Copper(II) Complexes of 2,2'-Bisdipyrrins: Synthesis, Characterization, Cell Uptake, and Radiolabeling with Copper-64.

Complexes prepared with positron-emitting copper-64 are of interest as imaging agents for positron emission tomography (PET). This work investigates the potential of using acyclic tetrapyrrolic 2,2'-bisdipyrrins as ligands to prepare charge-neutral, lipophilic, cell-permeable, redox active complexes with positron-emitting copper-64. The synthesis and characterization of a series of tetrapyrrolic 2,2'-bisdipyrrin copper(II) complexes are reported. Four 2,2'-bisdipyrrin copper(II) complexes were prepared with different functional groups in the meso-position of the ligands. Two of the new copper(II) complexes, one palladium(II) complex, and one nickel(II) complex were characterized by X-ray crystallography, which demonstrated that the copper(II) is in a distorted square planar environment. An investigation of the electrochemical properties of the complexes by cyclic voltammetry revealed that the complexes undergo multiple quasi-reversible processes. A comparison of the cyclic voltammetry of the copper complexes with their palladium(II) analogues suggests that these redox processes are ligand-based and not metal-based. The copper(II) complexes are cell-permeable in A431 mammalian cells and are nontoxic at concentrations of 50 µM. The ligands can be radiolabeled with copper-64 at room temperature.

Activation of rectus capitis posterior major muscles during voluntary retraction of the head in asymptomatic subjects.

OBJECTIVE: The purpose of this study was to assess levels of electromyographic activity measured from rectus capitis posterior major (RCPM) muscles of asymptomatic subjects as their heads moved from a self-defined neutral position to a retracted position. METHODS: A 2 × 2 within-subjects factorial research design was used. Disposable, intramuscular electrodes were used to collect electromyographic data from asymptomatic subjects between the ages of 20 and 40 years old. Data analysis was performed using mixed effects ß regression models. RESULTS: Activation of RCPM muscles was found to significantly increase (P < .0001) as the head moved from a self-defined neutral position to a retracted position. Rectus capitis posterior major muscle activation levels, measured as a function of head position, have not been previously reported. CONCLUSIONS: The findings from this study showed that RCPM muscle activation significantly increases during voluntary retraction of the head.

The effects of osteopathic manipulative treatment on pain and disability in patients with chronic low back pain: a single-blinded randomized controlled trial.

CONTEXT: The evidence for the efficacy of osteopathic manipulative treatment (OMT) in the management of low back pain (LBP) is considered weak by systematic reviews, because it is generally based on low-quality studies. Consequently, there is a need for more randomized controlled trials (RCTs) with a low risk of bias. OBJECTIVES: The objective of this study is to evaluate the efficacy of an OMT intervention for reducing pain and disability in patients with chronic LBP. METHODS: A single-blinded, crossover, RCT was conducted at a university-based health system. Participants were adults, 21-65 years old, with nonspecific LBP. Eligible participants (n=80) were randomized to two trial arms: an immediate OMT intervention group and a delayed OMT (waiting period) group. The intervention consisted of three to four OMT sessions over 4-6 weeks, after which the participants switched (crossed-over) groups. The primary clinical outcomes were average pain, current pain, Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v1.0 pain interference and physical function, and modified Oswestry Disability Index (ODI). Secondary outcomes included the remaining PROMIS health domains and the Fear Avoidance Beliefs Questionnaire (FABQ). These measures were taken at baseline (T0), after one OMT session (T1), at the crossover point (T2), and at the end of the trial (T3). Due to the carryover effects of OMT intervention, only the outcomes obtained prior to T2 were evaluated utilizing mixed-effects models and after adjusting for baseline values. RESULTS: Totals of 35 and 36 participants with chronic LBP were available for the analysis at T1 in the immediate OMT and waiting period groups, respectively, whereas 31 and 33 participants were available for the analysis at T2 in the immediate OMT and waiting period groups, respectively. After one session of OMT (T1), the analysis showed a significant reduction in the secondary outcomes of sleep disturbance and anxiety compared to the waiting period group. Following the entire intervention period (T2), the immediate OMT group demonstrated a significantly better average pain outcome. The effect size was a 0.8 standard deviation (SD), rendering the reduction in pain clinically significant. Further, the improvement in anxiety remained statistically significant. No study-related serious adverse events (AEs) were reported. CONCLUSIONS: OMT intervention is safe and effective in reducing pain along with improving sleep and anxiety profiles in patients with chronic LBP.

Establishing a baseline for multilingual capabilities of medical students at the Michigan State University College of Osteopathic Medicine.

