Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity.

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary ß subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.

Mouse mandibular-derived osteoclast progenitors have differences in intrinsic properties compared with femoral-derived progenitors.

Craniofacial osteoclasts are essential for site-specific processes such as alveolar bone resorption, tooth eruption, and orthodontic tooth movement. Much of the current understanding of osteoclast development and function comes from studies using long bone-derived cells. Minimal investigation has been done to explore skeletal site differences. The overall goal of this study was to determine if mandibular- and femoral-derived osteoclasts represent distinct populations. To test this hypothesis, bone marrow cells were initially analyzed from the mandible and femur of 2-month-old mice. It was shown that mandibular-derived osteoclasts have enhanced size (mm2) compared with femoral-derived osteoclasts. Since bone marrow macrophages are a heterogenous population, we additionally selected for monocytes and demonstrated that mandibular-derived monocytes also form osteoclasts with increased size compared with femoral-derived monocytes. Osteoclast precursor populations from both skeletal sites were analyzed by flow cytometry. A newly described Ly6CHigh+ population as well as the Ly6Cint population was increased in the mandibular-derived cells. The difference in differentiation potential between monocyte cultures suggests that the increase in the Ly6CHigh+ population may explain the enhanced differentiation potential in mandibular-derived cells. Monocyte genes such as Pu.1, C/ebp-a, and Prdm1 are increased in expression in mandibular-derived monocytes compared with femoral-derived monocytes. As expected with enhanced differentiation, osteoclast genes including Nfatc1, Dc-stamp, Ctsk, and Rank are upregulated in mandibular-derived osteoclast precursors. Future studies will determine how changes in the environment of the mandible lead to changes in percentages of osteoclast progenitors and their differentiation potential.

SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause the ongoing pandemic of coronavirus disease 2019 (COVID19). One key feature associated with COVID-19 is excessive pro-inflammatory cytokine production that leads to severe acute respiratory distress syndrome. Although the cytokine storm induces inflammatory cell death in the host, which type of programmed cell death mechanism that occurs in various organs and cells remains elusive. Using an in vitro culture model of polarized human airway epithelium (HAE), we observed that necroptosis, but not apoptosis or pyroptosis, plays an essential role in the damage of the epithelial barrier of polarized HAE infected with SARS-CoV-2. Pharmacological inhibitors of necroptosis, necrostatin-2 and necrosulfonamide, efficiently prevented cell death and epithelial barrier dysfunction caused by SARS-CoV-2 infection. Moreover, the silencing of genes that are involved in necroptosis, RIPK1, RIPK3, and MLKL, ameliorated airway epithelial damage of the polarized HAE infected with SARS-CoV-2. This study, for the first time, confirms that SARS-CoV-2 infection triggers necroptosis that disrupts the barrier function of human airway epithelia in vitro.

A comparison of isometric and isokinetic normalization methods for electromyographic data from sub-regions of supraspinatus and infraspinatus during dynamic tasks.

This study explored effects of using isometric versus isokinetic maximal voluntary contractions (MVCs) to normalize EMG data from supraspinatus and infraspinatus subregions during isokinetic tasks. Participants performed submaximal isokinetic external rotation (ER) and scaption tasks at two speeds. Three isometric MVCs were used: seated ER; side-lying scaption; side-lying abduction. Isokinetic MVCs were performed in the same position and speeds as the experimental tasks. Data were normalized using peak EMG from reference tasks: MVC which produced the greatest amplitude overall (MEA), isometric MVC with greatest amplitude (isometric best), isokinetic MVC with greatest amplitude (isokinetic best), and the greatest amplitude from the isokinetic MVC that matched the experimental task (isokinetic matched). Mean %MVC from each experimental task/ sub-region were compared by normalization method. The isokinetic matched method versus the MEA method was significantly different in all comparisons with isokinetic matched resulting in relative normalized task values up to 162% greater. The isometric best method resulted in significantly greater %MVC 37% of the time compared to the MEA method, whereas there were no differences when using isokinetic best compared to MEA. Isokinetic MVCs are less likely to overestimate %MVC than isometric and their use should be considered when normalizing data from dynamic tasks.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models.

