachii EMG recorded at 20% MVC torque. Surface EMG was used to assess global median frequency, and four fine-wire electrode pairs were used to obtain motor unit (MU) discharge rate from biceps brachii. Torque or EMG steadiness was also assessed throughout the fatiguing contractions., Results: MU discharge rate increased and torque steadiness decreased during the matched-torque contraction; however, MU discharge rate decreased during the matched-EMG contraction, and no changes occurred for EMG steadiness. Data pooled for the two contractions revealed a decrease in global median frequency. Lastly, a greater loss of MVC torque was observed immediately after the matched-torque compared with matched-EMG contraction., Conclusions: These findings indicate that, during a matched-torque fatiguing contraction, the nervous system increases MU discharge rates at the cost of poorer steadiness to maintain the requisite torque. In contrast, during a matched-EMG fatiguing contraction, a reduction of MU discharge rates allows for maintenance of EMG steadiness., (Copyright © 2024 by the American College of Sports Medicine.)

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflict of Interest and Sources of Funding: C.J.M. has received grants and contracts and/or participated in clinical trials with funding from BINX, Biomedical Advanced Research and Development Authority/GlaxoSmithKline, Becton Dickinson, US Centers for Disease Control and Prevention, Cepheid, Gilead, Hologic, Lupin, National Association of County and City Health Officials, and National Institutes of Health paid to her employer. M.D. and J.W. acknowledge support from US Centers for Disease Control and Prevention paid to their employer.

Acute exposure to hypoxia increases postural sway, but the underlying neurophysiological factors are unclear. Golgi tendon organs (GTOs), located within the musculotendinous junction (MTJ), provide inhibitory signals to plantar flexor muscles that are important for balance control; however, it is uncertain if GTO function is influenced by hypoxia. The aim of this study was to determine how normobaric hypoxia influences lower limb tendon-evoked inhibitory reflexes during upright stance. We hypothesized that tendon-evoked reflex area and duration would decrease during hypoxia, indicating less inhibition of postural muscles compared with normoxia. At baseline (BL; 0.21 fraction of inspired oxygen, F I O 2 ) and at ∼2 (H2) and 4 (H4) h of normobaric hypoxia (0.11 F I O 2 ) in a normobaric hypoxic chamber, 16 healthy participants received electrical musculotendinous stimulation (MTstim) to the MTJ of the left Achilles tendon. The MTstim was delivered as two sets of 50 stimuli while the participant stood on a force plate with their feet together. Tendon-evoked inhibitory reflexes were recorded from the surface electromyogram of the ipsilateral medial gastrocnemius, and center of pressure (CoP) variables were recorded from the force plate. Normobaric hypoxia increased CoP velocity ( P ≤ 0.002) but not CoP standard deviation ( P ≥ 0.12). Compared with BL, normobaric hypoxia reduced tendon-evoked inhibitory reflex area by 45% at H2 and 53% at H4 ( P ≤ 0.002). In contrast, reflex duration was unchanged during hypoxia. The reduced inhibitory feedback from the GTO pathway could likely play a role in the increased postural sway observed during acute exposure to hypoxia. NEW & NOTEWORTHY The Ib pathway arising from the Golgi tendon organ provides inhibitory signals onto motor neuron pools that modifies force and, hence, postural control. Although hypoxia influences standing balance (increases sway), the underlying mechanisms have yet to be unraveled. Our study identified that tendon-evoked inhibition onto a plantar flexor motoneuron pool is reduced by acute exposure to normobaric hypoxia. This reduction of inhibition may contribute to the hypoxia-related increase in postural sway.

