Integrated Lactate Is Improved with a Novel Pharmacologic Inducer of the Endogenous Cytoprotective Heat Shock Protein 70I Gga and Potential COVID Applications

Introduction: Lactate is a common biomarker used in multiple surgical subspecialties. No one has previously measured coronary sinus lactate reduction as a result of drug administration. We therefore tested the hypothesis that IV geranylgeranylacetone (GGA), a novel agent used to treat human peptic ulcer disease, would result in reduced coronary sinus lactate production. Method(s): New Zealand adult rabbits (N=5 each) received IV 50 mg/kg GGA 24 hours before intervention, which consisted of Langendorff perfusion, 30 min of global normothermic cardioplegic arrest, followed by reperfusion. Myocardial release of lactate was measured. HSP70 was quantified by western blot. Differences between GGA+ and GGA- groups pre- and post-ischemia were analyzed by unpaired t-tests. Result(s): In the GGA- group, lactate increased immediately at one minute and throughout the duration of reperfusion. However, in GGA+ hearts, lactate also increased at one min of reperfusion but then continued to decrease throughout the remainder of reperfusion. Lactate was significantly less at every time point of reperfusion in GGA+. Integrated lactate area was significantly less throughout reperfusion in GGA+. Conclusion(s): GGA induced caused a marked decrease in coronary sinus lactate release during reperfusion. Simultaneously intravenously GGA induced myocardial HSP70i and reduced myocardial damage. Further study of the effects and mechanisms involved is indicated. Application to other organs is useful as well. Heat shock proteins (HSPS) are also antithrombotic. Given the thrombotic nature of Covid, induction of HSPS may be beneficial in decreasing the cardiac thoracic and vascular complications of Covid and allowing faster resolution of this disease during to vascular complications.

Zooanthropogenic potential of SARS-CoV-2 virus: Implications for vaccine-mediated immunity

The human pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in December, 2019 is still continuing in various parts of the world. The SARS-CoV-2 has evolved through sporadic mutations and recombination events and the emergence of alternate variants following adaptations in humans and human-to-animal transmission (zooanthraponosis) has raised concerns over the efficacy of vaccines against new variants. The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV- 2-related viruses in bats and pangolins. A recent report of back-andforth transmission of SARS-CoV-2 between humans and minks on mink farms in the Netherlands has sparked widespread interest in zooanthroponotic transmission of SARS-CoV-2 followed by reemergence to infect human populations. The risk of animal to human transmission depends on virus-host interaction in susceptible species that may be short-term or long term risks. The short term risk might be due to infection to humans during the viremic stage in susceptible animals. The long term risk might be either due to persistence of the virus at population level or latency of infection leading to risk of evolution and re-emergence of the virus. Experimental studies have identified a range of animals that are susceptible and permissive to SARS-CoV-2 infection viz. cats, ferrets, hamsters, mink, non-human primates, tree shrews, raccoon dogs, fruit bats, and rabbits. The health impacts of SARS-CoV-2 infection in animals are unknown and it is likely that other susceptible species have not been discovered yet. Apart from farmed animals, stray cats and rodents have been identified as a potential opportunity for ongoing transmission in intense farming situations. Recognizing animal species that are most susceptible to infection is the first step in preventing ongoing transmission from humans. Minimizing the risk of zooanthraponosis requires multi-sectoral coordination that includes implementation of strict biosecurity measures such as controlled access to farms that house susceptible animals, bio-secure entry and exit protocols, disinfection protocols in farm, down time for animal transport vehicles and daily assessments of human handlers for exposure to SARS-CoV- 2. Hence, active surveillance in animal species that are prioritized based on risk assessment need to be initiated in coordination with health and environment sectors for early identification of emerging and re-emerging variants of SARS-CoV-2 virus in animals.

