Development of a Chronic Canine Ovariohysterectomy Model to Evaluate Vaginal Cuff Healing Using Two Closure Systems.

Background and Purpose. This study established a suitable animal model of ovariohysterectomy; characterized the course and pattern of vaginal healing after ovariohysterectomy; and compared healing obtained after closure of the vaginal cuff with a novel cuff-closure device (Zip-stitch® clips) and VICRYL® sutures. Research Design and Study Sample. This prospective, randomized, controlled, blinded animal study was conducted in 27 mongrel hounds according to an IACUC-approved protocol. Each animal underwent ovariohysterectomy followed by vaginal cuff closure with Zip-stitch or VICRYL. At two or six weeks, animals were sacrificed for gross and histological analysis. Data Collection. The primary endpoint was the difference in the fraction of vaginal cuff healed six weeks after application of the closure device. Secondary endpoints included histopathologic cellular and tissue responses, including inflammation, necrosis, infection, and vascular and muscle changes. Results. In the test group, there were two distinct locations where fibrotic or granular tissue fusion between the anterior and posterior vaginal walls was observed: in tissue "captured" by a clip or in tissue around the clip. The fraction of the vaginal cuff healed was similar in animals treated with Zip-stitch clips and those treated with sutures at six weeks (68±10% vs 67±18%; P=.148, test for non-inferiority) after surgery. The test article performed similarly or better than the control article in terms of the intensity or extent of the secondary endpoints. Conclusions. Subject to further confirmation, this study supports Zip-stitch clips as a method to maintain immediate post-operative approximation of the vaginal cuff leading to healing but did not achieve statistical significance in its primary endpoint.

The limited effectiveness of a home-based eccentric training for treatment of Achilles tendinopathy.

PURPOSE: Objective was to evaluate the outcome of a standardized heavy load eccentric training program in adults with chronic painful Achilles tendinopathy, and the presence of increased Colour Doppler activity in diseased and non-diseased adults. The hypothesis was that patient satisfaction would fall within the range of average satisfaction present in the literature (60 to 90%). METHODS: Twenty patients were instructed on a training program based on the Alfredson protocol of straight leg followed by bent knee heel drops and raises. Patient satisfaction was recorded as the primary outcome. Secondary outcomes included the VISA-A and Tegner scales. Twenty one subjects without present or history of lower extremity pain and seven patients presenting at the clinic but without Achilles tendinopathy were included as controls. RESULTS: Patient satisfaction was significantly lower when compared to the literature as two patients reported that they were satisfied with the treatment while the remaining 15 reported that they were unsatisfied. Three patients were excluded from the analysis as they were unable to complete the exercises. Increased Colour Doppler activity was present in only one participant without the disease and in all patients with the disease at the end of the study (increased Colour Doppler activity was present in 40% of patients with the disease at the beginning of the study). CONCLUSION: Although some patients' symptoms improved over time, eccentric training did not satisfy patient expectations of improvement following treatment despite compliance with the home based program. Although it is a mainstay of treatment, other options, which are both efficacious and effective, need to be provided for patients who prefer a conservative and relatively non-invasive treatment option from the start.

Autoimmune inflammatory reactions triggered by the COVID-19 genetic vaccines in terminally differentiated tissues.

As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display a wide distribution within the body, affecting tissues that are terminally differentiated and far away from the injection site. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesises non-self antigens, inevitably becomes the target of the immune system, and since the human body is not a strictly compartmentalised system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities to the critical need for biodistribution studies for the genetic vaccines against COVID-19, as well as for rational harm-benefit assessments by age group.

T-cell receptor triggering is critically dependent on the dimensions of its peptide-MHC ligand.

The binding of a T-cell antigen receptor (TCR) to peptide antigen presented by major histocompatibility antigens (pMHC) on antigen-presenting cells (APCs) is a central event in adaptive immune responses. The mechanism by which TCR-pMHC ligation initiates signalling, a process termed TCR triggering, remains controversial. It has been proposed that TCR triggering is promoted by segregation at the T cell-APC interface of cell-surface molecules with small ectodomains (such as TCR-pMHC and accessory receptors) from molecules with large ectodomains (such as the receptor protein tyrosine phosphatases CD45 and CD148). Here we show that increasing the dimensions of the TCR-pMHC interaction by elongating the pMHC ectodomain greatly reduces TCR triggering without affecting TCR-pMHC ligation. A similar dependence on receptor-ligand complex dimensions was observed with artificial TCR-ligand systems that span the same dimensions as the TCR-pMHC complex. Interfaces between T cells and APCs expressing elongated pMHC showed an increased intermembrane separation distance and less depletion of CD45. These results show the importance of the small size of the TCR-pMHC complex and support a role for size-based segregation of cell-surface molecules in TCR triggering.

