Association between COVID-19 vaccination and 28-day all-cause mortality in SARS-CoV-2-infected older people living in residential aged care facilities.

This retrospective cross-sectional study reviewed the association between COVID-19 vaccination and the 28-day all-cause mortality amongst SARS-CoV-2-infected older people living in residential aged care facilities. A lower mortality rate was observed in fully vaccinated residents compared with not fully vaccinated residents. Further research is required to investigate the optimal timing of vaccination boosters and vaccine efficacy as variants evolve.

Diagnostic Sensitivity of the Dynamic Appraisal of Situational Aggression to Predict Violence and Aggression by Behavioral Health Patients in the Emergency Department.

INTRODUCTION: The Dynamic Appraisal of Situational Aggression (DASA) is an assessment tool that has been validated to predict violent or aggressive behavior in psychiatric inpatient settings. Its validity has not been established for use in the emergency department. METHODS: The DASA was implemented within the electronic health record of an academic medical center with inpatient psychiatric services. A retrospective analysis was conducted using Spearman rank-correlation coefficients to compare a final risk score with the subsequent occurrence of violence or aggression, defined as the use of hard leather physical restraints or the administration of intramuscular sedative medication. A receiver operating characteristic curve was used to summarize the predictive accuracy of the tool to assess aggression in behavioral health patients in the emergency department. RESULTS: A total of 3,433 scores were analyzed, representing 1,548 patients. The DASA had predictive validity with increasing scores comparing all tested cutoff scores against incidence of violence and aggression. The area under the curve comparing scores of 0 versus more than 0 was 0.79. The median time to subsequent aggression was 110 minutes. DISCUSSION: The DASA has predictive validity for use in evaluating behavioral health patients in the ED setting in an urban academic medical center. The tool is capable of predicting violence or aggression within a time frame conducive to the implementation of noninvasive measures. The DASA should be tested in other ED settings to further establish its predictive validity.

Mitigation of acute radiation syndrome (ARS) with human umbilical cord blood.

PURPOSE: The growing concern over potential unintended nuclear accidents or malicious activities involving nuclear/radiological devices cannot be overstated. Exposure to whole-body doses of radiation can result in acute radiation syndrome (ARS), colloquially known as "radiation sickness," which can severely damage various organ systems. Long-term health consequences, such as cancer and cardiovascular disease, can develop many years post-exposure. Identifying effective medical countermeasures and devising a strategic medical plan represents an urgent, unmet need. Various clinical studies have investigated the therapeutic use of umbilical cord blood (UCB) for a range of illnesses, including ARS. The objective of this review is to thoroughly discuss ARS and its sub-syndromes, and to highlight recent findings regarding the use of UCB for radiation injury. UCB, a rich source of stem cells, boasts numerous advantages over other stem cell sources, like bone marrow, owing to its ease of collection and relatively low risk of severe graft-versus-host disease. Preclinical studies suggest that treatment with UCB, and often UCB-derived mesenchymal stromal cells (MSCs), results in improved survival, accelerated hematopoietic recovery, reduced gastrointestinal tract damage, and mitigation of radiation-induced pneumonitis and pulmonary fibrosis. Interestingly, recent evidence suggests that UCB-derived exosomes and their microRNAs (miRNAs) might assist in treating radiation-induced damage, largely by inhibiting fibrotic pathways. CONCLUSION: UCB holds substantial potential as a radiation countermeasure, and future research should focus on establishing treatment parameters for ARS victims.

Regulation of Zfp36 by ISGF3 and MK2 restricts the expression of inflammatory cytokines during necroptosis stimulation.

Necrosome activation following TLR- or cytokine receptor-signaling results in cell death by necroptosis which is characterized by the rupture of cell membranes and the consequent release of intracellular contents to the extracellular milieu. While necroptosis exacerbates various inflammatory diseases, the mechanisms through which the inflammatory responses are regulated are not clear. We show that the necrosome activation of macrophages results in an upregulation of various pathways, including the mitogen-activated protein kinase (MAPK) cascade, which results in an elevation of the inflammatory response and consequent expression of several cytokines and chemokines. Programming for this upregulation of inflammatory response occurs during the early phase of necrosome activation and proceeds independently of cell death but depends on the activation of the receptor-interacting protein kinase-1 (RipK1). Interestingly, necrosome activation also results in an upregulation of IFNß, which in turn exerts an inhibitory effect on the maintenance of inflammatory response through the repression of MAPK-signaling and an upregulation of Zfp36. Activation of the interferon-induced gene factor-3 (ISGF3) results in the expression of ZFP36 (TTP), which induces the post-transcriptional degradation of mRNAs of various inflammatory cytokines and chemokines through the recognition of AU-rich elements in their 3'UTR. Furthermore, ZFP-36 inhibits IFNß-, but not TNFα- induced necroptosis. Overall, these results reveal the molecular mechanism through which IFNß, a pro-inflammatory cytokine, induces the expression of ZFP-36, which in turn inhibits necroptosis and halts the maintenance of the inflammatory response.

