Search

ABSTRACT The objective of this study was to quantify the number and frequency of monocyte (MnOF) and multi-oocyte (MtOF) follicles in ovaries of bitches subjected to ovary salpingohysterectomy (OSH). Right and left ovaries of 38 bitches were collected after OSH, prepared, and a histological analysis was carried out. The ovaries were subjected to surface and deep histological cuts; the follicles were classified, and the number of follicles and cumulus oophorus complexes (COC) per follicle were quantified for each histological cut. MnOF and MtOF were found in all ovaries, at different developmental stages; primary follicles were grouped in the ovarian cortex, and follicles at other follicular stages presented a random distribution. MtOF containing two, three, four, or more COC were found in the ovaries of bitches, with a decreasing frequency trend, according to the number of COC in the MtOF. The effect of the age, number of estrus, estrus interval, and number of progenies per delivery was not significant for the number and frequency of MtOF in the ovaries of the bitches, whereas the size, number of pregnancies, use and number of contraceptive applications had some effect on the number and frequency of MtOF in the ovaries of the bitches.

Introdução: O futebol é o esporte mais praticado do mundo, abrangendo atletas profissionais e amadores, motivando a FIFA a elaborar o Manual 11+. Os exercícios de estabilização articular e de tronco assumem destaque no processo de reabilitação e prevenção de lesões objetivando a melhora do equilíbrio estático e/ou dinâmico. Existem técnicas de facilitação neuromuscular proprioceptiva (FNP) com o mesmo objetivo, como a estabilização rítmica pouco utilizada no meio esportivo. Objetivo: avaliar os efeitos agudos do protocolo dos exercícios de equilíbrio propostos pelo FIFA 11+ em comparação ao mesmo protocolo adicionado do conceito FNP no equilíbrio dinâmico de atletas de futebol de campo da equipe universitária. Caracterização da pesquisa: Ensaio Clínico. População: Atletas de futebol de campo da equipe universitária Ulbra-Canoas, sexo masculino (n=18). Procedimento de Coleta de dados: Foram avaliados com o instrumento SEBT na coleta de dados e imediatamente após a realização de uma única intervenção com FNP e FIFA 11+. Resultados: Intervenção com FNP aumentou a amplitude na direção AM e POST executados com membro inferior E (p

Introdução: A infecção por Papilomavírus Humano é a infecção sexualmente transmissível mais frequente na mulher. Cerca de 80% das mulheres sexualmente ativas entrarão em contato com esse vírus em algum momento. A maioria das infecções será transitória, mas quando ela é persistente, associada aos Papilomavírus Humano de alto risco oncogênico, poderá progredir para câncer, principalmente de colo de útero. A melhor forma de se prevenir da contaminação pelo vírus é por meio de vacina, disponível no sistema público do Brasil desde 2014. Objetivos: Avaliar os tipos de Papilomavírus Humano mais prevalentes no estado de Santa Catarina e suas mesorregiões, e se a maioria dos tipos diagnosticados estão contidos nas vacinas contra o Papilomavírus Humano atualmente disponíveis no mercado. Métodos: Foram avaliados 20 mil exames para diagnóstico da infecção genital pelo Papilomavírus Humano em mulheres de todo o estado. A prevalência da infecção foi comparada de acordo com a idade e a procedência dos exames. A detecção do Papilomavírus Humano deu-se pelos exames de biologia molecular pelas técnicas de captura híbrida (para diagnóstico do grupo de Papilomavírus Humano, alto ou baixo riscos oncogênicos) e de PCR (genotipagem viral). Resultados: Foram avaliados exames para diagnóstico da infecção de mulheres entre um e 102 anos de idade. A faixa etária de maior positividade, como era de ser esperado, foi dos 20 aos 25 anos (45.6%) e a menor depois dos 70 anos (7.1%). A maior positividade dos exames foi observada na região Serrana do estado (58.9% dos exames). O Papilomavírus Humano de alto risco oncogênico foi detectado em 93% dos casos positivos e foi o mais frequente em todas as faixas etárias. A infecção mista (Papilomavírus Humano de alto e baixo riscos) foi mais prevalente na faixa etária dos 66 aos 70 anos (29.3%) e na região Sul Catarinense (26.4%). Os genótipos mais frequentes no estado foram os Papilomavírus Humano de alto risco oncogênico não 16/18 (76.9% dos casos positivos). O Papilomavírus Humano 16 foi encontrado em 17.1% dos casos positivos e o Papilomavírus Humano 18 em 6.6%. Conclusão: Os tipos de Papilomavírus Humano mais prevalentes no estado de Santa Catarina, nos últimos seis anos, são os Papilomavírus Humano de alto risco oncogênico não 16/18, tipos virais não cobertos pelas atuais vacinas contra o Papilomavírus Humano disponíveis no Brasil.