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing-related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant (P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

Age at onset of alcohol consumption and its association with alcohol misuse in adulthood.

OBJECTIVE: This study aimed to explore the association between early age onset of alcohol consumption and alcohol misuse in adulthood. METHODS: The study sample consisted of 16 829 individuals' (8349 males, 8435 females) survey responses obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 through 2019. Alcohol dependence was measured using the AUDIT-C (Alcohol Use Disorder Identification Test-Consumption), and the ages at which alcohol consumption began were grouped into four categories: under 16, 16 to 18, 19 to 23, and over 24. Multiple logistic regression was used to examine the association between current alcohol misuse and age at onset of alcohol consumption. RESULTS: Compared to individuals who started drinking alcohol after the age of 24, those who began drinking alcohol before the age of 16 were more likely to score 8 or more on AUDIT-C questions (under 16: males, odds ratio [OR] 2.50, confidence interval [CI] 1.97-3.17; females, OR: 1.66, CI: 1.18-2.33). Similar to the main analysis, the earlier the onset of alcohol assumption starts, the more likely one is to develop alcohol misuse in adulthood according to subgroup analysis stratified by independent variables in both gender. CONCLUSION: The lower the age at the onset of alcohol consumption, the higher the likelihood of alcohol misuse in adulthood. While both males and females showed the same trend in response to the AUDIT-C questions, males tended to have a stronger association between early onset alcohol consumption and alcohol misuse.

Evaluation of a multidisciplinary, multimodal pain management protocol following pancreas transplantation.

INTRODUCTION: Patients undergoing solid-organ transplantation demonstrate pain arising from both the surgical intervention and pre-existing comorbidities. High levels of opioid use both pre- and post-transplant are associated with unfavorable transplant outcomes. Patient education, multimodal therapy, and discharge planning have all been demonstrated to reduce opioid use after transplant. METHODS: This is a single-center, retrospective study analyzing patients before and after implementation of a multimodal, multidisciplinary pain management protocol. Morphine milligram equivalents (MMEs) use during the index transplant hospitalization and the need for opioids at discharge was compared between the pre- and post-protocol groups. RESULTS: A total of 52 patients were included in the study, 31 in the pre and 21 in the post-protocol groups. Inpatient MME use was reduced from 135.5 to 67.5 MMEs after protocol implementation. Additionally, the number of patients discharged on opioids following transplant decreased from 90.3% to 47.6%. Pain scores, length of stay (LOS), and return of bowel function was not different between groups. CONCLUSION: The implementation of a multimodal, multidisciplinary pain management protocol significantly decreased opioid use during the post-surgical hospitalization and in the 6 months following transplantation. A combination of non-opioid analgesics, patient education, and discharge planning can be beneficial elements in pancreas transplant pain management.

Effect of Breast Reconstruction on Kinematics and Performance during Upper Limb-Focused Functional Tasks.

BACKGROUND: Breast reconstruction after curative breast cancer surgery is becoming increasingly common. There is evidence to suggest that these surgeries have negative effects on shoulder function, but to date there have been no investigations of shoulder biomechanics during functional tasks in this group. The purpose of this study was to define and compare upper limb motion of patients with breast cancer who underwent mastectomy only or mastectomy with reconstruction with a control group without cancer during a range of work-related functional tasks. METHODS: Ninety-five women participated: 25 controls, 25 patients with breast cancer who received a mastectomy only, and 45 patients with breast cancer who received a mastectomy with reconstruction (implant, latissimus dorsi flap, or deep inferior epigastric artery perforator flap). Motion of the torso, humeri, and scapulae were tracked during arm-focused functional tasks, involving reaching, dexterity, and lifting overhead, and joint angles were calculated. Mean, maximum, and minimum angles were calculated and compared among groups using one-way analyses of variance ( p < 0.05). RESULTS: The reconstruction group had significantly different kinematics than the other two groups. Throughout task performance, patients who had reconstruction had increased scapular posterior tilt and increased humeral external rotation. These findings are consistent with reconstruction surgical procedures and may highlight muscle pattern alterations that interfere with co-contraction, stability, and functional task performance. CONCLUSIONS: The findings suggest that breast reconstruction surgery influences functional task performance. Scapular and humeral kinematics may indicate movement pattern differences that are important to address in rehabilitation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Evidence of rotator cuff disease after breast cancer treatment: scapular kinematics of post-mastectomy and post-reconstruction breast cancer survivors.