Targeted Alpha Therapy (TAT) with Single-Domain Antibodies (Nanobodies).

The persistent threat of cancer necessitates the development of improved and more efficient therapeutic strategies that limit damage to healthy tissues. Targeted alpha therapy (TαT), a novel form of radioimmuno-therapy (RIT), utilizes a targeting vehicle, commonly antibodies, to deliver high-energy, but short-range, alpha-emitting particles specifically to cancer cells, thereby reducing toxicity to surrounding normal tissues. Although full-length antibodies are often employed as targeting vehicles for TαT, their high molecular weight and the presence of an Fc-region lead to a long blood half-life, increased bone marrow toxicity, and accumulation in other tissues such as the kidney, liver, and spleen. The discovery of single-domain antibodies (sdAbs), or nanobodies, naturally occurring in camelids and sharks, has introduced a novel antigen-specific vehicle for molecular imaging and TαT. Given that nanobodies are the smallest naturally occurring antigen-binding fragments, they exhibit shorter relative blood half-lives, enhanced tumor uptake, and equivalent or superior binding affinity and specificity. Nanobody technology could provide a viable solution for the off-target toxicity observed with full-length antibody-based TαT. Notably, the pharmacokinetic properties of nanobodies align better with the decay characteristics of many short-lived α-emitting radionuclides. This review aims to encapsulate recent advancements in the use of nanobodies as a vehicle for TαT.

The Evolving Role of Triage and Appointment-Based Admission to Improve Service, Care and Outcomes in Animal Shelters.

The historical norm for many animal shelters has been to admit animals on an unscheduled basis, without prior assessment of animal or client need or regard to the shelter's ability to deliver humane care or ensure appropriate outcomes. This approach allows little opportunity to provide finders or owners with alternatives to keep pets safe in their homes or community rather than being impounded. In addition to needlessly impounding animals and separating pets from families, unmanaged/unscheduled admission frequently results in animal influx exceeding shelter capacity, leading to crowding, stress, disease, and euthanasia of animals, as well as poor customer experience, compromised staffing efficiency and decreased organizational effectiveness. Many of these harmful consequences disproportionately impact vulnerable community members and their pets. Triage and appointment-based services have been well developed in healthcare and other service sectors allowing organizations to prioritize the most urgent cases, align services with organizational resources and provide situation-specific solutions that may include virtual support or referral as appropriate. This article discusses the trend in animal sheltering toward triage and appointment-based services that parallels the use of these practices in human healthcare. Reported positive results of this approach are detailed including improved staff morale, reduced disease rates and substantially reduced euthanasia. These positive outcomes support the endorsement of triage and appointment-based services by multiple North American animal welfare professional and academic organizations, recognizing that it better realizes the goals of shelters to serve the common good of animals and people in the most humane, equitable and effective possible way.

Rethinking the Animal Shelter's Role in Free-Roaming Cat Management.

Substantial societal investment is made in the management of free-roaming cats by various methods, with goals of such programs commonly including wildlife conservation, public health protection, nuisance abatement, and/or promotion of cat health and welfare. While there has been a degree of controversy over some of the tactics employed, there is widespread agreement that any method must be scientifically based and sufficiently focused, intensive and sustained in order to succeed. The vast majority of free-roaming cat management in communities takes place through local animal shelters. Throughout the 20th century and into the 21st, this consisted primarily of ad hoc admission of cats captured by members of the public, with euthanasia being the most common outcome. In North America alone, hundreds of millions of cats have been impounded and euthanized and billions of dollars invested in such programs. Given the reliance on this model to achieve important societal goals, it is surprising that there has been an almost complete lack of published research evaluating its success. Wildlife conservation and public health protection will be better served when debate about the merits and pitfalls of methods such as Trap-Neuter-Return is grounded in the context of realistically achievable alternatives. Where no perfect answer exists, an understanding of the potential strengths and shortcomings of each available strategy will support the greatest possible mitigation of harm-the best, if still imperfect, solution. Animal shelter function will also benefit by discontinuing investment in methods that are ineffective as well as potentially ethically problematic. This will allow the redirection of resources to more promising strategies for management of cats as well as investment in other important animal shelter functions. To this end, this article reviews evidence regarding the potential effectiveness of the three possible shelter-based strategies for free-roaming cat management: the traditional approach of ad hoc removal by admission to the shelter; admission to the shelter followed by sterilization and return to the location found; and leaving cats in place with or without referral to mitigation strategies or services provided by other agencies.