CONTEXT: The language proficiencies of Michigan State University College of Osteopathic Medicine (MSUCOM) medical students are unknown. As of 2015, approximately 8% (or roughly 25 million) of the US population over the age of five were considered "limited English proficient". Research indicates, however, that it is valuable to patients to be able to communicate in their primary language with their primary care physician. If medical students' language proficiencies were known, the medical school curriculum could be adapted to leverage or enhance a student's language proficiencies, preparing students to serve in communities where their patients language proficiencies align. OBJECTIVES: The aim of this pilot study was to survey MSUCOM medical students in order to assess their language proficiencies with two goals in mind: first, to develop medical school curriculum that would leverage student's language proficiencies, and second, to encourage student placement within diverse communities throughout the state of Michigan where these physicians-in-training speak or understand the primary language of the local community to better serve patients. METHODS: For this cross-sectional descriptive pilot study, a short, author-created survey was sent to 1,226 osteopathic medical students (OMS-I to OMS-IV) at MSUCOM. Participants were asked questions pertaining to language proficiency, number of languages spoken, prior exposure to education abroad, and demographic information. All participant data were only reported in grouped, collective, de-identified terms. Descriptive statistical analyses (frequencies, percentages) were calculated utilizing SPSS Version 25 software. RESULTS: Over the course of several months, 698 (58.7%) current MSUCOM medical students participated in the study. Of those students, 382 (54.7%) responded that they were multilingual. The top three second languages reported spoken were: English 332 (47.6%), Spanish 169 (24.2%), and Arabic 64 (9.2%). In addition, 249 (37.2%) said they had prior exposure to education abroad, and 177 (26.4%) said they had lived in another country for more than 6 months. CONCLUSIONS: The majority, 382 (54.7%), of the MSUCOM students who participated in the survey have some degree of multilingual capabilities. The student population at MSUCOM may benefit from completing primary care rotations in diverse communities within the state of Michigan. Likewise, the communities throughout Michigan may benefit from having bilingual and multilingual medical students serve in their medical facilities. Further research on the efficacy of leveraging language skills in various communities, as well as broadening the population sample, is warranted to refine and validate the observed pilot study results.

The effects of osteopathic manipulative treatment on pain and disability in patients with chronic neck pain: A single-blinded randomized controlled trial.

BACKGROUND: Neck pain (NP) affects up to 70% of individuals at some point in their lives. Systematic reviews indicate that manual treatments can be moderately effective in the management of chronic, nonspecific NP. However, there is a paucity of studies specifically evaluating the efficacy of osteopathic manipulative treatment (OMT). OBJECTIVE: To evaluate the efficacy of OMT in reducing pain and disability in patients with chronic NP. DESIGN: Single-blinded, cross-over, randomized-controlled trial. SETTING: University-based, osteopathic manipulative medicine outpatient clinic. PARTICIPANTS: Ninety-seven participants, 21 to 65 years of age, with chronic, nonspecific NP. INTERVENTIONS: Participants were randomized to two trial arms: immediate OMT intervention or waiting period first. The intervention consisted of three to four OMT sessions over 4 to 6 weeks, after which the participants switched groups. MAIN OUTCOME MEASURES: Primary outcome measures were pain intensity (average and current) on the numerical rating scale and Neck Disability Index. Secondary outcomes included Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) health domains and Fear Avoidance Beliefs Questionnaire. Outcomes obtained prior to the cross-over allocation were evaluated using general linear models and after adjusting for baseline values. RESULTS: A total of 38 and 37 participants were available for the analysis in the OMT and waiting period groups, respectively. The results showed significantly better primary outcomes in the immediate OMT group for reductions in average pain (-1.02, 95% confidence interval [CI] -1.72, -0.32; p = .005), current pain (-1.02, 95% CI -1.75, -0.30; p = .006), disability (-5.30%, 95% CI -9.2%, -1.3%; p = .010) and improved secondary outcomes (PROMIS) related to sleep (-3.25, 95% CI -6.95, -1.54; p = .003), fatigue (-3.26, 95% CI -6.04, -0.48; p = .022), and depression (-2.59, 95% CI -4.73, -0.45; p = .018). The effect sizes were in the clinically meaningful range between 0.5 and 1 standard deviation. No study-related serious adverse events were reported. CONCLUSIONS: OMT is relatively safe and effective in reducing pain and disability along with improving sleep, fatigue, and depression in patients with chronic NP immediately following treatment delivered over approximately 4 to 6 weeks.

Assessment of potential strain injury to rectus capitis posterior minor muscles during whiplash type distortions of the cervical spine.