BACKGROUND: Breast cancer survivors may be at risk of experiencing rotator cuff disease after treatment. Biomechanical alterations following surgery potentially predispose survivors to develop this disorder. OBJECTIVE: To examine scapular kinematics in breast cancer survivors with and without impingement pain during an overhead reach task. DESIGN: A cross-sectional study. METHODS: Three surgery groups were included: non-cancer controls, mastectomy-only survivors and post-reconstruction survivors. Breast cancer survivor groups were also categorized by the presence of impingement pain. Scapular motion was tracked during an overhead reach task, performed separately by both arms. Maximum scapular internal rotation, upward rotation and tilt were calculated. Two-way analyses of variance with interactions (p < .05) were used to test the effects of group (control, mastectomy-only, reconstruction) and impingement pain (pain, no pain) on each variable within a (left/right) side. RESULTS: Scapular kinematics varied with the group by pain interaction. On the right side, the mastectomy-pain group had reduced upward rotation, while the reconstruction-pain group had higher upward rotation (mastectomy-only: 22.9° vs. reconstruction: 31.2°). On the left side, the mastectomy-pain group had higher internal rotation, while the reconstruction-pain group had reduced internal rotation (mastectomy-only: 45.1° vs. reconstruction: 39.3°). However, time since surgery was longer in the mastectomy-pain group than reconstruction-pain group, suggesting there may be a temporal component to kinematic compensations. CONCLUSIONS: There are kinematic alterations in breast cancer survivors that may promote future development of rotator cuff disease. Compensations may begin as protective and progress to more harmful alterations with time.KEY MESSAGESScapular kinematics varied with surgery and pain interaction: upward rotation was lower and internal rotation higher in mastectomy-pain group, while upward rotation was higher and internal rotation lower in reconstruction-pain group.Kinematics alterations may also be associated with time since surgery, as the mastectomy-pain group had longer time since surgery than the reconstruction-pain group.Kinematic alterations may transition from protective to harmful over time.In-depth analyses by reconstruction type are needed to determine surgery-specific effects on kinematics and their potential impact on the development of rotator cuff disease.

A survey of dedicated PASC clinics: Characteristics, barriers and spirit of collaboration.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can produce prolonged multi-organ system dysfunction and a worsened quality of life, a condition known as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). In response, clinics have emerged dedicated to the treatment of individuals with PASC. OBJECTIVE: To better understand the current characteristics of these clinics, the barriers they face, and the interest in collaboration between clinics. DESIGN: A cross-sectional survey study. PARTICIPANTS: Clinicians working within dedicated PASC centers (N = 94) identified primarily through the Survivor Corps database of Post-COVID Care Centers. Additional clinics were found through news articles, an American Academy of Physical Medicine and Rehabilitation Database, and word of mouth. METHODS: The branching logic electronic survey consisting of up to 39 questions was sent electronically to potential participants. RESULTS: Complete survey responses were obtained from 45 clinics. There was a wide variety of different clinical models and specialties involved. The majority of clinics were homed in physical medicine and rehabilitation (40%), pulmonology (22%), and internal medicine (16%). Most clinics (73%) reported experiencing obstacles in the treatment of their patients, the most common of which included needing more established protocols (45%) and more clinical resources (24%). Most clinics (76%) also reported an interest in participating in a collaborative clinical network. CONCLUSION: Despite wide variability in current clinical models of PASC clinics, there are common practices such as using telemedicine, having initial visits longer than 30 minutes, involving certain specialties in the treatment team, and having the ability for follow-up. Clinicians involved with PASC clinics have a strong interest in collaboration to improve patient care and overcome clinical obstacles, the most common of which is the lack of clear treatment protocols. More research is needed to identify which clinical models lead to better patient outcomes.

