Emergency department visits for dog bite injuries in Missouri municipalities with and without breed-specific legislation: a propensity score-matched analysis.

Breed-Specific Legislation is a type of law that bans or restricts ownership of specific dog breeds. Some local governments - including over seventy municipalities in the state of Missouri - have enacted Breed-Specific Legislation to prevent injuries from dog bites. Several studies from the peer-reviewed literature have found that aggressive behavior is not associated with any particular dog breeds and, since 2018, at least a dozen municipalities in Missouri have repealed these laws. To evaluate the impact of Breed-Specific Legislation on public safety, the 2010-2015 rates of emergency department visits for dog bite-related injuries in Missouri municipalities with and without Breed-Specific Legislation were compared. Propensity-score matched negative binomial regression models were used to assess the effect of breed restrictions on injury rates while balancing the samples on population characteristics and estimates of dog ownership. After matching the sample on population, housing and dog ownership estimates, no association was found between emergency department visits for dog bite injuries and whether the municipality enacted Breed-Specific Legislation. However, the incidence rate ratio of emergency room visits for dog bite-related injuries increased by 13.8% for every 1% increase in the percentage of males aged 5 to 9 in the population (p < 0.01). This study has found breed discriminatory laws have not reduced the risk of emergency department visits for injury from dog bites in Missouri. There appears to be no greater risk to public safety as local governments move to repeal existing breed bans.

Race differences in patient trust and distrust from audio-recorded cardiology encounters.

OBJECTIVE: Many have reported racial disparities in self-reported trust in clinicians but have not directly assessed expressions of trust and distrust in physician-patient encounters. We created a codebook to examine racial differences in patient trust and distrust through audio-recorded cardiologist-patient interactions. METHODS: We analyzed data from a randomized controlled trial of audio-recorded outpatient cardiology encounters (50 White and 51 Black patients). We created a codebook for trust and distrust that was applied to recordings between White cardiologists and White and Black patients. We assessed differences in trust, distrust, and guardedness while adjusting for patient age, sex, and first appointment with the cardiologist. RESULTS: Compared to White patients, Black patients had significantly lower expressions of trust ([IRR] [95 % CI]: 0.59 [0.41, 0.84]) and a significantly lower mean guarded/open score ([ß] [95 % CI] -0.38 [-0.71, -0.04]). There was no statistically significant association between race and odds of at least one distrustful expression (OR [95 % CI] 1.36 [0.37, 4.94]). CONCLUSION AND PRACTICE IMPLICATIONS: We found that coders can reliably identify patient expressions of trust and distrust rather than relying on problematic self-reported measures. Results suggest that White clinicians can improve their communication with Black patients to increase expressions of trust.

Normative data for paediatric lymphocyte subsets: A pilot study from western India.

Background & objectives: Accurate diagnosis of immunodeficiencies requires a critical comparison of values with age-matched controls. In India, the existing reference values for rare lymphocyte subsets are currently not available and we rely on the data originating from other countries for the interpretation of the results. Furthermore, there is limited information on normal variation for these rare-subset parameters in Indian children. So, this study aimed to establish normative values for clinically important lymphocyte subsets in Indian children at different age groups. Methods: 148 children aged ≥16 yr were enrolled in this study. The study population included 61 per cent males and 39 per cent females and was divided into the following groups: cord blood (n=18), 0-6 months (n=9), 6-12 months (n=13), 1-2 yr (n=19), 2-5 yr (n=27), 5-10 yr (n=25) and 10-16 yr (n=37). The absolute and relative percentage of lymphocytes, T, B, natural killer cell, along with activated, naïve and memory subsets, was determined by flow cytometry. Results: Median values and the 10th and 90th percentiles were obtained for 34 lymphocyte sub-populations. The T and B naïve compartments showed a decreasing trend, whereas memory cells showed an increase with age. The activated T cell subset shows an increasing pattern up to one year and then declines gradually. Double negative T cells are relatively stable. TCRgd+T cell percentage increases with age. Interpretation & conclusions: This single-centre pilot study provides preliminary data that justifies the need for future large-scale multi centric studies to generate a reference range for interpreting extended immunophenotyping profiles in the paediatric age group, making it possible for clinicians to assess the immunological status in inborn errors of immunity, infectious and autoimmune diseases.

