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Mucosal barrier tissues and their mucosal associated lymphoid tissues (MALT) are attractive targets for vaccines and immunotherapies due to their roles in both priming and regulating adaptive immune responses. The upper and lower respiratory mucosae, in particular, possess unique properties: a vast surface area responsible for frontline protection against inhaled pathogens but also simultaneous tight regulation of homeostasis against a continuous backdrop of non-pathogenic antigen exposure. Within the upper and lower respiratory tract, the nasal and bronchial associated lymphoid tissues (NALT and BALT, respectively) are key sites where antigen-specific immune responses are orchestrated against inhaled antigens, serving as critical training grounds for adaptive immunity. Many infectious diseases are transmitted via respiratory mucosal sites, highlighting the need for vaccines that can activate resident frontline immune protection in these tissues to block infection. While traditional parenteral vaccines that are injected tend to elicit weak immunity in mucosal tissues, mucosal vaccines (i.e., that are administered intranasally) are capable of eliciting both systemic and mucosal immunity in tandem by initiating immune responses in the MALT. In contrast, administering antigen to mucosal tissues in the absence of adjuvant or costimulatory signals can instead induce antigen-specific tolerance by exploiting regulatory mechanisms inherent to MALT, holding potential for mucosal immunotherapies to treat autoimmunity. Yet despite being well motivated by mucosal biology, development of both mucosal subunit vaccines and immunotherapies has historically been plagued by poor drug delivery across mucosal barriers, resulting in weak efficacy, short-lived responses, and to-date a lack of clinical translation. Development of engineering strategies that can overcome barriers to mucosal delivery are thus critical for translation of mucosal subunit vaccines and immunotherapies. This review covers engineering strategies to enhance mucosal uptake via active targeting and passive transport mechanisms, with a parallel focus on mechanisms of immune activation and regulation in the respiratory mucosa. By combining engineering strategies for enhanced mucosal delivery with a better understanding of immune mechanisms in the NALT and BALT, we hope to illustrate the potential of these mucosal sites as targets for immunomodulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Seefeld, Templeton, Lehtinen, Sinclair, Yadav and Hartwell.)

Multi-drug resistance is emerging in Citrobacter freundii , which is the third most common carbapenemase-producing (CP) Enterobacteriaceae in humans in Finland due to recent outbreaks. The objective of this study was to determine if wastewater surveillance (WWS) could detect CP C. freundii strains causing infections in humans. Selective culturing was used to isolate CP C. freundii from the hospital environment, hospital wastewater, and untreated municipal wastewater in Helsinki, Finland, between 2019 and 2022. Species were identified using MALDI-TOF, and presumptive CP C. freundii isolates were subjected to antimicrobial susceptibility testing and further characterized by whole genome sequencing. A genomic comparison was conducted to compare isolates collected from the hospital environment, untreated municipal wastewater, and a selection of isolates from human specimens from two hospitals in the same city. We also examined the persistence of CP C. freundii in the hospital environment and the impact of our attempts to eradicate it. Overall, 27 bla KPC - 2 -carrying C. freundii were detected in the hospital environment (ST18; n = 23 and ST8; n = 4), while 13 bla KPC - 2 -carrying C. freundii (ST8) and five bla VIM - 1 -carrying (ST421) C. freundii were identified in untreated municipal wastewater. CP C. freundii was not identified in hospital wastewater. We found three clusters (cluster distance threshold ≤ 10 allelic difference) after comparing the recovered isolates and a selection of isolates from human specimens. The first cluster consisted of ST18 isolates from the hospital environment ( n = 23) and human specimens ( n = 4), the second consisted of ST8 isolates from the hospital environment ( n = 4), untreated municipal wastewater ( n = 6), and human specimens ( n = 2), and the third consisted of ST421 isolates from the untreated municipal wastewater ( n = 5). Our results support previous studies suggesting that the hospital environment could act as a source of transmission of CP C. freundii in clinical settings. Furthermore, the eradication of CP Enterobacteriaceae from the hospital environment is challenging. Our findings also showed that CP C. freundii is persistent throughout the sewerage system and demonstrate the potential of WWS for detecting CP C. freundii ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Heljanko, Johansson, Räisänen, Anttila, Lyytikäinen, Jalava, Weijo, Lehtinen, Lehto, Lipponen, Oikarinen, Pitkänen, Heikinheimo and WastPan Study Group.)