DeepLensNet: Deep Learning Automated Diagnosis and Quantitative Classification of Cataract Type and Severity.

PURPOSE: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs. DESIGN: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset. PARTICIPANTS: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants). METHODS: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students. MAIN OUTCOME MEASURES: Mean squared error (MSE). RESULTS: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC. CONCLUSIONS: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.

Colorectal Cancer Screening in the Elderly: Is Age Just a Number?

INTRODUCTION: Colorectal cancer screening improved outcomes for patients diagnosed between the age of 45-75. Present life expectancy is beyond this limit, yet there are no guidelines for these ages. We aim to identify outcomes after screening and intervention in patients ≥75 years and correlate with frailty. MATERIALS AND METHODS: Records between 2011 and 2019 were queried. Patients ≥75 screened and treated for colorectal cancer were included. Patient demographics, perioperative mortality, age at last colonoscopy and frailty score were calculated. A Modified Frailty Index from the Canadian Study of Health and Aging Frailty Index was used. A score of 1 to 11 was calculated based on patient comorbidities. The MFI was assigned from 0 to 11: 0 signified absence of frailty and 11 indicated maximum frailty. RESULTS: Of 179 patients were identified, 46.3% males. 171(95%) had elective and 8 (5%) had emergent surgery. The average age was 81.8 years. All colonoscopies were performed for symptoms. A modified frailty index was retrospectively calculated; 75% of patients scored between 0 and 2 and 1% scored >6. CONCLUSION: Older patients who underwent colonoscopy and surgery for symptomatic colon cancer had a low mortality, 2%. The average age was 6.8 years older than the recommended cutoff for colonoscopy screening. Most patients scored 0 to 2 on the modified frailty index, suggesting that not only are older patients more fit than previously thought, but also able to tolerate colorectal interventions more liberally. Utilizing frailty indices to identify screening patterns beyond 75 years of age might prove beneficial for this patient population. Further studies are recommended.

Surgical repair of the supraspinatus: pre- and postoperative architectural changes in the muscle.

INTRODUCTION: Shortening of the tendon and muscle is recognised as a strong predictor of surgical failure of supraspinatus tendon tears. Changes in muscle architecture following repair have not been thoroughly investigated. Hence, we aimed to compare the pre- and postoperative architecture of the supraspinatus. METHODS: We recruited eight participants with full-thickness supraspinatus tears. Images of the supraspinatus were captured preoperatively (pre-op) and postoperatively at one month (post-op1), three months (post-op2) and six months (post-op3) in relaxed and contracted states (0º and 60º glenohumeral abduction). Fibre bundle length (FBL), pennation angle (PA) and muscle thickness were quantified. Self-reported function, and maximal isometric abduction and external rotation strengths were assessed. RESULTS: The mean FBL increased from pre-op to post-op1 (p = 0.001) in the relaxed state and from pre-op to post-op2 (p = 0.002) in the contracted state. Decrease in FBL was observed from post-op2 to post-op3 in the relaxed state. The mean PA decreased from pre-op to post-op1 (p < 0.001) in the relaxed state, but increased from post-op2 to post-op3 in both relaxed (p = 0.006) and contracted (p = 0.004) states. At post-op3, external rotation (p = 0.009) and abduction (p = 0.005) strengths were greater than at post-op2. Overall function increased by 47.67% from pre-op to post-op3. CONCLUSION: Lengthening of the supraspinatus occurs with surgery, altering the length-tension relationship of the muscle, which can compromise muscle function and lead to inferior surgical outcomes. These findings may guide clinicians to optimise loads, velocities and shoulder ranges for effective postoperative rehabilitation.

