Oculomotor, vestibular, reaction time, and cognitive tests as objective measures of neural deficits in patients post COVID-19 infection.

Objective: An alarming proportion (>30%) of patients affected by SARS-CoV-2 (COVID-19) continue to experience neurological symptoms, including headache, dizziness, smell and/or taste abnormalities, and impaired consciousness (brain fog), after recovery from the acute infection. These symptoms are self-reported and vary from patient to patient, making it difficult to accurately diagnose and initiate a proper treatment course. Objective measures to identify and quantify neural deficits underlying the symptom profiles are lacking. This study tested the hypothesis that oculomotor, vestibular, reaction time, and cognitive (OVRT-C) testing using eye-tracking can objectively identify and measure functional neural deficits post COVID-19 infection. Methods: Subjects diagnosed with COVID-19 (n = 77) were tested post-infection with a battery of 20 OVRT-C tests delivered on a portable eye-tracking device (Neurolign Dx100). Data from 14 tests were compared to previously collected normative data from subjects with similar demographics. Post-COVID subjects were also administered the Neurobehavioral Symptom Inventory (NSI) for symptom evaluation. Results: A significant percentage of post COVID-19 patients (up to 86%) scored outside the norms in 12 out of 14 tests, with smooth pursuit and optokinetic responses being most severely affected. A multivariate model constructed using stepwise logistic regression identified 6 metrics as significant indicators of post-COVID patients. The area under the receiver operating characteristic curve (AUC) was 0.89, the estimated specificity was 98% (with cutoff value of 0.5) and the sensitivity was 88%. There were moderate but significant correlations between NSI domain key variables and OVRT-C tests. Conclusions: This study demonstrates the feasibility of OVRT-C testing to provide objective measures of neural deficits in people recovering from COVID-19 infection. Such testing may serve as an efficient tool for identifying hidden neurological deficits post COVID-19, screening patients at risk of developing long COVID, and may help guide rehabilitation and treatment strategies.

Equine insulin receptor and insulin-like growth factor-1 receptor expression in digital lamellar tissue and insulin target tissues.

REASONS FOR PERFORMING STUDY: Hyperinsulinaemia is implicated in the pathogenesis of endocrinopathic laminitis. Insulin can bind to different receptors: two insulin receptor isoforms (InsR-A and InsR-B), insulin-like growth factor-1 receptor (IGF-1R) and InsR/IGF-1R hybrid receptor (Hybrid). Currently, mRNA expression of these receptors in equine tissues and the influence of body type and dietary carbohydrate intake on expression of these receptors is not known. OBJECTIVES: The study objectives were to characterise InsR-A, InsR-B, IGF-1R and Hybrid expression in lamellar tissue (LT) and insulin responsive tissues from horses and examine the effect of dietary nonstructural carbohydrate (NSC) on mRNA expression of these receptors in LT, skeletal muscle, liver and two adipose tissue (AT) depots of lean and obese ponies. STUDY DESIGN: In vivo experiment. METHODS: Lamellar tissue samples were evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for receptor mRNA expression (n = 8) and immunoblotting for protein expression (n = 3). Archived LT, skeletal muscle, liver and AT from lean and obese mixed-breed ponies fed either a low (~7% NSC as dry matter; 5 lean, 5 obese) or high NSC diet (~42% NSC as dry matter; 6 lean, 6 obese) for 7 days were evaluated by RT-qPCR to determine the effect of body condition and diet on expression of the receptors in different tissues. Significance was set at P≤0.05. RESULTS: Lamellar tissue expresses both InsR isoforms, IGF-1R and Hybrid. LT IGF-1R gene expression was greater than either InsR isoform and InsR-A expression was greater than InsR-B (P≤0.05). Obesity significantly lowered IGF-1R, InsR-A and InsR-B mRNA expression in LT and InsR-A in tailhead AT. High NSC diet lowered expression of all three receptor types in liver; IGF-1R and InsR-A in LT and InsR-A in tailhead AT. CONCLUSIONS: Lamellar tissue expresses IGF-1R, InsR isoforms and Hybrids. The functional characteristics of these receptors and their role in endocrinopathic laminitis warrants further investigation.

Prophylactic digital cryotherapy is associated with decreased incidence of laminitis in horses diagnosed with colitis.

