ABSTRACT
The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human-rotavirus-specific immunity to the outer capsid, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.
Subject(s)
Antibodies, Viral , Capsid Proteins , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Animals , Rotavirus/immunology , Rotavirus/genetics , Mice , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Humans , Antibodies, Viral/immunology , Antibodies, Viral/blood , Capsid Proteins/immunology , Capsid Proteins/genetics , Rotavirus Vaccines/immunology , Rotavirus Vaccines/administration & dosage , Disease Models, Animal , Antigens, Viral/immunology , Antigens, Viral/genetics , Antibody Formation , Virus Shedding , Virus Replication , Feces/virology , Diarrhea/virology , Diarrhea/immunologyABSTRACT
We would like to acknowledge and thank the authors of "Defining the Plethoric IVC" [...].
ABSTRACT
BACKGROUND AND OBJECTIVES: The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by monovalent mRNA-based coronavirus disease 2019 vaccines in young children. METHODS: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected 1 month after primary vaccine series completion for the measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5). RESULTS: Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a previous history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, which is consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region. CONCLUSIONS: Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses 1 month after vaccination in young children. In addition, previous infection significantly enhanced the strength of antibody responses to Omicron subvariants. The authors of future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.
Subject(s)
2019-nCoV Vaccine mRNA-1273 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 , Immunogenicity, Vaccine , Humans , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Infant , 2019-nCoV Vaccine mRNA-1273/immunology , Child, Preschool , Male , Antibodies, Neutralizing/blood , Prospective Studies , Female , Immunogenicity, Vaccine/immunology , COVID-19/prevention & control , COVID-19/immunology , Antibodies, Viral/blood , SARS-CoV-2/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Cohort Studies , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
Acute right heart failure (ARHF) arises when the right ventricle fails to pump blood efficiently to the pulmonary circulation. This inefficiency leads to a decreased blood supply to various organs. ARHF is a significant health concern, often leading to increased hospital admissions and being associated with a higher risk of mortality. This condition underscores the importance of effective cardiac care and timely intervention to manage its complications and improve patient outcomes. Diagnosing ARHF involves a comprehensive approach that includes a physical examination to evaluate the patient's fluid status and heart-lung function, blood tests to identify potential triggers and help forecast patient outcomes and various imaging techniques. These imaging techniques include electrocardiograms, point-of-care ultrasounds, computed tomography, cardiac magnetic resonance imaging, and other advanced monitoring methods. These diagnostic tools collectively aid in a detailed assessment of the patient's cardiac and pulmonary health, essential for effective management of ARHF. The management of ARHF focuses on addressing the underlying causes, regulating fluid balance, and enhancing cardiac function through pharmacological treatments or mechanical support aimed at boosting right heart performance. This management strategy includes the use of medications that modulate preload, afterload, and inotropy; vasopressors; anti-arrhythmic drugs; ensuring proper oxygenation and ventilation; and the utilization of heart and lung assist devices as a bridge to potential transplantation. This review article is dedicated to exploring the pathophysiology of ARHF, examining its associated morbidity and mortality, evaluating the various diagnostic tools available, and discussing the diverse treatment modalities. The article seeks to provide a comprehensive understanding of ARHF, its impact on health, and the current strategies for its management.
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Cross-lagged panel designs were used to examine longitudinal and potential (bi)directional relationships between primary caregiver reported sibling relationship quality and the behaviors of children with intellectual disability (n = 297) and their closest in age siblings. The behavioral and emotional problems of the child with intellectual disability positively predicted sibling conflict over time. When accounting for control variables, this relationship was no longer present. Sibling warmth positively predicted the prosocial behaviors of the child with intellectual disability over time. When accounting for control variables, both sibling warmth and sibling conflict positively predicted the prosocial behaviors of the child with intellectual disability over time. Future research directions and clinical implications are discussed.
