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B cells are activated by two temporally distinct signals, the first provided by the binding of antigen to the B cell antigen receptor (BCR), and the second provided by helper T cells. Here we found that B cells responded to antigen by rapidly increasing their metabolic activity, including both oxidative phosphorylation and glycolysis. In the absence of a second signal, B cells progressively lost mitochondrial function and glycolytic capacity, which led to apoptosis. Mitochondrial dysfunction was a result of the gradual accumulation of intracellular calcium through calcium response–activated calcium channels that, for approximately 9 h after the binding of B cell antigens, was preventable by either helper T cells or signaling via the receptor TLR9. Thus, BCR signaling seems to activate a metabolic program that imposes a limited time frame during which B cells either receive a second signal and survive or are eliminated. B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.

Key events in T cell–dependent antibody responses, including affinity maturation, are dependent on the B cell’s presentation of antigen to helper T cells at critical checkpoints in germinal-center formation in secondary lymphoid organs. Here we found that signaling via Toll-like receptor 9 (TLR9) blocked the ability of antigen-specific B cells to capture, process and present antigen and to activate antigen-specific helper T cells in vitro. In a mouse model in vivo and in a human clinical trial, the TLR9 agonist CpG enhanced the magnitude of the antibody response to a protein vaccine but failed to promote affinity maturation. Thus, TLR9 signaling might enhance antibody titers at the expense of the ability of B cells to engage in germinal-center events that are highly dependent on B cells’ capture and presentation of antigen. The presentation of antigen by germinal-center B cells to follicular T cells engenders the process of antibody affinity maturation and humoral memory. Pierce and colleagues show that TLR9 signaling in B cells antagonizes B cell–mediated antigen presentation, which leads to the enhanced generation of short-lived plasma cells and the production of lower-affinity antibodies.

Amplification of chromosome 9p24.1 targeting PD-L1 , PD-L2 , and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1. Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 ≥ 2 and/or PDJ/9q34.1 ≥ 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ− TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC.

A ternary-blend concrete (65% cement, 25% slag, and 10% fly ash) containing fractionated reclaimed asphalt pavement (FRAP) as a partial replacement (0%, 20%, 35%, and 50%) for coarse aggregate was investigated through a comprehensive laboratory testing program. With increasing FRAP replacement, the concrete workability increased, unit weight decreased, and air content was mainly unaffected. The source of the measured strength and modulus reductions was linked to the interface between the FRAP particle and the paste. The incorporation of FRAP did not significantly impact the concrete free drying shrinkage but did reduce the restrained ring shrinkage strains. The freezing-and-thawing durability was acceptable for all tested FRAP contents. Fracture results indicated that FRAP addition did not statistically affect the initial or total fracture energy of the concrete. Mixtures containing up to 50% coarse FRAP may be used in concrete pavement and still produce acceptable fresh and hardened properties.

Enveloped respiratory viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be transmitted through aerosols and contact with contaminated surfaces. The stability of these viruses outside the host significantly impacts their transmission dynamics and the spread of diseases. In this study, we investigated the tenacity of Feline Coronavirus (FCoV) in aerosols and on surfaces under varying environmental conditions. We found that airborne FCoV showed different stability depending on relative humidity (RH), with higher stability observed at low and high RH. Medium RH conditions (50–60%) were associated with increased loss of infectivity. Furthermore, FCoV remained infectious in the airborne state over 7 h. On stainless-steel surfaces, FCoV remained infectious for several months, with stability influenced by organic material and temperature. The presence of yeast extract and a temperature of 4 °C resulted in the longest maintenance of infectivity, with a 5 log 10 reduction of the initial concentration after 167 days. At 20 °C, this reduction was achieved after 19 days. These findings highlight the potential risk of aerosol and contact transmission of respiratory viruses, especially in enclosed environments, over extended periods. Studying surrogate viruses like FCoV provides important insights into the behavior of zoonotic viruses like SARS-CoV-2 in the environment.