REASONS FOR PERFORMING THE STUDY: Recent research suggested that prophylactic digital cryotherapy (ICE) improved lameness scores, diminished histological changes and early laminar inflammatory signalling in horses following oligofructose administration. In clinical practice, horses at risk for sepsis-associated laminitis receive ICE. Evidence to support this practice is lacking. OBJECTIVES: To determine factors associated with development of laminitis in horses diagnosed with colitis, including ICE. STUDY DESIGN: Multicentre retrospective case series. METHODS: Medical records for horses admitted to 2 university hospitals diagnosed with colitis with evidence of systemic inflammatory response from 2002 to 2012 were reviewed. Horses were excluded if they exhibited signs of laminitis at admission, were ponies, miniature or draught breeds, or <2 years old. Data were analysed using univariate and multivariate logistic regression. RESULTS: Twenty-seven of 130 horses (21%) developed laminitis. Seven of 69 (10%) horses treated with ICE developed laminitis compared with 20/61 (33%) horses that developed laminitis but did not receive ICE. Factors associated with laminitis included site of hospitalisation, admission respiratory rate (↑) and blood L-lactate (↑), and ICE (↓), P<0.05. Horses treated with ICE had 10 times less odds of developing laminitis compared with horses treated without ICE (odds ratio 0.11, 95% confidence limit 0.03-0.44). Sixteen horses (16/130, 12%) were subjected to euthanasia in hospital. Fourteen of these horses had laminitis and 2 did not develop laminitis. Survival for horses with colitis that developed laminitis was 13/27 (48%) compared with survival for horses with colitis that did not develop laminitis, 101/103 (98%). CONCLUSION: Laminitis occurred in more clinically compromised horses. Use of ICE reduced the incidence of clinical laminitis in the study population suggesting that digital cryotherapy is an effective prophylactic strategy for the prevention of laminitis in horses with colitis.

Acceptance of flexible sigmoidoscopy as a screening examination for colorectal cancer in an outpatient clinic.

BACKGROUND AND STUDY AIM: Flexible sigmoidoscopy (FS) is a feasible examination technique and a suitable tool for population-based screening, but very little is known about determinants of endoscopic screening participation. The aim of this study was to determine the acceptance rate and the factors influencing the decision of participating in a screening program for patients in an outpatient clinic. MATERIALS AND METHODS: In this prospective study, a colorectal cancer screening by FS was offered to 631 patients older than 40 years. Three strategies were available, (1) to have the endoscopy on the same day, (2) to make an appointment for another day, or (3) to take time to think about if they wanted the procedure. The reasons for refusal of the FS were documented. RESULTS: 419 of the 631 (66.4%) patients had no interest to take part in the screening program during their outpatient visit. Two hundred twelve (33.6%) patients were primarily interested on FS, but only 110 of them were finally examined. In total, 102 patients did not make an appointment for FS or did not appear for the endoscopy. The participation rate was therefore 17.4% (110/631) of all patients. Of the patients who agreed to receive an on-site examination, 78.3% were examined compared to 18.8% of patients who fixed the appointment for another day or after taking time to reflect upon the FS procedure. More male than female patients accepted the FS screening. Recommended colonoscopy was finally performed in 76%. Thirty-three polyps were found during the screening program of which 18 were larger than 0.5 cm. No CRC was detected. All patients agreed to repeat the FS every 5 years. CONCLUSIONS: This study demonstrates that a screening examination will be most likely performed if it is done as an on-site examination. In contrast, the participation rate is low if the patient has to make an appointment by himself. Acceptance of FS screening is also dependent on the patient's gender and family history of cancer. Additional strategies are needed to further improve participation.

Irinotecan plus gemcitabine and 5-fluorouracil in advanced pancreatic cancer: a phase II study.