We assessed the effect of 28-homocatasterone on xylem functionality and its relationship with blossom end rot (BER) occurrence and the quality of 'BRS Montese' tomatoes. Tomato plants were cultivated in a protected environment, with a semi-hydroponic system. During full flowering, open flowers were selected, marked, and pollinated. After two days, the flowers received the application of 28-homocatasterone at a concentration of 10-6 M or deionized water (control). Treatments were reapplied weekly up to 24 days after the first application (DAFA). At 24 DAFA, fruits were harvested and evaluated for fresh mass, texture (skin rupture and pulp penetration forces), skin color, xylem functionality, membrane permeability, apoplastic calcium concentration, and BER incidence. The application of 28-homocatasterone at 10-6 M did not increase the fresh mass nor change the fruits' texture attributes. However, 28-homocatasterone increased or kept xylem functionality, which was assicated with increased apoplastic calcium concentration and reduced BER occurrence in 'BRS Montese' tomatoes. Thus, the application of 10-6 M catasterone could be an alternative for BER control in tomatoes.

Background: Sustained uptake of COVID-19 vaccines, including booster doses, will continue to be key to minimising morbidity and mortality caused by COVID-19. Because hesitancy can affect people’s motivation to get vaccinated, understanding and addressing factors influencing acceptance is critical to achieving high uptake. This is especially the case for adults with underlying health conditions, who are at increased risk of severe illness from COVID-19. The aim of this study was to investigate barriers and facilitators of COVID-19 vaccine acceptance in adults with underlying health conditions during the initial rollout of COVID-19 vaccines in Australia. Methods: We conducted semi-structured, qualitative interviews with 15 adults with underlying health conditions in New South Wales (NSW) in April 2021, focusing on their previous vaccination experiences and feelings about COVID-19 vaccination. We categorised participants as accepting, hesitant or refusing. We analysed interviews thematically, informed by the World Health Organization (WHO) Behavioural and Social Drivers of Vaccination framework. Results: Most (12/15) participants were hesitant about COVID-19 vaccination. Barriers to COVID-19 vaccine acceptance included concerns about vaccine safety and effectiveness; heightened perceptions of risk regarding the vaccines; low perceptions of COVID-19 risk; and negative social influences. Facilitators included perceived benefits of vaccination and positive social influences. Conclusions: For some adults with underlying health conditions, perceptions of heightened vulnerability to COVID-19 vaccine side effects contributed to vaccine hesitancy during the initial rollout of COVID-19 vaccines. We recommend supporting GPs and specialists to proactively reach out and recommend COVID-19 vaccination to this population; encouraging chronic disease organisations to act as trusted advocates of COVID-19 vaccination; and actively communicating evolving knowledge about vaccine safety.