CONTEXT: Whiplash type injuries resulting from a rear end motor vehicle accident (REMVA) are thought to be caused by excessive loading and displacement of structural components of the cervical spine. On impact, the seat propels the driver's torso forward relative to the head, resulting in forced flexion of the occipitoatlantal (OA) joint, accompanied by forced stretching of the rectus capitis posterior minor (RCPm) muscles. Flexion of the OA joint and stretching of the RCPm muscles continues to increase until the vehicle's headrest strikes the back of the driver's head. It is known that externally applied forces that attempt to move the OA joint beyond its anatomic barrier can result in fracture, dislocation, or soft tissue damage to its structural components. However, the magnitude of headrest backset, defined as the distance between the driver's head and the vehicle's headrest, that would result in RCPm muscles being stretched to a length that would put them at risk for a muscle strain injury is unknown. OBJECTIVES: To quantify the relationships among flexion of the OA joint, RCPm muscle stretch, and backset, and to quantify the biomechanical response of RCPm muscles to increasing levels of axial load due to stretching. METHODS: Unembalmed head and neck specimens from three White females aged 85, 63, and 70 years were obtained from the Anatomical Services Division at the University of Maryland. Donors had provided written consent allowing use of their body for research purposes. Using an analytic model of the OA joint, the relationships between flexion of the OA joint and RCPm muscle stretch as a function of backset were estimated. RCPm muscles were removed from the cadavers and forcibly stretched using a servomechanism controlled hydraulic testing machine to quantify the load/displacement properties. After testing, the tissues were sectioned, mounted, and stained using Masson's trichrome to selectively stain muscle fibers red and collagen blue. RESULTS: Forced flexion of the OA joint was seen to be directly related to the magnitude of headrest backset. For values of backset greater than 7.2 cm, biomechanical testing of the RCPm muscles revealed that strain injuries ranged from the tearing of a few muscle fibers to complete rupture of the muscle and separation of the tendon at the posterior process of C1. CONCLUSIONS: Results showed that headrest backset at the time of vehicle impact is an important factor in estimating the risk of muscle strain injury to RCPm muscles. Muscle strain injury would be expected to impact the functional relationship between the RCPm muscles and the pain sensitive spinal dura. Physicians should be alert to the possibility that cervicogenic pain patients who have experienced whiplash associated with REMVA may show clinically relevant structural damage to the RCPm muscles on MRI.

Stability threshold during seated balancing is sensitive to low back pain and safe to assess.

Challenging trunk neuromuscular control maximally using a seated balancing task is useful for unmasking impairments that may go unnoticed with traditional postural sway measures and appears to be safe to assess in healthy individuals. This study investigates whether the stability threshold, reflecting the upper limits in trunk neuromuscular control, is sensitive to pain and disability and is safe to assess in low back pain (LBP) patients. Seventy-nine subjects with non-specific LBP balanced on a robotic seat while rotational stiffness was gradually reduced. The critical rotational stiffness, KCrit, that marked the transition between stable and unstable balance was used to quantify the individual's stability threshold. The effects of current pain, 7-day average pain, and disability on KCrit were assessed, while controlling for age, sex, height, and weight. Adverse events (AEs) recorded at the end of the testing session were used to assess safety. Current pain and 7-day average pain were strongly associated with KCrit (current pain p < 0.001, 7-day pain p = 0.023), reflecting that people experiencing more pain have poorer trunk neuromuscular control. There was no evidence that disability was associated with KCrit, although the limited range in disability scores in subjects may have impacted the analysis. AEs were reported in 13 out of 79 total sessions (AE Severity: 12 mild, 1 moderate; AE Relatedness: 1 possibly, 11 probably, 1 definitely-related to the study). Stability threshold is sensitive to pain and appears safe to assess in people with LBP, suggesting it could be useful for identifying trunk neuromuscular impairments and guiding rehabilitation.

Implied Evidence of the Functional Role of the Rectus Capitis Posterior Muscles.

