Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

OBJECTIVES: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. STUDY DESIGN: The study presented was conducted as part of the prospective CoVacSer cohort study. METHODS: This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. RESULTS: Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. CONCLUSION: In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.

Measurement of Differential Branching Fractions of Inclusive B→X_{u}ℓ

The first measurements of differential branching fractions of inclusive semileptonic B→X_{u}ℓ^{+}ν_{ℓ} decays are performed using the full Belle data set of 711 fb^{-1} of integrated luminosity at the ϒ(4S) resonance and for ℓ=e, µ. With the availability of these measurements, new avenues for future shape-function model-independent determinations of the Cabibbo-Kobayashi-Maskawa matrix element |V_{ub}| can be pursued to gain new insights in the existing tension with respect to exclusive determinations. The differential branching fractions are reported as a function of the lepton energy, the four-momentum-transfer squared, light-cone momenta, the hadronic mass, and the hadronic mass squared. They are obtained by subtracting the backgrounds from semileptonic B→X_{c}ℓ^{+}ν_{ℓ} decays and other processes, and corrected for resolution and acceptance effects.

[Current indications for plasma therapy in dermatology]. / Aktuelle Indikationen der Plasmatherapie in der Dermatologie.

BACKGROUND: Plasma medicine is gaining increasing interest and provides a multitude of dermatological applications. Cold atmospheric pressure plasma (CAP) can be used in clinical applications without harming the treated tissue or in a tissue destructive manner. It consists of a complex mixture of biologically active agents, which can act synergistically on the treated material or tissue. OBJECTIVES: A summary of the current research findings regarding dermatological applications of CAP is provided. METHODS: Literature on CAP applications in dermatology has been screened and summarized. RESULTS: CAP exerts antimicrobial, tissue-stimulating, blood-flow-stimulating but also pro-apoptotic effects. By exploiting these properties, CAP is successfully applied for disinfection and treatment of chronic ulcerations. Furthermore, positive effects of CAP have been shown for the treatment of tumors, actinic keratosis, scars, ichthyosis, atopic eczema as well as for alleviation of pain and itch. CONCLUSIONS: While the use of CAP for disinfection and wound treatment has already moved into clinical practice, further applications such as cancer treatment are still exploratory.

Search for a Light CP-odd Higgs Boson and Low-Mass Dark Matter at the Belle Experiment.

We report on the first Belle search for a light CP-odd Higgs boson, A^{0}, that decays into low mass dark matter, χ, in final states with a single photon and missing energy. We search for events produced via the dipion transition ϒ(2S)→ϒ(1S)π^{+}π^{-}, followed by the on-shell process ϒ(1S)→γA^{0} with A^{0}→χχ, or by the off-shell process ϒ(1S)→γχχ. Utilizing a data sample of 157.3×10^{6} ϒ(2S) decays, we find no evidence for a signal. We set limits on the branching fractions of such processes in the mass ranges M_{A^{0}}<8.97 GeV/c^{2} and M_{χ}<4.44 GeV/c^{2}. We then use the limits on the off-shell process to set competitive limits on WIMP-nucleon scattering in the WIMP mass range below 5 GeV/c^{2}.

Inhibition of sialidase activity and cellular invasion by the bacterial vaginosis pathogen Gardnerella vaginalis.

Bacterial vaginosis is a genital tract infection, thought to be caused by transformation of a lactobacillus-rich flora to a dysbiotic microbiota enriched in mixed anaerobes. The most prominent of these is Gardnerella vaginalis (GV), an anaerobic pathogen that produces sialidase enzyme to cleave terminal sialic acid residues from human glycans. Notably, high sialidase activity is associated with preterm birth and low birthweight. We explored the potential of the sialidase inhibitor Zanamavir against GV whole cell sialidase activity using methyl-umbelliferyl neuraminic acid (MU-NANA) cleavage assays, with Zanamavir causing a 30% reduction in whole cell GV sialidase activity (p < 0.05). Furthermore, cellular invasion assays using HeLa cervical epithelial cells, infected with GV, demonstrated that Zanamivir elicited a 50% reduction in cell association and invasion (p < 0.05). Our data thus highlight that pharmacological sialidase inhibitors are able to modify BV-associated sialidase activity and influence host-pathogen interactions and may represent novel therapeutic adjuncts.

Cryotherapy induces an increase in muscle stiffness.