Effects of dietary lysine supplementation on upper respiratory and ocular disease and detection of infectious organisms in cats within an animal shelter.

OBJECTIVE: To determine within a cat shelter effects of dietary lysine supplementation on nasal and ocular disease and detection of nucleic acids of Chlamydophila felis, feline calicivirus (FCV), and feline herpesvirus (FHV-1). ANIMALS: 261 adult cats. PROCEDURES: Cats were fed a diet containing 1.7% (basal diet; control cats) or 5.7% (supplemented diet; treated cats) lysine for 4 weeks. Plasma concentrations of lysine and arginine were assessed at the beginning (baseline) and end of the study. Three times a week, cats were assigned a clinical score based on evidence of nasal and ocular disease. Conjunctival and oropharyngeal swab specimens were tested for FHV-1, FCV, and C felis nucleic acids once a week. RESULTS: Data were collected from 123, 74, 59, and 47 cats during study weeks 1, 2, 3, and 4, respectively. By study end, plasma lysine concentration in treated cats was greater than that in control cats and had increased from baseline. There was no difference between dietary groups in the proportion of cats developing mild disease. However, more treated cats than control cats developed moderate to severe disease during week 4. During week 2, FHV-1 DNA was detected more commonly in swab specimens from treated versus control cats. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary lysine supplementation in the amount used in our study was not a successful means of controlling infectious upper respiratory disease within a cat shelter. Rather, it led to increases in disease severity and the incidence of detection of FHV-1 DNA in oropharyngeal or conjunctival mucosal swab specimens at certain time points.

Shelter housing for cats: Principles of design for health, welfare and rehoming.

Practical relevance: Shelters and rehoming centres are a valuable tool in the population management and rehoming of cats. However, housing large numbers of a relatively asocial species in close proximity poses significant challenges. Well-designed accommodation enables improved standards of husbandry, as well as a better working environment for staff. This can have a significant benefit in expediting rehoming, as cats are healthier, and more likely to display natural behaviors and have positive interactions with potential adopters. Global importance: As cat overpopulation is such a widespread issue, cat shelters are common in many countries. This review will be of interest to those involved in the design and construction of cat shelters, and to those caring for the cats within them. The principles discussed also apply to boarding, breeding, research and hospitalization facilities. Challenges: Shelter housing poses substantial challenges in terms of maintaining positive health and wellbeing while sustaining adoption at an optimum rate. Disease control and biosecurity are typically facilitated by having a relatively barren, easily cleanable environment. However, this must be weighed against the provision of opportunities for cats to perform natural behaviors such as hiding, perching and interacting if they wish. A more enriched environment has also been shown to expedite adoption. AIMS: This review, the first in a two-part series, discusses practical aspects of housing and shelter design for the health, welfare and adoption of shelter cats. Evidence base: There is a relatively small body of empirical evidence to inform shelter design recommendations. The recommendations in this article are based on a careful review of the available evidence, some of which has come from allied fields such as the care of experimental animals. Where evidence is not yet available, recommendations have been based on field experience and collective expert opinion.

Shelter housing for cats: Practical aspects of design and construction, and adaptation of existing accommodation.

Practical relevance: Not every cat shelter will have purpose-built accommodation but housing designed with the basic needs of cats in mind, whether purpose-built or adapted from existing housing, will improve the experience of cats passing through the facility. Challenges: Designing and building accommodation for cats in shelters should be a thoughtful process. There is a range of different housing types available. A variety of factors, such as expected length of stay, type of cat, cost and disease risk, will influence which design is most appropriate. AIMS: This review, the second in a two-part series, provides an overview of some of the essential requirements for housing shelter cats, either singly or in groups. Specific practical aspects of housing, including design, space allowances, cage furnishings and suitable construction materials, are discussed, and suggestions made for upgrading existing housing where extensive rebuilding is not feasible or realistic. Evidence base: There is a relatively small body of empirical evidence to inform shelter design recommendations. The recommendations in this article are based on a careful review of the available evidence, some of which has come from allied fields such as the care of experimental animals. Where evidence is not yet available, recommendations have been based on field experience and collective expert opinion.