Perceptions of a tattooed college instructor.

128 undergraduates' perceptions of tattoos on a model described as a college instructor were assessed. They viewed one of four photographs of a tattooed or nontattooed female model. Students rated her on nine teaching-related characteristics. Analyses indicated that the presence of tattoos was associated with some positive changes in ratings: students' motivation, being imaginative about assignments, and how likely students were to recommend her as an instructor.

Tattoos can harm perceptions: a study and suggestions.

OBJECTIVE: Health researchers have claimed that perceptions toward a person with a tattoo are more negative than are perceptions toward nontattooed persons. However, support for this has been obtained almost completely by nonexperimental research. PARTICIPANTS: In 2 experiments with 158 community college student participants, the authors found that tattoos harmed perceptions. METHODS: Students viewed a photograph of a female model with and without a visible tattoo, and rated her on 13 personal characteristics. RESULTS: In Experiment 1, ratings of a model with a dragon tattoo were significantly more negative (p < .05) on 5 of the 13 personal characteristics than were ratings of the same model shown without the tattoo. In Experiment 2, which included different participants, a different model, and a different tattoo, the authors found that a dolphin tattoo led to more negative ratings on 2 of the 13 characteristics. CONCLUSIONS: The authors discuss possible impacts of tattoos on person perception as well as implications of the results for college student healthcare providers.

The effect of tranexamic acid in fibrin sealant on adhesion formation in the rat.

The objective of the research was to determine the effect of the type, dose, and volume of anti-fibrinolytic agents (tranexamic acid, aprotinin) added to fibrin formulations, on adhesion development. Adhesions were induced in 228 male rats by creating apposing parietal and visceral peritoneal defects. Animals were randomized to receive no treatment or a fibrin formulation containing aprotinin or tranexamic acid. Seven days later the incidence of adhesions, and the force and energy required to detach them, were determined. Adhesions developed in 13/13 rats in the control and aprotinin groups. Treatment with fibrin (100 mg/ml tranexamic acid) resulted in adhesions in 4/14 rats (as strips, p < or = 0.0005), 4/10 rats (as spray, p < or = 0.0036), and 12/15 rats (by drip). The reduction of adhesions was dependent on the concentration of tranexamic acid with strip and spray application. Using commercial formulations, tranexamic-acid-containing fibrin (10/15, p = 0.042), but not aprotinin-containing fibrin (13/15), reduced the incidence of side-wall adhesions from 15/15 in controls. Fibrin containing either tranexamic or aprotinin reduced the incidence and severity of adhesions. This effect was greater when tranexamic acid was used and was dependent on the mode of administration, the volume, and to a degree, the concentration of tranexamic acid.

Evaluation of a fibrin preparation containing tranexamic acid (Adhexil) in a rabbit uterine horn model of adhesions with and without bleeding and in a model with two surgical loci.

OBJECTIVE: To compare the efficacy of a fibrin preparation supplemented with tranexamic acid (Adhexil) with that of established devices, and to determine whether its effect is limited to the site of application. DESIGN: Rabbit uterine horns were abraded in nonbleeding and bleeding variants of an established adhesions model. In a separate study, a sidewall excision with approximation of the abraded cecum was added. Animals randomly received Adhexil at both, neither, or either loci. SETTING: Laboratory study. ANIMAL(S): Seventy-two female New Zealand White rabbits (Oryctolagus cuniculus). INTERVENTION(S): Adhexil, Seprafilm or SprayGel and Interceed. MAIN OUTCOME MEASURE(S): The extent of adhesions was evaluated 13 to 16 days after surgery. RESULT(S): Adhexil reduced adhesions (15 +/- 7%; 15 +/- 4%) compared with controls (74 +/- 13%; 78 +/- 9%) in the bleeding and nonbleeding models, respectively. The reductions resulting from the use of Seprafilm (39 +/- 17%; 34 +/- 14%) or SprayGel (61 +/- 18%; 43 +/- 14%) (n = 4) were not statistically significant. In the bleeding model, Interceed (48 +/- 15%) reduced adhesions only modestly. CONCLUSION(S): In the combined uterine and sidewall model, Adhexil reduced selectively the extent and incidence of adhesions. The absolute and relative performance of Adhexil in an established adhesions model and in the presence of bleeding justifies its further investigation.

Disorders of adhesions or adhesion-related disorder: monolithic entities or part of something bigger--CAPPS?