Post-Transplantation Cyclophosphamide for the Prevention of Graft-Versus-Host Disease Should Not Limit Transplantation for Acute Lymphoblastic Leukemia in People with Trisomy 21

Introduction: Use of hematopoietic cell transplantation (HCT) in patients with trisomy 21 (+21) is infrequent given concerns about increased toxicity with cytotoxic chemotherapy.1 Due to increasing evidence of benefit from post-HCT cyclophosphamide (PTCy) for graft-vs.-host disease (GVHD) prophylaxis and lack of prior descriptions in patients with +21,2-4 we report on 2 patients with +21 and acute lymphoblastic leukemia (ALL) who underwent HCT with PTCy. Method(s): Retrospective data were collected from 2 patients with ALL and +21 who underwent allogeneic HCT with PTCybased GVHD prophylaxis from 2019 to 2021. Data collected included age, disease risk, HCT-CI, GVHD incidence, and survival. Result(s): Patient 1 is a 22-year-old male and patient 2 a 25-year-old female. Both had Ph-negative, B-cell ALL. Patient 1 had ETV6/RUNX1 rearrangement, del 12p, gain of X, and he had recurrence of measurable residual disease (MRD) after initial MRD-negative CR with two lines of therapy pre-HCT. Patient 2 had normal cytogenetics and relapsed disease with 4 prior lines of therapy. Both achieved MRD-negativity pre-HCT. Both received fludarabine and melphalan conditioning, and patient 1 also received thiotepa 2.5 mg/kg. PTCy was given on days +3 and 4 at 50 mg/kg with sirolimus and tacrolimus for GVHD prophylaxis. Patient 1 had a haploidentical donor and received one dose of rabbit ATG (1 mg/kg) on day +5. Patient 2 had a matched unrelated donor. There was no significant delay in engraftment of ANC (day 16-19) or platelets (day 15-16). Patient 2 developed acute GVHD at day 30 (stage I skin, stage II GI) that resolved with steroids which were tapered off by day 96 without recurrence. Sirolimus stopped at day 79 (pt 1) and 103 (pt 2) and tacrolimus was stopped at day 274 (pt 1) and 469 (pt 2). Patient 1 developed a sirolimus-induced pericardial effusion at day 84 which did not recur after sirolimus discontinuation. Patient 2 developed moyamoya 8 months post-HCT during tacrolimus taper without other GVHD symptoms. Response to steroids was noted, so tacrolimus was restarted for residual neurological deficit. Neither patient developed chronic GVHD or left ventricular ejection fraction decline, and neither patient had disease relapse at follow-up of 30 and 16 months respectively. Patient 2 developed COVID pneumonia 16 months post-HCT and died while in CR. Patient 1 remains alive, in CR, and off immunosuppression nearly 3 years post HCT. Conclusion(s): Allogeneic HCT with PTCy at standard doses did not appear prohibitively toxic in patients with +21 when administered after reduced-intensity conditioning. In this case series, GVHD rates seemed consistent with larger series in patients without +21. Moyamoya development is associated with autoimmunity in patients with +21 and hence may have been GVHD-related5. Trisomy 21 should not be a barrier to patients otherwise eligible for HCT, even with PTCy prophylaxis.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Improving the timeliness of health expenditure tracking in OECD and low-and middle-income countries

The COVID-19 pandemic has highlighted that access to timely health spending data is crucial for informed policy-making. This Health Working Paper summarises and compares the methodologies applied in around half of OECD countries to estimate public and private health spending for the most recent year (i.e. t-1) as well as the approaches taken by the OECD Secretariat to fill existing data gaps for the remaining OECD countries. For the first time, the paper also explores the feasibility of nowcasting health spending for the current year (i.e. t) and examines data sources that could be potentially useful in such an exercise. While this review should help OECD countries that do not yet have experience in estimating health spending for year t-1 to improve the timeliness in their data reporting, a special focus in this paper lies on testing the applicability of the methods in low- and middle-income countries (LMIC), using the WHO Western Pacific Region (WPRO) as an example. Generally, different data sources exist in many countries that would allow for a more timely estimation for health spending aggregates.