The utility of the acromion marker cluster (AMC) in a clinical population.

INTRODUCTION: The acromion marker cluster (AMC) is a non-invasive scapular motion tracking method. However, it lacks testing in clinical populations, where unique challenges may present. This investigation resolved the utility of the AMC approach in a compromised clinical population. METHODS: The upper body of breast cancer survivors (BCS) and controls were tracked via motion capture and scapular landmarks palpated and recorded using a digitizer at static neutral to maximum elevation postures. The AMC tracked the scapula during dynamic maximum arm abduction. Both single (SC) and double calibration (DC) methods were applied to calculate scapular angles. The influences of calibration method, elevation, and group on mean and absolute error with two-way fixed ANOVAs with interactions (p < 0.05). Root mean square errors (RMSE) were calculated and compared. RESULTS: DC improved AMC estimation of palpated scapular orientation over SC, especially at higher arm elevations; RMSE averaged 11° higher for SC than DC at maximum elevation, but the methods were only 2.2° different at 90° elevation. DC of the AMC yielded mean error values of ∼5-10°. These approximate errors reported for AMC with young, lean adults. CONCLUSIONS: The AMC with DC is a non-invasive method with acceptable error for measuring scapular motion of BCS and age-matched controls.

Regional activation of supraspinatus and infraspinatus sub-regions during dynamic tasks performed with free weights.

Growing evidence supports the existence of distinct anatomical sub-regions within supraspinatus and infraspinatus, but only recently has attention turned to exploring their potential functional differences. Using indwelling fine-wire electromyography, muscle activity was investigated from these sub-regions in 15 participants (mean 34 yr, 170 cm, 71.9 kg) during dynamic external rotation (ER), abduction, flexion, and scaption tasks with and without free weights corresponding to 50% and 75% of the participant's five repetition maximum. Electromyography data were normalized to isometric and isokinetic maximal voluntary contractions and activation ratios for each sub-region compared. Differences in mean regional activation ratios for supraspinatus and infraspinatus varied by arm posture, but were not influenced by load. Relative activation of posterior supraspinatus was greater during an ER task performed in side lying compared to an ER task performed with 90° of humeral elevation in seated and prone postures. Relative activation of superior infraspinatus was greater during an ER task in prone and side lying postures compared to flexion and scaption. Similar results were found when comparing regional muscle activation ratios for infraspinatus between tasks regardless of normalization method employed. These findings may impact exercise selection in the non-operative management of rotator cuff tears.

Regional Electromyography of the Infraspinatus and Supraspinatus Muscles During Standing Isometric External Rotation Exercises.