A Clinical Conundrum with Diagnostic and Therapeutic Challenge: a Tale of Two Disorders in One Case.

Living organisms are exposed to exogenous and endogenous agents that affect genomic integrity by creating DNA double strand breaks (DSBs). These breaks are repaired by DNA repair proteins to maintain homeostasis. Defects in DNA repair pathways also affect lymphocyte development and maturation, as DSB sites are critical intermediates for rearrangements required for V(D)J recombination. Recent classifications for inborn errors of immunity (IEIs) have listed DNA repair defect genes in a separate group, which suggests the importance of these genes for adaptive and innate immunity. We report an interesting case of a young female (index P1) with mutations in two different genes, DCLRE1C and FANCA, involved in DNA repair pathways. She presented with clinical manifestations attributed to both defects. With the advent of NGS, more than one defect is increasingly identified in patients with IEIs. Familial segregation studies and appropriate functional assays help ascertain the pathogenicity of these mutations and provide appropriate management and genetic counseling.

Patient and Caregiver Expression of Reluctance and Ambivalence During Palliative Care Encounters.

Context: Patients with serious illness and their caregivers often face challenging decisions. When faced with these decisions, patients and caregivers may display signs of ambivalence and reluctance toward end-of-life decision making. Methods: We recruited 22 palliative care clinicians to participate in a communication coaching study. Clinicians audio recorded four of their palliative care encounters with adult patients and family caregivers. A team of 5 coders used inductive coding methods to create a codebook and then coded instances of patients and caregivers expressing ambivalence and reluctance. They also coded when the decision-making process was initiated and whether a decision was made. The group coded 76 encounters, and 10% (n = 8) of those encounters were double coded to assess inter-rater reliability. Results: We found that ambivalence occurred in 82% (n = 62) of the encounters, while reluctance occurred in 75% (n = 57) of the encounters. The overall prevalence of either was 89% (n = 67). The presence of ambivalence was negatively associated with a decision being made once initiated (r = -0.29, p = 0.06). Conclusion: We found that coders can reliably identify patient and caregiver reluctance and ambivalence. Further, reluctance and ambivalence occur frequently in palliative care encounters. When patients and caregivers have ambivalence, decision making might be hampered.

Clinical, immunological and molecular findings of patients with DOCK-8 deficiency from India.

DOCK8 deficiency affects various cell subsets belonging to both the innate and adaptive immune systems. Clinical diagnosis is challenging, as many cases present with severe atopic dermatitis as the only initial manifestation. Though flow cytometry helps in the presumptive diagnosis of DOCK8-deficient patients by evaluating their DOCK8 protein expression, it requires subsequent confirmation by molecular genetic analysis. Currently, haematopoietic stem cell transplantation (HSCT) is the only curative treatment option available for these patients. There is a paucity of data from India on the clinical diversity and molecular spectrum of DOCK8 deficiency. In the present study, we report the clinical, immunological and molecular findings of 17 DOCK8-deficient patients from India diagnosed over the last 5 years.

Hematologically important mutations: Leukocyte adhesion deficiency (second update).

Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing, accompanied by neutrophilia. In LAD-I, characterized directly after birth by delayed separation of the umbilical cord, mutations are found in ITGB2, the gene that encodes the ß subunit (CD18) of the ß2 integrins. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Lea and Leb blood group antigens. Finally, in LAD-III, the conformational activation of the hematopoietically expressed ß integrins is disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells, involved in the regulation of ß integrin conformation. This article contains an update of the mutations that we consider to be relevant for the various forms of LAD.

Barriers to and facilitators of pet grooming among clients served by a subsidized grooming service program.

