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High efficacy in terms of protection from severe COVID-19 has been demonstrated for several SARS-CoV-2 vaccines. However, patients with compromised immune status develop a weaker and less stable immune response to vaccination. Strong immune response may not always translate into clinical benefit, therefore it is important to synthesise evidence on modified schemes and types of vaccination in these population subgroups for guiding health decisions. As the literature on COVID-19 vaccines continues to expand, we aimed to scope the literature on multiple subgroups to subsequently decide on the most relevant research questions to be answered by systematic reviews.To provide an overview of the availability of existing literature on immune response and long-term clinical outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters, and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes.We searched the Cochrane COVID-19 Study Register, the Web of Science Core Collection, and the World Health Organization COVID-19 Global literature on coronavirus disease on 6 December 2021. SELECTION CRITERIA: We included studies that published results on immunity outcomes after vaccination with BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, Sputnik V or Sputnik Light, BBIBP-CorV, or CoronaVac on predefined vulnerable subgroups such as people with malignancies, transplant recipients, people undergoing renal replacement therapy, and people with immune disorders, as well as pregnant and breastfeeding women, and children. We included studies if they had at least 100 participants (not considering healthy control groups); we excluded case studies and case series.We extracted data independently and in duplicate onto an online data extraction form. Data were represented as tables and as online maps to show the frequency of studies for each item. We mapped the data according to study design, country of participant origin, patient comorbidity subgroup, intervention, outcome domains (clinical, safety, immunogenicity), and outcomes. MAIN RESULTS: Out of 25,452 identified records, 318 studies with a total of more than 5 million participants met our eligibility criteria and were included in the review. Participants were recruited mainly from high-income countries between January 2020 and 31 October 2021 (282/318); the majority of studies included adult participants (297/318). Haematological malignancies were the most commonly examined comorbidity group (N = 54), followed by solid tumours (N = 47), dialysis (N = 48), kidney transplant (N = 43), and rheumatic diseases (N = 28, 17, and 15 for mixed diseases, multiple sclerosis, and inflammatory bowel disease, respectively). Thirty-one studies included pregnant or breastfeeding women. The most commonly administered vaccine was BNT162b2 (N = 283), followed by mRNA-1273 (N = 153), AZD1222 (N = 66), Ad26.COV2.S (N = 42), BBIBP-CorV (N = 15), CoronaVac (N = 14), and Sputnik V (N = 5; no studies were identified for Sputnik Light). Most studies reported outcomes after regular vaccination scheme. The majority of studies focused on immunogenicity outcomes, especially seroconversion based on binding antibody measurements and immunoglobulin G (IgG) titres (N = 179 and 175, respectively). Adverse events and serious adverse events were reported in 126 and 54 studies, whilst SARS-CoV-2 infection irrespective of severity was reported in 80 studies. Mortality due to SARS-CoV-2 infection was reported in 36 studies. Please refer to our evidence gap maps for more detailed information.Up to 6 December 2021, the majority of studies examined data on mRNA vaccines administered as standard vaccination schemes (two doses approximately four to eight weeks apart) that report on immunogenicity parameters or adverse events. Clinical outcomes were less commonly reported, and if so, were often reported as a secondary outcome observed in seroconversion or immunoglobulin titre studies. As informed by this scoping review, two effectiveness reviews (on haematological malignancies and kidney transplant recipients) are currently being conducted.

Objectives The aim of this study was to analyze athlete-specific psychological strain among Olympic athletes following the postponement of the Tokyo 2020 Olympic games due to the COVID-19 pandemic. Methods A survey that comprised three sub-sections (Psychological Strain Questionnaire (APSQ), Patient Health Questionnaire—Depression Module (PHQ-8) and Participant characteristic) concerning mental health, performance issues and concerns about the postponement of the Tokyo Olympics, was distributed online and sent to 102 Olympic athletes. Results A total of 85 participants from 11 Olympic sports were enrolled. Results indicated that most athletes showed psychological strain related to concerns regarding the postponement of the Tokyo Olympics. Depression severity was positively associated with maladaptive avoidance coping patterns, negative effects in training, worries and fear. Depression severity was also negatively associated with motivation and adaptive factors such as chances and opportunities that can be drawn from the pandemic. Conclusion The present sample of Olympic athletes reported suffering from psychological uncertainty associated with the postponement of the Olympic games. Sports federations should therefore, provide ongoing wellbeing support to athletes and offer them, for example, sports psychological support in order to be able to better deal with pandemic-related uncertainties and changes.