Subject(s)
Cognitive Dysfunction , Disabled Children , Intellectual Disability , Child , Humans , Siblings/psychology , Intellectual Disability/psychology , Sibling RelationsABSTRACT
The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.
Subject(s)
COVID-19 , Viral Vaccines , Animals , Humans , Infant , SARS-CoV-2 , COVID-19 Vaccines , Macaca mulatta , BNT162 Vaccine , Antibodies, Viral , Antibodies, NeutralizingABSTRACT
The Ebola virus has caused outbreaks in Central and West Africa, with high rates of morbidity and mortality. Clinical trials of recombinant virally vectored vaccines did not explicitly include pregnant or nursing women, resulting in a gap in knowledge of vaccine-elicited maternal antibody and its potential transfer. The role of maternal antibody in Ebola virus disease and vaccination remains understudied. Here, we demonstrate that a protein subunit vaccine can elicit robust humoral responses in pregnant mice, which are transferred to pups in breastmilk. These findings indicate that an intramuscular protein subunit vaccine may elicit Ebola-specific IgG capable of being transferred across the placenta as well as into the breastmilk. We have previously shown protective efficacy with these vaccines in non-human primates, offering a potential safe and practical alternative to recombinant virally vectored vaccines for pregnant and nursing women in Ebola endemic regions.
Subject(s)
Ebola Vaccines , Ebolavirus , Hemorrhagic Fever, Ebola , Female , Animals , Mice , Protein Subunits , Democratic Republic of the Congo , Disease Models, Animal , Antibodies, Viral , Immunization , Vaccination , Primates , Vaccines, SyntheticABSTRACT
BACKGROUND: CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors. METHODS: This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics. RESULTS: Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties. CONCLUSIONS: Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice.
Subject(s)
CHARGE Syndrome , Intellectual Disability , Self-Injurious Behavior , Sleep Wake Disorders , Aggression , CHARGE Syndrome/complications , CHARGE Syndrome/epidemiology , Humans , Intellectual Disability/complications , Intellectual Disability/epidemiology , Intellectual Disability/psychology , Self-Injurious Behavior/epidemiology , Self-Injurious Behavior/psychologyABSTRACT
Type 2 diabetes mellitus (T2DM) affects a large number of the American population. When compared to their representation in the general American population, a disproportionate number of Latinx individuals are affected. Within the Latinx American population, T2DM prevalence rates vary among individuals based on their country of origin. Deaths from T2DM among Latinx American population are also more compared to other ethnicities. This disparity underlines the importance of understanding the cultural considerations of T2DM disease presentation and management in Latinx communities, including risk factors, socioeconomic variables, and other social determinants of health such as access to care. There are various modifiable and non-modifiable risk factors for the development of T2DM, regardless of race. Staple foods in the diet of Latinx American communities, such as tortillas, rice, and beans, can cause spikes in blood sugar levels and can lead to obesity, which predisposes patients to develop T2DM. Latinx American populations suffer from lower access to healthcare than the general population due to many reasons, including language proficiency, immigration status, socioeconomic status, and level of acculturation. This study utilized the format of a commentary, while incorporating elements of a scoping review for data collection, to further explore these disparities and their impact on these populations. Understanding the cultural beliefs of Latinx individuals and how these beliefs contribute to the perceived development of T2DM is essential to properly treat these unique populations. Despite high rates of T2DM affecting Latinx individuals, non-adherence to prescribed diabetes medications is high among these populations. Interventions in the form of culturally tailored preventative education, in addition to active T2DM management, are necessary to combat the toll of this disease on Latinx Americans. Generic interventional techniques and methods should be replaced entirely by those that acknowledge, highlight, and utilize the sociocultural characteristics of Latinx Americans.