Grooming is an important aspect of basic hygiene care for most companion animals. The consequences of not receiving routine grooming care can pose significant risks to animals' health and wellbeing. The current study examined barriers and facilitators of maintaining pets' grooming needs among clients of a subsidized grooming service program in New York City (N = 167), as well as the impact of a tailored nail-trimming demonstration on clients' confidence trimming pets' nails. Ninety-two percent of the sample reported experiencing at least one barrier to maintaining their pet's grooming (e.g., income, transportation) and nearly half (46%) experienced three or more barriers to providing grooming. Ninety-one percent endorsed that at least one supply/support (e.g., brush/comb, behavioral support) would be beneficial in maintaining their pet's grooming needs at home and more than half reported that three or more supplies/services would be beneficial. Differences in the prevalence of specific barriers to grooming were found across income groups, service locations, and service settings. Clients who received nail-trimming demonstrations, on average, reported statistically significant increases in confidence trimming nails following their appointment. We discuss the implications of these findings for improving animal welfare and veterinary professionals' capacity for preventing grooming-related omissions of care and increasing communities' capacity to support pet owners' access to essential pet care supplies and supports. Future research is needed to determine (a) how and for whom grooming demonstrations and subsidized services are most effective, (b) whether an increase in pet owner confidence following nail trimming demonstrations is associated with maintaining nail trimming at home over time, and (c) whether providing clients with supplies and supports is an effective way of preventing and/or ameliorating future grooming-related omissions of care and hygiene-related health concerns observed by veterinarians, animal control professionals, shelter staff, and law enforcement.

Examining the relationship between clinician communication and patient participatory behaviors in cardiology encounters.

OBJECTIVES: Examine the association of coder ratings of cardiologist behaviors and global scores of cardiologist communication style with patient participation in clinic encounters. METHODS: We coded transcripts of clinic encounters for patient participatory behaviors: asking questions, assertive statements, and expressing negative emotions; clinician behavior counts: reflective statements, open-ended questions, empathic statements, and eliciting questions. We used general linear regression models to examine associations of mean number of patient participatory behaviors with clinician behaviors. RESULTS: Our sample included 161 patients of 40 cardiologists. Patient female gender was associated with on average 2.1 (CI: 0.06, 4.1; p = 0.04) more patient participatory behaviors. In an adjusted model, clinician reflective statements were associated with on average 0.3 (CI: 0.04, 0.4; p = 0.02) more patient participatory behaviors. A clinician making at least one empathic statement was associated with on average 3.7 (CI: 0.2, 7.1; p = 0.04) more patient participatory behaviors. CONCLUSIONS: These results demonstrate that some individual clinician behaviors are associated with higher patient participation in cardiology encounters. PRACTICE IMPLICATIONS: Clinician reflective and empathic statements may be important targets in communication training to increase patient participation. SECTION: Communication Studies.

Veterinary needs for animal cruelty recognition and response in the United States center on training and workplace policies.

OBJECTIVE: To better understand the experiences and perceptions of veterinary professionals in the US responding to suspected cases of animal cruelty. SAMPLE: 1,027 US veterinary professionals. PROCEDURES: An anonymous survey was distributed via social media and veterinary professional associations between October 15 and November 15, 2020. RESULTS: Responses indicated that more cases of suspected animal cruelty were seen by those who reported having had cruelty training and in workplaces with emergency intake or a relationship with law enforcement. In addition, suspected cases were more likely to be reported to authorities by respondents who indicated there was a workplace policy for handling cruelty cases and by individuals who indicated that they were aware that they were mandated reporters. CLINICAL RELEVANCE: The important needs for veterinary professionals in relation to animal cruelty are more training to recognize animal cruelty, workplace policies for reporting, and knowledge of reporting laws.

Clinical and Genetic Spectrum of Inborn Errors of Immunity in a Tertiary Care Center in Southern India.

OBJECTIVES: To study the incidence, clinical manifestations, and genetic spectrum of primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) in a tertiary care hospital in Southern India. METHODS: A retrospective analysis of all patients with a clinical suspicion of PID/IEI seen at a tertiary care hospital was performed. All patients had at least one or more warning signs of PID. Serum immunoglobulin levels and other targeted investigations were performed as warranted by the clinical presentation. All families with suspected PID were counseled and offered genetic testing. RESULTS: A total of 225 children were evaluated for PID during the study period of 6 y. Fifty-six of them did not meet the European Society of Immunodeficiencies (ESID) criteria (working definition of clinical diagnosis) and were excluded. An IEI was found in 30/49 (61.2%) patients. The most frequent reason for referral was recurrent/unusual or serious infections (28%), or cytopenia (16%). Group IV diseases of immune dysregulation was the most common category (19%), followed by group III predominant antibody deficiencies in 23/163 (14%), as per the International Union of Immunological Societies (IUIS) classification. CONCLUSIONS: This study highlights the heterogeneity of the present cohort, the underuse of genetic tests, and efforts to provide optimal care for children with possible IEI in this center.

Understanding memory B cell selection.