Background/Objectives: Assessing the hydration status (HS) in geriatric patients remains challenging due to multimorbidity, polypharmacy, and cognitive impairment. Common indicators like reduced skin turgor and dry mucous membranes are unreliable. The Hydr-Age-Study is a prospective observational pilot study with a post hoc analysis to evaluate the diagnostic accuracy of clinical, laboratory, and instrumental methods to assess HS in hospitalised older adults. Methods: Upon admission, patients underwent an assessment including their medical history, a clinical evaluation, laboratory tests, ultrasound examination, and bioimpedance analysis. These data were collected and independently reviewed by two experts who diagnosed each patient’s current HS. This diagnosis served as the clinical reference standard for evaluating the diagnostic accuracy of each method. Results: Twenty-six methods were examined, of which four achieved an AUC > 0.8. Axillary dryness showed a high diagnostic accuracy for hypohydration (AUC = 0.854), with a sensitivity of 83.3% and a specificity of 82.8%. Inferior vena cava (IVC) ultrasound effectively detected both hypo- and hyperhydration. A subxiphoid IVC diameter ≤ 1.95 cm identified hypohydration with 90.9% sensitivity and 50.6% specificity. For hyperhydration, a diameter of ≥2.15 cm provided strong diagnostic performance in both subxiphoid and transcostal views. Conclusions: Axillary dryness and IVC sonography demonstrated the highest diagnostic accuracy. No other methods exceeded an AUC of 0.80. In the absence of a gold standard, a structured clinical consensus provides a feasible and reproducible approach to establish a clinical reference standard. These findings may contribute to the development of a standardised assessment protocol in geriatric medicine.

Oropharyngeal dysphagia (OD) is a highly prevalent and growing condition in the older population. Although OD may cause very severe complications, it is often not detected, explored, and treated. Older patients are frequently unaware of their swallowing dysfunction which is one of the reasons why the consequences of OD, ie, aspiration, dehydration, and malnutrition, are regularly not attributed to dysphagia. Older patients are particularly vulnerable to dysphagia because multiple age-related changes increase the risk of dysphagia. Physicians in charge of older patients should be aware that malnutrition, dehydration, and pneumonia are frequently caused by (unrecognized) dysphagia. The diagnosis is particularly difficult in the case of silent aspiration. In addition to numerous screening tools, videofluoroscopy was the traditional gold standard of diagnosing OD. Recently, the fiberoptic endoscopic evaluation of swallowing is increasingly utilized because it has several advantages. Besides making a diagnosis, fiberoptic endoscopic evaluation of swallowing is applied to evaluate the effectiveness of therapeutic maneuvers and texture modification of food and liquids. In addition to swallowing training and nutritional interventions, newer rehabilitation approaches of stimulation techniques are showing promise and may significantly impact future treatment strategies.

Despite the variety of pathogens that are transmitted via the airborne route, few data are available on factors that influence the tenacity of airborne pathogens. In order to better understand and thus control airborne infections, knowledge of these factors is important. In this study, three agents, S . aureus , G . stearothermophilus spores and the MS2 bacteriophage, were aerosolized at relative humidities (RH) varying between 30% and 70%. Air samples were then analyzed to determine the concentration of the agents. S . aureus was found to have significantly lower survival rate in the aerosol at RH above 60%. It showed the lowest recovery rates of the three agents, ranging from 0.13% at approximately 70% RH to 4.39% at 30% RH. G . stearothermophilus spores showed the highest tenacity with recovery rates ranging from 41.85% to 61.73% with little effect of RH. For the MS2 bacteriophage, a significantly lower tenacity in the aerosol was observed with a recovery rate of 4.24% for intermediate RH of approximately 50%. The results of this study confirm the significant influence of the RH on the tenacity of airborne microorganisms depending on the specific agent. These data show that the behavior of microorganism in bioaerosols is varies under different environmental conditions.

