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This phase 3, randomized, partially double-blind study investigated the safety, tolerability, and immunogenicity of 20-valent pneumococcal conjugate vaccine (PCV20) in healthy toddlers ≥12–<24 months of age who had previously received 2 infant doses of 13-valent PCV (PCV13). Participants were randomized to receive 1 or 2 doses of PCV20 (the second dose was administered 56–70 days after the first dose), or 1 dose of PCV13. The primary pneumococcal immunogenicity endpoint was the percentages of participants with predefined serotype-specific immunoglobulin G (IgG) concentrations (≥0.35 μg/mL) for the 7 additional serotypes 1 month after the last vaccination. Percentages of participants with predefined IgG concentrations for the 13 matched serotypes, IgG geometric mean concentrations, and opsonophagocytic activity (OPA) geometric mean titers were also evaluated for all 20 vaccine serotypes. Safety endpoints included local reactions, systemic events, adverse events, and serious adverse events. Overall, 356 participants were randomized (2-dose PCV20, n = 121; 1-dose PCV20, n = 118; PCV13, n = 117). One month after 1 PCV20 dose, ≥75.9 % of participants had IgG concentrations ≥0.35 μg/mL for all 7 additional serotypes, except serotype 12F (54.6 %). After 2 PCV20 doses, the percentage of participants with IgG concentrations ≥0.35 μg/mL for the 7 additional serotypes was ≥91.2 %. PCV20 elicited IgG and OPA responses for all 20 serotypes including serotype 12F. IgG distributions were well differentiated and substantially higher in PCV20 groups than the PCV13 group for the 7 additional serotypes, and generally similar between all groups for the 13 matched serotypes. In conclusion, a single toddler dose of PCV20 after 2 infant PCV13 doses elicited immune responses expected to help provide protection against the 7 additional serotypes and to provide similar protection against the 13 matched serotypes as PCV13. These data support a transition from PCV13 to PCV20 at the toddler dose. The safety and tolerability profile of PCV20 was similar to PCV13. Trial registration:Clinicaltrials.gov, NCT05408429. •PCV20 safety, tolerability, and immunogenicity in healthy toddlers was investigated.•Participants had previously received 2 infant doses of PCV13.•PCV20 single toddler dose expected to help protect against 7 additional serotypes.•PCV20 expected to provide similar protection as PCV13 against 13 matched serotypes.•The safety/tolerability profile of PCV20 toddler doses was similar to PCV13.

What unlikely candidates for friendship: George Washington, the model of a Virginia gentleman, famed in his time and ours for faultless rectitude and reserved behavior, and Gouverneur Morris, a cosmopolitan New Yorker twenty years Washington’s junior, an irrepressible jokester with a reputation that led Richard Brookhiser, one of his most recent biographers, to subtitle his studyThe Rake Who Wrote the Constitution.¹ The unlikely nature of that friendship accounts for the persistence of one of the best-known (although thoroughly discredited) apocryphal stories of the early republic. The story gained credence when Max Farrand included it in an appendix of “Anecdotes”

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

In June 2003, monkeypox was diagnosed in several patients in the midwestern United States who presented with fever, sweats, skin lesions, and lymphadenopathy. This investigation describes the initial 11 patients in the outbreak, all of whom had contact with ill pet prairie dogs from the same distributor. The infection was traced to rodents imported from West Africa. Monkeypox is an uncommon viral zoonosis caused by a member of the genus orthopoxvirus. 1 Monkeypox was initially recognized in 1958 as a viral eruption of captive primates. The first cases in humans were reported in 1970 in Zaire (now the Democratic Republic of Congo). 1 Since then, monkeypox has occurred sporadically in humans throughout that region 2 – 9 but has not been reported outside Africa. During May and June 2003, an outbreak of febrile illness with skin eruptions occurred among residents of the midwestern United States. 10 All patients reported having contact with sick pet prairie dogs (cynomys species) obtained through a common . . .

RationaleTolerance to cannabinoids could limit their therapeutic potential. Male mice expressing a desensitization-resistant form (S426A/S430A) of the type-1 cannabinoid receptor (CB1R) show delayed tolerance to delta-9-tetrahydrocannabinol (∆9-THC) but not CP55,940. With more women than men using medical cannabis for pain relief, it is essential to understand sex differences in cannabinoid antinociception, hypothermia, and resultant tolerance.ObjectiveOur objective was to determine whether female mice rely on the same molecular mechanisms for tolerance to the antinociceptive and/or hypothermic effects of cannabinoids that we have previously reported in males. We determined whether the S426A/S430A mutation differentially disrupts antinociceptive and/or hypothermic tolerance to CP55,940 and/or Δ9-THC in male and female S426A/S430A mutant and wild-type littermates.ResultsThe S426A/S430A mutation conferred an enhanced antinociceptive response for ∆9-THC and CP55,940 in both male and female mice. While the S426A/S430A mutation conferred partial resistance to ∆9-THC tolerance in male mice, disruption of CB1R desensitization had no effect on tolerance to ∆9-THC in female mice. The mutation did not alter tolerance to the hypothermic effects of ∆9-THC or CP55,940 in either sex. Interestingly, female mice were markedly less sensitive to the antinociceptive effects of 30 mg/kg ∆9-THC and 0.3 mg/kg CP55,940 compared with male mice.ConclusionsOur results suggest that disruption of the GRK/βarrestin2 pathway of desensitization alters tolerance to Δ9-THC but not CP55,940 in male but not female mice. As tolerance to Δ9-THC appears to develop differently in males and females, sex should be considered when assessing the therapeutic potential and dependence liability of cannabinoids.

A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum. Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

High-level isolation units (HLIUs) are specially designed facilities for care and management of patients with suspected or confirmed high-consequence infectious diseases (HCIDs), equipped with unique infrastructure and operational features. While individual HLIUs have published on their experiences caring for patients with HCIDs and two previous HLIU consensus efforts have outlined key components of HLIUs, we aimed to summarise the existing literature that describes best practices, challenges and core features of these specialised facilities. A narrative review of the literature was conducted using keywords associated with HLIUs and HCIDs. A total of 100 articles were used throughout the manuscript from the literature search or from alternate methods like reference checks or snowballing. Articles were sorted into categories (eg, physical infrastructure, laboratory, internal transport); for each category, a synthesis of the relevant literature was conducted to describe best practices, experiences and operational features. The review and summary of HLIU experiences, best practices, challenges and components can serve as a resource for units continuing to improve readiness, or for hospitals in early stages of developing their HLIU teams and planning or constructing their units. The COVID-19 pandemic, a global outbreak of mpox, sporadic cases of viral haemorrhagic fevers in Europe and the USA, and recent outbreaks of Lassa fever, Sudan Ebolavirus, and Marburg emphasise the need for an extensive summary of HLIU practices to inform readiness and response.