Khurram, Obaid U

The present study provides novel physiological insights into aging by measuring airway compliance and residual volume via forced oscillation perturbations using a programmable mechanical ventilator (flexiVent—currently considered a gold standard for in vivo lung function measurements). In addition, dynamic measurements of lung inflation reported herein may serve as early indicators of altered elastic properties. Taken together, the findings offer a comprehensive assessment of age-related changes in lung structure and function.

ABSTRACT Objective To evaluate demographic and clinical factors influencing survival in patients with major salivary gland tumors (MSGTs) using the surveillance, epidemiology, and end results (SEER) database. Study Design A retrospective cohort study using SEER data from 2000 to 2021. Setting Data were collected from the SEER registry, a comprehensive database capturing cancer statistics across the United States. Methods Patients diagnosed with major salivary gland malignancies were analyzed for demographic factors, including age, sex, race, marital status, and income, as well as clinical variables, including tumor grade and site. Stratification by sex was done to assess sex‐specific outcomes. Results The cohort included 13,869 patients. Key findings include that older age and male sex were associated with worse survival outcomes. Single patients had better survival than married individuals, likely due to younger age at diagnosis. Additionally, higher income and Asian/Pacific Islander race conferred a survival advantage. There were disparate impacts between males and females in income, marital status, and race, with higher income and marriage providing a survival advantage for male patients but none for females. Additionally, Black females but not Black males, and widowed females but not widowed males, had slightly increased hazard ratios compared to White individuals. Conclusion Men and women experience disparate effects that impact survival and outcomes in major salivary gland tumors. These findings highlight the need for targeted interventions to address disparities in care and improve survival outcomes while emphasizing the importance of further research to understand the underlying mechanisms driving these disparities.

Abstract Motoneurons are the final common pathway for all motor commands and possess intrinsic electrical properties that must be tuned to control muscle across the full range of motor behaviours. Neuromodulatory input from the brainstem is probably essential for adapting motoneuron properties to match this diversity of motor tasks. A primary mechanism of this adaptation, control of dendritic persistent inward currents (PICs) in motoneurons by brainstem monoaminergic systems, generates both amplification and prolongation of synaptic inputs. While essential, there is an inherent tension between this amplification and prolongation. Although amplification by PICs allows for quick recruitment and acceleration of motoneuron discharge, PICs must be deactivated to derecruit motoneurons upon movement cessation. In contrast, during stabilizing or postural tasks, PIC‐induced prolongation of synaptic inputs is critical for sustained motoneuron discharge. Here, we designed two motor tasks that challenged the inhibitory control of PICs, generating unduly PIC prolongation that increases variability in human torque control. This included a paradigm combining a discrete motor task with a stabilizing task and another involving muscle length‐induced changes to the balance of excitatory and inhibitory inputs available for controlling PICs. We show that prolongation from PICs introduces difficulties in ankle torque control and that these difficulties are further degraded at shorter muscle lengths when PIC prolongation is greatest. These results highlight the necessity for inhibitory control of PICs and showcase issues introduced when inhibitory control is constrained. Our findings suggest that, like sensory systems, errors are inherent in motor systems. These errors are not due to problems in the perception of movement‐related sensory input but are embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) where pathological shifts in monoamines may further amplify these errors. image Key points All motor commands are processed via spinal motoneurons, whose intrinsic electrical properties are adapted by brainstem neuromodulatory input. The effects of these neuromodulatory inputs (i.e. persistent inward currents; PICs) must be tightly regulated by inhibitory inputs to allow for the large repertoire of human motor behaviours. We designed two motor tasks to restrict the ability of inhibitory synaptic inputs to control PICs and show that this generates substantial errors that reduce the precision of motor output in humans. Our findings suggest that errors are inherent in motor systems and embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) and may, speculatively, shed light on contributing factors to muscle cramps.

The neuromotor control of the diaphragm muscle (DIAm) in response to hypercapnia is not well understood. We show that both the number of motor units recruited and their discharge rates increase with hypercapnia, consistent with increased respiratory drive during hypercapnia. Potentially in response to this increased drive, the greatest effect of hypercapnia is on during the postinspiratory (descending) ramp of DIAm EMG activity, which shortens to facilitate higher respiratory rates.

The heterogeneity of diaphragm muscle (DIAm) activity in awake animals reflects real motor behavior diversity but makes assessments of eupneic breathing challenging. The present article uses an unsupervised machine learning model to identify eupneic breathing amidst a deluge of different DIAm electromyography (EMG) burst patterns in awake rats. This technique offers a scalable and reliable tool that improves efficiency of DIAm EMG analysis and minimizes potential sources of bias.