BACKGROUND: Whole-muscle electromyography (EMG) data of the rotator cuff support external rotation (ER) strengthening exercises during shoulder rehabilitation. However, distinct neuroanatomic regions in the supraspinatus and infraspinatus exist. Differences in regional muscle activity occur during rehabilitation exercises, but little information is available for ER exertions. HYPOTHESIS: Regional infraspinatus and supraspinatus muscle activity during standing ER exertions will differ with posture and intensity. STUDY DESIGN: Descriptive laboratory study. LEVEL OF EVIDENCE: Level 5. METHODS: Twenty healthy individuals (12 men, 8 women) participated. Fine wire electrodes were inserted into 2 supraspinatus and 3 infraspinatus muscle regions. EMG data were recorded during standing isometric ER exertions at 2 intensities (maximal, submaximal) and in 7 postures defined by the angle (0°, 30°, 90°) and plane (abduction, scaption, flexion) of arm elevation. EMG data were normalized to maximum voluntary isometric contraction (% MVIC) to examine the influences of posture, intensity and their interaction on muscle activity. RESULTS: Superior infraspinatus activity was higher in 0° of elevation (50.9% ± 5.7% MVIC) versus 30° of flexion (37.4% ± 3.9% MVIC) at maximal intensity. Inferior infraspinatus activity was higher in 90° of scaption (max = 59.8% ± 2.8% MVIC, submax = 29.4% ± 1.9% MVIC) versus 0° of elevation (max = 42.3% ± 4.5% MVIC, submax = 22.4% ± 2.8% MVIC) (P = 0.02, P = 0.05, respectively). Anterior supraspinatus activity was highest in 90° of adbuction (max = 61.6% ± 3.1% MVIC; submax = 39.1% ± 3.8% MVIC) and lowest in 30° of flexion (max = 29.0% ± 3.4% MVIC, submax = 15.6% ± 1.7% MVIC) and 90° of flexion (max = 34.6% ± 2.4% MVIC, submax = 14.8% ± 1.9% MVIC). Posterior suprasptinatus activity was lowest in 0° of elevation (34.2% ± 3.0% MVIC), 30° of flexion (33.0% ± 3.6% MVIC) and highest in 90° of abduction (56.2% ± 4.1% MVIC) and 90° of scaption (46.7% ± 2.8% MVIC) (all Ps < 0.04). CONCLUSION: Regional infraspinatus and supraspinatus muscle activity differed with posture and intensity. Superior and middle infraspinatus muscle activities were similar across postures, but inferior infraspinatus activity was highest in 90° of arm elevation. Anterior and posterior supraspinatus activities were higher in the abduction and scaption planes, especially at 90° of elevation, as compared with the flexion plane. CLINICAL RELEVANCE: In shoulder rehabilitation of supraspinatus tendon injuries, ER exercises in the flexion plane challenge the whole infraspinatus muscle and require lower supraspinatus muscle activity.

Relation of Abdominal Obesity to Risk of Atrial Fibrillation (From the Reasons for Geographic and Racial Differences in Stroke [REGARDS] Study).

Our knowledge of the association between abdominal obesity (AO) and the risk of atrial fibrillation (AF) after adjusting for body mass index (BMI) is limited. We included 11,617 Black and White participants (mean age 63.0 ± 8.4 years) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) national cohort study who were free of AF at baseline. A multivariable logistic regression model was used to estimate the odds ratio (OR) with 95% confidence interval (CI) of incident AF associated with AO. We also evaluated the association between waist circumference (WC) and incident AF. Over a median follow-up of 9.4 years, 999 participants developed AF. AO was associated with an increased risk of AF in a multivariable model adjusted for sociodemographic, lifestyle, and cardiovascular risk factors (OR 1.43, 95% CI 1.24 to 1.65, p <0.001). The association was attenuated after adjusting for BMI (OR 1.13, 95% CI 0.95 to 1.35, p = 0.16). There was no evidence of interaction between AO and incident AF by age category (age >65 vs age ≤65), gender, race, obesity, or BMI category. Conversely, a 10cm increase in WC was associated with a higher incidence of AF after controlling for BMI (OR 1.18 95% CI 1.09 to 1.29, p <0.001), in both nonobese (OR 1.14, 95% CI 1.03 to 1.28, p = 0.02) and obese (OR 1.26, 95% CI 1.11 to 1.42, p <0.001) people. In conclusion, there was an association between AO and incident AF, but the association was weakened after adjusting for BMI. There was a significant association between WC and incident AF, after taking other AF risk factors and BMI into account. WC is a potentially modifiable risk factor for AF, and further research is warranted to explore the effect of decreasing WC on the population AF burden.