Background: Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, >90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs., Methods: Randomized controlled trial to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)-amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted., Results: Of 284 participants, 72 (25.3%) were deemed high risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg, and 4 (4.2%) after 250-mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics., Conclusions: An easy-to-administer risk-assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis. Clinical Trials Registration. Clinicaltrials.gov (NCT04620746)., Competing Interests: Potential conflicts of interest. L. A. B. reports research funding support from NIH, Nabriva, Hologic, and SpeeDx, and participation on a Data and Safety Monitoring Board for an NIH-funded study on the Bexsero vaccine (looking at mucosal immunity). C. J. M. reports receiving research funding from BARDA/GSK, the Centers for Disease Control and Prevention, GlaxoSmithKline, Cepheid, Gilead, Hologic, and the National Association of County and CityHealth Officials and consulting honoraria from the Infectious Diseases Society of America, Contraceptive Technologies, Core Concepts in Health, and AHEC (Area Health Education Centers); and participation on a Data Safety Monitoring Board or Advisory Board for the NIH (unpaid) and Advisory Board for Talis Biomedical (payment to their institution); and receipt of study product provided to their institution from Lupin. J. M. Z. reports compensation for service on Data Safety Monitoring Committees for Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N<50). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions., Methods: Activations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD (N=664 in activation analyses, N=474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD, N=290 in activation analyses, N=214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces., Results: Compared to controls, LMDD was associated with increased activations in left amygdala (P FWE =0.031,k E =4) and left DLPFC (P FWE =0.002,k E =33), increased mean bilateral amygdala activation (β=0.0715,P=0.0314), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time., Limitations: Most studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time., Conclusions: LMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of 'bottom-up' limbic-prefrontal effective connectivity in depression., Competing Interests: Declaration of competing interest JDS previously received research funding from Wyeth and Indivior. AMM previously received research grant support from Pfizer, Eli Lilly and Janssen, as well as speaker fees from Illumina. HCW previously received research grant support from Pfizer. None of these funding sources are connected to the present study. No potential conflicts of interest are reported for other authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Proctitis is an inflammatory condition of the distal rectum that can be associated with common sexually transmitted infections (STIs), such as gonorrhea, chlamydia, and syphilis. For persons presenting with ulcerative findings on examination, in addition to syphilis, Mpox, lymphogranuloma venereum, and herpes simplex virus should be in the differential. Providers should also be aware that there are evolving data to support a role for Mycoplasma genitalium in proctitis. Performing a comprehensive history, clinical evaluation including anoscopy, and rectal nucleic amplification STI testing may be useful in identifying the cause of proctitis and targeting treatment., Competing Interests: Disclosures In the past 12 months, C.J. McNeil has received research grants or contracts from Centers for Disease Control and Prevention, BARDA, United States/GSK, Becton Dickinson (BD), Cepheid, United States, Gilead, Hologic, United States, National Institutes of Health, United States paid to Wake Forest University School of Medicine. C.J. McNeil is on the advisory board for Talis Biomedical. L.F. Barroso has received grants or contracts funding from the National Institutes of Health and the AIDS Malignancy Consortium paid to Wake Forest University School of Medicine. K. Workowski has received grants or contracts from Gilead, Abbvie, United States, Centers for Disease Control and Prevention, United States, National Institutes of Health paid to Emory University., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program., Methods: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo., Results: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability., Conclusion: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments., Competing Interests: Declaration of Conflicting InterestsCEG served in a consulting role for Gilead and received research support from Gilead. HS reports being a full-time employee of ViiV Healthcare. CJM has received grants, contracts and/or participated in clinical trials with Becton Dickinson, Biomedical Advanced Research and Development Authority/GlaxoSmithKline, Centers for Disease Control and Prevention, Cepheid, Hologic, Lupin, The National Association of County and City Health Officials, and the National Institutes of Health, and is on the advisory board for Talis Biomedical paid to her employer Wake Forest University School of Medicine. CLG has received research support from ViiV Healthcare, Moderna and Novavax. All other authors have no conflicts to disclose.

Hypoxia increases postural sway compared to normoxia, but the underlying sensorimotor factors remain unclear. An important contributor to balance control is cutaneous feedback arising from the feet, which can be partially characterized by electrically evoking a reflex from a purely cutaneous nerve (i.e., sural) and sampling the subsequent motor activity of a muscle. The purpose of the present study was to determine how normobaric hypoxia influences sural nerve reflex parameters during a standing posture. It was hypothesized that normobaric hypoxia would reduce cutaneous reflex area compared to normoxia. Participants (n = 16; 5 females, 11 males) stood with their feet together while receiving two trials of 50 sural nerve stimulations (200-Hz, 5-pulse train, presented randomly every 3-6 s) at baseline (BL; normoxia), and at 2 (H2) and 4 (H4) h of normobaric hypoxia (~ 0.11 fraction of inspired oxygen in a hypoxic chamber). The sural nerve reflex was recorded using surface electromyography from the left medial gastrocnemius, and characterized by area and duration of the initial positive and negative peaks of the response. When normalized to pre-stimulus electromyography, the area of the peak-to-peak cutaneous reflex was not different than BL (p ≥ 0.14) for up to 4 h of normobaric hypoxia (BL: 0.26 ± 0.22, H2: 0.19 ± 0.19, H4: 0.22 ± 0.20 A.U.). Furthermore, the duration of the response was not different during hypoxia (BL: 73.2 ± 42.4; H2: 75.2 ± 47.0; H4: 77.6 ± 54.6 ms; p ≥ 0.13) than BL. Thus, reflexes arising from cutaneous afferents of the lateral border of the foot are resilient to at least 4 h of normobaric hypoxia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based intervention for substance use. Health care professionals may not receive SBIRT training or know of substance use's intersection with sexual activity. This pilot survey inquired about SBIRT training history, attitudes, and comfort among outpatient health care professionals, including assessing sexual activity-related use., Methods: We conducted a snowball cross-sectional survey of outpatient health care professionals at a large southeastern academic medical center in June 2021 with 4-point Likert questions covering demographics, substance use attitudes, SBIRT training history, and comfort implementing SBIRT. Analysis used descriptive statistics and stratification by demographic and practice characteristics., Results: Seventy-three professionals responded, of whom 82% were White and 66% were female. Forty-seven percent were 30 to 39 years old, 33% were internal medicine professionals, and 59% reported previous SBIRT training. All participants reported believing substance use is a significant health issue. Most reported that they were comfortable or somewhat comfortable assessing patients for substance use (85%), dropping to 60% discussing sexual activity. Advanced practice providers and physicians identified more comfort with rapport building around substance use than other health care respondents. Professionals in infectious diseases and psychiatry reported the greatest comfort assessing substance use with concurrent sexual activity., Conclusions: There are gaps in SBIRT training and beliefs among health care professionals. Although health care workers report that assessing substance use is important, some professionals endorsed more comfort discussing substance use with patients than others, especially when inquiring about sexual activity. Future work could replicate the pilot to inform increasing comfort through training in the intersection of substance use and sexuality., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflict of interest to declare. This work was supported by the National Institutes of Health (grant number UL1TR001420). The funding source did not play a role in study design, data analyses and interpretation, writing of the manuscript, or the decision to submit this manuscript for publication., (Copyright © 2023 American Sexually Transmitted Diseases Association. All rights reserved.)