We characterized three phases of neuromotor control—motor unit recruitment, sustained activity, and derecruitment—based on statistical assessments of stationarity of the diaphragm muscle (DIAm) EMG activity in awake rats. Our findings may allow indirect estimates of the contribution of motor unit recruitment and frequency coding toward generating force and provide novel insights about the temporal aspects of DIAm neuromotor control and descending respiratory drive in unanesthetized animals.

Midcervical spinal cord contusion injury results in tissue damage, disruption of spinal pathways, and motor neuron loss. Unilateral C4 contusion results in loss of 40%–50% of phrenic motor neurons ipsilateral to the injury (~25% of the total phrenic motor neuron pool). Over time after unilateral C4 contusion injury, diaphragm muscle (DIAm) electromyogram activity increases both contralateral and ipsilateral to the side of injury in rats, suggesting compensation because of increased activation of the surviving motor neurons. However, the impact of contusion injury on DIAm force generation is less clear. Transdiaphragmatic pressure (Pdi) was measured across motor behaviors over time after unilateral C4 contusion injury in adult male Sprague-Dawley rats. Maximum Pdi (Pdimax) was elicited by bilateral phrenic nerve stimulation at 7 days postinjury. We hypothesized that Pdimaxis reduced following unilateral C4 contusion injury, whereas ventilatory behaviors of the DIAm are unimpaired. In support of our hypothesis, Pdimaxwas reduced by ~25% after unilateral C4 contusion, consistent with the extent of phrenic motor neuron loss following contusion injury. One day after contusion injury, the Pdi amplitude during airway occlusion was reduced from ~30 to ~20 cmH2O, but this reduction was completely reversed by 7 days postinjury. Ventilatory behaviors (~10 cmH2O), DIAm-specific force, and muscle fiber cross-sectional area did not differ between the laminectomy and contusion groups. These results indicate that the large reserve capacity for DIAm force generation allows for higher-force motor behaviors to be accomplished despite motor neuron loss, likely reflecting changes in motor unit recruitment.NEW & NOTEWORTHY Respiratory muscles such as the diaphragm generate the pressures necessary to accomplish a variety of motor behaviors ranging from ventilation to near-maximal expulsive behaviors. However, the impact of contusion injury on diaphragm pressure generation across behaviors is not clear. The present study shows that contusion injury impairs maximal pressure generation while preserving the ability of the diaphragm to accomplish lower-force motor behaviors, likely reflecting changes in diaphragm motor unit recruitment.

Respiratory muscles such as the diaphragm are active across a range of behaviors including ventilation and higher-force behaviors necessary for maintenance of airway patency, and minimal information is available regarding anesthetic effects on the capacity of respiratory muscles to generate higher forces. The purpose of the present study was to determine whether diaphragm EMG activity during lower-force behaviors, such as eupnea and hypoxia-hypercapnia, is differentially affected compared with higher-force behaviors, such as a sigh, in lightly anesthetized animals. In adult male rats, chronically implanted diaphragm EMG electrodes were used to measure the effects of low-dose ketamine (30 mg/kg) and xylazine (3 mg/kg) on root mean square (RMS) EMG amplitude across a range of motor behaviors. A mixed linear model was used to evaluate the effects of ketamine-xylazine anesthesia on peak RMS EMG and ventilatory parameters, with condition (awake vs. anesthetized), behavior (eupnea, hypoxia-hypercapnia, sigh), side (left or right hemidiaphragm), and their interactions as fixed effects and animal as a random effect. Compared with the awake recordings, there was an overall reduction of peak diaphragm RMS EMG across behaviors during anesthesia, but this reduction was more pronounced during spontaneous sighs (which require ~60% of maximal diaphragm force). Respiratory rates and duty cycle during eupnea and hypoxia-hypercapnia were higher in awake compared with anesthetized conditions. These results highlight the importance of identifying anesthetic effects on a range of respiratory motor behaviors, including sighs necessary for maintaining airway patency.NEW & NOTEWORTHY Respiratory muscles accomplish a range of motor behaviors, with forces generated for ventilatory behaviors comprising only a small fraction of their maximal force generating capacity. Induction of anesthesia exerts more robust effects on the higher-force diaphragm motor behaviors such as sighs compared with eupnea. This novel information on effects of low, sedative doses of a commonly used anesthetic combination (ketamine-xylazine) highlights the importance of identifying anesthetic effects on a range of respiratory motor behaviors.