Cage size, movement in and out of housing during daily care, and other environmental and population health risk factors for feline upper respiratory disease in nine North American animal shelters.

Upper respiratory infection (URI) is not an inevitable consequence of sheltering homeless cats. This study documents variation in risk of URI between nine North American shelters; determines whether this reflects variation in pathogen frequency on intake or differences in transmission and expression of disease; and identifies modifiable environmental and group health factors linked to risk for URI. This study demonstrated that although periodic introduction of pathogens into shelter populations may be inevitable, disease resulting from those pathogens is not. Housing and care of cats, particularly during their first week of stay in an animal shelter environment, significantly affects the rate of upper respiratory infection.

Virulent systemic feline calicivirus infection: local cytokine modulation and contribution of viral mutants.

Virulent systemic feline calicivirus (VS-FCV) is a novel, emerging pathogen with mortality up to 67% even in previously healthy adult cats; VS-FCV has resulted in at least six epidemics since 1998. Affected cats have systemic vascular compromise and hemorrhagic-fever like signs in part due to viral invasion of epithelium and endothelium, coupled with host cytokine responses. Affected skin tissues had, on average, 3.8 elevated cytokines compared with control tissue, with prominent upregulation in IL-10, TNF-alpha, and MIP-1alpha. Sequencing of most of the genomes of two VS-FCV strains documented patterns of virus relatedness and implicated changes in the capsid gene in the emerging phenotype, possibly through initiation of immune mechanisms manifest in the cytokine changes. Understanding the features contributing to the emergence of this disease is critical for management and prevention of this and similar outbreaks attributable to RNA viruses in animals and humans.

The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel report.

Vaccination is a medical procedure, and the decision to vaccinate should be based on a risk-based assessment for each cat and each vaccine.

2006 AAHA canine vaccine guidelines.

In 2005, AAHA's Canine Vaccine Task Force met to reexamine and revise guidelines on the use of vaccines in dogs. The results of the Task Force's work are summarized and tabulated in this article and are published in their entirety on the AAHA website (www.aahanet.org). The 2006 AAHA Canine Vaccine Guidelines contain information on new technological developments in vaccines, an introduction to conditionally licensed vaccines, and detailed recommendations on the use of available vaccines. Perhaps the most noteworthy addition to the guidelines is a separate set of recommendations created for shelter facilities. Vaccines are classified as core (universally recommended), noncore (optional), or not recommended. The Task Force recognizes that vaccination decisions must always be made on an individual basis, based on risk and lifestyle factors.

Feline infectious disease control in shelters.

No single factor determines whether a population remains healthy or disease rages out of control. All host and environmental factors taken together provide a number of tools to protect the vulnerable feline shelter population,however. A well-conceived infectious disease control program contributes to improved public perception, increased adoptions, and a healthier feline population within the shelter and in the community in general.

The Use of a Shelter Software (a) to Track Frequency and Selected Risk Factors for Feline Upper Respiratory Infection.

Objective-Feline upper respiratory infection (URI) is a common, multi-factorial infectious disease syndrome endemic to many animal shelters. Although a significant cause of morbidity and mortality in shelter cats, URI is seldom formally monitored in shelter cat populations. Without monitoring, effective control and prevention of this often endemic disease is difficult. We looked at an integrated case management software system (a) for animal care organizations, widely used in shelters across the United States. Shelter staff routinely enter information regarding individual animals and disease status, but do not commonly use the software system to track frequency of disease. The purpose of this study was to determine if the software system (a) can be used to track URI frequency and selected risk factors in a population, and to evaluate the quality and completeness of the data as currently collected in a shelter. Design (type of study)-Descriptive Survey. Animals (or Sample)-317 cats in an animal shelter. Procedures-Reports from the software system (a) containing data regarding daily inventory, daily intake, animal identification, location, age, vaccination status, URI diagnosis and URI duration were evaluated. The reports were compared to data collected manually by an observer (Ann Therese Kommedal) to assess discrepancies, completeness, timeliness, availability and accuracy. Data were collected 6 days a week over a 4 week period. Results-Comparisons between the software system (a) reports and manually collected reports showed that 93% of inventory reports were complete and of these 99% were accurate. Fifty-two percent of the vaccination reports were complete, of which 97% were accurate. The accuracy of the software system's age reports was 76%. Two-hundred and twenty-three cats were assigned a positive or negative URI diagnosis by the observer. The predictive value of the URI status in the software system (a) was below 60% both for positive and negative URI diagnosis. Conclusions and Clinical Relevance-data currently collected and entered into the software systems in the study shelter, was not useful for tracking URI frequency and risk factors, due to issues with both data quality and capture. However, the potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases. Relevant data points, i.e., health status at intake and outcome, vaccination date and status, as well as age, should be made mandatory to facilitate more useful data collection and reporting.

