Long-term reversal of chronic pain behavior in rodents through elevation of spinal agmatine.

Chronic pain remains a significant burden worldwide, and treatments are often limited by safety or efficacy. The decarboxylated form of L-arginine, agmatine, antagonizes N-methyl-d-aspartate receptors, inhibits nitric oxide synthase, and reverses behavioral neuroplasticity. We hypothesized that expressing the proposed synthetic enzyme for agmatine in the sensory pathway could reduce chronic pain without motor deficits. Intrathecal delivery of an adeno-associated viral (AAV) vector carrying the gene for arginine decarboxylase (ADC) prevented the development of chronic neuropathic pain as induced by spared nerve injury in mice and rats and persistently reversed established hypersensitivity 266 days post-injury. Spinal long-term potentiation was inhibited by both exogenous agmatine and AAV-human ADC (hADC) vector pre-treatment but was enhanced in rats treated with anti-agmatine immunoneutralizing antibodies. These data suggest that endogenous agmatine modulates the neuroplasticity associated with chronic pain. Development of approaches to access this inhibitory control of neuroplasticity associated with chronic pain may yield important non-opioid pain-relieving options.

Impact of Interhospital Transfer on Outcomes in Non-emergency Colorectal Surgery.

BACKGROUND: A paucity of data exists on the impact of transfer status on outcomes for patients undergoing non-emergency (urgent) colorectal surgery. This study characterized transferred patients undergoing urgent colorectal surgery and determined which patient comorbidities significantly contributed to poor outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2013 was used. Urgent direct admissions undergoing colon, rectum, or small bowel operations were compared to urgent transfers using bivariate and multivariable analysis models. Primary outcomes were overall complications, hospital length of stay, and mortality. RESULTS: A total of 82,151 admissions were analyzed. After multivariable analysis, direct admission patients had nearly similar risk of complications (RR = 0.95; 95% CI 0.91-0.99) and length of hospital stay (7% shorter; 95% CI 4-9%), as well as no difference in mortality (RR = 0.94; 95% CI 0.80-1.11). CONCLUSIONS: Transfer status alone confers minimal risk toward higher complication rates and longer hospital length of stay in patients undergoing urgent colorectal surgery, and the poor outcomes observed in this cohort are largely due to patient comorbidities and disease severity. Our results suggest that outcomes in transferred colorectal surgery patients undergoing urgent operations depend mainly on operative acuity and clinical factors, and to a lesser degree transfer status.

Force Perception Thresholds in Cochlear Implantation Surgery.

Tissue trauma is a frequent complication of cochlear implantation (CI) surgery, but the relationship between intracochlear trauma, electrode insertion forces, and surgeons' ability to perceive these forces is poorly understood. In this study, we simulated CI surgery using a benchtop apparatus to repeatedly apply small forces to the subjects' hands while reducing the variability in their hand movements. We used a psychophysical testing procedure to estimate the force perception thresholds of 10 otologic surgeons and found a median threshold of 20.4 mN. The results suggest that surgeons have the capability to sense at least some insertion forces and are likely to perceive severe trauma such as occurs when the electrode crosses from one scala to the other.

Initial radiographic tumor control is similar following single or multi-fractionated stereotactic radiosurgery for jugular paragangliomas.

OBJECTIVE: To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic referral center. PATIENTS: Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18months of post-treatment follow up (FU). INTERVENTION: Patients were treated with either single fraction or fractionated SRS. MAIN OUTCOME MEASURE: Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression. RESULTS: Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55years (range 35-79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15-18Gy), and 9 (64.3%) fractionated therapy (dose 3-7Gy×3-15 fractions). Median tumor volume was 3.78cm(3) (range 1.15-30.6). Median FU was 28.8months (range 18.6-56.1), with a mean of 31.7months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p=0.88) or progression (p=0.48) rates between groups (unpaired t-test). CONCLUSIONS: At a median follow up of 28months, both single fraction and fractionated SRS appear to have comparable radiographic tumor control outcomes and toxicity profiles.