CONTEXT: Osteopathic physicians often target the rectus capitis posterior minor (RCPm) and rectus capitis posterior major (RCPM) muscles when using muscle energy or soft tissue cervical techniques to treat patients with head and neck pain. The RCPm and RCPM muscles are located deep within the posterior occipitoatlantal and atlantoaxial interspaces, respectively. OBJECTIVE: To characterize the functional role of RCPm and RCPM muscles by comparing electromyographic (EMG) activation patterns of these muscles with EMG activation patterns of specific flexor and extensor muscles of the head and neck, the sternocleidomastoid (SCM), and the splenius capitis (SC) muscles, respectively. METHODS: Asymptomatic participants were recruited from the Michigan State University College of Osteopathic Medicine student body. Disposable 25-gauge, bipolar fine-wire intramuscular electrodes were used to collect EMG data from the right and left RCPm and RCPM muscles. Surface electrodes were used to collect EMG data from the right and left SCM and SC muscles. Data were collected as participants performed 4 cycles of flexion and extension with an external 4-lb force applied to the back of the head and the forehead. RESULTS: In RCPM muscles, EMG activity was significantly greater (P<.003) during flexion and extension of the head and neck when an external force was applied to the back of the head. EMG activity in SCM muscles was significantly greater (P<.0001) during flexion and extension of the head and neck when an external force was applied to the forehead. The authors observed that EMG activity in SC muscles was significantly greater (P<.015) during flexion and extension of the head and neck when an external force was applied to the back of the head. No significant difference was found in EMG activity in RCPm muscles (P<.834) during flexion and extension of the head and neck, regardless of whether the external force was applied to the back of the head or the forehead. CONCLUSION: The EMG activation patterns of the RCPm muscles suggest that their functional role may be to stabilize the occipitoatlantal joint by helping maintain congruency of the joint surfaces. In contrast, the EMG activation patterns of the RCPM muscles suggest that their functional role may be to contribute to extension of the head, primarily at the occipitoatlantal and the atlantoaxial joints.

Magnetic Resonance Imaging Parameters Selected for Optimal Visualization of the Occipitoatlantal Interspace.

CONTEXT: Disorders of the rectus capitis posterior minor (RCPm) muscles have been associated with chronic headache. Magnetic resonance (MR) imaging protocols currently used in clinical settings do not result in image sets that can be used to adequately visualize the integrity of occipitoatlantal structures or to definitively quantify time-dependent functional morphologic changes. OBJECTIVE: To develop an MR imaging protocol that provides the superior image quality needed to visualize occipitoatlantal soft tissue structures and quantify time-dependent pathologic changes. METHODS: Asymptomatic participants were recruited from the Michigan State University College of Osteopathic Medicine student body. Magnetic resonance imaging data were collected from each participant at enrollment and 2 weeks after enrollment using a 3T magnet. A conventional spin-echo pulse sequence was used to construct 24 axial, T1-weighted images with the following measurement parameters: repetition time, 467 milliseconds; echo time, 13.5 milliseconds; number of excitations, 4; slice thickness, 3.0 mm; and in-plane resolution, 0.625×0.625 mm. Image planes were aligned approximately perpendicular to the long axes of the RCPm muscles to facilitate the authors' ability to accurately draw regions of interest around the specific muscle boundaries. Cross-sectional area (CSA) of the right and left RCPm muscles was quantified for each participant at the 2 points in time. The null hypothesis was that there would be no significant difference between mean values of muscle CSA collected at enrollment and 2 weeks after enrollment for a given participant and a given side of his or her body. RESULTS: Thirteen participants were enrolled. No significant difference was found between mean values of either right or left RCPm muscle CSA for any of the participants measured at enrollment and 2 weeks after enrollment (all P>.05). CONCLUSION: The protocol achieves the superior image quality necessary to compare the functional form of occipitoatlantal structures at progressive points in time.

A standardized protocol for needle placement in suboccipital muscles.

The objective of this study was to assess the safety and accuracy of using common anatomic landmarks to guide the placement of needle electrodes into suboccipital muscles. Atrophic changes in suboccipital muscles have been reported in some patients who have tension-type headaches, and in some patients who have headaches resulting from whiplash-type injuries. These atrophic changes most likely result from disuse or denervation. Needle electromyography is a definitive technique for determining the cause of muscle atrophy, but requires that needle electrodes be inserted into the muscle. Suboccipital muscles present a challenge to the electromyographer in that they are physically small and are located in close proximity to one another. Atrophied muscles with fatty replacement and the presence of critical structures such as the vertebral artery further complicate the procedure. Using a standardized protocol, three investigators attempted blind needle insertions into each of the suboccipital muscles of eight embalmed cadavers. A dissector then assessed targeted muscle penetrations, final resting positions of the wires, and their proximity to critical structures. Eighty-one percent of 181 attempted insertions penetrated the targeted muscles: 83% for the rectus capitis posterior minor, 83% for the rectus capitis posterior major, 94% for the obliquus capitis superior, and 63% for the obliquus capitis inferior muscles, respectively. It was concluded that readily palpable external landmarks can be used to safely and reliably guide the insertion of needle electrodes into three of the four pairs of suboccipital muscles.

Forward Head Posture and Activation of Rectus Capitis Posterior Muscles.