Human papillomavirus (HPV) vaccination among adolescents in rural, western North Carolina (NC) remains suboptimal. Data are needed to understand the barriers to HPV vaccination in these communities. We conducted a cross-sectional pilot study of parental attitudes and provider practices regarding HPV vaccination in rural western NC counties with lower HPV vaccination rates. Eight health department clinics were enrolled in the study. Further, 29 provider and 32 parent surveys were analyzed along with environmental scans. Median provider comfort regarding knowledge of HPV-associated diseases was 85% (IQR = 75-95), on a scale of 0-100% (100% representing complete comfort). Median parental comfort level regarding knowledge of HPV-associated diseases and the HPV vaccine was 75% (IQR = 50-89) and 75% (IQR = 49-96), respectively. Less than 25% of parents rated the HPV vaccine as 'extremely effective' against genital (16.7%) and anal cancers (17.9%). Parents were more likely to rate the vaccine as 'extremely effective' to 'very effective' if their child was female. There was no significant difference between parental- and provider-reported comfort with knowledge about HPV-associated diseases ( p = 0.0725) and the HPV vaccine ( p = 0.167). This study identified multiple opportunities to increase HPV vaccine coverage among unvaccinated adolescents at parental, provider, and clinic levels. Health education of rural NC residents and providers in public health settings may identify future interventions to increase HPV vaccine uptake.

According to current guidelines, when measuring voluntary activation (VA) using transcranial magnetic stimulation (TMS), stimulator output (SO) should not exceed the intensity that, during a maximal voluntary contraction (MVC), elicits a motor evoked potential (MEP) from the antagonist muscle >15%-20% of its maximal M-wave amplitude. However, VA is based on agonist evoked-torque responses [i.e., superimposed twitch (SIT) and estimated resting twitch (ERT)], which means limiting SO based on electromyographic (EMG) responses will often lead to a submaximal SIT and ERT, possibly underestimating VA. Therefore, the purpose of this study was to compare elbow flexor VA calculated using the original method (i.e., intensity based on MEP size; SO MEP ) and a method based solely on eliciting the largest SIT at 50% MVC torque (SO SIT ), regardless of triceps brachii MEP size. Fifteen healthy, young participants performed 10 sets of brief contractions at 100%, 75%, and 50% MVC torque, with TMS delivered at SO MEP (73.0 ± 13.5%) or SO SIT (92.0 ± 10.8%) for five sets each. Although the mean ERT torque was greater using SO SIT (15.2 ± 4.8 Nm) compared with SO MEP (13.0 ± 3.7 Nm; P = 0.031), the SIT amplitude at 100% MVC torque was not different (SO MEP : 0.69 ± 0.49 Nm vs. SO SIT : 0.74 ± 0.52 Nm; P = 0.604). Despite the ERT disparity, VA scores were not different between SO MEP (94.6 ± 3.5%) and SO SIT (95.0 ± 3.3%; P = 0.572). Even though SO SIT did not lead to a higher VA score than the SO MEP method, it has the benefit of yielding the same result without the need to record antagonist EMG or perform MVCs when determining SO, which can induce fatigue before measuring VA. NEW & NOTEWORTHY When using transcranial magnetic stimulation (TMS) to determine voluntary activation (VA) of the elbow flexors, we hypothesized that a stimulator output designed to limit antagonist muscle activity would evoke submaximal agonist superimposed twitch amplitudes, thus underestimating VA. Contrary to our hypothesis, VA was not greater with an output based on maximal superimposed twitch amplitude. Nevertheless, our findings advance methodological practices by simplifying the equipment and minimizing the time required to determine VA using TMS.