Summary: Background: It remains unclear whether persistent loneliness is related to brain structures that are associated with cognitive decline and development of Alzheimer's disease (AD). This study aimed to investigate the relationships between different loneliness types, cognitive functioning, and regional brain volumes. Methods: Loneliness was measured longitudinally, using the item from the Center for Epidemiologic Studies Depression Scale in the Framingham Heart Study, Generation 3, with participants’ average age of 46·3 ± 8·6 years. Robust regression models tested the association between different loneliness types with longitudinal neuropsychological performance (n = 2,609) and regional magnetic resonance imaging brain data (n = 1,829) (2002-2019). Results were stratified for sex, depression, and Apolipoprotein E4 (ApoE4). Findings: Persistent loneliness, but not transient loneliness, was strongly associated with cognitive decline, especially memory and executive function. Persistent loneliness was negatively associated with temporal lobe volume (β = −0.18, 95%CI [−0.32, −0.04], P = 0·01). Among women, persistent loneliness was associated with smaller frontal lobe (β = −0.19, 95%CI [−0.38, −0.01], P = 0·04), temporal lobe (β = −0.20, 95%CI [−0.37, −0.03], P = 0·02), and hippocampus volumes (β = −0.23, 95%CI [−0.40, −0.06], P = 0·007), and larger lateral ventricle volume (β = 0.15, 95%CI [0.02, 0.28], P = 0·03). The higher cumulative loneliness scores across three exams, the smaller parietal, temporal, and hippocampus volumes and larger lateral ventricle were evident, especially in the presence of ApoE4. Interpretation: Persistent loneliness in midlife was associated with atrophy in brain regions responsible for memory and executive dysfunction. Interventions to reduce the chronicity of loneliness may mitigate the risk of age-related cognitive decline and AD. Funding: US National Institute on Aging.

Abstract Background Preoperative assessment of mental health rarely occurs within routine surgery. Any screening tool selected to form part of this process must be deemed practical, acceptable and valid by clinicians and consumers alike. This study aims to assess the acceptability and face validity of two existing mental health screening tools to select one for further development and use in the routine surgical setting. Methods A survey of clinicians and consumers was conducted from October 2020 to March 2021 at a tertiary hospital in Sydney, Australia. Using a Likert scale (1–5, lowest to highest rating), the clinicians evaluated four domains for acceptability and two for validity (six overall) and the consumers four domains for acceptability and one for validity (five overall) on the preoperative use of the amended Kessler Psychological Distress Scale (K10) and the Somatic and Psychological Health Report-12 (SPHERE-12). Consensus was achieved through a rating of 4 or 5 being given by 70% or more of participants with domains able to remain unchanged. Free text responses were analysed into themes. Results A total of 73 participants (51 clinicians; 22 consumers) were included. The K10 received consensus scores (≥ 70%) in four out of six domains for clinicians (4/4 acceptability; 0/2 validity), and all five domains for consumers (4/4 acceptability; 1/1 validity). The SPHERE-12 received consensus scores (≥ 70%) in three domains for clinicians (3/4 acceptability; 0/2 validity), and three domains for consumers (3/4 acceptability; 0/1 validity). Six qualitative themes were described including (1) amendments to tool structure and language; (2) scale response options; (3) difficulty with somatic questions; (4) practicality and familiarity with K10; (5) challenges for specific patient cohorts and (6) timing considerations for patients. Conclusion Adequate acceptability was established for the K10. However further development is required to strengthen its validity for this specific surgical cohort and purpose. Future research to determine the feasibility and acceptability of implementing and using the K10 in the routine surgical setting is now needed.

Purpose Anastomotic leak (AL) after a low pelvic anastomosis is a devastating complication, with short- and long-term morbidity and increased mortality. Surgeons may employ various adjuncts in an attempt to reduce AL rates or mitigate their impact. These include the use of temporary diverting ileostomy (TDI), transanal or rectal tubes and pelvic drains. This questionnaire evaluates the preferences and routine use of these adjuncts in Australasian colorectal surgeons. Methods A cross-sectional survey was administered to Australian and New Zealand colorectal surgeons on September 20, 2018. The study survey consisted of 15 questions exploring basic demographics and the number of rectal resections and ileal pouches performed in 12 months, along with the surgeon’s preference for the use of diverting stomas, rectal tubes, and pelvic drains. Results There were 90 respondents to the survey (31.6%). Surgeons in Western Australia (71.4%) were more likely to use a mandatory TDI in colorectal extraperitoneal anastomoses than surgeons in Queensland (14.3%). South Australian surgeons are more likely to employ a mandatory TDI (100%) for ileal pouches than Queensland surgeons (42.9%). Rectal tubes are not commonly utilized (40.0% never use them), and pelvic drains are (45.6% in all cases). Surgeons consider a median AL rate of 15% was felt to justify the use of a TDI in low pelvic anastomoses and a median AL rate of 10% for ileal pouches Conclusion There is considerable geographical variation in colorectal surgical practice throughout Australia and New Zealand. While surgeons interrogate the same literature, there are presumably other factors that see translation into variations in clinical practice.