The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely selected earlier in the affinity maturation process and have lower affinity. We propose that this memory B cell selection process may be an approximate solution to two optimization problems: optimizing for affinity to similar antigens in the future despite mutations or other minor differences, and optimizing to warm start the generation of plasma B cells in the future. We use simulations to provide evidence for our hypotheses, taking into account data showing that certain B cell mutations are more likely than others. Our findings are consistent with memory B cells having high-affinity to mutated antigens, but do not provide strong evidence that memory B cells will be more useful than selected naive B cells for seeding the secondary germinal centers.

CD8 + T Cells Exhibit an Exhausted Phenotype in Hemophagocytic Lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome mainly caused by uncontrolled activation of antigen presenting cells and CD8 T cells. CD8 T cell exhaustion is a known phenomenon in chronic viral infections and cancer. However, the role of T cell exhaustion is not yet identified in HLH in the background of persistent inflammation. So, currently, we have characterized the CD8 T cells using flow cytometry to understand the phenomenon of exhaustion in these cells in HLH. METHODS: We have comprehensively evaluated lymphocyte subsets and characterized CD8 T cells using immunophenotypic markers like PD1, TIM3, LAG3, Ki67, Granzyme B, etc. in a cohort of 21 HLH patients. Effector cytokine secretion and degranulation by CD8 T cells are also studied. RESULTS: Our findings indicate skewed lymphocyte subsets and aberrantly activated CD8 T cells in HLH. CD8 T cells exhibit significantly increased expression of PD1, TIM3, and LAG3 prominently in primary HLH as compared to controls. PD1 + CD8 T cells express elevated levels of Granzyme B and Ki67. Moreover, CD8 T cells are hypofunctional as evidenced by significantly reduced cytokine secretion and compromised CD107a degranulation. CONCLUSION: The study has revealed that CD8 + cytotoxic T lymphocytes from HLH patients exhibited high expression of exhaustion markers with overall impaired function. To the best of our understanding, this is the first report suggesting functional exhaustion of CD8 T cells in both primary and secondary HLH. Future studies to understand the association of exhaustion with disease outcome are needed for its probable therapeutic implementation.

Glutathione as a Molecular Marker of Functional Impairment in Patients with At-Risk Mental State: 7-Tesla 1H-MRS Study.

A substantial number of individuals with clinical high-risk (CHR) mental state do not transition to psychosis. However, regardless of future diagnostic trajectories, many of these individuals develop poor social and occupational functional outcomes. The levels of glutathione, a crucial cortical antioxidant, may track variations in functional outcomes in early psychosis and prodromal states. Thirteen clinical high-risk and 30 healthy control volunteers were recruited for a 7-Tesla magnetic resonance spectroscopy scan with a voxel positioned within the dorsal anterior cingulate cortex (ACC). Clinical assessment scores were collected to determine if any association was observable with glutathione levels. The Bayesian Spearman's test revealed a positive association between the Social and Occupational Functioning Assessment Scale (SOFAS) and the glutathione concentration in the clinical high-risk group but not in the healthy control group. After accounting for variations in the SOFAS scores, the CHR group had higher GSH levels than the healthy subjects. This study is the first to use 7-Tesla magnetic resonance spectroscopy to test whether ACC glutathione levels relate to social and occupational functioning in a clinically high-risk group and offers preliminary support for glutathione levels as a clinically actionable marker of prognosis in emerging adults presenting with risk features for various severe mental illnesses.

Accurate large-scale phylogeny-aware alignment using BAli-Phy.

MOTIVATION: BAli-Phy, a popular Bayesian method that co-estimates multiple sequence alignments and phylogenetic trees, is a rigorous statistical method, but due to its computational requirements, it has generally been limited to relatively small datasets (at most about 100 sequences). Here, we repurpose BAli-Phy as a 'phylogeny-aware' alignment method: we estimate the phylogeny from the input of unaligned sequences, and then use that as a fixed tree within BAli-Phy. RESULTS: We show that this approach achieves high accuracy, greatly superior to Prank, the current most popular phylogeny-aware alignment method, and is even more accurate than MAFFT, one of the top performing alignment methods in common use. Furthermore, this approach can be used to align very large datasets (up to 1000 sequences in this study). AVAILABILITY AND IMPLEMENTATION: See https://doi.org/10.13012/B2IDB-7863273_V1 for datasets used in this study. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India.

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.