A Comprehensive Review of 275 Kidney Transplants Performed over 3 1/2 Years;a Single Center Experience

Introduction: Access to kidney transplantation has always been a problem in the African countries with many patients having to travel to other medically advanced countries in Asia, Europe and America. This involves unnecessary excessive expenditure and the travails of journey and stay in an unknown foreign land. To ease this situation and to provide affordable Renal transplant services in their home land, we have made an effort to start the transplant services at our medical facility and have successfully carried out about 275 transplants over a period starting from Nov 2018 till September 2022. Method(s): All the Kidney transplants done between the period Nov 2018- September 2022 (275 cases) were included in the analysis. All the transplants were performed at a single center and the data were collected progressively during their Pre transplant evaluation, perioperative course and post op follow up. All the laboratory and radiological tests were done locally at the center except the HLA cross matches and tissue typing, which were outsourced to Transplant immunology labs outside the country. All the patients with positive DSA titres [about 70%], underwent Plasmapheresis and received IVIg before the transplantation. immunological assessment was done by NGS high resolution, for A B C DP DQ DR loci and X match was done by SAB analysis for class 1 and Class II antigens. All the patients underwent laparoscopic donor nephrectomy. All Patients received vaccinations for Hepatitis B, Pneumonia, Infuenza & Covid. Result(s): A series of 275 kidney transplants were performed over a period of 42 months [ Nov 2018- September 2022] at a private hospital successfully. All the cases were live donor kidney transplants with majority of the donors being 1st or 2nd degree relatives or spousal donors. About 70% of the patients had some degree of sensitization in the form of weakly positive B cell X match, or positive for DSAs at CL I, CLII with MFIs > 1000. All high-risk patients received induction with rabbit Thymoglobulin, and IV methyl prednisolone. Around 50 patients received Basiliximab. Of all patients, 4were HBsAg positive, and 6 were HIV positive,& HCV 1 patient. 8 patients required pretransplant Parathyroidectomy for refractory hyperparathyroidism, 3 patients required simultaneous native kidney nephrectomy at the time of transplant. 25 patients had multiple renal vessels which were double barreled and anastamosed.4 patients had lower urinary tract abnormalities requiring simultaneous/subsequent repair. Overall, 4 patients underwent 2nd transplant. All the donors underwent laparoscopic nephrectomy. Most of the patients had good immediate graft function except in 40 patients, who had delayed graft function;most of them improving over 2 - 6 weeks. 6 Patients had hyperacute rejection and the graft was lost,.4patients had main renal artery thrombosis, Renal allograft biopsy was done in 20 patients. Overall, the Patient survival was 95 %.at 1 year and graft survival 90%. Conclusion(s): Our experience shows that kidney transplantation is a viable and practical option for End stage kidney disease and can be performed even in resource constrained centers in third world countries and the survival rates of patients and the grafts are comparable to other centers across the world. No conflict of interestCopyright © 2023

Evaluation of antiviral effects and toxicity of herbal medicine Vipdervir capsules

Background: Antiviral vaccine is not effective, synthetic antiviral drugs are highly toxic, leading to increased interest in herbal medicines as promising antiviral drugs. Recently, Vipdervir has been developed from medicinal herbs with the aim to support and treat diseases caused by viruses such as H5N1 and SARSCoV- 2. In the present study, we assessed Vipdervir's antiviral activity against H5N1 and SARS-CoV-2. In addition, we also evaluated the acute toxicity and repeated dose toxicity of Vipdervir in mice and rabbits, respectively. Methods: H5N1 inhibitory effect of Vipdervir was assessed using hemagglutination inhibition assay. Vipdervir's SARS-CoV-2 inhibitory effect was evaluated by Plaque Reduction Neutralization assay. Acute and repeated dose oral toxicities of Vipdervir were determined according to OECD 423 and OECD 407 guidelines, respectively. Results: Data show that Vipdervir is effective against both H5N1 and SARSCoV- 2. At concentrations of 3 mg/mL and 5 mg/mL Vipdervir completely inhibits H5N1. At a concentration of 50 g/mL Vipdervir showed an inhibitory effect on SARS-CoV-2. Acute toxicity data revealed that the LD50 of Vipdervir is greater than 35200 mg/kg, b.wt. in mice. Repeated toxicity data indicated that Vipdervir did not induce significant differences in body weight gain, hematology and clinical biochemistry in compared to the control group. The No Observed Adverse Effect Level of Vipdervir is greater than 613.8 mg/kg b.wt./day in rabbits. No delayed toxicity effects of Vipdervir were observed. Conclusion: Vipdervir capsules were found to be antiviral effective and relatively safe in the tested doses and experimental conditions.

