The Omicron variant of SARS-CoV-2 exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term ...durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron although the boosted titers decline rapidly within 2 months from the peak response compared to boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared to homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared to BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrial.gov# NCT04889209.
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•Vaccine boost substantially increases Omicron neutralizing antibody titers•Boosted neutralization titers to Omicron but not prototypic D614G decline rapidly•Ad26.COV2.S is better as prime or boost with mRNA vaccines than as homologous boost•Omicron sublineages exhibit 5-12 times reduced neutralization by mRNA-1273 boost sera
Following COVID-19 vaccine prime and boost, Lyke et al. find higher Omicron neutralization titers for homologous mRNA boost and heterologous mRNA and Ad26.COV2.S boost, compared to homologous Ad26.COV2.S boost. Omicron titers rapidly decline by Day 91 compared to prototypic D614G. Moderate differences in neutralization (<3-fold) was noted among Omicron sublineages.
As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing ...antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.
The absence of analytical controls for polymerase chain reaction (PCR)-based diagnostic tests for
Bordetella pertussis limits their clinical utility. In this study, multiplex PCR simultaneously ...targeted two specific
Bordetella pertussis sequences, the chromosomal repeated insertion sequence IS
481 (IS) and the pertussis toxin promoter region (PT). A multi-target hybridization-EIA (Hyb-EIA) method in a 96-well microtiter-plate format was used to detect amplicons. Forty-seven (15%) of the 318 nasopharygeal specimens tested positive for at least one DNA target of
B. pertussis by PCR, including the 10 known positive samples by culture and/or direct fluorescent antibody (DFA). Forty-six of the 47 PCR positive samples were considered positive for
B. pertussis using the consensus interpretation criteria. Simultaneous detection of multiple chromosomal regions may identify false-positive and -negative results due to analytical variations or potential sequence polymorphism, and uncover a wider range of pathogenic strains.
Arthrogenic muscle inhibition is an important underlying factor in persistent quadriceps muscle weakness after knee injury or surgery.
To determine the magnitude and prevalence of volitional ...quadriceps activation deficits after knee injury.
Web of Science database.
Eligible studies involved human participants and measured quadriceps activation using either twitch interpolation or burst superimposition on patients with knee injuries or surgeries such as anterior cruciate ligament deficiency (ACLd), anterior cruciate ligament reconstruction (ACLr), and anterior knee pain (AKP).
Means, measures of variability, and prevalence of quadriceps activation (QA) failure (<95%) were recorded for experiments involving ACLd (10), ACLr (5), and AKP (3).
A total of 21 data sets from 18 studies were initially identified. Data from 3 studies (1 paper reporting data for both ACLd and ACLr, 1 on AKP, and the postarthroscopy paper) were excluded from the primary analyses because only graphical data were reported. Of the remaining 17 data sets (from 15 studies), weighted mean QA in 352 ACLd patients was 87.3% on the involved side, 89.1% on the uninvolved side, and 91% in control participants. The QA failure prevalence ranged from 0% to 100%. Weighted mean QA in 99 total ACLr patients was 89.2% on the involved side, 84% on the uninvolved side, and 98.5% for the control group, with prevalence ranging from 0% to 71%. Thirty-eight patients with AKP averaged 78.6% on the involved side and 77.7% on the contralateral side. Bilateral QA failure was commonly reported in patients.
Quadriceps activation failure is common in patients with ACLd, ACLr, and AKP and is often observed bilaterally.
The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through ...genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.
The neuromuscular consequences of anterior cruciate ligament (ACL) injury are important considerations because these deficits play a crucial role in a patient's recovery following ACL injury or ...reconstruction. The purpose of this article is to review and synthesize the known neuromuscular consequences of ACL injury and reconstruction. Specifically, changes in somatosensation, muscle activation, muscle strength, atrophy, balance, biomechanics, and patient-oriented outcomes are discussed. Understanding neuromuscular consequences aids in the construction of optimized rehabilitation strategies.
To determine whether transcutaneous electrical nerve stimulation (TENS) and focal knee joint cooling will affect the quadriceps central activation ratio (CAR) in patients with tibiofemoral ...osteoarthritis.
Thirty-three participants with diagnosed tibiofemoral osteoarthritis were randomly allocated to the 45-min TENS treatment (six males and four females, 56 +/- 10.1 yr, 174.11 +/- 10.78 cm, 89.34 +/- 21.3 kg), the 20-min focal knee joint cooling treatment (six males and five females, 58 +/- 8.4 yr, 176.41 +/- 8.29 cm, 83.18 +/- 17.97 kg), or the control group (five males and seven females, 54 +/- 9.9 yr, 166.37 +/- 13.07 cm, 92.14 +/- 25.37 kg). Volitional quadriceps activation, maximal voluntary isometric contraction, and subjective pain measurements were conducted at baseline and at 20, 30, and 45 min. The 20-min focal knee joint cooling intervention consisted of two 1.5-L ice bags to the anterior and posterior aspects of the knee. The TENS group received 45 min of a sensory, biphasic square wave stimulation (150-mus phase duration and 150 pps) from four 2 x 2-inch electrodes positioned around the patella.