According to Fitts' Law, the time to reach a target (movement time, MT) increases with distance. A violation of Fitts' Law occurs when target positions are outlined before and during movement, as MTs are not different when reaching to the farthest and penultimate targets. One hypothesis posits that performers cognitively process the edges of a target array before the center, allowing for corrective movements to be completed more quickly when moving to edge targets compared to middle targets. The objective of this study was to test this hypothesis by displaying a target range rather than outlines of individual targets in an effort to identify the effects of array edges. Using a touch-screen laptop, participants (N = 24) were asked to reach to one of three targets which would appear within a presented range. Separately, targets were also presented without a range to determine if the display protocol could evoke Fitts' Law. Movements were assessed with the touch screen and optical position measurement. A main effect was found for relative position within a range (touch: F 2,44  = 15.4, p < 0.001, η 2 p  = 0.412; position: F 2,40  = 15.6, p < 0.001, η 2 p  = 0.439). As hypothesised, MT to the farthest target in a range was not significantly different than MT to the middle target (touch: p = 0.638, position: p = 0.449). No violation was found when a target range was not presented (touch: p = 0.003, position: p = 0.001). Thus, a target range reproduces the Fitts' Law violation previously documented with individually outlined targets, which supports and extends the discussed hypothesis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A potentiating conditioning contraction (CC) has been shown to increase silent period duration, an index of corticospinal inhibition; however, it is unknown if the CC must induce potentiation for corticospinal inhibition to increase. Ten healthy, young adults (four females) completed this study to assess potentiation and silent period (SP) duration before and after four types of CCs: voluntary and electrically evoked maximal CCs to optimize potentiation, and voluntary and electrically evoked submaximal CCs (∼40% of maximal voluntary force) that induced minimal potentiation. Stimulation was applied to the ulnar nerve to evoke twitches for the assessment of potentiation and to evoke tetanic CCs of the first dorsal interosseous muscle. The SP was elicited by applying transcranial magnetic stimulation to the motor cortex during brief contractions at 25% of maximal voluntary force. Changes to twitch force and SP duration were not different for voluntary and tetanic contractions, so data were pooled. Twitch force increased by 81.2 ± 35.7% ( P < 0.001) and 3.2 ± 6.5% ( P = 0.039) following maximal and submaximal CCs, respectively. The SP was prolonged following maximal (12.6 ± 6.3%; P < 0.001) and submaximal (4.8 ± 4.9%; P < 0.001) CCs. Correlations between post-CC twitch force and SP duration were not significant for maximal or submaximal conditions ( r = -0.068; r = 0.067; P ≥ 0.780, respectively). Duration of the SP increased not only following maximal-intensity CCs but also after submaximal-intensity CCs that induced virtually no potentiation (∼3%). Thus, we suggest that corticospinal inhibition is not directly related to mechanisms of muscle potentiation per se, but, rather, the level of muscle contraction likely mediates feedback from large diameter afferents that affect the SP. NEW & NOTEWORTHY The transcranial magnetic stimulation-induced silent period reflects a transient state of corticospinal inhibition that is influenced by recent history of muscle activation, which may include an effect of potentiation. We demonstrate that silent period duration increases following both voluntary and electrically evoked maximal and submaximal conditioning contractions, even though the latter intensity produced virtually no muscle potentiation. Feedback from group Ia and Ib muscle afferents is proposed as the cause of the increased corticospinal inhibition.

Sleep deprivation (SD) is prevalent and impairs motor function; however, little is known about its effect on perceived and performance fatigability, especially in females. To examine the effects of 24 h of SD on these attributes of fatigue, nine females completed a 20-min isometric, sustained elbow flexion contraction, followed by 10 min of recovery. The superimposed twitch (SIT) elicited via transcranial magnetic stimulation (TMS) assessed supraspinal drive. Biceps brachii electromyographic data indicated neural excitability in response to stimulation over the motor cortex (motor evoked potential; MEP), corticospinal tract (cervicomedullary motor evoked potential; CMEP), and brachial plexus (maximal M-wave; Mmax). MEPs and CMEPs were recorded during a TMS-induced silent period. At baseline, ratings of perceived effort (RPE; 2.9 vs. 1.6) and fatigue (RPF; 6.9 vs. 2.9), were higher for SD than control. Across the 20-min contraction, RPE increased from 2.2 to 7.6, SIT and MEP/CMEP increased by 284 and 474%, respectively, whereas maximal voluntary isometric contraction (MVC) torque and CMEP/Mmax decreased by 26 and 57%, respectively. No differences were found across conditions for MVC, SIT, Mmax, CMEP/Mmax, or MEP/CMEP prior to, during, and after the fatiguing task. During recovery, RPE (4.9 vs. 3.4), RPF (7.6 vs. 2.8), and perception of task difficulty (5.5 vs. 4.5) were greater for SD than control. Acute SD does not appear to alter performance fatigability development and subsequent recovery; however, it increases perceptions of fatigue, effort, and task difficulty. Thus, the disconnect between perceived and actual neuromuscular capacity following a sustained, submaximal isometric task is exacerbated by SD. Highlights Sleep deprivation did not alter supraspinal drive or neural excitability during and after a 20-min submaximal elbow flexion contractionSleep deprivation increased perceived fatigue and perception of task difficultyThe disconnect between perceived and performance fatigability is exacerbated in a sleep-deprived state.