Surgical repair of the supraspinatus: pre- and postoperative architectural changes in the muscle

INTRODUCTION@#Shortening of the tendon and muscle is recognised as a strong predictor of surgical failure of supraspinatus tendon tears. Changes in muscle architecture following repair have not been thoroughly investigated. Hence, we aimed to compare the pre- and postoperative architecture of the supraspinatus.@*METHODS@#We recruited eight participants with full-thickness supraspinatus tears. Images of the supraspinatus were captured preoperatively (pre-op) and postoperatively at one month (post-op1), three months (post-op2) and six months (post-op3) in relaxed and contracted states (0º and 60º glenohumeral abduction). Fibre bundle length (FBL), pennation angle (PA) and muscle thickness were quantified. Self-reported function, and maximal isometric abduction and external rotation strengths were assessed.@*RESULTS@#The mean FBL increased from pre-op to post-op1 (p = 0.001) in the relaxed state and from pre-op to post-op2 (p = 0.002) in the contracted state. Decrease in FBL was observed from post-op2 to post-op3 in the relaxed state. The mean PA decreased from pre-op to post-op1 (p < 0.001) in the relaxed state, but increased from post-op2 to post-op3 in both relaxed (p = 0.006) and contracted (p = 0.004) states. At post-op3, external rotation (p = 0.009) and abduction (p = 0.005) strengths were greater than at post-op2. Overall function increased by 47.67% from pre-op to post-op3.@*CONCLUSION@#Lengthening of the supraspinatus occurs with surgery, altering the length-tension relationship of the muscle, which can compromise muscle function and lead to inferior surgical outcomes. These findings may guide clinicians to optimise loads, velocities and shoulder ranges for effective postoperative rehabilitation.

A case of "smoldering" immune-mediated thrombotic thrombocytopenic purpura manifesting as recurrent cardioembolic stroke.

Prompt recognition and treatment for thrombotic thrombocytopenic purpura (TTP) are critical to prevent the irreversible manifestations of this rare and quickly fatal hematologic disorder. Untreated TTP is typically a rapid-onset disease with mortality exceeding 90% within days in the absence of appropriate treatment. In the current report, we describe a case of immune-mediated TTP (iTTP) in a 62-year-old man manifesting as longstanding thrombocytopenia, recurrent cardioembolic strokes, and valvular thrombogenesis over a period of 3 years. We provide correlative evidence to support the potential contribution of adalimumab, a TNFα inhibitor, to the development of iTTP. We offer several educational insights regarding the identification of atypical presentations of iTTP owing to the longstanding disease course and numerous clinical comorbidities seen in this patient.

Time of Day Influences Psychophysical Measures in Women With Burning Mouth Syndrome.

Burning mouth syndrome (BMS) is a chronic orofacial pain condition that mainly affects postmenopausal women. BMS type I patients report little to no spontaneous pain in the morning and increases in pain through the day, peaking in the afternoon. Quantitative sensory testing (QST) findings from BMS type 1 patients are inconsistent as they fail to capture this temporal variation. We examined how QST in BMS type 1 (n = 18) compared to healthy participants (n = 33) was affected by time of day. QST of the face and forearm included warmth detection threshold (WDT), cold detection threshold (CDT), and heat pain thresholds (HPT), ratings of suprathreshold heat, and pressure pain thresholds (PPT), and was performed twice: once in the morning and once in the afternoon. Compared to healthy participants, BMS patients had higher pain sensitivity to phasic heat stimuli at most temperatures (35°C U = 126.5, p = 0.0006, 39°C U = 186.5, p = 0.0386, 41°C U = 187.5, p = 0.0412, 43°C U = 171, p = 0.0167, 45°C U = 168.5, p = 0.0146) on the forearm, but no differences in pain thresholds (HPT and PPT) regardless of time of day or body area tested. BMS patients had higher WDT (U = 123, p = 0.0172), and lower CDT (U = 98, p = 0.0021) of the forearm and lower WDT of the face (U = 55, p = 0.0494). The differences in forearm WDT (U = 71.5, p = 0.0113) and CDT (U = 70, p = 0.0096) were most pronounced in the morning. In summary, BMS type I patients had increased pain sensitivity on the forearm, but no differences in pain thresholds on the face or forearm. Patients also showed altered thermal sensitivity, which depended on body area tested (heightened in the orofacial region but blunted on the forearm), and was more pronounced in the morning plausibly due to hypervigilance.