Background Clostridium difficile infections (CDI) are the most frequent cause of diarrhoea in hospitals. Geriatric patients are more often affected by the condition, by a relapse and complications. Therefore, a crucial question is how often colonization with toxigenic Clostridium difficile strains occurs in elderly patients without diarrhoea and whether there is a “risk pattern” of colonized patients that can be defined by geriatric assessment. Furthermore, the probability for those asymptomatic carriers to develop a symptomatic infection over time has not been sufficiently explored. Methods We performed a cohort study design to assess the association of clinical variables with Clostridium difficile colonization. The first stool sample of 262 consecutive asymptomatic patients admitted to a geriatric unit was tested for toxigenic Clostridium difficile using PCR (GeneXpert, Cepheid). A comprehensive geriatric assessment (CGA) including Barthel Index, Mini Mental State Examination (MMSE) and hand grip-strength was performed. In addition, Charlson Comorbidity Index, body mass index, number and length of previous hospital stays, previous treatment with antibiotics, institutionalization, primary diagnoses and medication were recorded and evaluated as possible risk factors of colonization by means of binary logistic regression. Secondly, we explored the association of C. difficile colonization with subsequent development of CDI during hospital stay. Results At admission, 43 (16.4%) patients tested positive for toxin B by PCR. Seven (16.3%) of these colonized patients developed clinical CDI during hospital stay, compared to one out of 219 patients with negative or invalid PCR testing (Odds ratio 12,3; Fisher’s exact test: p  = 0.000). Overall, 7 out of 8 (87.5%) CDI patients had been colonized at admission. Risk factors of colonization with C. difficile were a history of CDI, previous antibiotic treatment and hospital stays. The parameters of the CGA were not significantly associated with colonization. Conclusion Colonization with toxigenic Clostridium difficile strains occurs frequently in asymptomatic patients admitted to a geriatric unit. Previous CDI, antibiotic exposure and hospital stay, but not clinical variables such as CGA, are the main factors associated with asymptomatic Clostridium difficile carriage. Colonization is a crucial risk factor for subsequent development of symptomatic CDI.

Measures to facilitate patient medication adherence should be considered an integral part of the comprehensive care of older patients with multiple diseases. However, impairment of cognitive functions and dementia, in particular, may substantially compromise adherence behaviour. Therefore, a literature review was performed to identify factors associated with adherence to medication in patients with cognitive impairment or dementia, and to discuss strategies for improvement of non-adherence. Evidence-based information on how to deal with adherence to medication in patients with dementia is scarce because of a lack of specific studies. However, there is increasing knowledge about factors influencing medication adherence behaviour in older age, and emerging insight into the relationships between adherence behaviour and cognitive capacity, memory and executive function, in particular. Nevertheless, understanding elderly persons’ strategies for maintaining regular use of even complex drug regimens is still limited. Progress of research in this field is needed. It is notable that measures to improve adherence consist of combinations of educational interventions and cognitive support but assessment of study participants’ cognitive function is rare. In clinical practice, awareness of non-adherence as a result of cognitive impairment is relatively low. The most important step is early detection of cognitive impairment when this is impacting negatively on medication management. A practical geriatric screening test is recommended to identify memory problems and further functional impairments associated with cognitive impairment. Performance-based assessments might be useful for screening medication management capacity, in addition to a careful drug history, inspection of all medicines used (including over-the-counter drugs) and proxy information. However, no feasible screening methods have as yet found their way into clinical practice. Patients with impaired executive function, lack of awareness of illness and personality traits such as independency and high self-confidence may be at particular risk of non-adherence. The question is when to switch patient medication self-management to another person’s responsibility if cognitive decline progresses. Further research is needed on measures to differentiate cognitive function and the relationships between memory concerns, memory strategy use and medication management. Also, studies evaluating the influence of personal support, health status and depression on the memory strategies used are needed. It is important to assess patients’ attitudes toward medication and their relationship with proxies. Strategies for facilitating medication adherence in patients with dementia include prescribing as few medicines as possible, tailoring dose regimens to personal habits, and coordinating all drug dosing schedules as much as possible. When providing medication organizers, it is important to observe the patient’s ability to use devices appropriately. In addition, automated computer-based reminding aids, online medication monitoring and telemonitoring may be helpful for patients with mild dementia. The decision as to when assistance with medication self-management is needed has to be made taking into account patient independency and safety aspects. This holds true for medicines with a narrow therapeutic range, in particular. Interactions among the individual patient’s cognitive status, mood, level of self-efficacy and particular living situation must also be taken into consideration when searching for the optimal medication adherence strategy. No evidence-based recommendations can be given as yet. However, comprehensive assessment of the individual patient and careful consideration of all potential drug-related problems will probably help facilitate adherence and prevent compromised health outcomes in patients with dementia.