Despite the perceived importance of antagonist muscle activity, it is unknown if motor unit (MU) behavior at recruitment differs when a muscle acts as an antagonist versus agonist. Fourteen healthy participants performed ramped, isometric elbow flexor or extensor contractions to 50% or 100% maximal voluntary contraction (MVC) torque. Surface and fine-wire intramuscular electromyographic (EMG) recordings were sampled from biceps and triceps brachii. During agonist contractions, low-threshold MUs (recruited at <10% MVC torque) were sampled in all participants, with a total of 107 and 90 for biceps and triceps brachii, respectively. For ramped MVCs, antagonist surface EMG coactivation (% amplitude during agonist MVC) was 8.3 ± 6.6% for biceps and 15.2 ± 7.3% for triceps brachii. However, antagonist single MU activity was recorded from only four participants, with only one of these individuals having antagonist MUs recorded from both muscles. All antagonist MUs were successfully detected during agonist contractions, but many (∼40%) had a recruitment threshold >10% MVC torque. For MUs recorded during both agonist and antagonist contractions, discharge rate at recruitment was seemingly lower for antagonist than agonist contractions. Coexistence of typical levels of surface EMG-derived coactivation with scant antagonist MU recordings suggests that coactivation in these muscles is primarily the result of cross talk. Based on the limited antagonist MU data detected, MUs recruited early during an agonist contraction are not necessarily among those first recruited during an antagonist contraction. These findings highlight the possibility of a modification of orderly recruitment when a motoneuron pool is acting as an antagonist. NEW & NOTEWORTHY Modest levels of coactivation are widely considered essential for appropriate motor control; however, minimal attention has been given to recruitment patterns of motor units (MUs) from antagonist muscles. Despite the successful recording of many low-threshold MUs during agonist contractions, we recorded no antagonist MUs in most participants. Of the units recorded, only ∼60% matched those recruited at <10% of maximal torque when the muscle acted as an agonist, which suggests a modified recruitment order for antagonist MUs.

Skeletal muscle atrophy, dysfunction, and fatigue are important complications of chronic obstructive pulmonary disease (COPD). Greater reliance on glycolytic metabolism and increased type III/IV muscle afferent activity increase ventilatory drive, promote ventilatory constraint, amplify exertional dyspnea, and limit exercise tolerance. To investigate whether muscular adaptation with resistance training (RT) could improve exertional dyspnea, exercise tolerance, and intrinsic neuromuscular fatigability in individuals with COPD ( n = 14, FEV 1  = 62 ± 21% predicted), we performed a proof-of-concept single-arm efficacy study utilizing 4 wk of individualized lower-limb RT (3 times/wk). At baseline, dyspnea (Borg scale), ventilatory parameters, lung volumes (inspiratory capacity maneuvers), and exercise time were measured during a constant-load test (CLT) at 75% maximal workload to symptom limitation. On a separate day, fatigability was assessed using 3 min of intermittent stimulation of the quadriceps (initial output of ∼25% maximal voluntary force). Following RT, the CLT and fatigue protocols were repeated. Compared with baseline, isotime dyspnea was reduced (5.9 ± 2.4 vs. 4.5 ± 2.4 Borg units, P = 0.02) and exercise time increased (437 ± 405 s vs. 606 ± 447 s, P < 0.01) following RT. Isotime tidal volume increased ( P = 0.01), whereas end-expiratory lung volumes ( P = 0.02) and heart rate ( P = 0.03) decreased. Quadriceps force, relative to initial force, was higher at the end of the stimulation protocol posttraining (53.2 ± 9.1 vs. 46.8 ± 11.9%, P = 0.04). This study provides evidence that 4 wk of RT attenuates exertional dyspnea and improves exercise tolerance in individuals with COPD, which in part, is likely due to delayed ventilatory constraint and reduced intrinsic fatigability. A pulmonary rehabilitation program beginning with individualized lower-limb RT may help mitigate dyspnea before performing aerobic training in individuals with COPD. NEW & NOTEWORTHY This study presents the novel finding that 4-wk resistance training (RT) focused specifically on the lower limbs can reduce exertional dyspnea during constant-load cycling, improve exercise tolerance, and reduce intrinsic fatigability of the quadriceps in individuals with COPD.