Vaccine hesitancy and refusal have undermined COVID-19 vaccination efforts of nursing staff. This study aimed to identify behavioral factors associated with COVID-19 vaccine uptake among unvaccinated nursing staff in long-term care facilities (LTCF) in Finland. Methodology: The study was based on the Theoretical Domains Framework. Data were collected through qualitative in-depth interviews among nursing staff and managers of LTCFs. The analysis was based on thematic analysis. We identified seven behavioral domains, with several themes, that reduced the staff's intention to get vaccinated: knowledge (information overload, inability to identify trustworthy information sources, lack of vaccine-specific and understandable scientific information), beliefs about consequences (incorrect perceptions about the vaccine effectiveness, and lack of trust in the safety of the vaccine), social influences (influence of family and friends), reinforcement (limited abilities of the management to encourage vaccination), beliefs about capabilities (pregnancy or desire to get pregnant), psychological factors (coping with changing opinion), and emotions (confusion, suspicion, disappointment, and fatigue). We also identified three behavioral domains that encouraged vaccine uptake: social influences (trust in health authorities), environmental context and resources (vaccination logistics), and work and professional role (professional pride). The study findings can help authorities to develop tailored vaccine promotion strategies for healthcare workers in LTCFs.

Background: Recently, new non-alcohol-based hand disinfection formulae have come to the market. Although they have passed the EN1500 test, data on their clinical efficacy compared with alcohol-based hand rubs are scarce, mainly covering benzalkonium chloride (BAC)., Aim: To test the efficacy of silver-polymer-based, lactic-acid-based and BAC-based hand disinfectant foams and an alcohol-based hand rub gel to reduce bacterial counts on the fingertips of healthcare workers working on hospital wards., Methods: Each of the 84 participants tested one of the four products during their morning shift on a hospital ward using the 'fingertips on Petri dish' method before and after rubbing their hands with the product. After incubation, two independent readers assessed bacterial counts on the culture plates., Findings: The alcohol-based hand rub efficiently reduced bacteria on testers' fingertips in the test situation, whereas the lactic-acid- and BAC-based disinfectants did not have any detectable efficacy. The silver-polymer-based formula had some effect but requires further study., Conclusion: Non-alcohol-based hand rubs require careful consideration and further study before they can be accepted for clinical use., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Emulsion electrospinning provides a tunable system for the development of porous scaffolds for controlled, localized drug delivery in tissue engineering applications. This study aimed to elucidate the role of model drug interactions with emulsion chemistry on loading and release rates from fibers with controlled fiber diameter and fiber volume fraction. Nile Red and Rhodamine B were used as model drugs and encapsulation efficiency and release rates were determined from poly(caprolactone) (PCL) electrospun fibers spun either with no surfactant (Span 80), surfactant, or water-in-oil emulsions. Drug loading efficiency and release rates were modulated by both surfactant and aqueous internal phase in the emulsions as a function of drug molecule hydrophobicity. Overall, these results demonstrate the role of intermolecular interactions and drug phase solubility on the release from emulsion electrospun fibers and highlight the need to independently control these parameters when designing fibers for use as tunable drug delivery systems.