CONTEXT: Rectus capitis posterior (RCP) muscles have physical attachments to the pain-sensitive spinal dura. Atrophy of these muscles is associated with chronic headache in some patients. The authors suspect that the significance of atrophy in the RCP muscles has been undervalued because the functional role of these muscles is not well defined. OBJECTIVE: To determine whether a statistically significant change in normalized levels of electromyographic activity in RCP muscles occurs when the head is voluntarily moved from a self-selected neutral head position to a protruded head position. METHODS: Fine wire, intramuscular electrodes were used to collect electromyographic data as asymptomatic participants moved their head from a neutral head position into a forward head position and back into the neutral head position. This sequence was repeated 4 times. Normalized levels of electromyographic activity were quantified using a 2-head position × 2 sides of the body repeated measures design that incorporated mixed-effects ß regression models. RESULTS: Twenty participants were studied. Electromyographic activity collected from RCP muscles was found to increase as the head was voluntarily moved from a self-selected neutral head position (11% of maximum voluntary isometric contraction [MVIC] in RCP minor, 14% of MVIC in RCP major) into a protruded head position (35% of MVIC in RCP minor, 39% of MVIC in RCP major) (P<.001). CONCLUSION: Rectus capitis posterior muscles may contribute to segmental stabilization of the occipitoatlantal and atlantoaxial joints by helping to maintain joint congruency during movement of the head.

Electromyographic activity of rectus capitis posterior minor muscles associated with voluntary retraction of the head.

BACKGROUND CONTEXT: The functional role of rectus capitis posterior minor (RCPm) muscles is not well defined. To the best of our knowledge, electromyographic (EMG) data from RCPm muscles in humans have never been collected and analyzed. PURPOSE: To test the null hypothesis that there will be no difference in normalized levels of EMG activity measured from RCPm muscles with the head in a neutral position and with the head in a retracted position. STUDY DESIGN: A repeated measures design intended to quantify normalized levels of EMG activity measured from RCPm muscles. METHODS: Disposable 25-gauge, bipolar fine wire hooked electrodes were used to collect EMG data from both right and left RCPm muscles from 17 asymptomatic subjects. Data were collected while subjects performed five trials with the head maintained in a neutral position; performed three maximal voluntary isometric contraction efforts; performed four trials with the head maintained in a retracted position. Mixed effects beta regression models were used to analyze the data. RESULTS: Normalized EMG activity of RCPm muscles collected with the subject's head held in a retracted position was significantly higher (p<.0001) than normalized EMG activity collected with the subject's head held in a self-selected, neutral position. CONCLUSIONS: Rectus capitis posterior minor muscles are active when the head is held in a neutral position and show a significant increase in activity when the head is held in a retracted position.

The effect of osteopathic manipulative treatment on postoperative medical and functional recovery of coronary artery bypass graft patients.

CONTEXT: Several studies have investigated the use of osteopathic manipulative treatment (OMT) after coronary artery bypass graft (CABG) operations; however, there is little information regarding the effect of OMT in the postoperative recovery of patients undergoing CABG operations. METHODS: Patients scheduled to undergo a CABG operation were voluntarily enrolled and randomly assigned to receive 1 of 3 treatment protocols after their surgical procedure: standardized daily OMT and conventional postoperative care (the OMT group), daily time-matched placebo OMT and conventional postoperative care (the placebo group), or conventional postoperative care only (the control group). Specific OMT techniques used were thoracic inlet myofascial release, standard rib raising (with paraspinal muscle stretch to the L2 vertebral level), and soft tissue cervical paraspinal muscle stretch (with suboccipital muscle release). Primary outcome measures included time to discharge, time to postoperative bowel movement, and FIM functional assessment scores. RESULTS: Fifty-three patients completed the study protocol: 17 in the OMT group, 18 in the placebo group, and 18 in the control group. After surgical procedures, patients were discharged to home at a mean (standard deviation [SD]) rate of 6.1 (1.4), 6.3 (1.5), and 6.7 (3.0) days for the OMT group, placebo group, and control group, respectively. Patients in the OMT group were discharged 0.55 days earlier than those in the control group and 0.16 days earlier than those in the placebo group. The mean (SD) number of days to first postoperative bowel movement was 3.5 (0.9), 4.0 (0.8), and 4.0 (0.9) for the OMT group, the placebo group, and the control group, respectively. On day 3 after surgery, the mean (SD) total score on the FIM was 19.3 (6.7), 15.4 (7.3), and 18.6 (6.5) for the OMT, the placebo, and the control group, respectively; total score for the OMT group was 0.81 greater than that of the control group and 3.87 greater than that of the placebo group. None of the differences achieved statistical significance (P<.05) CONCLUSION: A daily postoperative OMT protocol improved functional recovery of patients who underwent a CABG operation.