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Nature Medicine Sep 2023Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label,... (Randomized Controlled Trial)
Randomized Controlled Trial
Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Broadly Neutralizing Antibodies
PubMed: 37640860
DOI: 10.1038/s41591-023-02503-4 -
The Journal of Infectious Diseases Aug 2023Immune mechanisms that modulate human immunodeficiency virus-1 (HIV-1) reservoir size in neonates are poorly understood. Using samples from neonates who initiated...
Immune mechanisms that modulate human immunodeficiency virus-1 (HIV-1) reservoir size in neonates are poorly understood. Using samples from neonates who initiated antiretroviral therapy shortly after birth, we demonstrate that interleukin-8-secreting CD4 T cells, which are selectively expanded in early infancy, are more resistant to HIV-1 infection and inversely correlated with the frequency of intact proviruses at birth. Moreover, newborns with HIV-1 infection displayed a distinct B-cell profile at birth, with reduction of memory B cells and expansion of plasmablasts and transitional B cells; however, B-cell immune perturbations were unrelated to HIV-1 reservoir size and normalized after initiation of antiretroviral therapy. Clinical Trials Registration. NCT02369406.
Topics: Humans; Infant, Newborn; HIV-1; Anti-Retroviral Agents; HIV Infections; Proviruses; CD4-Positive T-Lymphocytes; Viral Load
PubMed: 37201510
DOI: 10.1093/infdis/jiad173 -
Multiple Sclerosis (Houndmills,... Dec 2023Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging...
BACKGROUND
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging (MRI) features but differ in prognosis and management. Early POMS diagnosis is essential to avoid disability accumulation. Central vein sign (CVS), paramagnetic rim lesions (PRLs), and central core lesions (CCLs) are susceptibility-based imaging (SbI)-related signs understudied in pediatric populations that may help discerning POMS from MOGAD.
METHODS
T2-FLAIR and SbI (three-dimensional echoplanar imaging (3D-EPI)/susceptibility-weighted imaging (SWI) or similar) were acquired on 1.5T/3T scanners. Two readers assessed CVS-positive rate (%CVS+), and their average score was used to build a receiver operator curve (ROC) assessing the ability to discriminate disease type. PRLs and CCLs were identified using a consensual approach.
RESULTS
The %CVS+ distinguished 26 POMS cases (mean age 13.7 years, 63% females, median EDSS 1.5) from 14 MOGAD cases (10.8 years, 35% females, EDSS 1.0) with ROC = 1, < 0.0001, (cutoff 41%). PRLs were only detectable in POMS participants (mean 2.1±2.3, range 1-10), discriminating the two conditions with a sensitivity of 69% and a specificity of 100%. CCLs were more sensitive (81%) but less specific (71.43%).
CONCLUSION
The %CVS+ and PRLs are highly specific markers of POMS. After proper validation on larger multicenter cohorts, consideration should be given to including such imaging markers for diagnosing POMS at disease onset.
Topics: Female; Child; Humans; Adolescent; Male; Myelin-Oligodendrocyte Glycoprotein; Imaging, Three-Dimensional; Veins; Autoantibodies; Multiple Sclerosis
PubMed: 37897254
DOI: 10.1177/13524585231204414 -
Rheumatology International Sep 2023Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied...
Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb-June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35-58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2-7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period.
Topics: Animals; Female; Humans; Male; Middle Aged; Autoimmune Diseases; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Myositis; Simian Acquired Immunodeficiency Syndrome; Vaccination
PubMed: 37351634
DOI: 10.1007/s00296-023-05345-y -
Cureus Nov 2023The gut-brain axis (GBA) is a two-way communication system that is influenced by signals from the nervous system, hormones, metabolism, the immune system, and microbes.... (Review)
Review
The gut-brain axis (GBA) is a two-way communication system that is influenced by signals from the nervous system, hormones, metabolism, the immune system, and microbes. The GBA may play a key role in gastrointestinal and neurological illnesses. Signaling events from the gut can regulate brain function. As a result, mounting data point to a connection between autoimmune disorders (AIDs), both neuroinflammatory and neurodegenerative diseases, and the GBA. Clinical, epidemiological, and experimental studies have shown that a variety of neurological illnesses are linked to alterations in the intestinal environment, which are suggestive of disease-mediated inter-organ communication between the gut and the brain. This review's objective is to draw attention to the clinical and biological relationship between the gut and the brain, as well as the clinical importance of this relationship for AIDs, neurodegeneration, and neuroinflammation. We also discuss the dysbiosis in the gut microbiota that has been linked to various AIDs, and we make some assumptions about how dietary changes such as prebiotics and probiotics may be able to prevent or treat AIDs by restoring the composition of the gut microbiota and regulating metabolites.
PubMed: 38090441
DOI: 10.7759/cureus.48655 -
Nature Communications Dec 2023Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated...
Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.