[Not Available]. / Atemwegsmanagement - Tracheotomie Revisited.

Since 5000 years tracheotomy is a common way for airway management. Generally, Tracheotomy will be divided in a surgical tracheotomy the percutaneous Tracheotomy. The surgical Tracheotomy takes place in the operation theater. The percutaneous Tracheotomy is one of the standard procedures in the Intensive care unit. There are many methods to perform the percutaneous Tracheotomy. The gist of every method is the seldinger procedure. Bronchoscopic supervision during the whole procedure is one of the most important things to prevent complications. However percutaneous and surgical tracheotomy are safe and have a low rate of complications.

A case of sensorineural hearing loss involving a fibroepithelial polyp of the middle ear.

Primary middle ear neoplasms are rare, and commonly cause conductive hearing loss. When aural masses result in sensorineural hearing loss, malignant etiologies are often suspected. Fibroepithelial polyps are benign lesions commonly found in the skin and genitourinary tract and are not commonly identified as primary lesions of the middle ear. Here, we present a case of a benign fibroepithelial polyp of the middle ear causing sensorineural hearing loss and describe its surgical management. Imaging and histologic characteristics are reviewed.

Protein kinase Cε is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs.

We recently showed that spinal synergistic interactions between δ opioid receptors (δORs) and α2A adrenergic receptors (α2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between δORs and α2AARs using the tail flick assay of thermal nociception in mice. Only a PKCε inhibitor abolished synergy between a δOR agonist and an α2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCε knock-out mice and found that all four combinations of a δOR agonist and an α2AAR agonist required PKCε for antinociceptive synergy. None of the combinations of a µOR agonist with an α2AR agonist required PKCε. Immunohistochemistry confirmed that PKCε could be found in the population of peptidergic primary afferent nociceptors where δORs and α2AARs have been found to extensively colocalize. Immunoreactivity for PKCε was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCε is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between δORs and α2AARs.

Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

Rocking motion of an optical wing: theory.

The intensity-dependent rocking frequency of an illuminated semicylindrical refractive rod (or "optical wing") on a flat, nonslip surface is investigated. Both longitudinal and transverse radiation pressure forces (scatter and lift forces), as well as radiation pressure torque, transform the mechanical system into one having a bistable potential energy above a critical intensity. The equation of motion may be written as a parametrically driven nonlinear bistable harmonic oscillator, resulting in complex rocking dynamics. The effects of linear and sinusoidal intensity modulation schemes are explored, and experimental conditions to verify these results are discussed.

Clinical characteristics associated with isolated unilateral utricular dysfunction.

PURPOSE: The ocular vestibular evoked myogenic potential (oVEMP) represents the sound-induced activation of extraocular muscles and is believed to originate from the utricle and superior vestibular nerve. Isolated unilateral oVEMP abnormalities with otherwise normal balance function test (BFT) results have not yet been characterized in a large patient series, and their clinical significance remains unclear. MATERIALS AND METHODS: Retrospective review of adult patients with vestibular complaints at a tertiary academic neurotologic referral center was performed. Patients with isolated unilateral oVEMP abnormalities were identified. The prevalence of vestibular symptoms and results of the Dizziness Handicap Inventory (DHI) and Hospital Anxiety and Depression Scale (HADS) were compared between these patients and those with normal BFT results. RESULTS: Thirty-one adult patients with isolated unilateral oVEMP abnormalities were identified (71% female, mean age 48 ± 14 years). Presenting complaints included vertigo in 53%, non-vertiginous dizziness in 68%, postural instability in 52%, and swaying/rocking sensation in 13%. Significant differences were observed in the percentage of patients with postural instability (p=0.046) and swaying/rocking sensation (p=0.04) when comparing the abnormal oVEMP group to patients with a normal BFT battery. No differences were observed when comparing other symptoms, age, gender, diagnoses, and DHI/HADS scores between groups. CONCLUSION: This is the largest series to date reporting on patients with isolated unilateral oVEMP abnormalities. Our results suggest this population may demonstrate an increased prevalence of postural instability and swaying/rocking sensation. Other measures of postural stability may further characterize the vestibular impairments associated with isolated unilateral utricular dysfunction.

