Background: Clinical testing for the integrity of the subscapularis muscle includes the belly-press, lift-off, and bear-hug examinations. While these tests have been widely applied in clinical ...practice, there is considerable variation in arm positioning within each clinical examination.
Hypothesis: To determine the ideal arm and shoulder positions for isolating the subscapularis muscle while performing the bear-hug, belly-press, and lift-off tests.
Study Design: Controlled laboratory study.
Methods: The activity of 7 muscles was monitored in 20 healthy participants: upper and lower divisions of the subscapularis, supraspinatus, infraspinatus, latissimus dorsi, teres major, triceps, pectoralis major. Electromyogram data were collected and compared across each clinical test at varying arm positions: bear-hug (ideal position, 10° superior, 10° inferior to the shoulder line), belly-press (ideal position, maximum shoulder external rotation, and maximal shoulder internal rotation), and lift-off (ideal position, hand position 5 in. 12.7 cm superior and 5 in. 12.7 cm inferior to the midlumbar spine).
Results: Regardless of arm and shoulder position, the upper and lower subscapularis muscle activities were significantly greater than all other muscles while performing each test. No significant differences were observed between the upper and lower subscapularis divisions at any position within and across the 3 tests. There were no significant differences in subscapularis electromyogram activities across the 3 tests.
Conclusion: The level of subscapularis muscle activation was similar among the bear-hug, belly-press, and lift-off tests. The 3 tests activated the subscapularis significantly more than all other muscles tested but were not different from one another when compared across tests and positions. Although the bear-hug and lift-off tests have been described to activate differential portions of the subscapularis, the findings of this study do not support the preferential testing of a specific subscapular division across the 3 tests. As such, all 3 tests are effective in testing the integrity of the entire subscapularis muscle, although there does not appear to be an ideal position for selectively testing its divisions.
Clinical Relevance: Clinicians may feel comfortable in using any of the 3 tests, depending on the patient, to isolate the function of the subscapularis as a single muscle. Furthermore, clinicians should not solely focus on a patient’s arm position when administering an examination but also compare the affected arm to the contralateral shoulder when appropriate.
Abstract
Immune checkpoint inhibitors (ICI) for cancer therapy have improved outcomes for a variety of malignancies, however many patients fail to benefit. To date, most pre-clinical studies ...investigating the tumor microenvironment (TME) have utilized different spontaneous or implanted tumor lines to separately investigate immunologically cold or hot TMEs. These models are often in different mouse strains, leading to confounding variables and a disconnect as to whether the tumor or the host is contributing to the observed immunological phenotype. To account for host diversity and reduce variation on the part of the tumor, we have developed immunotherapy models using genetically heterogeneous Diversity Outbred (DO) and recombinant inbred Collaborative Cross (CC) mice. We crossed DO mice with C57BL/6 (B6) to generate DOB6F1 mice that reliably accept B6-syngeneic B16F0 tumors after subcutaneous inoculation. DOB6F1 mice (n=142) treated with combined anti-PD1/anti-CTLA-4 ICI on days 3, 6, and 10 after inoculation exhibited a wide variation in tumor latency, up to a maximum of 65 days, with 19 mice never developing tumor. Quantitative Trait Locus analysis revealed multiple loci influencing response to ICI. We utilized this data to challenge 12 CCB6F1 strains selected based on predicted response where ICI outcomes range from non-responsive to near complete response. In addition, we show evidence that the DOB6F1 model recreates acquired resistance to ICI, with 9 mice having an extremely delayed tumor latency (>40 days). Melanin-free regions were observed in 3/9 of these tumors, suggesting tumor editing. Acquired resistance was also noted 3/10 ICI-treated CC051B6F1 mice. Whole transcriptomic analysis compared tumors from non-responder versus delayed latency DOB6F1 mice. Despite implantation within genetically heterogeneous mice, transcriptomic profiles from late-onset tumors cluster together. Gene Set Enrichment Analysis identified immune processes, with antigen processing and presentation as the most significantly dysregulated gene set. Many of the upregulated genes in late-onset tumors are driven by IFNγ, suggesting IFNγ signaling may contribute to immune escape. We tested this directly by culturing B16 cells with IFNγ prior to inoculation. Short exposure of B16 to IFNγ results in aggressive growth regardless of treatment, but long exposure increases tumor immunogenicity and responsiveness to ICI in inbred B6 mice. Experiments in ICI-responsive CT26-bearing BALB/c mice indicate IFNγ signaling contributes to ICI response, as demonstrated by increased tumor burden after a single 250 µg dose of neutralizing anti-IFNγ antibody concurrent with ICI treatment. Collectively, our DO and CC F1 models allow for reduced tumor variation with a focus on the host and associated TME, and we show differential roles of IFNγ in response to ICI based on the timing of IFNγ exposure.