Background: In Finland, the surveillance of healthcare-associated infections (HAI) became obligatory by the renewed Communicable Diseases Act on the 1 st March 2017., Aim: To introduce HAI surveillance protocol (HALT-2 by ECDC) in primary care hospitals in the largest hospital district in Finland, and to measure the burden of HAIs and antimicrobial use patterns for improvement., Methods: Two identical point prevalence surveys (PPS) were organized in autumn 2015 and in spring 2017. The infection control persons (ICP) in the hospitals were inducted to the HAI definitions and the study protocol to collect the data with questionnaires on the study days. The data were checked and analyzed by the areal infection control unit. The hospitals were provided feedback of the results and HAI prevention methods., Findings: In 2015, 2218 patients from 22 hospitals and in 2017, 2343 patients from 25 hospitals were studied. The prevalence of HAI was 11% in both surveys (ranges per hospital 4-24% and 4-31%, respectively). Of all HAIs, 37% originated from referring hospitals. Respiratory tract, urinary tract and skin were the most frequent sites of infection. One fourth of all patients received at least one systemic antimicrobial. The process showed that recognition of HAIs may be difficult for non-experienced ICPs., Conclusions: The HALT-2 protocol proved useful in introducing HAI surveillance and prevention in primary care hospitals with active patient transfer from other hospitals and relatively high prevalence of HAI and antimicrobial use. For annually repeated surveys, slightly shorter electronic questionnaires are essential., (© 2021 The Authors.)

Emulsion electrospinning is a versatile technique used to create fibrous meshes for applications in drug delivery and tissue engineering. In this study, the effects of surfactant and increasing internal phase volume fraction on emulsion electrospun fiber morphology were investigated. The fiber diameter, surface topography, internal architecture, mesh hydrophobicity, and fiber volume fraction were all characterized and the resulting effects on model drug release and cell response were determined. Surfactant relocation to the fiber surface resulted in alterations to fiber surface topography and internal morphology, increased rate of water adsorption into the mesh, and reduced burst effects of drug release. Increasing the internal phase volume fraction within the emulsion resulted in minimal change to fiber diameter, surface morphology, fiber volume fraction, and rate of water adsorption illustrating the ability to increase drug loading without affecting fiber properties. Lastly, all meshes promoted cell adhesion and good viability with a trend of increased MTT absorbance from cells on the surfactant and emulsion fibers possibly suggesting that an increase in surface area via smaller fiber diameter and fiber volume fraction increases metabolic activity. Overall, these studies indicate that fiber morphology and mesh hydrophobicity can be tuned by controlling surfactant location within fibers and internal phase volume fraction. Modulating fiber properties within the emulsion electrospun mesh is important to achieve controlled drug release and cell response for tissue engineering applications.

In order to assess the changes in nerve function 5 years after the diagnosis of diabetes mellitus and the determinants of progression of neuropathy, we studied 113 Type 2 (non-insulin-dependent) diabetic patients and 127 non-diabetic control subjects. Motor and sensory nerve conduction velocities were measured at the time of diagnosis of diabetes and 5 years later. At both examinations conduction velocities and response amplitudes were lower in diabetic patients than in control subjects. During the follow-up sural nerve conduction was impaired in both diabetic and control subjects, but, in general, changes in neurophysiological parameters were slight and inconsistent. In 12 diabetic patients nerve function deteriorated significantly during the follow-up. These patients had higher glycaemic indices at both examinations and lower baseline blood pressure levels as compared to the rest of the diabetic patients. No differences between these patient groups were found in other baseline risk factors (age, obesity, use of alcohol, smoking, serum insulin levels, albuminuria, lipids). In conclusion, Type 2 diabetic patients have disturbed nerve function at the time of diagnosis, but neurophysiological impairment during the next 5 years is on the average slight. Poor glycaemic control seems to be the most important risk factor in the deterioration of nerve function in these patients.