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BACKGROUND: Existing research has predominately focused on dyadic relationships in families of children with intellectual disabilities. The aim of this study was to build on emerging literature exploring triadic relationships between a mother, sibling, and child with intellectual disability, investigating how they influence each other's well-being. METHOD: An online survey was used to collect information regarding the mother's mental health and the emotional and behavioural problems of the sibling and the child with intellectual disability in 573 families. RESULTS: Using structural equation modelling, we found that maternal psychological distress was associated with higher levels of behaviour problems in the sibling, and the behaviour problems of the child with intellectual disability were associated with higher levels of maternal distress. CONCLUSIONS: Family member well-being is inter-related in families of children with intellectual disabilities. Clinical interventions that improve the behaviours of children with intellectual disabilities should be considered.
Subject(s)
Intellectual Disability , Problem Behavior , Child , Female , Humans , Intellectual Disability/psychology , Mothers , Siblings/psychology , Surveys and QuestionnairesABSTRACT
Molar pregnancies are rare complications that can have potentially devastating effects, including neoplastic disease. Given the potential for malignant conversion, proper diagnosis of molar pregnancy is crucial. This case demonstrates the utility of point-of-care ultrasound (POCUS) for molar pregnancy in the emergency department (ED). The patient was a 43-year-old G8P1, 8-week-pregnant female who presented to the emergency department for evaluation of abdominal pain. Her physical exam was notable for abdominal tenderness and a normal pelvic exam. Evaluation included basic labs with a quantitative serum beta human chorionic gonadotropin (ßhCG), urinalysis, and vaginal wet mount. Her results were unremarkable with the exception of elevated ßhCG to 83,000 mIU/mL. A transabdominal POCUS was performed which showed a heterogeneous mass with several anechoic areas, concerning for a molar pregnancy. Patient was seen by obstetrics and gynecology (OB-GYN) and a transvaginal ultrasound showed similar findings. Dilation and evacuation were performed approximately 5 hours after initial diagnosis on POCUS. Use of POCUS was crucial for expedient diagnosis and appropriate treatment in this patient, highlighting the utility of POCUS for pregnant patients in the ED. Topics: Molar pregnancy, gestational trophoblastic disease, hydatidiform mole, point of care ultrasound.
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Posttraumatic stress disorder (PTSD) is a risk factor for adolescent suicidal ideation (SI). This study explored the relation between PTSD symptom clusters and SI, and whether social support moderates this association, in a cross-sectional, adolescent, clinical sample (N = 125). We hypothesized that each cluster would be positively associated with SI severity and that social support would buffer these associations. Only the persistent avoidance cluster was significantly associated with SI severity. Further, social support moderated this association. Results highlight the positive association between persistent avoidance symptoms of PTSD and SI and suggest that bolstering social support serves a protective function.
Subject(s)
Stress Disorders, Post-Traumatic , Suicidal Ideation , Adolescent , Cross-Sectional Studies , Humans , Social Support , Stress Disorders, Post-Traumatic/diagnosis , SyndromeABSTRACT
INTRODUCTION: Medical education is oftentimes stressful and has been documented to compromise student well-being, hinder performance, and contribute to burnout. Many medical schools aim to foster students' sense of well-being. This can be accomplished by peer-assisted learning (PAL), which has the potential to improve student wellness and performance in medical school. METHODS: The PAL program at Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine provides first-year medical students with educational sessions related to their curriculum, led by second-year medical students. The goal of this study was to determine the efficacy of PAL in promoting wellness and enhancing knowledge. Pre- and post-program surveys were distributed to students prior to and after the completion of PAL. Data analysis included frequencies of responses, qualitative analysis, and chi-square analysis. RESULTS: Thirty-eight out of 51 first-year medical students responded to the pre-program survey (response rate 75%) and 23 out of 51 responded to the post-program survey (response rate 45%). A majority of respondents from the pre-survey believed that PAL would provide them with tools necessary to be successful. These findings were similar in the post-program survey with a majority of attendees sharing that PAL enhanced their knowledge, reduced test-taking anxiety, and provided useful skills. DISCUSSION: Results from the pre- and post-program surveys suggest that PAL can enhance student well-being while improving knowledge of the material taught in medical school. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01381-0.