Abstract Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.

Abstract Organic matter is an important constituent of soils that controls many soil functions and is of vital importance for ecosystem services like climate regulation and food security. Soil organic matter (SOM consists of a wide spectrum of different organic substances that are highly heterogeneous in terms of chemical composition, stability against microbial decomposition and turnover time. SOM is heterogeneously distributed in the soil profile impeding its fast assessment. A technique to accurately measure SOM quality and quantity with a high spatial resolution in the soil profile is presently lacking. Imaging visible light and near infrared spectroscopy (imVisIR) is a promising technique for the fast and spatially resolved assessment of SOM quality and quantity. In this study, we evaluate the potential of imVisIR to quantitatively map the labile particulate organic matter fraction in undisturbed cores from mineral soils.

Abstract Forest restoration is a prime goal within the 2021–2030 UN “Decade of Ecosystem Resoration”. As part of these activities, natural regeneration has to be promoted for biological as well as for economic reasons. For this, the processes of seed dispersal, seed predation and germination have to be understood in the original as well as in degraded vegetation formations. We used seed removal experiments to assess post-dispersal processes that influence recruitment along a gradient of forest degradation in Madagascar analyzing seeds of three animal dispersed tree species. The percentage of seeds consumed or dispersed, declined from forest (28.6%) to degraded forest (17.2%) to savanna (10.8%). Only three out of 1080 seeds were cached and remained intact during the 14-day experiment. All three seeds were cached in the forest habitat and none in the degraded forest and savanna. The low percentage of seeds removed may be due to the lack of endemic rodents caching seeds, as only introduced rats were recorded in the area. The species-poor fauna of potential secondary seed dispersers of the region and especially in the degraded areas might represent an obstacle for diverse regeneration in degraded regions of Madagascar.

BackgroundWith population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms. ObjectiveIn this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic. MethodsWith a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID. ResultsRecruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database. ConclusionsThis study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID. Trial RegistrationGerman Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt International Registered Report Identifier (IRRID)DERR1-10.2196/38718

This study analyzed the effect of rootstocks G.213, M.9 and Marubakaido with M.9 interstem of 30 and 20 cm (MB/M.9-30cm and MB/M.9-20cm) on postharvest quality, mineral composition and functional properties of 'Maxi Gala' apples. The evaluations was performed using fruits from a commercial orchard located in Vacaria, RS, Brazil. Fruits were stored for 135 and 147 days in the 2014/2015 and 2015/2016 seasons, respectively, and analyzed one day after harvest and after cold storage (1.0±0.2 °C) followed by seven days in ambient condition. The mineral composition of fruits showed small and inconsistent differences between rootstocks. The MB/M.9-20cm provided higher total antioxidant activity and levels of total phenolic compounds in fruit peel than MB/M.9-30cm. For 2014/2015 season, soluble solids content at harvest was higher in fruits from trees with G.213 rootstock, not differing only from MB/M.9-30cm. In 2015/2016 season, G.213 and M.9 provided higher soluble solids content after storage compared to MB/M.9-30 cm and MB/M.9-20cm. G.213 rootstock anticipated fruit maturity compared to M.9 in 2014/2015 season. Other quality attributes of ‘Maxi Gala’ apples, at harvest and after cold storage, were similar between rootstocks G.213, M.9 and Maruba with M.9 interstem of 30 and 20cm.