Primate liver tissue substrate in indirect immunofluorescence diagnostics for patients with dermatitis herpetiformis and celiac disease.

Introduction: Dermatitis herpetiformis (DH) is a rare autoimmune, polymorphous blistering disorder, characterized by severe itch or burning sensation, which represents the cutaneous manifestation of celiac disease (CD). The current estimation of DH versus CD is around 1:8 and the affected individuals have a genetic predisposition. Pathogenetically, IgA autoantibodies against the epidermal transglutaminase, an essential constituent of the epidermis, cause DH and are reported to develop through cross-reaction with the tissue transglutaminase, with IgA auto-antibodies causing CD. Immunofluorescence techniques allow for a rapid diagnostics of the disease using patient sera. Evaluation of IgA endomysial deposition with indirect immunofluorescence on monkey oesophagus is highly specific, but moderately sensitive, with some operator-dependent variability. Recently, indirect immunofluorescence with monkey liver as a substrate has been proposed as an alternative, well-functioning diagnostic approach with higher sensitivity in CD. Methods: The objective of our study was to evaluate whether monkey oesophagus or liver tissue shows advantage for diagnostics in patients with DH, compared to CD. To that end, sera of 103 patients with DH (n=16), CD (n=67) and 20 controls ere compared by 4 blinded experienced raters. Results: For DH, we found a sensitivity of 94.2% for monkey liver (ML) compared to 96.2% in monkey oesophagus (ME), while specificity in ML was superior (91.6% versus 75%) to ME. In CD, ML had a sensitivity of 76.9% (ME 89.1%) and specificity of 98.3% (ME 94.1%). Discussion: Our data show that ML substrate is well suitable for DH diagnostics.

The European Tertiary Education Register, the reference dataset on European Higher Education Institutions.

The European Tertiary Education Register (ETER) is the reference dataset on European Higher Education Institutions (HEIs). ETER provides data on nearly 3,500 HEIs in about 40 European countries, including descriptive information, geographical information, students and graduates (with various breakdowns), revenues and expenditures, personnel, and research activities; as of March 2023, data cover the years from 2011-2020. ETER complies with OECD-UNESCO-EUROSTAT standards for educational statistics; most data are collected from National Statistical Authorities (NSAs) or ministries of participating countries and are subject to extensive checks and harmonization. The development of ETER has been funded by the European Commission and is part of the current efforts to establish a European Higher Education Sector Observatory; it is closely connected to the establishment of a broader data infrastructure in the field of science and innovation studies (RISIS). The ETER dataset is widely used in the scholarly literature on higher education and science policy, as well as for policy reports and analyses.

Sonographic Aeration Scoring Indicates Disease Severity in Critically Ill Patients with COVID-19.

AIMS AND METHODS: We evaluated an ultrasound score from 0 to 32 points in eight pulmonary regions to monitor critically ill COVID-19 patients. The score was correlated to surrogate parameters of disease severity, i.e., the oxygenation index, respiratory support, mortality, plasma interleukin-6, and WHO and ARDS classifications. RESULTS: A total of 27 patients were repeatedly examined, and 71 examinations were evaluated. Patients with severe COVID-19 scored higher (median 17) than those with moderate disease (median 11, p < 0.01). The score did not differentiate between stages of ARDS as defined by the Berlin criteria (p = 0.1) but could discern ARDS according to the revised ESICM definition (p = 0.002). Non-survivors had higher ultrasound scores than survivors (median 18.5 vs. 14, p = 0.04). The score correlated to the oxygenation index (ρ = -0.56, p = 0.03), and changes in the score between examinations correlated to changes in oxygenation (ρ = -0.41, p = 0.16). The correlation between the score and interleukin-6 was ρ = 0.35 (p < 0.001). The interrater reliability for the score was ICC = 0.87 (p < 0.001). CONCLUSIONS: The ultrasound score is a reliable tool that might help monitor disease severity and may help stratify the risk of mortality.