Although cold application (ie, cryotherapy) may be useful to treat sports injuries and to prevent muscle damage, it is unclear whether it has adverse effects on muscle mechanical properties. This study aimed to determine the effect of air-pulsed cryotherapy on muscle stiffness estimated using ultrasound shear wave elastography. Myoelectrical activity, ankle passive torque, shear modulus (an index of stiffness), and muscle temperature of the gastrocnemius medialis were measured before, during an air-pulsed cryotherapy (-30°C) treatment of four sets of 4 minutes with 1-minute recovery in between and during a 40 minutes postcryotherapy period. Muscle temperature significantly decreased after the second set of treatment (10 minutes: 32.3±2.5°C; P<.001), peaked at 29 minutes (27.9±2.2°C; P<.001) and remained below baseline values at 60 minutes (29.5±2.0°C; P<.001). Shear modulus increased by +11.5±11.8% after the second set (10 minutes; P=.011), peaked at 30 minutes (+34.7±42.6%; P<.001), and remained elevated until the end of the post-treatment period (+25.4±17.1%; P<.001). These findings provide evidence that cryotherapy induces an increase in muscle stiffness. This acute change in muscle mechanical properties may lower the amount of stretch that the muscle tissue is able to sustain without subsequent injury. This should be considered when using cryotherapy in athletic practice.

The trans-10,cis-12 conjugated linoleic acid increases triacylglycerol hydrolysis in yeast Saccharomyces cerevisiae.

AIMS: The trans-10,cis-12 conjugated linoleic acid (CLA) is known for its antilipogenic effect but the mechanism is not fully clear. In this study, the potential of yeast (Saccharomyces cerevisiae) metabolism to offer evidence for the mechanism was investigated. METHODS AND RESULTS: The inhibitory effect of CLA on lipid accumulation was studied by analysing the transcript abundance of selected genes involved in triacylglycerol synthesis (LRO1, DGA1, ARE1 and ARE2) in the presence of the two bioactive CLA isomers: trans-10,cis-12 and the cis-9,trans-11 CLA. None of the enzymes was reduced in transcription but the expression of ARE2 was induced by trans-10,cis-12 CLA. However, the ARE2 overexpression did not contribute to lipid accumulation. The expression of the Δ9 desaturase gene, OLE1, was reduced by the cis-9,trans-11 but not by the trans-10,cis-12 isomer. In the TGL3/TGL4-knockout strain the triacylglycerol content also remained high in the CLA fed cells. CONCLUSIONS: Triacylglycerol hydrolysis rather than synthesis was the most probable reason for the reduced lipid content in yeast induced by CLA. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed new aspects of the functionality of CLA in eukaryotic lipid metabolism. Yeast was proven to be an applicable model to study further the mechanism of trans-10,cis-12 CLA functionality on lipid metabolism.

Fitness differences between parapatric lake and stream stickleback revealed by a field transplant.

Molecular comparisons of populations diverging into ecologically different environments often reveal strong differentiation in localized genomic regions, with the remainder of the genome being weakly differentiated. This pattern of heterogeneous genomic divergence, however, is rarely connected to direct measurements of fitness differences among populations. We here do so by performing a field enclosure experiment in threespine stickleback fish residing in a lake and in three replicate adjoining streams, and displaying weak yet heterogeneous genomic divergence between these habitats. Tracking survival over 29 weeks, we consistently find that lake genotypes transplanted into the streams suffer greatly reduced viability relative to local stream genotypes and that the performance of F1 hybrid genotypes is intermediate. This observed selection against migrants and hybrids combines to a total reduction in gene flow from the lake into streams of around 80%. Overall, our study identifies a strong reproductive barrier between parapatric stickleback populations, and cautions against inferring weak fitness differences between populations exhibiting weak overall genomic differentiation.

From gifted to high potential and twice exceptional: A state-of-the-art meta-review.