Topics: Humans; Female; Animals; Mice; Hyaluronoglucosaminidase; Skin; Acne Vulgaris; Propionibacterium acnes; Amino Acids
PubMed: 38052825
DOI: 10.1038/s41467-023-43833-8 -
Eastern Mediterranean Health Journal =... Jan 2024Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak...
BACKGROUND
Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019.
AIMS
To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person.
METHODS
Self-referred persons were tested for HIV using the national testing protocol. Local epidemiology of HIV was reviewed to generate hypotheses. An infection prevention and control (IPC) team conducted site visits and reviewed IPC practices.
RESULTS
Between 25 April and 27 June 2019, a total of 30 191 persons were tested for HIV in Larkana District, and 876 of them tested positive. Of those who tested positive, 719 (82%) were children aged <15 years. Traditional skin piercing procedures and transmission from high-risk populations to children were ruled out during the investigation. Informative interviews with parents or guardians of a convenience sample of 211 children aged <15 years showed that 99% of children had an injection or infusion for medical treatment within the past 12 months. Our investigation identified lack of HIV prevalence data for the general population including tuberculosis patients and those who attended antenatal care services.
CONCLUSIONS
Investigations indicate that unsafe healthcare practices in formal and informal healthcare settings as the most likely cause of the 2019 outbreak of HIV infection in Larkana, Pakistan. Measures should be taken to improve IPC practices at the facility level, especially in pediatric and antenatal care clinics.
Topics: Humans; Child; Female; Pregnancy; HIV Infections; Pakistan; Disease Outbreaks; Risk Factors; Prenatal Care
PubMed: 38415337
DOI: 10.26719/emhj.24.002 -
Children (Basel, Switzerland) Nov 2023The aim of this systematic review is to explore the pathology, diagnosis, treatment, and genetic basis of Primary Failure of Eruption (PFE) in the field of pediatric... (Review)
Review
AIM
The aim of this systematic review is to explore the pathology, diagnosis, treatment, and genetic basis of Primary Failure of Eruption (PFE) in the field of pediatric dentistry and orthodontics.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this review. The databases PubMed, Science Direct, Scopus, and Web of Science were searched from 1 July 2013 to 1 July 2023, using keywords "primary failure of tooth eruption" OR "primary failure of eruption" OR "tooth eruption failure" OR "PFE" AND "orthodontics". The study selection process involved screening articles based on the inclusion and exclusion criteria.
RESULTS
A total of 1151 results were obtained from the database search, with 14 papers meeting the inclusion criteria. The review covers various aspects of PFE, including its clinical features, diagnosis, treatment options, and genetic associations with mutations in the PTH1R gene. Differentiation between PFE and Mechanical Failure of Eruption (MFE) is crucial for accurate treatment planning. Orthodontic and surgical interventions, along with multidisciplinary approaches, have been employed to manage PFE cases. Genetic testing for PTH1R mutations plays a significant role in confirming the diagnosis and guiding treatment decisions, although some cases may not be linked to this mutation.
CONCLUSIONS
This systematic review provides valuable insights into the diagnosis, treatment, and genetic basis of PFE. Early diagnosis and personalized treatment planning are crucial for successful management. Genetic testing for PTH1R mutations aids in accurate diagnosis and may influence treatment decisions. However, further research is needed to explore the complex genetic basis of PFE fully and improve treatment outcomes for affected individuals.
PubMed: 38002872
DOI: 10.3390/children10111781 -
Cureus Dec 2023Artificial intelligence (AI) is transforming healthcare, offering potential benefits and challenges. In healthcare, AI enhances efficiency, streamlines processes, and... (Review)
Review
Artificial intelligence (AI) is transforming healthcare, offering potential benefits and challenges. In healthcare, AI enhances efficiency, streamlines processes, and supports decision-making. However, challenges include potential errors and biases in algorithms, data privacy concerns, legal and ethical issues, and resistance to change. In nursing, a delicate balance emerges between AI and human touch. While AI aids in data-driven decision-making and administrative tasks, it lacks the emotional intelligence, empathy, and nuanced understanding crucial to nursing care. Nurses excel in critical thinking, adaptability to dynamic situations, patient advocacy, collaboration, and establishing human connections. AI supports these functions by automating routine tasks and offering decision support tools, yet its rigidity in dynamic situations and lack of human touch pose limitations. This review underscores the necessity of careful AI integration in healthcare, acknowledging its advantages while mitigating drawbacks. In nursing, the symbiosis between AI and human qualities is vital. The role of AI should be to complement, not replace, the unique skills and empathetic aspects of nursing care. Addressing concerns related to bias, transparency, data privacy, and professional training is essential for maximizing the benefits of AI in healthcare while preserving the human touch in patient care. This article explores whether AI can replace unique nursing roles.
PubMed: 38283483
DOI: 10.7759/cureus.51150 -
Nature Communications Oct 2023The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess...
The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0-43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%-10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.
Topics: Male; Humans; Female; Adult; Spain; Homosexuality, Male; Mpox (monkeypox); Monkeypox virus; Sexual and Gender Minorities
PubMed: 37783731
DOI: 10.1038/s41467-023-40490-9