AIMS: The aim of the present study was to evaluate the 6-month survival rate of patients with inoperable or metastatic pancreatic cancer treated with irinotecan and gemcitabine plus 5-fluorouracil. Secondary efficacy end points included response rate, time to progression (TTP), overall survival (OS) and toxicity. PATIENTS AND METHODS: 30 patients with histologically proven pancreatic carcinoma and at least one bidimensionally measurable lesion were enrolled. Of the patients, 83% had metastatic and 17% locally advanced disease. One cycle, lasting 21 days, comprised treatment on days 1 and 8 consisting of 75 mg/m(2) irinotecan i.v. for 90 min, 1,000 mg/m(2) gemcitabine i.v. for 30 min and 2,000 mg/m(2) fluorouracil (5-FU) for 24 h. A total of six cycles was planned for each patient. RESULTS: 28 patients competed at least one treatment cycle and were therefore assessable for efficacy, and 75% of them achieved the primary end point of the study (survival after 6 months). One-year survival was 25%. Stabilization (partial response and stable disease) was observed in 35.7% (10/28) and partial remission in 7.1% (2/28). The objective response rate was 7.1% (2/28) after completion of the six cycles. Median TTP was 3.4 months (1.2-11.5), and median OS was 8.3 months (2.1-36.2). Regarding severe hematological toxicities, only neutropenia was observed (grade 3 20.7%, 6/29, and grade 4 3.5%, 1/29). In spite of anti-emetic supportive care, nausea affected most of the patients: 79.3% (23/29). Grade 3 vomiting was observed in 4 of the 29 patients (13.8%) and grade 4 in 1 patient (3.5%). Only 1 patient experienced diarrhea grade 3 (3.5%) and 1 patient (3.5%) suffered from a grade 3 peroneal nerve enervation. CONCLUSIONS: A combination of irinotecan, gemcitabine and 5-FU is feasible and shows considerable efficacy in patients with inoperable or metastatic pancreatic cancer. Due to its low toxicity, this combination might be an interesting cytotoxic regimen in addition to targeted therapies.

Proliferation of nickel-sensitive human lymphocytes by corrosion products of orthodontic appliances.

Lymphocyte transformation tests were performed on peripheral blood taken from individuals with a history of contact dermatitis who also presented with a positive patch test to nickel sulphate, and from individuals with no history of contact dermatitis. The results implied that nickel leached out from metallic orthodontic appliances in sufficient amounts and of a chemical nature adequate to stimulate proliferation of lymphocytes from some of the nickel-sensitive subjects.

An assessment of the physical properties and biocompatibility of three silicone elastomers.

The physical properties of two room-temperature vulcanizing (RTV) silicones, A-2186 and Silbione 71556, and one high-temperature vulcanizing (HTV) material, Mollomed, were compared. The potential cytotoxicity of the silicone materials was assessed with the agarose overlay test. The properties that were investigated were tensile strength, percentage elongation, modulus, permanent set, tear strength, and hardness. The properties tested were selected because of their clinical significance for fabricating facial prostheses. The results of this study indicate that the A-2186 material has a better combination of high tear strength and elongation at break with a softer surface compared with Mollomed silicone, and Silbione 71556 silicone proved to be the weakest material. All materials demonstrated absence of cytotoxicity in the cell culture tests.

Denture adhesives: cytotoxicity, microbial contamination, and formaldehyde content.

Denture adhesives are extensively used to enhance retention of dentures. Denture adhesives and their leachable components are ingested, but reports on the biologic aspects of denture adhesives are scarce. This study investigated some biological properties of 19 commercially available denture adhesives. The adhesives were assessed by the agar overlay technique and analyzed for microbial contamination and formaldehyde content. In the agar overlay test, all of the materials caused severe cytotoxic effects. Sabouraud dextrose agar was used for cultivation of fungi and tryptone soya broth for cultivation of aerobes, including fungi. Most of the samples tested showed microbial growth. The formaldehyde test revealed the presence of substantial amounts in four products and minor amounts in two products.