Pathology of animal models of COVID-19

This paper describes the pathogenesis and immunology of Macaca mulatta, Macaca fascicularis, ferrets, Syrian golden hamsters (Mesocricetus auratus), mice, cats, mink, pigs and rabbits used as models for SARS-CoV-2 infection.

Reproductive and developmental safety of nirmatrelvir (PF-07321332), an oral SARS-CoV-2 Mpro inhibitor in animal models

Nirmatrelvir (PF-07321332;NMV) the antiviral component of PAXLOVID PACK is a potent and selective inhibitor of the SARSCoV- 2 main protease (Mpro), which plays a critical role in viral replication. PAXLOVID PACK, comprised of nirmatrelvir and ritonavir (used as a pharmacokinetic enhancer), is an oral therapy currently in development as a therapeutic option for those infected with SARS-CoV-2 to prevent progression to severe disease, hospitalization, and death. It is also being tested for its potential benefit in the post-exposure prophylactic setting. Given that males and females of reproductive age are included in the intended patient population, we assessed the potential effects of NMV up to the limit dose of 1000 mg/kg/day in ICH guideline embryo-fetal development studies in rats and rabbits, and a fertility and early embryonic development study in rats. There were no effects on male and female fertility or early embryonic development in rats, and no severe manifestations of developmental toxicity in rats or rabbits. The lack of adverse findings reported here in nonclinical species is consistent with the intended therapeutic target of NMV (a virus specific protein not present in mammalian cells), the favorable off-target selectivity profile, and lack of genetic toxicity. All procedures performed on the animals in these studies were in accordance with regulations and established guidelines and were reviewed and approved by an Institutional Animal Care and Use Committee or through an ethical review process.

Identification of Persistent Sars-Ncov-2 Viral Presence in the Intestines of Multiple Pediatric Patients Suggests Possible Common Etiology of Gi Long Covid