This historical review summarizes the major advances - particularly from the last 50 years - in transcutaneous motor-level electrical stimulation, which can be used either as a tool to investigate neuromuscular function and its determinants (electrical stimulation for testing; EST) or as a therapeutic/training modality to improve neuromuscular and physical function (neuromuscular electrical stimulation; NMES). We focus on some of the most important applications of electrical stimulation in research and clinical settings, such as the investigation of acute changes, chronic adaptations and pathological alterations of neuromuscular function with EST, as well as the enhancement, preservation and restoration of muscle strength and mass with NMES treatment programs in various populations. For both EST and NMES, several major advances converge around understanding and optimizing motor unit recruitment during electrically-evoked contractions, also taking into account the influence of stimulation site (e.g., muscle belly vs nerve trunk) and type (e.g., pulse duration, frequency, and intensity). This information is equally important both in the context of mechanistic research of neuromuscular function as well as for clinicians who believe that improvements in neuromuscular function are required to provide health-related benefits to their patients., 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 © 2023 Elsevier Ltd. All rights reserved.)

Abstract: We describe a case of persistent 5-nitroimidazole-resistant trichomoniasis cured after 14 days of oral secnidazole and intravaginal boric acid. Secnidazole may be an important treatment option for resistant trichomoniasis, particularly in women who fail other regimens, including higher doses of oral metronidazole and tinidazole for longer durations of time., Competing Interests: Conflict of Interest and Sources of Funding: C.J.M. has received grants or contracts from Biomedical Advanced Research and Development Authority/GlaxoSmithKline, Becton Dickinson, Binx, Cepheid, the Centers for Disease Control and Prevention, Gilead, Hologic, the National Association of County and City Health Officials, and the National Institutes of Health, paid to her employer, the Wake Forest University School of Medicine. J.C.W. has no conflicts of interest to declare. C.A.M. has received research grant support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, Lupin Pharmaceuticals, Gilead Sciences, Inc, Visby Medical, and Abbott Molecular; is a consultant for Lupin Pharmaceuticals, BioNTech, Scynexis, and Cepheid; and has received honoraria from Visby Medical, Elsevier, Abbott Molecular, Cepheid, Roche Diagnostics, and Lupin Pharmaceuticals., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Sexually transmitted infections (STIs) have been increasing in older adults. Sexual health remains an important part of overall health care at any age. There are several barriers and facilitators to addressing sexual health in this population. Changes attributable to normal physiologic aging as well as sexual dysfunction can affect sexuality in older adults. When it comes to preventing STIs, combination prevention strategies remain applicable in older adults. Addressing sexual health using a tailored approach is critical to stem the tide of increasing STIs rates in older adults., (Published by Elsevier Inc.)

Introduction: With acclimatization to high altitude (HA), adaptations occur throughout the nervous system and at the level of the muscle, which may affect motor unit (MU) characteristics. However, despite the importance of MUs as the final common pathway for the control of voluntary movement, little is known about their adaptations with acclimatization., Methods: Ten lowlanders and Sherpa participated in this study 7 to 14 d after arrival at HA (5050 m), with seven lowlanders repeating the experiment at sea level (SL), 6 months after the expedition. The maximal compound muscle action potential (M max ) was recorded from relaxed biceps brachii. During isometric elbow flexions at 10% of maximal torque, a needle electrode recorded the MU discharge rate (MUDR) and MU potential (MUP) characteristics of single biceps brachii MUs., Results: Compared with SL, acclimatized lowlanders had ~10% greater MUDR, ~11% longer MUP duration, as well as ~18% lower amplitude and ~6% greater duration of the first phase of the M max (all P < 0.05). No differences were noted between SL and HA for variables related to MUP shape (e.g., jitter, jiggle; P > 0.08). Apart from lower near-fiber MUP area for Sherpa than acclimatized lowlanders ( P < 0.05), no M max or MU data were different between groups ( P > 0.10)., Conclusions: Like other components of the body, MUs in lowlanders adapt with acclimatization to HA. The absence of differences between acclimatized lowlanders and Sherpa suggests that evolutionary adaptations to HA are smaller for MUs than components of the cardiovascular or respiratory systems., (Copyright © 2022 by the American College of Sports Medicine.)