Citation Format: Justin B. Hackett, James Glassbrook, Nasrin Movahhedin, Madeline Bross, Alicia Kevelin, Maria Múniz, Heather Gibson. Genetically heterogeneous mouse models identify IFNg signaling as a shared signature of acquired resistance to immune checkpoint inhibitors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB065.
Bacterial pathogenesis requires proteins that sense host microenvironments and respond by regulating virulence gene transcription. For Salmonellae, one such regulatory system is PhoP-PhoQ, which ...regulates genes required for intracellular survival and resistance to cationic peptides. Analysis by mass spectrometry revealed that Salmonella typhimurium PhoP-PhoQ regulated structural modifications of lipid A, the host signaling portion of lipopolysaccharide (LPS), by the addition of aminoarabinose and 2-hydroxy-myristate. Structurally modified lipid A altered LPS-mediated expression of the adhesion molecule E-selectin by endothelial cells and tumor necrosis factor-α expression by adherent monocytes. Thus, altered responses to environmentally induced lipid A structural modifications may represent a mechanism for bacteria to gain advantage within host tissues.
Abstract Background All currently available antipsychotic medications bind to both the dopamine-2 (D2) and dopamine-3 (D3) receptors in vitro . However, there is conflicting evidence from in vivo ...studies about whether or not antipsychotic medications bind to the D3 receptor (D3R). The purpose of this study was to determine whether acute doses of risperidone bind to the D3R in humans. Methods We performed PET scans on an mCT scanner with 11 C-(+)-PHNO injected as a bolus, before and after a 2 mg oral dose of risperidone in five medication free subjects with schizophrenia. The subjects were scanned for 120 min and underwent an MRI scan for region of interest delineation and coregistration. Cerebellum was used as a reference region. Simplified reference tissue modeling (SRTM) was used to calculate BPND. Results We observed binding to the D3R receptor by risperidone as evidenced by observable occupancy in regions in which the 11 C-(+)-PHNO signal is almost exclusively from the D3R ( i.e. , substantia nigra/ventral tegmental area). Using a regression model to estimate D2R:D3R selectivity, we observed a D2R:D3R selectivity of 2.1 for risperidone. Conclusion Our preliminary results provide further support that acute doses of antipsychotic medications bind to the D3R and provide additional support for the further development of this receptor as a treatment target in schizophrenia.
Introduction
Erectile dysfunction (ED) is common in older age and in diabetes mellitus (DM). Phosphodiesterase type 5‐inhibitors (PDE5‐is) are the first‐line for ED. We investigated how the type of ...diabetes and age of males affect the PDE5‐i use in the primary care setting.
Methods
From 2018 to 2019, the general practice level quantity of all PDE5‐i agents was taken from the general practice (GP) Prescribing Dataset in England. The variation in outcomes across practices was examined across one year, and for the same practice against the previous year.