The purpose of this article is to review progress in the field of abdominopelvic adhesions and the validity of its two underlying assumptions: (1) The formation of adhesions results in infertility, bowel obstruction, or other complications. Reducing or avoiding adhesions will curb these sequelae. (2) "Adhesions" is a monolithic entity to be tackled without regard to any other condition. Evidence is discussed to validate the first assumption. We reviewed progress in the field by examining hospital data. We found a growing trend in the number and cost of discharges for just two adhesion-related diagnoses, and the low usage of adhesion barriers appears in at most 5% of appropriate procedures. Data from an Internet-based survey suggested that the problem may be partly due to ignorance among patients and physicians about adhesions and their prevention. Two other surveys of patients visiting the adhesions.org Web site defined more fully adhesion-related disorder (ARD). The first survey ( N = 466) described a patient with chronic pain, gastrointestinal disturbances, an average of nine bowel obstructions, and an inability to work or maintain family or social relationships. The second survey (687 U.S. women) found a high (co-) prevalence of abdominal or pelvic adhesions (85%), chronic abdominal or pelvic pain (69%), irritable bowel syndrome (55%), recurrent bowel obstruction (44%), endometriosis (40%), and interstitial cystitis (29%). This pattern suggests that although "adhesions" may start out as a monolithic entity, an adhesions patient may develop related conditions (ARD) until they merge into an independent entity where they are practically indistinguishable from patients with multiple symptoms originating from other abdominopelvic conditions such as pelvic or bladder pain. Rather than use terms that constrain the required multidisciplinary, biopsychosocial approach to these patients by the paradigms of the specialty related to the patient's initial symptom set, the term complex abdominopelvic and pain syndrome (CAPPS) is proposed. It is essential to understand not only the pathogenesis of the "initiating" conditions but also how they progress to CAPPS. In our ARD sample, not only was the frequency of women with hysterectomies (56%) higher than expected (21 to 33%), but also the rates of the "initiating" conditions was 40 to 400% higher in patients with hysterectomies than in those without. This may represent increased surgical trauma or the loss of protection against oxidative stress. Related was the higher frequency of ARD patients reporting hemochromatosis (HC; 5%) than expected (~0.5%) and the higher rates (20 to 700%) of initiating conditions in patients with HC than in those without HC. Together with findings related to the toxicity of Intergel, these findings raise the possibility that heterozygotes for genes regulating oxidative stress are at greater risk of developing surgical complications as well as more severe and progressive conditions such as CAPPS.

Influenza H2 haemagglutinin activates B cells via a MyD88-dependent pathway.

Influenza viruses are serious respiratory pathogens, responsible for half a million deaths each year. The viral surface haemagglutinin (HA) protein has been shown to be an important determinant of viral pathogenicity. HA is the virion attachment and fusion protein, and the major target for neutralizing antibodies; however, it is also involved in triggering innate responses that may have an important impact on the disease course. We have examined the role of the toll-like receptor (TLR) family in innate responses to influenza virus and influenza HA. TLR7 has recently been found to mediate recognition of influenza RNA. Here, we show for the first time that influenza HA of the H2 subtype induces innate responses in murine B lymphocytes via a MyD88-dependent pathway distinct from that involved in sensing viral RNA. We also show that inactivated influenza virus induces activation of human B cells. Our findings suggest that the molecule mediating these responses may be a novel member of the TLR family.

Next-generation hydrogel films as tissue sealants and adhesion barriers.

BACKGROUND: The development of conveniently sprayed, tissue-adherent, inert hydrogel films has made possible the creation of novel products that can serve a dual function, as a surgical sealant to achieve immediate hemostasis, and as a barrier to prevent adhesion formation over time. METHODS: A sprayable, in situ formed absorbable hydrogel film was evaluated as a tissue sealant in a heparinized canine carotid artery graft model. PTFE grafts with leaking end-to-side anastomoses were treated with the synthetic sealant, and hemostasis was evaluated upon restoration of blood flow. Also, the hydrogel films were evaluated as an adhesion barrier in a rabbit pericardial abrasion model. RESULTS: The sprayable, in situ forming hydrogel film was shown to immediately seal carotid-PTFE anastomoses in six of six applications. Hydrogel application in a rabbit pericardial abrasion model resulted in a statistically significant reduction in the number and tenacity of adhesions. CONCLUSIONS: This novel in situ formed sprayable hydrogel film has demonstrated a dual function as an effective tissue sealant and as an adhesion barrier in cardiovascular preclinical models. These next generation synthetic biomaterials are currently undergoing clinical investigations.