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Papillary carcinoma of the breast is rare, comprising only 0.5% incidence of all breast cancers. Clinically the disease presents in postmenopausal women as a painless breast lump with possible bloody nipple discharge. Prognosis is favorable due to its slow growth. We present a 61-year-old woman incidentally diagnosed with papillary breast carcinoma after presenting with a trauma-induced hematoma of the right breast. The patient presented to our surgery oncology clinic for persistent right breast swelling secondary to a fall, despite initial incision and drainage (I&D) six weeks prior. She had no history of breast cancer. On presentation, her right breast was distended demonstrating an approximately 20cm ill-defined solid mass with skin changes consistent with a tense hematoma. CT scan demonstrated a large complex cystic and solid breast mass measuring 15.2cmx11.8cmx15.2cm with irregular peripheral solid hyperdense polypoid components. She then underwent a right breast incisional biopsy and hematoma evacuation. Frozen sections of the mass outer cavity wall and papillary projections were consistent with encapsulated papillary carcinoma (EPC). The patient was lost to follow-up and did not obtain definitive treatment. Breast cancer rarely presents as a breast hematoma. However, as in this case, if the hematoma fails to resolve, further investigation is warranted. The prognosis of EPC is excellent when identified and treated appropriately.
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Ebola (EBOV), Marburg (MARV) and Sudan (SUDV) viruses are the three filoviruses which have caused the most fatalities in humans. Transmission from animals into the human population typically causes outbreaks of limited scale in endemic regions. In contrast, the 2013-16 outbreak in several West African countries claimed more than 11,000 lives revealing the true epidemic potential of filoviruses. This is further emphasized by the difficulty seen with controlling the 2018-2020 outbreak of EBOV in the Democratic Republic of Congo (DRC), despite the availability of two emergency use-approved vaccines and several experimental therapeutics targeting EBOV. Moreover, there are currently no vaccine options to protect against the other epidemic filoviruses. Protection of a monovalent EBOV vaccine against other filoviruses has never been demonstrated in primate challenge studies substantiating a significant void in capability should a MARV or SUDV outbreak of similar magnitude occur. Herein we show progress on developing vaccines based on recombinant filovirus glycoproteins (GP) from EBOV, MARV and SUDV produced using the Drosophila S2 platform. The highly purified recombinant subunit vaccines formulated with CoVaccine HT™ adjuvant have not caused any safety concerns (no adverse reactions or clinical chemistry abnormalities) in preclinical testing. Candidate formulations elicit potent immune responses in mice, guinea pigs and non-human primates (NHPs) and consistently produce high antigen-specific IgG titers. Three doses of an EBOV candidate vaccine elicit full protection against lethal EBOV infection in the cynomolgus challenge model while one of four animals infected after only two doses showed delayed onset of Ebola Virus Disease (EVD) and eventually succumbed to infection while the other three animals survived challenge. The monovalent MARV or SUDV vaccine candidates completely protected cynomolgus macaques from infection with lethal doses of MARV or SUDV. It was further demonstrated that combinations of MARV or SUDV with the EBOV vaccine can be formulated yielding bivalent vaccines retaining full efficacy. The recombinant subunit vaccine platform should therefore allow the development of a safe and efficacious multivalent vaccine candidate for protection against Ebola, Marburg and Sudan Virus Disease.