Despite the abundant literature on intelligence and high potential individuals, there is still a lack of international consensus on the terminology and clinical characteristics associated to this population. It has been argued that unstandardized use of diagnosis tools and research methods make comparisons and interpretations of scientific and epidemiological evidence difficult in this field. If multiple cognitive and psychological models have attempted to explain the mechanisms underlying high potentiality, there is a need to confront new scientific evidence with the old, to uproot a global understanding of what constitutes the neurocognitive profile of high-potential in gifted individuals. Another particularly relevant aspect of applied research on high potentiality concerns the challenges faced by individuals referred to as "twice exceptional" in the field of education and in their socio-affective life. Some individuals have demonstrated high forms of intelligence together with learning, affective or neurodevelopmental disorders posing the question as to whether compensating or exacerbating psycho-cognitive mechanisms might underlie their observed behavior. Elucidating same will prove relevant to questions concerning the possible need for differential diagnosis tools, specialized educational and clinical support. A meta-review of the latest findings from neuroscience to developmental psychology, might help in the conception and reviewing of intervention strategies.

Evidence for B- → τ- ν(τ) with a hadronic tagging method using the full data sample of Belle.

We measure the branching fraction of B- → τ- ν(τ) using the full Υ(4S) data sample containing 772×10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Events with BB pairs are tagged by reconstructing one of the B mesons decaying into hadronic final states, and B- → τ- ν(τ) candidates are detected in the recoil. We find evidence for B- → τ- ν(τ) with a significance of 3.0 standard deviations including systematic errors and measure a branching fraction B(B- → τ- ν(τ))=[0.72(-0.25)(+0.27)(stat)±0.11(syst)]×10(-4).

Search for bottomonium states in exclusive radiative Υ(2S) decays.

We search for bottomonium states in Υ(2S) → (bb)γ decays with an integrated luminosity of 24.7 fb(-1) recorded at the Υ(2S) resonance with the Belle detector at KEK, containing (157.8±3.6)×10(6) Υ(2S) events. The (bb) system is reconstructed in 26 exclusive hadronic final states composed of charged pions, kaons, protons, and K(S)(0) mesons. We find no evidence for the state recently observed around 9975 MeV (X(bb)) in an analysis based on a data sample of 9.3×10(6) Υ(2S) events collected with the CLEO III detector. We set a 90% confidence level upper limit on the branching fraction B[Υ(2S) → X(bb)γ] × ∑(i)B[X(bb) → h(i)] < 4.9×10(-6), summed over the exclusive hadronic final states employed in our analysis. This result is an order of magnitude smaller than the measurement reported with CLEO data. We also set an upper limit for the ηb(1S) state of B[Υ(2S) → ηb(1S)γ] × ∑(i)B[ηb(1S) → h(i)] < 3.7×10(-6).

Study of e+ e- → π+ π- J/ψ and observation of a charged charmoniumlike state at Belle.

The cross section for ee+ e- → π+ π- J/ψ between 3.8 and 5.5 GeV is measured with a 967 fb(-1) data sample collected by the Belle detector at or near the Υ(nS) (n = 1,2,…,5) resonances. The Y(4260) state is observed, and its resonance parameters are determined. In addition, an excess of π+ π- J/ψ production around 4 GeV is observed. This feature can be described by a Breit-Wigner parametrization with properties that are consistent with the Y(4008) state that was previously reported by Belle. In a study of Y(4260) → π+ π- J/ψ decays, a structure is observed in the M(π(±)J/ψ) mass spectrum with 5.2σ significance, with mass M = (3894.5 ± 6.6 ± 4.5) MeV/c2 and width Γ = (63 ± 24 ± 26) MeV/c2, where the errors are statistical and systematic, respectively. This structure can be interpreted as a new charged charmoniumlike state.

Evidence of a new narrow resonance decaying to χ(c1)γ in B→χ(c1)γK.

We report measurements of B→χ(c1)γK and χ(c2)γK decays using 772×10(6) BB[over ¯] events collected at the Υ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. Evidence of a new resonance in the χ(c1)γ final state is found with a statistical significance of 3.8σ. This state has a mass of 3823.1±1.8(stat)±0.7(syst) MeV/c(2), a value that is consistent with theoretical expectations for the previously unseen 1(3)D(2) cc[over ¯] meson. We find no other narrow resonance and set upper limits on the branching fractions of the X(3872)→χ(c1)γ and χ(c2)γ decays.

Complement C3c as a biomarker in heart failure.