Background: The phenomenon known as "Long Covid," (LC) marked by post-infectious symptoms of a wide variety, and typically not associated with initial infectious severity, has the potential to become a tremendous public health burden as infections continue at a high rate. Variations of LC may impact over 80% of patients, with unclear pathogenesis, although many speculate that persistent viral presence in end-organ tissue may drive local changes. We previously published a case report noting persistent SARS-nCoV-2 activity in the cecum of a patient 3 months after initial infection (Arostegui et al, JPGN Reports, 2022). We have sought to expand that finding by assessing additional patients who have undergone endoscopic evaluation for presence of SARS-nCoV-2 nucleocapsid, seeking to expand our understanding of the clinical effects of persistent infection. Method(s): We identified 6 patients with onset of symptoms in the post-SARS-nCoV-2 window, who had undergone EGD/colonoscopy without histopathological diagnosis. New blank slides were cut and sent for staining at Histowiz inc (Brooklyn, NY), with rabbit monoclonal SARS-CoV-2 nucleocapsid antibody (GTX635686, 1:10,000). Resulting slides underwent blinded pathology review to identify positives. Chart review was completed on patients who were identified as positive, including histopathology data from endoscopy, medical history, presentation, laboratory results and clinical course. Result(s): Including our initial report, we have identified 4 female patients ages 11-16 to date. Viral presence was identified in the duodenum and TI, but only in one patient in the colon (cecum). Patients presented for evaluation of a variety of GI manifestations including chronic abdominal pain (100%), nausea and vomiting (50%), loss of appetite (50%), tenesmus (50%), hematochezia (25%) as well as weight loss (50%). Notably, of the 4 patients identified, only 1 had a known history of confirmed SARS-nCoV-2 infection. Endoscopic findings in the intestine were normal with the exception of edema noted in the cecum of two patients. Mucosal biopsies were also positive for notable (if typically felt to be non-pathologic) lymphoid aggregates in the Colon (75%) as well as in the Terminal Ileum (50%). Clinical information is summarized in Table 1. Conclusion(s): Additional identification of persistent SARS-nCoV-2 presence in patients ranging from 3-18 months after symptom onset demonstrates a high likelihood that persistent viral presence contributes to post-infectious symptoms in many patients. Patients demonstrated "red flag" symptoms like nighttime awakening with pain, weight loss, and elevated inflammatory markers or calprotectin, but symptomatically improved over time and with measures targeted at IBS. Our limited sample size prevents determination of typical location of persistent viral activity, but it is notable that symptoms for colonic vs. SI persistence were clinically consistent, with diarrhea in colonic persistence and early satiety/pain characterizing SI persistence. Most notably, we have identified a tendency for persistent infection to occur, potentially explaining at least a subset of persistent IBS-like symptoms associated with GI LC. Further work is necessary to determine exactly the prevalence of this issue, as well as to characterize the natural history of the clinical course, and possible effective therapies. (Table Presented).

CAVITATORY LUNG RHIZOPUS INFECTION IN RENAL TRANSPLANT RECIPIENT: RARE CASE REPORT

Introduction: Mucormycosis is a life threatening fungal infection commonly seen in diabetics and immunocompromised individuals. It is caused by one of the members of mucoraceae family which includes mucor, rhizopus, rhizomucor, absidia and others. Its prevalence has become more common in covid pandemic. Methods: We report a rare case of large cavitatory Rhizopus infection in a renal transplant recipient. Patient was initiated on antitubercular therapy for tubercular lymphadenitis two months prior to transplant. He was given rabbit ATG as induction agent and was on triple maintenance immunosuppression with tacrolimus/ mycophenolate mofetil/ steroids. Patient developed post transplant Diabetes mellitus. Four months post transplant he presented with cough, fever and left sided chest and shoulder pain for 10 days. Covid RT PCR was done twice and it came out to be negative. High Resolution Computed tomography Chest revealed thick walled cavity abutting the chest wall (10.3 x 7.1cm) in left upper lobe. Blood culture was sterile after five days of incubation. Serum Beta galactomannan was negative. He was empirically started on broad spectrum antibiotics and antifungals (oral voriconazole). He underwent bronchoscopy on day 4 of admission. As tuberculosis was a differential, gene expert, tubercular culture and AFB stain was obtained on Bronchoalveolar(BAL) fluid which all came out to be negative. Microbiological sample from BAL Fluid revealed growth of Rhizopus species. He was started on Liposomal amphotericin B. Since the cavitatory lesion occupied almost the entire left lung, surgical resection was offered to the patient to which patient refused. Results: He improved symptomatically after 10 days of Liposomal amphotericin B. Total of 10 weeks of Liposomal amphotericin B was given. Follow up CT after 40 days showed significant reduction in size of cavity to 7.5cm. A surprising complete resolution of the lung cavity was seen after 4 months. Conclusions: This case is one of the very few reported cases of invasive pulmonary rhizopus infections. It emphasizes how medical treatment alone can lead to complete resolution of such large cavitatory lesions without surgical intervention. No conflict of interest

Nanoparticles: Efficient, safe and affordable platforms for developing vaccines against coronaviruses