In vitro effects of pentoxifylline on smooth muscle cell migration and blood monocyte production of chemotactic activity for smooth muscle cells: potential therapeutic benefit in the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a severe lung condition characterized by an acute lung injury leading to a massive intra-alveolar fibrosis with rapid lung failure. ARDS intra-alveolar fibrosis results from the migration of mesenchymal cells (mainly smooth muscle cells [SMC]) into the alveoli through alveolar epithelial basement membrane gaps resulting from the injury. SMC migration is followed by their replication and production of extracellular matrix, which leads to fibrosis. Thus, any pharmacologic agent able to prevent SMC migration should prevent, at least in part, intra-alveolar fibrosis. SMC migration is thought to be due to the presence, in the alveolar spaces, of chemotactic factors for mesenchymal cells, such as fibronectin and platelet-derived growth factor (PDGF). The local presence of these chemotactic factors can be due to plasmatic leakage, platelet degranulation, and mononuclear phagocyte activation. Pentoxifylline is a methylxanthine interacting with the biology of several types of cells, including red blood cells, neutrophils, blood monocytes, and endothelial cells. Pentoxifylline prescription has been suggested in ARDS with respect to its activity on neutrophils, its inhibition of tumor necrosis factor-alpha (TNF) release by mononuclear phagocytes, and its prevention of TNF-induced lung injury. Since pentoxifylline can modulate the migration of several cell types, we hypothesized that it could interfere with mesenchymal cell migration. SMC migratory response was measured in vitro with modified Boyden chemotactic chambers in the presence of PDGF, fibronectin, "platelet extract," and activated blood monocyte supernatants. Pentoxifylline, at therapeutic levels, significantly reduced SMC migration in response to the presence of these chemotactic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxic effect of orthodontic appliances.

The use of orthodontic appliances may contribute to local gingivitis, often attributed to increased plaque retention. Gingivitis of bacterial origin cannot clinically be distinguished from local tissue irritation caused by corrosion products. The purpose of this investigation was to assess the cytotoxic effect of various metallic components used in orthodontics. Multicomponent devices such as facebows, molar bands, and brackets along with single-component brackets and archwires were tested by the agar overlay cytotoxicity test with mouse fibroblast cells. None of the archwires caused any cytotoxic effect, even though some contained 54 per cent nickel. However, the multi-component devices, which were joined with silver- and copper-based brazing alloys were more cytotoxic than the single-component devices. Copper is more cytotoxic than nickel, which could explain the greater cytotoxic effect of the samples with brazing materials. It is speculated that cytotoxic corrosion products from orthodontic appliances might contribute to localized gingivitis.

Effects of In and Zn on properties of low noble metal alloys.

Four low noble metal alloys with high In and Zn contents were investigated with regard to porosity in castings, structure, tarnish, hardening mechanism and cytotoxicity. Fumes were observed above the melt, due to the high Zn content and low boiling point of this metal. This Zn evaporation during melting created a small amount of porosity in the castings. This porosity diminished when the Zn content was reduced from 4 to 2%. Scanning electronmicroscopy, microprobe analyses and X-ray diffraction analyses revealed a face-centred cubic (fcc) matrix enriched in Au and Ag and a body-centred cubic (bcc) phase enriched in Pd, In and Zn which had a yellow gold-like appearance. After immersion in a 2% Na2S solution for 72 h, no tarnish attack was observed on the PdlnZn-rich phase. The matrix phase was found to be slightly tarnished. The alloys remained yellow by visual inspection. The agar overlay technique displayed a very slight cytotoxic effect of a sandblasted specimen and no cytotoxic effect of a polished specimen.

Electrophysiological characterization of the class III activity of sotalol and its enantiomers. New interpretation of use-dependent effects.

1. Sotalol (Sotalex) and both its optical isomers were studied in electrophysiological experiments with respect to their class III activity of antiarrhythmic drugs. The three substances prolonged action potentials (AP) of guinea-pig papillary muscle and left atrium in concentrations greater than or equal to 3 mumol/l, whereas other AP parameters (resting potential, amplitude and upstroke velocity) remained unchanged. Similar results were observed if papillary muscles were partially depolarized by elevating the extracellular potassium concentration from 4.7 mmol/l to 10-12 mmol/l. 2. The effects of sotalol showed marked frequency dependence (0.017-2 Hz): At slow driving rates sotalol brought about an enhanced AP prolongation as measured by APD30 and APD90. 3. The results were compatible with numerical AP simulation studies on the basis of the assumption that sotalol inhibits time-dependent K-outward current. This leads to the consequence that longer control APs (at low driving rates) are prolonged more effectively by sotalol than shorter ones (at high driving rates). 4. Sotalol effects dynamically followed APD changes due to alterations of driving rate: If APD was decreased under increasing driving frequencies, AP prolongation was diminished. 5. Paired pulse experiments showed that class III activity of sotalol was preserved in premature or delayed single action potentials.