Subject(s)
Ebola Vaccines/pharmacology , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/prevention & control , Marburg Virus Disease/prevention & control , Marburgvirus/immunology , Animals , Ebola Vaccines/genetics , Ebola Vaccines/immunology , Ebolavirus/genetics , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/genetics , Hemorrhagic Fever, Ebola/immunology , Humans , Macaca fascicularis , Marburg Virus Disease/epidemiology , Marburg Virus Disease/genetics , Marburg Virus Disease/immunology , Marburgvirus/genetics , Vaccines, SyntheticABSTRACT
Background Improper utilization of emergency departments (EDs) in the United States is an issue that places a large burden on the healthcare system. Previous studies have shown that differences in race, gender, and income level have been associated with avoidable ED visits. Broward County, Florida, is diverse with people from many different socioeconomic backgrounds. The objective of this study is to determine the impact that race/ethnicity, gender, and payment methods have on the rates of avoidable ED visits at hospitals in Broward County, Florida. Methods This study utilized a dataset from the Broward Regional Health Planning Council that included ED visits in Broward County in 2019. Secondary data analysis was conducted utilizing a one-way analysis of variance (ANOVA) with post-hoc analysis to compare the proportions of non-emergent, emergent primary care-treatable, and emergent preventable ED visits amongst different race/ethnicities, genders, and payment/insurance methods. Results Compared to non-Hispanic white patients, non-Hispanic black and Hispanic patients had higher mean rates of non-emergent ED visits. Women had greater mean rates compared to men for non-emergent ED visits; males had higher mean rates than females for emergent primary care-treatable and emergent preventable. Patients covered by Medicaid had greater mean rates of non-emergent and emergent primary care-treatable visits compared to patients using other payment or insurance methods. Conclusions This study identified demographics within Broward County associated with avoidable ED visits. To reduce the burden of ED overutilization on the healthcare system, healthcare providers must better educate the at-risk populations about proper ED use. In addition, a comprehensive assessment of social determinants of health in patients overutilizing the ED will allow for better alignment of resources and policy changes to improve healthcare access and community health.
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The current COVID-19 pandemic has claimed hundreds of thousands of lives and its causative agent, SARS-CoV-2, has infected millions, globally. The highly contagious nature of this respiratory virus has spurred massive global efforts to develop vaccines at record speeds. In addition to enhanced immunogen delivery, adjuvants may greatly impact protective efficacy of a SARS-CoV-2 vaccine. To investigate adjuvant suitability, we formulated protein subunit vaccines consisting of the recombinant S1 domain of SARS-CoV-2 Spike protein alone or in combination with either CoVaccine HT™ or Alhydrogel. CoVaccine HT™ induced high titres of antigen-binding IgG after a single dose, facilitated affinity maturation and class switching to a greater extent than Alhydrogel and elicited potent cell-mediated immunity as well as virus neutralizing antibody titres. Data presented here suggests that adjuvantation with CoVaccine HT™ can rapidly induce a comprehensive and protective immune response to SARS-CoV-2.
Subject(s)
Adjuvants, Immunologic/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/immunology , Animals , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunization , Immunoglobulin G/immunology , Male , Mice , Mice, Inbred BALB C , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunologyABSTRACT
The current COVID-19 pandemic has claimed hundreds of thousands of lives and its causative agent, SARS-CoV-2, has infected millions, globally. The highly contagious nature of this respiratory virus has spurred massive global efforts to develop vaccines at record speeds. In addition to enhanced immunogen delivery, adjuvants may greatly impact protective efficacy of a SARS-CoV-2 vaccine. To investigate adjuvant suitability, we formulated protein subunit vaccines consisting of the recombinant S1 domain of SARS-CoV-2 Spike protein alone or in combination with either CoVaccine HT™ or Alhydrogel. CoVaccine HT™ induced high titres of antigen-binding IgG after a single dose, facilitated affinity maturation and class switching to a greater extent than Alhydrogel and elicited potent cell-mediated immunity as well as virus neutralising antibody titres. Data presented here suggests that adjuvantation with CoVaccine HT™ can rapidly induce a comprehensive and protective immune response to SARS-CoV-2.