ABSTRACT Resistance to antibiotics is an increasing problem and necessitates novel antibacterial therapies. The polyketide antibiotics cervimycin A to D are natural products of Streptomyces tendae HKI 0179 with promising activity against multidrug-resistant staphylococci and vancomycin-resistant enterococci. To initiate mode of action studies, we selected cervimycin C- and D-resistant (CmR) Staphylococcus aureus strains. Genome sequencing of CmR mutants revealed amino acid exchanges in the essential histidine kinase WalK, the Clp protease proteolytic subunit ClpP or the Clp ATPase ClpC, and the heat shock protein DnaK. Interestingly, all characterized CmR mutants harbored a combination of mutations in walK and clpP or clpC. In vitro and in vivo analyses showed that the mutations in the Clp proteins abolished ClpP or ClpC activity, and the deletion of clpP rendered S. aureus but not all Bacillus subtilis strains cervimycin-resistant. The essential gene walK was the second mutational hotspot in the CmR S. aureus strains, which decreased WalK activity in vitro and generated a vancomycin-intermediate resistant phenotype, with a thickened cell wall, a lower growth rate, and reduced cell lysis. Transcriptomic and proteomic analyses revealed massive alterations in the CmR strains compared to the parent strain S. aureus SG511, with major shifts in the heat shock regulon, the metal ion homeostasis, and the carbohydrate metabolism. Taken together, mutations in the heat shock genes clpP, clpC, and dnaK, and the walK kinase gene in CmR mutants induced a vancomycin-intermediate resistant phenotype in S. aureus, suggesting cell wall metabolism or the Clp protease system as primary target of cervimycin. IMPORTANCE Staphylococcus aureus is a frequent cause of infections in both the community and hospital setting. Resistance development of S. aureus to various antibiotics is a severe problem for the treatment of this pathogen worldwide. New powerful antimicrobial agents against Gram-positives are needed, since antibiotics like vancomycin fail to cure vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-resistant enterococci (VRE) infections. One candidate substance with promising activity against these organisms is cervimycin, which is an antibiotic complex with a yet unknown mode of action. In our study, we provide first insights into the mode of action of cervimycins. By characterizing cervimycin-resistant S. aureus strains, we revealed the Clp system and the essential kinase WalK as mutational hotspots for cervimycin resistance in S. aureus. It further emerged that cervimycin-resistant S. aureus strains show a VISA phenotype, indicating a role of cervimycin in perturbing the bacterial cell envelope.

Pain is known to reduce hemodialysis treatment adherence, reduce quality of life, and increase mortality. The absence of effective strategies to treat pain without medications has contributed to poor health outcomes for people with end-stage kidney disease (ESKD) on hemodialysis. It is now recognized that symbiotic microbiota in the gut play a critical role in health and disease, and new evidence sheds light on the role of the microbiome in chronic pain. The pilot study protocol presented here (BIOME-HDp) employs a longitudinal repeated measures design to interrogate the effects of a nonpharmacological pain intervention on the composition and function of the gut microbiome and circulating metabolites. This pilot study is an ancillary study of the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis, which is part of the NIH's Helping to End Addiction Long-term (HEAL) initiative. The BIOME-HDp pilot study will establish clinical microbiome research methods and determine the acceptability and feasibility of fecal microbiome and serum metabolite sample collection.

In this contribution, we want to share the experiences we had in a project that aimed at helping students select their own learning paths. Learning paths were a specific sequence of 'edublocks' (learning activities) first-year students at the University of Barcelona could choose in a course: “Uses, possibilities and limits of information and communication technologies in social education”. Students were provided with a technology-based network of learning communities of peers, teams of teachers and tutors and a large set of learning 'edublocks'. At the center of the network we placed an App that allowed teachers and tutors to give very differentiated quantitative and qualitative feedback to their students, which turned out to be of great value for students who were confronted with the task of organizing their learning paths during their first semester. Results showed that students were very satisfied with the feedback they received while at the same time, teachers indicated that using the App did not place an additional burden on them. The strategy of individualization of learning with synchronous and asynchronous human support, managed through technological tools, encourages self-regulated learning. We start our contribution with an overview of different approaches to controlling learning paths, present some theoretical considerations concerning our Edublocks project, describe the project in detail and then offer and discuss results and our insights.

Congenital lower urinary tract obstructions (LUTO) are most often caused by posterior urethral valves (PUV), a male limited anatomical obstruction of the urethra affecting 1 in 4,000 male live births. Little is known about the genetic background of PUV. Here, we report the largest genome-wide association study (GWAS) for PUV in 4 cohorts of patients and controls. The final meta-analysis included 756 patients and 4,823 ethnicity matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts. No genome-wide significant locus was identified, but 33 variants showed suggestive significance (P < 1 × 10−5). When considering only loci with multiple variants residing within < 10 kB of each other showing suggestive significance and with the same effect direction in all 4 cohorts, 3 loci comprising a total of 9 variants remained. These loci resided on chromosomes 13, 16, and 20. The present GWAS and meta-analysis is the largest genetic study on PUV performed to date. The fact that no genome-wide significant locus was identified, can be explained by lack of power or may indicate that common variants do not play a major role in the etiology of PUV. Nevertheless, future studies are warranted to replicate and validate the 3 loci that yielded suggestive associations.