The purpose of the present study was to assess among a representative group of middle-aged newly diagnosed type 2 diabetics and control subjects the baseline prevalence and 5-year incidence of arterial calcifications of aorta and lower limb and their relationship to cardiovascular morbidity. The relationship of baseline risk factors to the development of arterial calcifications was also studied. At the time of diagnosis the age-adjusted prevalence of aortic and lower limb intimal calcifications was higher in diabetics than in control subjects (aortic calcifications: 29 vs. 17% for men, P = 0.05; 26 vs. 19% for women, P = 0.06; lower limb intimal calcifications: 24 vs. 12% for men, P = 0.02; 10 vs. 7% for women; P = NS), whereas no significant difference in baseline prevalence of lower limb medial calcifications was observed (15 vs. 21% for men, 9 vs. 10% for women). The 5-yr incidence of aortic calcifications in both sexes and of lower limb calcifications in men was similar in diabetic and control subjects, but the incidence of lower limb calcifications was higher in diabetic women than in control women (intimal: 33 vs. 11%, P = 0.009: medial: 29 vs. 14%, P = 0.05). The baseline prevalence of abdominal aortic (37 vs. 22%, P = NS for diabetics; 42 vs. 16%, P = 0.02 for control subjects), lower limb intimal (24 vs. 16% for diabetics, P = NS; 15 vs. 7% for control subjects, P = NS) and medial calcifications (23 vs. 7% for diabetics, P = 0.03) were higher in subjects who developed intermittent claudication during the follow-up than in those free of it at the 5-yr examination. Abnormalities in VLDL-metabolism and high systolic blood pressure were associated with the development of aortic calcification in diabetic subjects. In conclusion, already at the time of diagnosis atherosclerotic calcifications are more prevalent in type 2 diabetics than in nondiabetic subjects. During the follow-up diabetic women, but not men, had higher incidence of lower limb intimal and medial calcifications than non-diabetic subjects. Arterial calcifications tended to be associated with the development of intermittent claudication during the follow-up in diabetic and control subjects.

Incidence of CT abnormalities and their correlation with clinical and EEG features were evaluated in a consecutive series of 202 adult patients with newly diagnosed epileptic seizures. Abnormal CT findings were found in 36% of these patients; the abnormalities consisted of brain tumors (17%), atrophic lesions (11%) and other organic findings (8%) such as arteriovenous malformations. Focal features of seizures, in neurological examination and/or in EEG, correlated significantly with CT abnormalities. The absence of these findings did, however, not exclude the possibility of brain lesions, which in many cases were treatable by surgery.

We evaluated the prevalence of peripheral neuropathy by clinical and electrophysiological criteria and the prevalence of autonomic parasympathetic nerve dysfunction by heart-rate variation during deep breathing (expiration-to-inspiration ratio [E:1]) in 132 newly diagnosed non-insulin-dependent diabetic (NIDDM) subjects aged 45-64 yr and 142 randomly selected nondiabetic control subjects. The relationship of nerve dysfunction to the degree of hyperglycemia and insulin-secretion capacity were also investigated. Single and scattered symptoms and signs of peripheral neuropathy were found in both diabetic and control subjects. Symptomatic polyneuropathy was found in 1.5% of diabetic subjects but none of the control subjects. Polyneuropathy defined by clinical signs was found in 2.3% of the diabetic subjects and 1.4% of the control subjects. No subjects with both symptoms and signs were seen. Nerve conduction velocities (NCVs) were significantly slower in diabetic than control subjects. Polyneuropathy according to electrophysiological criteria was found in 15.2% of diabetic subjects but was not found in any control subjects. Electromyographic abnormalities were more common in diabetic than control women, but not significant differences were found in men. The resting heart rate was higher in diabetic than control women, but no significant difference was found in men. The mean E:I was significantly lower in diabetic men and women than control men and women. An abnormally low E:I was found in 9.2% of the diabetic men, 3.3% of the control men, 3.3% of the diabetic women, and none of the control women. NCV parameters, but not E:I, were inversely correlated with fasting blood glucose and glycosylated hemoglobin levels. A positive correlation between NCV and fasting and postglucose serum insulin levels was found in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized placebo-controlled double-blind cross-over study was conducted in order to examine the effect of an aldose reductase inhibitor, sorbinil (100 mg daily for 4 weeks), on red cell sorbitol concentration and clinical and electrophysiological parameters of diabetic neuropathy. A total of 31 diabetic patients with either clinically or electrophysiologically verified diabetic neuropathy were studied. Red cell sorbitol levels decreased significantly to the levels reported in non-diabetic subjects, but there were no significant changes in symptoms, signs, vibration perception thresholds or nerve conduction variables. One patient had transient skin rash, fever, myalgia and leucopenia, but no other significant adverse effects were found.