: TENS resulted in a significantly higher percent change in CAR scores compared with control at 20 min (6.4 +/- 4.8 vs -3.5 +/- 8, P = 0.006), 30 min (9.7 +/- 10.16 vs -1 +/- 7.9, P = 0.025), and 45 min (11.25 +/- 6.96 vs 0.81 +/- 9.4, P = 0.029). Focal knee joint cooling resulted in significantly higher percent change scores compared with the control group at 20 min (5.75 +/- 7.25 vs -3.5 +/- 8, P = 0.009) and trended to be higher at 45 min (9.06 +/- 9.63 vs 0.81 +/- 9.4, P = 0.098). No significant differences in percent change for CAR were found between the TENS and the focal knee joint cooling group.
Both TENS and focal knee joint cooling increased the quadriceps CAR immediately after application in participants with tibiofemoral osteoarthritis.
Objective- Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within ...progressing and regressing atherosclerotic plaques. Approach and Results- In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders. Thus, to test macrophage dynamics in plaques over a longer period of time in progressing and regressing disease, we quantified displacement of nondegradable phagocytic particles within macrophages for up to 6 weeks. In progressing plaques, macrophage-associated particles appeared to mobilize to deeper layers in plaque, whereas in regressing plaques, the label was persistently located near the lumen. By measuring the distance of the particles from the floor of the plaque, we discovered that particles remained at the same distance from the floor regardless of plaque progression or regression. The apparent deeper penetration of labeled cells in progressing conditions could be attributed to monocyte recruitment that generated new superficial layers of macrophages over the labeled phagocytes. Conclusions- Although there may be individual exceptions, as a population, newly differentiated macrophages fail to penetrate significantly deeper than the limited depth they reside on initial entry, regardless of plaque progression, or regression. These limited dynamics may prevent macrophages from escaping areas with unfavorable conditions (such as hypoxia) and pose a challenge for newly recruited macrophages to clear debris through efferocytosis deep within plaque.
The objective of this study was to evaluate the effects of a 20-min focal knee joint cooling intervention on quadriceps central activation ratio (CAR) in healthy volunteers. A counterbalanced, ...cross-over study assessed the effects of a focal joint cooling intervention compared with a control condition 3-14 days apart. Eleven healthy volunteers (6 males, 5 females; age 25 ± 5 years; height 1.71 ± 0.1 m, mass 77 ± 21 kg) were included in the final analysis. The joint cooling intervention consisted of two 1.5-litre ice bags applied to the knee joint for 20 min, in one of two counterbalanced sessions, completed 3-14 days apart. In the control session, participants sat quietly between the baseline and 20-min measurements. Quadriceps CAR was assessed at 70° of knee flexion at four instants (baseline, 20, 30, and 45 min). There was a significant treatment × time interaction (F
3,30
= 5.9, P = 0.003) and post hoc analyses revealed that CAR was higher in the focal knee joint cooling session than the control session at 20 min (0.79 ± 0.12 vs. 0.70 ± 0.12; t
10
= 3.9, P = 0.003) and 45 min (0.77 ± 0.10 vs. 0.69 ± 0.12; t
10
= 3.1, P = 0.01). The CAR tended to be higher during the experimental session than the control session at 30 min (0.79 ± 0.13 vs. 0.74 ± 0.11; t
10
= 2.1, P = 0.07).Volitional activation increased following focal knee joint cooling in healthy volunteers.
Wireless neural stimulators are being developed to address problems associated with traditional lead-based implants. However, designing wireless stimulators on the sub-millimeter scale (<1 mm
) is ...challenging. As device size shrinks, it becomes difficult to deliver sufficient wireless power to operate the device. Here, we present a sub-millimeter, inductively powered neural stimulator consisting only of a coil to receive power, a capacitor to tune the resonant frequency of the receiver, and a diode to rectify the radio-frequency signal to produce neural excitation. By replacing any complex receiver circuitry with a simple rectifier, we have reduced the required voltage levels that are needed to operate the device from 0.5 to 1 V (e.g., for CMOS) to ~0.25-0.5 V. This reduced voltage allows the use of smaller receive antennas for power, resulting in a device volume of 0.3-0.5 mm
. The device was encapsulated in epoxy, and successfully passed accelerated lifetime tests in 80°C saline for 2 weeks. We demonstrate a basic proof-of-concept using stimulation with tens of microamps of current delivered to the sciatic nerve in rat to produce a motor response.
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