Spiroplasma citri is the pathogen that causes citrus stubborn disease (CSD). Infection of citrus with S. citri has been shown to cause leaf mottling, reduce fruit yield, and stunt tree growth. Fruit from trees exhibiting symptoms of CSD are misshapen and discolored. The symptoms of CSD are easily confused with nutrient deficiencies or symptoms of citrus greening disease. In this study, young Washington navel oranges ( Citrus sinensis ) were graft-inoculated with budwood originating from trees confirmed to be infected with S. citri . Leaf samples were collected monthly for 10 months for metabolomics and differential gene expression analyses. Significant differences in the concentration of metabolites and expressed genes were observed between control and S. citri- infected trees throughout the experiment. Metabolites and genes associated with important defense and stress pathways, including jasmonic acid signaling, cell wall modification, amino acid biosynthesis, and the production of antioxidant and antimicrobial secondary metabolites, were impacted by S. citri throughout the study, and even prior to symptom development. This work fills a current gap in knowledge surrounding the pathogenicity of S. citri and provides an updated mechanistic explanation for the development of CSD symptoms in S. citri- infected plants.

Neural drive originating in higher brain areas reaches exercising limb muscles through the corticospinal-motoneuronal pathway, which links the motor cortex and spinal motoneurones. The properties of this pathway have frequently been observed to change during fatiguing exercise in ways that could influence the development of central fatigue (i.e. the progressive reduction in voluntary muscle activation). However, based on differences in motor cortical and motoneuronal excitability between exercise modalities (e.g. single-joint vs. locomotor exercise), there is no characteristic response that allows for a categorical conclusion about the effect of these changes on functional impairments and performance limitations. Despite the lack of uniformity in findings during fatigue, there is strong evidence for marked 'inhibition' of motoneurones as a direct result of voluntary drive. Endogenous forms of neuromodulation, such as via serotonin released from neurones, can directly affect motoneuronal output and central fatigue. Exogenous forms of neuromodulation, such as brain stimulation, may achieve a similar effect, although the evidence is weak. Non-invasive transcranial direct current stimulation can cause transient or long-lasting changes in cortical excitability; however, variable results across studies cast doubt on its claimed capacity to enhance performance. Furthermore, with these studies, it is difficult to establish a cause-and-effect relationship between brain responsiveness and exercise performance. This review briefly summarizes changes in the corticomotoneuronal pathway during various types of exercise, and considers the relevance of these changes for the development of central fatigue, as well as the potential of non-invasive brain stimulation to enhance motor cortical excitability, motoneuronal output and, ultimately, exercise performance., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26-72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available., Methods: We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I 2 ., Findings: Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28-38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined CHR was estimated to be 14.1% (95% credible interval, 7.5-25.0, I 2 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2-74.0, I 2 81.4%), 21.7% (7.2-52.1, I 2 57.7%), and 5.8% (3.2-9.4, I 2 92.4%) during the pre-2017, 2017-2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. CFR was estimated to be 0.03% (0.0-0.44, I 2 99.9%), with evidence of large heterogeneity between the studies., Interpretation: There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR., Funding: None., Competing Interests: CJM acknowledges support from BINX, 10.13039/100012399Biomedical Advanced Research and Development Authority, 10.13039/100004330GlaxoSmithKline, Becton Dickinson, United States Center for Disease Control and Prevention, 10.13039/100017037Cepheid, Gilead, 10.13039/100015160Hologic, Lupin, National Association of County and City Health Officials, and 10.13039/100000002National Institutes of Health paid to her employer., (© 2022 The Author(s).)

Adult aging is associated with a myriad of changes within the neuromuscular system, leading to reductions in contractile function of old adults. One of the consequences of these age-related neuromuscular adaptations is altered performance fatigability, which can limit the ability of old adults to perform activities of daily living. Whereas age-related fatigability during isometric tasks has been well characterized, considerably less is known about fatigability of old adults during dynamic tasks involving movement about a joint, which provides a more functionally relevant task compared with static contractions. This review provides a comprehensive summary of age-related fatigability during dynamic contractions, where the importance of task specificity is highlighted with a brief discussion of the potential mechanisms responsible for differences in fatigability between young and old adults. The angular velocity of the task is critical for evaluating age-related fatigability, as tasks that constrain angular velocity (i.e., isokinetic) produce equivocal age-related differences in fatigability, whereas tasks involving unconstrained velocity (i.e., isotonic-like) consistently induce greater fatigability for old compared with young adults. These unconstrained velocity tasks, which are more closely associated with natural movements, offer an excellent model to uncover the underlying age-related mechanisms of increased fatigability. Future work evaluating the mechanisms of increased age-related fatigability during dynamic tasks should be evaluated using contraction modes that are specific to the task (i.e., dynamic), rather than isometric, particularly for the assessment of spinal and supra spinal components. Advancing our understanding of age-related fatigability is likely to yield novel insights and approaches for improving mobility limitations in old adults.