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BACKGROUND: Adolescents who experience symptoms of borderline personality disorder (BPD) are at high risk for alcohol misuse, yet little is known about why these adolescents drink and what factors heighten or mitigate this risk. The current study explores factors that may impact risk for alcohol misuse among youth with BPD symptoms: using alcohol to self-medicate or to rebel and perceived coping skills. METHOD: A sample of 181 psychiatrically hospitalized adolescents (Mage = 15.04 years, SD = 1.31 years; 71.8% female, 83.4% White) was recruited as part of a larger study from the northeastern United States. Assessments and diagnostic interviews were administered to adolescents. RESULTS: Use of alcohol for self-medication and perceived coping skills, but not using alcohol for rebellion, moderated the relationship between BPD symptoms and alcohol misuse. A significant positive relationship between BPD symptoms and alcohol frequency and/or problems was only found among adolescents who reported lower use of alcohol for self-medication purposes or higher perceived coping skills. CONCLUSIONS: Youth with more BPD symptoms are at high risk for alcohol misuse. Moderation effects for self-medication motives and perceived coping skills were counter to hypotheses; lower levels of self-medication motives contributed to greater alcohol problems, as did higher levels of perceived coping skills. Results suggest the importance of assessing how much youth are drinking or experiencing consequences, as well as why they are using alcohol. It is possible adolescents with more BPD symptoms may be reporting more coping skills, but actually exhibiting the phenomenon of apparent competence (i.e., present as 'in control', but actually experiencing extreme distress and lacking sufficient coping skills); collateral reports of adolescents' coping skills may provide a more objective measure of actual skill level. KEY PRACTITIONER MESSAGE: What is known? Adolescents who experience symptoms of borderline personality disorder (BPD) are at high risk for alcohol misuse, yet little is known about why these adolescents drink and what factors heighten or mitigate this risk. What is new? Adolescents who use alcohol to self-medicate or rebel are at high risk for alcohol problems, regardless of presence of BPD symptoms. Contrary to expectations, higher perceived coping skills strengthened the relation between BPD and alcohol misuse. Apparent competence (i.e., present as 'in control' but lack sufficient skills) may be at play. What is significant for clinical practice? Clinicians are encouraged to assess why adolescents are using alcohol and teach alternative coping strategies when self-medication and/or rebellion is an identified use. Clinicians are encouraged to collect collateral reports of adolescent's coping abilities rather than relying solely on self-report.
Subject(s)
Adaptation, Psychological/physiology , Adolescent Behavior/physiology , Borderline Personality Disorder/physiopathology , Motivation/physiology , Underage Drinking/psychology , Adolescent , Adolescent, Hospitalized/statistics & numerical data , Borderline Personality Disorder/epidemiology , Female , Humans , Male , New England/epidemiology , Risk , Underage Drinking/statistics & numerical dataABSTRACT
INTRODUCTION: Physician burnout, wellness, and resilience have become increasingly important topics of discussion worldwide. While studies have assessed burnout globally in various individual countries, few studies directly compare or analyze gender-based physician burnout among different global regions. METHODS: Female physicians attending the Medical Women's International Association (MWIA) Centennial Congress completed the Copenhagen Burnout Inventory (CBI) which evaluates personal-, work-, and patient-related burnout using a scale of 0 to 100. Results were analyzed using descriptive statistics and 1-way ANOVA to compare burnout scores amongst women physicians from different global regions. RESULTS: Of 100 physicians invited to participate, 76 provided responses and 71 met the inclusion criteria. Mean burnout scores were highest amongst women from Africa in all categories. Mean work-related, patient-related, and personal-related burnout scores were significantly lower for physicians in Europe compared to Africa (p = 0.05) when evaluated using a 1-way ANOVA, with no statistically significant differences between other regions. DISCUSSION: The data suggests that there may be regional differences in the prevalence of burnout in women physicians. Various factors could play a role in explaining the higher burnout scores in female physicians in Africa, including younger average age, establishing practice during childbearing years, and significant physician shortage. Through this study, we have begun to explore the cultural and geographical context related to women's mental and physical wellbeing in the medical field. Further research should focus on the gender-specific contributors to burnout among different global regions, so that methods can be implemented on a systemic level to alleviate burnout.