Results
We included 5761 larger practices supporting 25.8 million men of whom 4.2 million ≥65 years old. Of these, 1.4 million had T2DM, with 0.8 million of these >65. About 137 000 people had T1DM. About 28.8 million tablets of PDE5‐i were prescribed within the 12 months (2018‐2019) period in 3.7 million prescriptions (7.7 tablets/prescription), at total costs of £15.8 million (£0.55/tablet). The NHS ED limit of one tablet/user/wk suggests that 540 000 males are being prescribed a PDE5‐i at a cost of £29/y each. With approximately 30 000 GPs practising, this is equivalent to one GP providing 2.5 prescriptions/wk to overall 18 males. There was a 3x variation between the highest decile of practices (2.6 tablets/male/y) and lowest decile (0.96 tablets/male/y). The statistical model captured 14% of this variation and showed that T1DM males were the largest users, while men age <65 with T2DM were being prescribed four times as much as non‐DM. Those T2DM >65 were prescribed 80% of the non‐DM amount.
Conclusion
There is a wide variation in the use of PDE5‐is. With only 14% variance capture, other factors including wide variation in patient awareness, prescribing rules of local health providers, and recognition of the importance of male sexual health by GP prescribers might have a significant impact.
Bonding and Bridging Larsen, Larissa; Harlan, Sharon L.; Bolin, Bob ...
Journal of planning education and research,
09/2004, Letnik:
24, Številka:
1
Journal Article
Recenzirano
This study investigates the relationship between social connections and collective civic action. Measuring social capital in eight Phoenix, Arizona, neighborhoods allowed the authors to determine ...that individuals with strong social bonding (i.e., association and trust among neighbors) are more likely to take civic action. However, while social capital lessens the relationship between an individual’s social status and the likelihood of taking action, it does not eliminate the positive relationship. The analysis also suggests that bonding and bridging are distinct forms of social capital that have some different antecedents
Progress tests assess against the standard expected for the ultimate aim (e.g. graduating from medical school, or final membership exams), without this, benefits of progress testing are lost ...(Dijksterhuis et al. 2013). For undergraduates in USA, progress testing is associated with higher pass rates on the national licensing examination (Norman et al. 2010). Progress tests could potentially be a tool to help improve trainee development and exam performance, but further research is required.
Objective
The aim of the present study was to describe the characteristics and outcomes of patients presenting to Australian EDs with suspected and confirmed COVID‐19 during 2020, and to determine ...the predictors of in‐hospital death for SARS‐CoV‐2 positive patients.
Methods
This analysis from the COVED Project presents data from 12 sites across four Australian states for the period from 1 April to 30 November 2020. All adult patients who met local criteria for suspected COVID‐19 and underwent testing for SARS‐CoV‐2 in the ED were eligible for inclusion. Study outcomes were mechanical ventilation and in‐hospital mortality.
Results
Among 24 405 eligible ED presentations over the whole study period, 423 tested positive for SARS‐CoV‐2. During the ‘second wave’ from 1 July to 30 September 2020, 26 (6%) of 406 SARS‐CoV‐2 patients received invasive mechanical ventilation, compared to 175 (2%) of the 9024 SARS‐CoV‐2 negative patients (odds ratio OR 3.5; 95% confidence interval CI 2.3–5.2, P < 0.001), and 41 (10%) SARS‐CoV‐2 positive patients died in hospital compared to 312 (3%) SARS‐CoV‐2 negative patients (OR 3.2; 95% CI 2.2–4.4, P = 0.001). For SARS‐CoV‐2 positive patients, the strongest independent predictors of hospital death were age (OR 1.1; 95% CI 1.1–1.1, P < 0.001), higher triage category (OR 3.5; 95% CI 1.3–9.4, P = 0.012), obesity (OR 4.2; 95% CI 1.2–14.3, P = 0.024) and receiving immunosuppressive treatment (OR 8.2; 95% CI 1.8–36.7, P = 0.006).
Conclusions
ED patients who tested positive for SARS‐CoV‐2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.
The aim of COVED‐5 was to describe the characteristics and outcomes of patients presenting to Australian emergency departments (EDs) with suspected and confirmed COVID‐19 during 2020, and to determine the predictors of in‐hospital death for SARS‐CoV‐2 positive patients. ED patients who tested positive for SARS‐CoV‐2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.
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