An outbreak of virulent systemic feline calicivirus disease.

OBJECTIVE: To describe clinical and epidemiologic features of an outbreak of feline calicivirus (FCV) infection caused by a unique strain of FCV and associated with a high mortality rate and systemic signs of disease, including edema of the face or limbs. DESIGN: Observational study. Animals-54 cats naturally infected with a highly virulent strain of FCV. PROCEDURE: Information was collected on outbreak history, clinical signs, and characteristics of infected and exposed cats. RESULTS: A novel strain of FCV (FCV-Kaos) was identified. Transmission occurred readily via fomites. Signs included edema and sores of the face and feet. Mortality rate was 40%, and adults were more likely than kittens to have severe disease (odds ratio, 9.56). Eleven (20%) cats had only mild or no clinical signs. Many affected cats had been vaccinated against FCV. Viral shedding was documented at least 16 weeks after clinical recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Outbreaks of highly virulent FCV disease are increasingly common. Strains causing such outbreaks have been genetically distinct from one another but caused similar disease signs and were resistant to vaccination. All cats with suspicious signs (including upper respiratory tract infection) should be handled with strict hygienic precautions. Sodium hypochlorite solution should be used for disinfection following suspected contamination. All exposed cats should be isolated until negative viral status is confirmed. Chronic viral shedding is possible but may not be clinically important. This and similar outbreaks have been described as being caused by hemorrhagic fever-like caliciviruses, but hemorrhage is uncommonly reported. Virulent systemic FCV infection is suggested as an alternative description.

Update on feline calicivirus: new trends.

In addition to being important upper respiratory tract pathogens of cats, FCVs are increasingly reported as a cause of a highly contagious febrile hemorrhagic syndrome. Strains causing this syndrome are genetically different from the vaccine strain and other nonhemorrhagic FCV isolates. They apparently differ from one outbreak to another. The syndrome is characterized variably by fever; cutaneous edema and ulcerative dermatitis; upper respiratory tract signs; anorexia; occasionally icterus, vomiting, and diarrhea; and a mortality that approaches 50%. Adult cats tend to be more severely affected than kittens, and vaccination does not appear to have a significant protective effect. Rapid recognition of the disease through identification of clinical signs and appropriate testing, followed by strict institution of disinfection, isolation, and quarantine measures, are essential to prevent widespread mortality resulting from the infection.

Elimination behavior of shelter dogs housed in double compartment kennels.

For animals in confinement housing the housing structure has tremendous potential to impact well being. Dogs in animal shelters are often housed in one of two types of confinement housing - single kennels and rooms or double compartment kennels and rooms most often separated by a guillotine door. This study examines the effect of housing on the location of elimination behavior in dogs housed in double compartment kennels were the majority of the dogs were walked daily. One side of the kennel contained the food, water and bed and the other side was empty and available except during cleaning time. Location of urination and defecation was observed daily for 579 dogs housed in indoor double compartment kennels for a total of 4440 days of observation. There were 1856 days (41.9%) when no elimination was noted in the kennel. Feces, urine or both were observed in the kennel on 2584 days (58.1%). When elimination occurred in the kennel the probability of fecal elimination on the opposite side of the bed/food/water was 72.5% (95% CI 69.05% to 75.69%). The probability of urination on the opposite side of the bed/food/water was 77.4% (95% CI 74.33% to 80.07%). This study demonstrates the strong preference of dogs to eliminate away from the area where they eat, drink and sleep. Double compartment housing not only allows this - it allows staff the ability to provide safe, efficient, humane daily care and confers the added benefits of reducing risks for disease transmission for the individual dog as well as the population.