Introduction: Vaccines need to be rationally designed to be delivered to the immune system for maximizing induction of dynamic immune responses. Virus-like nanoparticles (VLPs) are ideal platforms for such 3D vaccines. Coronaviruses have recently gained a lot of attention, due to the ongoing pandemic caused by SARS-CoV-2 and previous endemics by MERS-CoV. Methods: We have provided proof of concepts in murine models for effective development of VLP-based vaccines against MERS-CoV and SASR-CoV-2. We have used chemical conjugation or genetic fusion techniques to display receptor-binding domain or motif on our immunologically optimized (CuMVTT -VLPs). These VLPs incorporate a tetanus toxin epitope and ssRNA, TLR7/8 ligands. The vaccines were tested in murine models. Results: The vaccines are stable for more than a year at 4°C and highly scalable. Vaccination using subcutaneous or intranasal routes are feasible with nanoparticles. We demonstrated that these vaccines are highly immunogenic in mice as well as rabbits and can induce high avidity antibodies compared to convalescent human sera. Furthermore, the induced antibodies are cross-reactive with different VoCs (in case of SARS-CoV-2). The longevity of the induced immune response lasted longer than 120 days. Conclusion: Collectively, we show that VLP-based vaccines can efficiently induce high specific anti-RBD and spike antibodies that effectively neutralize different Coronaviruses and their VoCs. As Coronaviruses represent a continuous global threat to human health, it seems rational to further develop these vaccines.

Serum IgM and IgG antibody response six months post-COVID-19 vaccination

Objective: To determine the serum IgM and IgG antibody levels post-COVID-19 vaccination, and provide scientific evidence for COVID-19 antibody response after vaccination.

Evaluation of Antiviral Effects and Toxicity of Herbal Medicine Vipdervir Capsules

Background: Antiviral vaccine is not effective, synthetic antiviral drugs are highly toxic, leading to increased interest in herbal medicines as promising antiviral drugs. Recently, Vipdervir has been developed from medicinal herbs with the aim to support and treat diseases caused by viruses such as H5N1 and SARSCoV- 2. In the present study, we assessed Vipdervir's antiviral activity against H5N1 and SARS-CoV-2. In addition, we also evaluated the acute toxicity and repeated dose toxicity of Vipdervir in mice and rabbits, respectively. Methods: H5N1 inhibitory effect of Vipdervir was assessed using hemagglutination inhibition assay. Vipdervir's SARS-CoV-2 inhibitory effect was evaluated by Plaque Reduction Neutralization assay. Acute and repeated dose oral toxicities of Vipdervir were determined according to OECD 423 and OECD 407 guidelines, respectively. Results: Data show that Vipdervir is effective against both H5N1 and SARSCoV- 2. At concentrations of 3 mg/mL and 5 mg/mL Vipdervir completely inhibits H5N1. At a concentration of 50 μg/mL Vipdervir showed an inhibitory effect on SARS-CoV-2. Acute toxicity data revealed that the LD50 of Vipdervir is greater than 35200 mg/kg, b.wt. in mice. Repeated toxicity data indicated that Vipdervir did not induce significant differences in body weight gain, hematology and clinical biochemistry in compared to the control group. The No Observed Adverse Effect Level of Vipdervir is greater than 613.8 mg/kg b.wt./day in rabbits. No delayed toxicity effects of Vipdervir were observed. Conclusion: Vipdervir capsules were found to be antiviral effective and relatively safe in the tested doses and experimental conditions.

Infectious disease management in animal shelters

This second edition contains 24 new and updated chapters on aetiology, epidemiology, prevalence, pathogenesis, clinical signs, treatment, prevention and control of infectious diseases in cats, dogs and exotic small companion mammals in animal shelters. These include an introduction to infectious disease management in animal shelters, wellness, data surveillance, diagnostic testing, necropsy techniques, outbreak management, pharmacology, sanitation, canine and feline vaccinations and immunology, canine infectious respiratory disease, canine distemper virus, canine influenza, feline infectious respiratory disease, canine parvovirus and other canine enteropathogens, feline panleukopenia, feline coronavirus and feline infectious peritonitis, internal parasites, heartworm disease, external parasites, dermatophytoses, zoonoses, rabies, feline leukaemia and feline immunodeficiency viruses and conditions in exotic companion mammals (ferrets, rabbits, guineapigs and rodents). It is intended for shelter veterinarians, managers and workers.