INTRODUCTION: Experimental data indicates an important role of the innate immune system in cardiac remodeling and heart failure (HF). Complement is a central effector pathway of the innate immune system. Animals lacking parts of the complement system are protected from adverse remodeling. Based on these data, we hypothesized that peripheral complement levels could be a good marker for adverse remodeling and prognosis in patients with HF. METHODS AND RESULTS: Since complement activation converges on the complement factor C3, we measured serum C3c, a stable C3-conversion product, in 197 patients with stable systolic HF. Subgroups with normal and elevated C3c levels were compared. C3c levels were elevated in 17% of the cohort. Patients with elevated C3c levels exhibited a trend to better survival, slightly higher LVEF, and lower NTpro-BNP values in comparison to patients with normal C3c values. No differences were found regarding NYHA functional class. Significantly more patients with elevated C3c had preexisting diabetes. The prevalence of CAD, arterial hypertension, and atrial fibrillation was not increased in patients with elevated C3c. CONCLUSION: Elevated C3c levels are associated with less adverse remodeling and improved survival in patients with stable systolic heart failure.

[Differential diagnosis of myeloproliferative neoplasms. Quantitative NF-E2 immunohistochemistry for differentiating between essential thrombocythemia and primary myelofibrosis]. / Differenzialdiagnose myelproliferativer Neoplasien. Quantitative NF-E2-Immunhistochemie zur Unterscheidung zwischen essenzieller Thrombozythämie und primärer Myelofibrose.

BACKGROUND: Besides essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) the myeloproliferative neoplasms (MPN) defined by the World Health Organization (WHO) comprise the entity of unclassifiable MPNs (MPN, U). The exact differential diagnosis of the specific MPN entities can be challenging particularly at early stages of the diseases. So far, pathologists have had to rely only on histomorphological evaluation of bone marrow biopsies in combination with laboratory data because helpful ancillary tests are not yet available. Even molecular tests, such as JAK2 mutation analysis are not helpful particularly in the differential diagnosis of ET and PMF because both entities are associated with the V617F mutation in 50 % of the cases. Recently overexpression of the transcription factor NF-E2 in MPN was described. MATERIALS AND METHODS: A collective of samples consisting of 163 bone marrow biopsies including 139 MPN cases was stained immunohistochemically for NF-E2 and analyzed regarding the subcellular localization of NF-E2 in erythroid progenitor cells. The results were compared between the MPN entities as well as the controls and statistical analyses were conducted. RESULTS AND DISCUSSION: This study showed that NF-E2 immunohistochemistry and analysis of the proportion of nuclear positive erythroblasts of all erythroid precursor cells can help to distinguish between ET and PMF even in early stages of the diseases. An MPN, U case showing a proportion of more than 20 % nuclear positive erythroblasts can be classified as a PMF with 92 % accuracy.

Fabrication of magnetic artificial atoms.

We have fabricated gated vertical quantum dots made from a II-VI semiconductor heterostructure containing a paramagnetic quantum well. The absence of a known Schottky gate metal compatible with ZnSe based material precludes the traditional method of using a self-aligning shadow evaporated gate. Instead, we make use of a multi-step electron beam lithography process to surround a pillar with an insulating dielectric and gate. This process allows for the processing of dots with diameters down to 250 nm. Preliminary transport data confirming the magnetic nature of the resulting artificial atom are presented.

Clinical impact of the use of 16S rRNA sequencing method for the identification of "difficult-to-identify" bacteria in immunocompromised hosts.

Molecular method of 16S rRNA sequencing is reported to be helpful in the accurate identification of organisms with ambiguous phenotypic profiles. We analyzed the use of 16S rRNA sequencing method to identify clinically significant, "difficult-to-identify" bacteria recovered from clinical specimens, and evaluated its role in patient management and consequent clinical outcome. Among the 172 "difficult-to-identify" bacteria recovered over a 4-year period, 140 were gram-positive cocci or gram-negative bacilli; identification by 16S rRNA did not play a role in the management of patients infected with these bacteria. From 32 patients, 33 "difficult-to-identify" gram-positive bacilli were identified; the organisms were mycobacteria, Nocardia, Tsukamurella, Rhodococcus, and Gordonia. In 24 patients for whom clinical data were available, results from the 16S rRNA sequencing method led to treatment change in 14 immunocompromised patients (including 7 hematopoietic stem cell recipients and 1 liver transplant recipient). Therapy was modified in 9 patients, initiated in 3 patients, and discontinued in 2 patients. Most patients' therapy was switched to oral antibiotics with discontinuation of intravascular catheters, facilitating early hospital discharge. All 14 patients were alive 30 days after infection onset. The present study demonstrates the clinical application of 16S rRNA sequencing method to identify "difficult-to-identify" mycobacteria and other gram-positive bacilli in clinical specimens, particularly in immunocompromised hosts.