The purpose of this study was to assess how severe acute hypoxia alters the neural mechanisms of muscle activation across a wide range of torque output in a fatigued muscle. Torque and electromyography responses to transcranial and motor nerve stimulation were collected from 10 participants (27 years ± 5 years, 1 female) following repeated performance of a sustained maximal voluntary contraction that reduced torque to 60% of the pre-fatigue peak torque. Contractions were performed after 2 h of hypoxic exposure and during a sham intervention. For hypoxia, peripheral blood oxygen saturation was titrated to 80% over a 15-min period and remained at 80% for 2 h. Maximal voluntary torque, electromyography root mean square, voluntary activation and corticospinal excitability (motor evoked potential area) and inhibition (silent period duration) were then assessed at 100%, 90%, 80%, 70%, 50% and 25% of the target force corresponding to the fatigued maximal voluntary contraction. No hypoxia-related effects were identified for voluntary activation elicited during motor nerve stimulation. However, during measurements elicited at the level of the motor cortex, voluntary activation was reduced at each torque output considered (P = .002, η p 2  = .829). Hypoxia did not impact the correlative linear relationship between cortical voluntary activation and contraction intensity or the correlative curvilinear relationship between motor nerve voluntary activation and contraction intensity. No other hypoxia-related effects were identified for other neuromuscular variables. Acute severe hypoxia significantly impairs the ability of the motor cortex to voluntarily activate fatigued muscle across a wide range of torque output., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objectives: In the United States, sexually transmitted infections (STIs) disproportionately affect men who have sex with men (MSM) and transwomen of color. Partner services can prevent STI transmission by facilitating testing and treatment for partners of individuals diagnosed with an STI. Understanding client perspectives towards partner services is critical to their acceptance and uptake. This study examined perceptions, experiences, and preferences for partner services among Black and Latino MSM and transwomen in North Carolina., Design: We conducted seven audio-recorded focus groups in English ( n  = 5) and Spanish ( n  = 2). The audio was transcribed verbatim and we inductively analyzed data using field notes, systematic coding, and thematic comparison., Results: Black MSM reported the most exposure and experiences with partner services, and most perceived partner services negatively. Feeling supported and having flexibility characterized positive experiences with partner services among Black MSM; feeling judged or harassed characterized negative experiences. Black transwomen had less exposure to partner services and had a mix of positive reactions to the approach, along with concerns about client confidentiality. Most Latino participants were unaware of partner services and expressed openness to their potential. All participants preferred self-notifying and wanted flexible, discreet, supportive partner services with linkages to other wellness resources., Conclusion: Building off positive partner services experiences and responding to client preferences can enhance trust, acceptability, and service use.

Abstract: Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded before enrollment because of bacterial sexually transmitted infection coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) was common. Study findings highlight the need for comprehensive bacterial sexually transmitted infection screening in patients with syphilis., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare no conflict of interest., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence, but less is known about the sexual dimorphism of these relationships. In this paper, sex differences in the relationship between brain structural complexity and general intelligence (g) in two diverse geographic and cultural populations (UK and Indian) are investigated. 3D T1-weighted magnetic resonance imaging (MRI) data and a battery of cognitive tests were acquired from participants belonging to three different cohorts: Mysore Parthenon Cohort (MPC); Aberdeen Children of the 1950s (ACONF) and UK Biobank. We computed MRI derived structural brain complexity and g estimated from a battery of cognitive tests for each group. Brain complexity and volume were both positively corelated with intelligence, with the correlations being significant in women but not always in men. This relationship is seen across populations of differing ages and geographical locations and improves understanding of neurobiological sex-differences., (© 2022. The Author(s).)

Sleep deprivation is commonplace and impairs memory, inhibition, cognitive flexibility and attention. However, little is known about the neurophysiological impact of sleep deprivation in the context of go/no-go (GNG) task performance and emotion processing. To address this knowledge gap, 12 females performed two computerized GNG tasks (shapes; emotional facial expressions) and an object hit and avoid (OHA) task after a night of typical sleep and 24 h without sleep. Electroencephalographic (EEG) recordings were taken during a 3-minute eyes-open resting period as well as during GNG task performance. Resting EEG power in the theta band was 33% higher for the sleep-deprived than control condition (p < 0.05), whereas alpha activity was unchanged. When sleep deprived, participants had ~6% slower response times (go trials) and made ~7% more total errors during GNG tasks (p < 0.05). Reaction time and overall accuracy were ~25% and ~9% worse for the emotional compared to shape GNG task (p < 0.05), respectively, which suggests interference of emotion processing on task performance. Smaller differences in amplitude between go and no-go trials for the N2 and both the N2 and P3 event-related potential components were found during sleep deprivation for the emotional and shape GNG tasks, respectively (p < 0.05). No changes to the N170 component were found. Lastly, participants hit more distractors during the OHA task when sleep deprived (p < 0.05). Altogether, these results indicate sleep deprivation slows neural processing and impairs inhibitory task performance, possibly due to a more bottom-up, stimulus-driven approach to inhibiting motor responses., (Copyright © 2022 Elsevier B.V. All rights reserved.)