A preoperative anemia is an independent risk factor for the occurrence of complications during and after surgical interventions. It is associated with an increased length of hospital stay, higher mortality and an increased use of blood transfusions. Anemia affects some 30-70% of patients suffering from inflammatory rheumatic diseases, mostly caused by iron deficiency and/or chronic inflammation. The possibilities to treat anemia in rheumatic patients were extremely limited for a long period of time as older studies showed life-threatening side effects, the need of high doses of iron supplements or the occurrence of many nonresponders. Further development of the supplements, new dosage schemes and the combination of supplements increased the efficacy and reduced the occurrence of side effects to a minimum. In addition to orthopedic surgical interventions for rheumatism that despite new therapeutic options in some cases still represent the only way to alleviate the complaints, more and more patients with inflammatory rheumatic diseases also need surgical interventions due to comorbidities. Therefore, anemia should be clarified and preoperatively treated in accordance with the new study situation, to minimize additional complications due to anemia and to increase patient safety.Eine präoperative Anämie stellt einen eigenständigen Risikofaktor für das Auftreten von Komplikationen während und nach chirurgischen Eingriffen dar. Sie ist mit einer längeren Krankenhausverweildauer, einer höheren Sterblichkeitsrate und vermehrtem Einsatz von Bluttransfusionen verbunden. Etwa 30–70 % der Patienten mit entzündlich rheumatischen Erkrankungen leiden an einer Anämie, in den meisten Fällen durch Eisenmangel und/oder durch die chronische Entzündung verursacht. Die Behandlungsmöglichkeiten einer Anämie beim Rheumatiker waren durch ältere Studien mit teilweise lebensbedrohlichen Nebenwirkungen, der Notwendigkeit von sehr hohen Medikamentendosen oder dem Auftreten von vielen Non-Respondern stark eingeschränkt. Durch die Weiterentwicklung der Präparate, neuer Dosierungsschemata und die Kombination von Präparaten konnte die Wirksamkeit deutlich verbessert und das Auftreten von Nebenwirkungen bis auf ein Minimum reduziert werden. Neben rheumaorthopädischen Eingriffen, die trotz neuer Therapiemöglichkeiten in einigen Fällen nach wie vor den einzigen Ausweg darstellen, eine Linderung der Beschwerden herbeizuführen, benötigen Patienten mit rheumatisch entzündlichen Erkrankungen auch vermehrt operative Interventionen aufgrund von Komorbiditäten. Eine Anämie sollte im Vorfeld abgeklärt und unter Berücksichtigung der neuen Studienlage behandelt werden, um zusätzliche Komplikationen, die durch die Anämie verursacht werden, zu minimieren und die Patientensicherheit zu erhöhen.

Disinfection and prevention of re-infection are the decisive treatment steps in endodontic therapy. In this study, boron-doped diamond (BDD) electrodes have been fabricated and used for disinfecting the root canals of extracted human teeth, which had been covered with bacterial biofilms formed by Bacillus subtilis and Staphylococcus epidermidis. The growth of B. subtilis could be successfully impaired, achieving a complete disinfection after 8.5 min treatment time with the success of disinfection depending on the insertion depth of the electrode in the root canal. S. epidermidis could completely be removed after 3.5 min treatment time. A clinically applicable electrode array led to complete disinfection after treatment times of 10 min for S. epidermidis and 25 min for B. subtilis. BDD electrode application allowed for the improved disinfection of root canals and dentin tubules based on a continuous production of reactive oxygen species and their enhanced penetration of dentin tubules most likely due the formation of a continuous stream of small gas bubbles. The treatment times that are required here will be shortened in clinical application, as mechanical shaping of the canal system would precede the disinfection process.

Aim The best time to commence cervical ripening with a balloon catheter is unknown. The aim of this study was to evaluate whether application of a balloon catheter in the morning or in the evening is better when sequential prostaglandin application is planned. Methods This multicenter historical cohort study included 415 women with an unfavorable cervix undergoing labor induction at term. Labor was induced with a double-balloon catheter and the sequential use of oral misoprostol if necessary. The balloon catheter was placed in the morning group between 02:00–15:00 and in the evening group between 15:00–02:00. The primary outcome measure was the cesarean section rate. Secondary outcome measures included failed labor induction (no vaginal delivery within 72 h). Results The cesarean section rate did not differ between the groups (morning 26.9%, evening 24.3%; P = 0.5553); however, more women in the morning group did not deliver within 72 h (8.8% vs 3.1%; P = 0.0138). In nulliparous women, labor induction failed more often in the morning group (12% vs. 4%, P = 0.043). In parous women, the induction-to-delivery interval was longer in the morning group (1756 vs. 1349 min; P = 0.046), and there were fewer deliveries within 24 h (35% vs. 56%, P = 0.016). Conclusions When sequential use of a double-balloon catheter and oral misoprostol for labor induction is planned, the preferable time for catheter placement is in the evening. This resulted in fewer failed inductions in nulliparous women and a shorter induction-to-delivery interval and more deliveries within 24 h in parous women.

Summary Virulence traits are often controlled by transcription regulators, i.e. sequence-specific DNA-binding proteins. The regulators that sustain microbial proliferation in the host typically work by promoting the expression of the genes that mediate such traits. Here, we report a singular example in the human fungal pathogen Candida albicans in which a transcription regulator functions by repressing the expression of virulence genes, yet its overall role is to promote virulence. We explain this apparent paradox by establishing that a major function of this protein, Zcf21p, is to set a default state of low expression of multiple cell wall components which include virulence determinants. These components comprise GPI-anchored proteins, adhesins and enzymes that synthesize cell wall sugar decorations. Deletion or overexpression of ZCF21 results in cell wall structure modifications that influence recognition and elimination of the fungus by macrophages. By leveling off the expression of adhesins, ZCF21 also prevents C. albicans self-aggregation. Balancing the expression of cell wall components – virulence determinants included – is, therefore, critical for C. albicans to assemble a cell surface configuration that is suitable to colonize mammalian tissues and evade immune surveillance.

Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms., Author summary The very same microbes that cause life-threatening human diseases are often harmless inhabitants on our mucosal surfaces. Yet the hallmarks of this so-called ‘commensal’ state remain underexplored. In this report we investigate the case of Candida albicans, the most prominent fungal species living in the human intestine but also a common cause of deep-seated, fatal infections. Mice carrying their own natural intact flora are not readily colonized by C. albicans implying a fundamental incompatibility between the indigenous mouse microbiota and this fungus. We explore the patterns of colonization of C. albicans in mice completely devoid of other microbes. We show that the fungus adopts its normal commensal morphology in these animals indicating that this experimental system is a suitable proxy to clearly dissect its commensal lifestyle in vivo. Gaining insights into the mechanisms that sustain the commensal features of C. albicans and other microbes is key to understand—and be able to prevent—what goes awry when these microorganisms invade other tissues and cause disease.

The best time to commence cervical ripening with a balloon catheter is unknown. The aim of this study was to evaluate whether application of a balloon catheter in the morning or in the evening is better when sequential prostaglandin application is planned.This multicenter historical cohort study included 415 women with an unfavorable cervix undergoing labor induction at term. Labor was induced with a double-balloon catheter and the sequential use of oral misoprostol if necessary. The balloon catheter was placed in the morning group between 02:00-15:00 and in the evening group between 15:00-02:00. The primary outcome measure was the cesarean section rate. Secondary outcome measures included failed labor induction (no vaginal delivery within 72 h).The cesarean section rate did not differ between the groups (morning 26.9%, evening 24.3%; P = 0.5553); however, more women in the morning group did not deliver within 72 h (8.8% vs 3.1%; P = 0.0138). In nulliparous women, labor induction failed more often in the morning group (12% vs. 4%, P = 0.043). In parous women, the induction-to-delivery interval was longer in the morning group (1756 vs. 1349 min; P = 0.046), and there were fewer deliveries within 24 h (35% vs. 56%, P = 0.016).When sequential use of a double-balloon catheter and oral misoprostol for labor induction is planned, the preferable time for catheter placement is in the evening. This resulted in fewer failed inductions in nulliparous women and a shorter induction-to-delivery interval and more deliveries within 24 h in parous women.

Virulence traits are often controlled by transcription regulators, i.e. sequence-specific DNA-binding proteins. The regulators that sustain microbial proliferation in the host typically work by promoting the expression of the genes that mediate such traits. Here, we report a singular example in the human fungal pathogen Candida albicans in which a transcription regulator functions by repressing the expression of virulence genes, yet its overall role is to promote virulence. We explain this apparent paradox by establishing that a major function of this protein, Zcf21p, is to set a default state of low expression of multiple cell wall components which include virulence determinants. These components comprise GPI-anchored proteins, adhesins and enzymes that synthesize cell wall sugar decorations. Deletion or overexpression of ZCF21 results in cell wall structure modifications that influence recognition and elimination of the fungus by macrophages. By leveling off the expression of adhesins, ZCF21 also prevents C. albicans self-aggregation. Balancing the expression of cell wall components - virulence determinants included - is, therefore, critical for C. albicans to assemble a cell surface configuration that is suitable to colonize mammalian tissues and evade immune surveillance.

Children of older fathers carry an increased risk for developing autism and other disorders. To elucidate the underlying mechanisms, we investigated the correlation of sperm DNA methylation with paternal age and its impact on the epigenome of the offspring. Methylation levels of nine candidate genes and LINE-1 repeats were quantified by bisulfite pyrosequencing in sperm DNA of 162 donors and 191 cord blood samples of resulting children (conceived by IVF/ICSI with the same sperm samples). Four genes showed a significant negative correlation between sperm methylation and paternal age. For FOXK1 and KCNA7, the age effect on the sperm epigenome was replicated in an independent cohort of 188 sperm samples. For FOXK1, paternal age also significantly correlated with foetal cord blood (FCB) methylation. Deep bisulfite sequencing and allele-specific pyrosequencing allowed us to distinguish between maternal and paternal alleles in FCB samples with an informative SNP. FCB methylation of the paternal FOXK1 allele was negatively correlated with paternal age, whereas maternal allele was unaffected by maternal age. Since FOXK1 duplication has been associated with autism, we studied blood FOXK1 methylation in 74 children with autism and 41 age-matched controls. The FOXK1 promoter showed a trend for accelerated demethylation in the autism group. Dual luciferase reporter assay revealed that FOXK1 methylation influences gene expression. Collectively, our study demonstrates that age-related DNA methylation changes in sperm can be transmitted to the next generation and may contribute to the increased disease risk in offspring of older fathers.