Diagnosis clinical criteria of sport related concussion: Toward an operational criteria definition in France.

OBJECTIVE: An expert working group was set up at the initiative of the French Ministry of Sports with the objective of harmonising the management of sport related concussion (SRC) in France, starting with its definition and diagnosis criteria. RESULTS: Definition: A clinical definition in 4 points have been established as follows: Concussion is a brain injury: 1) caused by a direct or indirect transmission of kinetic energy to the head; 2) resulting in an immediate and transient dysfunction of the brain characterised by at least one of the following disorders: a) Loss of consciousness, b) loss of memory, c) altered mental status, d) neurological signs; 3) possibly followed by one or more functional complaints (concussion syndrome); 4) the signs and symptoms are not explained by another cause. Diagnosis criteria: In the context of the direct or indirect transmission of kinetic energy to the head, the diagnosis of concussion may be asserted if at least one of the following signs or symptoms, observed or reported, is present within the first 24hours and not explained by another cause: 1) loss of consciousness; 2) convulsions, tonic posturing; 3) ataxia; 4) visual trouble; 5) neurological deficit; 6) confusion; 7) disorientation; 8) unusual behaviour; 9) amnesia; 10) headaches; 11) dizziness; 12) fatigue, low energy; 13) feeling slowed down, drowsiness; 14) nausea; 15) sensitivity to light/noise; 16) not feeling right, in a fog; 17) difficulty concentrating. CONCLUSION: Sharing the same definition and the same clinical diagnostic criteria for concussion is the prerequisite for common rules of management for all sports and should allow the pooling of results to improve our knowledge of this pathology.

Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting.

Transepithelial transport of antigens and pathogens across the epithelial barrier by M cells may be a prerequisite for induction of mucosal immunity in the intestine. Efficient transport of antigens and pathogens requires adherence to M cell apical surfaces. Coupling of antigen-containing particles to the pentameric binding subunit of cholera toxin (CTB) has been proposed as a means for increasing antigen uptake because the CTB receptor, ganglioside GM1, is a glycolipid present in apical membranes of all intestinal epithelial cells. To test the accessibility of enterocyte and M cell membrane glycolipids to ligands in the size ranges of viruses, bacteria, and particulate mucosal vaccines, we analyzed binding of CTB probes of different sizes to rabbit Peyer's patch epithelium. Soluble CTB-fluorescein isothiocyanate (diameter 6.4 nm) bound to apical membranes of all epithelial cells. CTB coupled to 14 nm colloidal gold (final diameter, 28.8 nm) failed to adhere to enterocytes but did adhere to M cells. CTB-coated, fluorescent microparticles (final diameter, 1.13 microns) failed to adhere to enterocytes or M cells in vivo or to well-differentiated Caco-2 intestinal epithelial cells in vitro. However, these particles bound specifically to GM1 on BALB/c 3T3 fibroblasts in vitro and to undifferentiated Caco-2 cells that lacked brush borders and glycocalyx. Measurements of glycocalyx thickness by electron microscopy suggested that a relatively thin (20 nm) glycocalyx was sufficient to prevent access of 1-micron microparticles to glycolipid receptors. Thus, the barrier function of the intestinal epithelial cell glycocalyx may be important in limiting microbial adherence to membrane glycolipids, and in CTB-mediated targeting of vaccines to M cells and the mucosal immune system.

Primary structure of lymphocyte function-associated antigen 3 (LFA-3). The ligand of the T lymphocyte CD2 glycoprotein.

We have isolated the cDNA for human lymphocyte function-associated antigen 3 (LFA-3), the ligand of the T lymphocyte CD2 molecule. The identity of the clones was established by comparison of the deduced amino acid sequence to the LFA-3 NH2-terminal and tryptic peptide sequences. The cDNA defines a mature protein of 222 amino acids that structurally resembles typical membrane-anchored proteins. An extracellular domain with six N-linked glycosylation sites is followed by a hydrophobic putative transmembrane region and a short cytoplasmic domain. The mature glycoprotein is estimated to be 44-68% carbohydrate. Southern blots of human genomic DNA indicate that only one gene codes for human LFA-3. Northern blot analysis demonstrates that the LFA-3 mRNA of 1.3 kb is widely distributed in human tissues and cell lines.