This study presents an analysis of the possible use of a viscose rayon (CV) fiber from textile industry wastes to develop a reinforced cementitious composite as an alternative for textile discharge valorization. Several techniques were used to characterize precursor fibrous waste material such as SEM, FT-IR, DSC, and TGA. The experimental studies were conducted based on a conventional cementitious mortar (control) and four different fiber contents (0.5, 1, 2, and 4 wt%). For mechanical behavior analysis, uniaxial compressive strength tests were carried out at different ages (7, 14, and 28 days after production). The results showed favorable CV fiber addition as reinforcement up to a maximum limit. The optimum concentration of fiber was 0.5 wt% (FRC0.5), which provided 28 days of higher compression strength. The addition of CV waste as reinforcement in cementitious matrix resulted in an improved compressive strength above 20.6% compared to the conventional non-reinforced mortar. Furthermore, CV fiber addition improved the ductile behavior of the new composite allowing a controlled failure, even after maximum rupture loading.

Objective While greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with high BMI.Methods GARFIELD-AF is a prospective registry of 52 057 newly diagnosed AF patients. The study population comprised 40 482 participants: 703 underweight (BMI

The field of medicine is undergoing a fundamental change, transforming towards a modern data-driven patient-oriented approach. This paradigm shift also affects perinatal medicine as predictive algorithms and artificial intelligence are applied to enhance and individualize maternal, neonatal and perinatal care. Here, we introduce a pharmacometrics-based mathematical-statistical computer program (PMX-based algorithm) focusing on hyperbilirubinemia, a medical condition affecting half of all newborns. Independent datasets from two different centers consisting of total serum bilirubin measurements were utilized for model development (342 neonates, 1,478 bilirubin measurements) and validation (1,101 neonates, 3,081 bilirubin measurements), respectively. The mathematical-statistical structure of the PMX-based algorithm is a differential equation in the context of non-linear mixed effects modeling, together with Empirical Bayesian Estimation to predict bilirubin kinetics for a new patient. Several clinically relevant prediction scenarios were validated, i.e., prediction up to 24 h based on one bilirubin measurement, and prediction up to 48 h based on two bilirubin measurements. The PMX-based algorithm can be applied in two different clinical scenarios. First, bilirubin kinetics can be predicted up to 24 h based on one single bilirubin measurement with a median relative (absolute) prediction difference of 8.5% (median absolute prediction difference 17.4 μmol/l), and sensitivity and specificity of 95.7 and 96.3%, respectively. Second, bilirubin kinetics can be predicted up to 48 h based on two bilirubin measurements with a median relative (absolute) prediction difference of 9.2% (median absolute prediction difference 21.5 μmol/l), and sensitivity and specificity of 93.0 and 92.1%, respectively. In contrast to currently available nomogram-based static bilirubin stratification, the PMX-based algorithm presented here is a dynamic approach predicting individual bilirubin kinetics up to 48 h, an intelligent, predictive algorithm that can be incorporated in a clinical decision support tool. Such clinical decision support tools have the potential to benefit perinatal medicine facilitating personalized care of mothers and their born and unborn infants.

While the relationship between loneliness and psychological distress is well documented, the mechanisms underlying this relationship are less clear. One factor known to be related to loneliness as well as psychological distress, is social support, with some studies suggesting that support–both received and provided–can serve as a mechanism to reduce the distress associated with loneliness. In this paper we examine the mediating role of both aspects of support in the relationship between loneliness and psychological distress in the COVID-19 context. We used a multi-country dataset collected at two timepoints during the pandemic; the first during the early stages (N = 6,842, 11 countries) and the second collected for a subset of countries (N = 1,299, 3 countries) 3 months later. Across all eleven countries, results revealed significant positive associations between loneliness and distress. Furthermore, using longitudinal data, we investigated the directionality of this relationship and found that increased loneliness over time was associated with increased psychological distress. The data also showed that both feeling unsupported and feeling unable to provide support to others mediated this relationship. These findings point to the need to facilitate people's ability to draw effective social support and help others–particularly at times when social connectedness is threatened–as a way of alleviating the psychological distress that commonly presents with loneliness.

Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococci evade killing by complement by binding factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized as a single chain. Gonococci bind FH through domains 6 and 7, and C-terminal domains 18 through 20. Previously, we showed that a chimeric protein comprising (from the N- to C-terminus) FH domains 18-20 (containing a point mutation in domain 19 to prevent lysis of host cells) fused to human IgG1 Fc (called FH*/Fc1) killed gonococci in a complement-dependent manner and reduced the duration and bacterial burden in the mouse vaginal colonization model of gonorrhea. Considering the N. gonorrhoeae-binding FH domains 18-20 are C-terminal in native FH, we reasoned that positioning Fc N-terminal to FH* (Fc1/FH*) would improve binding and bactericidal activity. Although both molecules bound gonococci similarly, Fc1/FH* displayed a 5-fold lower IC50 (the concentration required for 50% killing in complement-dependent bactericidal assays) than FH*/Fc1. To further increase complement activation, we replaced human IgG1 Fc in Fc1/FH* with Fc from human IgG3, the most potent complement-activating IgG subclass, to obtain Fc3/FH*. Bactericidal activity was further increased ~2.3-fold in Fc3/FH* compared to Fc1/FH*. Fc3/FH* killed (defined by

In breast cancer, p53 expression levels are better predictors of outcome and chemotherapy response than TP53 mutation. Several molecular mechanisms that modulate p53 levels and functions, including p53 isoform expression, have been described, and may contribute to deregulated p53 activities and worse cancer outcomes. In this study, TP53 and regulators of the p53 pathway were sequenced by targeted next-generation sequencing in a cohort of 137 invasive ductal carcinomas and associations between the identified sequence variants, and p53 and p53 isoform expression were explored. The results demonstrate significant variability in levels of p53 isoform expression and TP53 variant types among tumours. We have shown that TP53 truncating and missense mutations modulate p53 levels. Further, intronic mutations, particularly polymorphisms in intron 4, which can affect the translation from the internal TP53 promoter, were associated with increased Δ133p53 levels. Differential expression of p53 and p53 isoforms was associated with the enrichment of sequence variants in p53 interactors BRCA1, PALB2, and CHEK2. Taken together, these results underpin the complexity of p53 and p53 isoform regulation. Furthermore, given the growing evidence associating dysregulated levels of p53 isoforms with cancer progression, certain TP53 sequence variants that show strong links to p53 isoform expression may advance the field of prognostic biomarker study in breast cancer.

Abstract Purpose This systematic review and meta‐analysis investigates the efficacy of intraoperative sling procedures in reducing postprostatectomy urinary incontinence compared to having no slings. Methods A comprehensive search of PubMed, Medline, Embase, and the Cochrane library from inception to November 2020 was performed. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and Newcastle‐Ottawa Scale for nonrandomized studies. The GRADE approach was used for critical appraisal of evidences and meta‐analyses were conducted using random‐effects models. Results Ten studies were included (n = 1,447). Quality of evidence ranged from moderate to very low. Sling procedure was generally favorable for short‐term continence outcomes, although discrepancies exist due to variability in continence definition. Sling procedure resulted in reduced urinary pad weight at 1 month postoperatively (MD: 21.55; 95%CI: 12.58 to 30.52). Patient‐reported questionnaires were also favorable for the sling group for up to 3 months (IPSS; (MD: 1.44; 95%CI: 0.14 to 2.74), ICIQ‐SF; (MD: 2.25; 95%CI: 1.26 to 3.24), EPIC‐U; (MD: 5.30; 95%CI: 1.12 to 9.39)) postoperatively. Sling procedure improved the number of continent patients at 1 month with continence definition of zero pad use/day (RR:1.41; 95%CI: 1.10 to 1.83) but not with the definition of ≤ 1pad/day. Similarly, it reduced the time to continence with the ≤ 1 pad/day definition (MD: 0.5; 95%CI: 0.1 to 0.9) but not with the zero pad/day definition. Conclusion The current literature suggests that intraoperative sling procedures during radical prostatectomy may promote early return of continence compared to having no sling, however, there are no long‐term differences.