Quarterly report of investigations of suspected exotic diseases: July to September 2021

Exotic pest and disease investigations are managed and reported by the Ministry for Primary Industries' (MPI's) Diagnostic and Surveillance Directorate. This article presents a summary of investigations of suspect exotic and emerging pests and diseases in New Zealand during the period from July to September 2021.

CHEMICALLY DECORATED DECELLULARIZED CORNEA AS FULL-THICKNESS STROMAL SUBSTITUTE

During the ongoing Covid-19 pandemic, collection and donation of human cadaveric corneas are cumbersome. Decellularized corneas (DC) have gained intense popularity as a possible scaffold for corneal remodeling and as an alternative tissue source for corneal replacement. However, DC elicits immune response inspite of elimination of the cellular contents/antigens due to distortion of the collagen fibrils that exposes certain antigenic sites, which often lead to graft rejection. Therefore, here, we tested the hypothesis that cross-linking DC with chondroitin sulfate (CS) may help in restoring distorted conformational changes of the fibrous matrix and would reduce graft rejection. An in vitro immune response study confirmed that the cross-linked DC elicited the least immune response than DC. We implanted three sets of corneal scaffolds obtained from goat, i.e., native, decellularized, and DC conjugated with CS into rabbit stroma. Histology analysis, three months post-implantation confirmed seamless graft integration, cell migration, and no sign of inflammation in the crosslinked cornea. However, so far we have checked the immunogenic potential of decellularized and crosslinked cornea among cross-species(goat to rabbit). Now, before moving to a human clinical trial (patients with infectious keratitis), we are validating the decellularization of the human stromal layer using discarded human corneas not suitable for implantation, for the regeneration of the corneal endothelial layer. The decellularized, chemically decorated cornea will be tectonically strong, offer less immunogenicity, can be sterilized, and will have a longer shelf life. Through this novel study, we can meet the demand for alternative bioengineered human cornea for keratitis patients.

Coronary Sinus Integrated Lactate Decreases After Ischemia and Reperfusion with GGA Induced hsp70

Purpose: Background: Ischemia reperfusion(IR) increases lactate. No one has examined if cardiac-specific coronary sinus lactate(CSL) can be reduced with prior cytoprotective heat shock protein 70(hsp70i) induction. We previous demonstrated improved IR in vivo with inducted hsp70i. Geranylgeranylacetone(GGA), an hsp70i inducer, has never been administered IV preischemically. Interventions to decrease CSL may improve clinical parameters. Methods: Rabbit hearts underwent 30 cold cardioplegic ischemia then 60 min reperfusion. One group received IVGGA 24 hours prior(GGA+) and the other vehicle(GGA-). CSlactate was collected prior to ischemia and throughout reperfusion. We aimed to determine IVGGA effects on myocardial hsp70i and lactate. Hsp70 western blot was performed. Results: Baseline CSlactate was similar between GGA+ and GGA-(Figure 1). Both peaked CSlactate at 1 minute reperfusion. However GGA+ peak was less. At every time point GGA+ was less. GGA+ CSlactate continued to decrease throughout reperfusion however in GGA- CSlactate increased later. Integrated CS lactate area was less for GGA+(Figure 1). Conclusion: In summary, protective IVGGA resulted in five lactate benefits: lactate was less at 1 minute reperfusion peak,decreased faster in early reperfusion, was reduced at all time points, does not have a second rise and lastly results in overall less integrated lactate production in GGA+. GGA induced hsp70. IVGGA may have clinical applications in endothelial protection in IR and COVID.

Conference on humane innovations in education Ibrahim Arnautovic, Sarajevo, Bosnia and Herzegovina, 12-13 November 2021

This issue contains 14 articles on students' self-study and self-assessment during the veterinary anatomy course at the University of Zagreb, Croatia;cost-effectiveness of 3d printing of anatomical models;solving the formalin issue in the veterinary anatomy teaching;alternative methods for vasopuncturing in veterinary medicine using an artificial rabbit ear;humane innovations in veterinary anatomy education in India;glycaemia as a reliable indicator for diabetes mellitus in dogs and cats;humane innovations and the advantages of replacing animal experiments and dissection;anatomical learning materials for the digital age;usage of dummies for training purposes in laboratory animal science;enhancing veterinary education and training through the use of the Elnady Technique (et) specimens;virtual reality (vr) in veterinary anatomy teaching;smart 3D meat inspection;educational animal use and alternatives;students' perspectives and attitude about the shift to emergency remote learning of veterinary anatomy during the COVID-19 pandemic;a new way of education-virtual reality;sonography as educational tool for recognition of anatomical structures in bovine ovaries;the sketchfab platform as a tool in veterinary anatomy education and students' assessment of the use of different neuroanatomical specimens in veterinary anatomy practical classes.

Evolutionary analysis of mammalian ACE2 and the key residues involved in binding to the Spike protein revealed potential SARS-CoV-2 hosts

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) spilled over to humans via wild mammals, entering the host cell using angiotensin-converting enzyme 2 (ACE2) as receptor through Spike (S) protein binding. While SARS-CoV-2 became fully adapted to humans and globally spread, some mammal species were infected back. The present study evaluated the potential risk of mammals becoming hosts for SARS-CoV-2 through bioinformatics prediction based on ACE2 receptors.

64th Annual Meeting of the Pathology Section of the German Veterinary Medical Association

These proceedings contain 25 papers from the 64th Annual Meeting of the Pathology Section of the German Veterinary Medical Association. Topics include tumour infiltrating lymphocytes in mammary carcinomas in domestic rabbits;what decides good or bad? - global gene expression analysis of the adenoma of the hepatoid perianal glands and adenocarcinoma the canine apocrine anal sac glands;the canine cutaneous histiocytoma - boring or perspective in immuno-oncology?;impact of antibiotic pretreatment on ventilator-induced lung injury: contradiction between histology and transcriptome analysis?;characterization of murine satellite glial cells of the dorsal root ganglia - a unique cell population with potential regenerative capacities;impact of antibiotic pretreatment on ventilator-induced lung injury: contradiction between histology and transcriptome analysis?;primary diffuse leptomeningeals oligodendrogliomatosis in a cat;pathomorphological studies of fibroadnexal dysplasia in dogs;pyogranulomatous inflammation in multiple Organs of a dog with evidence of Corynebacterium tuberculostearicum;ovary tumors in cats - overview of the examination material from 2009-2020 and case report of a recurrent dysgerminoma;atherosclerosis in the dog;spinal neuroenteric cyst in one Saint Bernard;MENX - an endogenous model for pseudohypoxic pheochromocytomas;molecular Level Evolution II: similarities of CLCA2 in sauropsids and mammals;in vivo detection of double-stranded Ribonucleic acid (RNA) as an early detection marker unclear viral infections using the example of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in experimental infected hamsters;the role of different mast cell subtypes in the context of intestinal carcinogenesis - a species-comparative approach;an underestimated treasure in paraffin - establishment of a global transcriptome analysis canine tumors from FFPE material based on QuantSeq 3' technology;well researched? - an approximation of the role of CLCA1 in joints through usage molecular databases;integration of digitized historical and cytopathology into an open source DICOM database and viewer system;3R 3D: skin model for the study of viral infections;CARD9 signaling promotes hippocampal neurogenesis and cytokine balance in a mouse model of virus-induced encephalitis;neuropathological changes after intranasal infection with Rift Valley fever virus - a murine model for human encephalitis;a T-cell a day keeps Theiler away - the influence non-reactive T-cells on the course of a Theiler virus infection in mice with C57BL/6 background;digitization in pathology - new opportunities and their obstacles;and specific features of satellite glial cells of dog and pig.