E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis.

Dendritic cells (DCs) play a pivotal role in controlling the balance between tolerance and immunity in the intestine. Gut conditioned CD103(+) DCs promote regulatory T (Treg) cell responses; however, little is known about DCs that drive inflammation in the intestine. Here, we show that monocyte-derived inflammatory DCs that express E-cadherin, the receptor for CD103, promote intestinal inflammation. E-cadherin(+) DCs accumulated in the inflamed mesenteric lymph nodes and colon, had high expression of toll-like receptors, and produced colitogenic cytokines, such as IL-6 and IL-23, after activation. Importantly, adoptive transfer of E-cadherin(+) DCs into T cell-restored immunodeficient hosts increased Th17 cell responses in the intestine and led to exacerbation of colitis. These results identify a monocyte-derived inflammatory DC subset that is associated with the pathogenesis of intestinal inflammation, providing a therapeutic target for the treatment of inflammatory bowel disease.

Bilateral effects of hospital patient-safety procedures on nurses' job satisfaction.

AIM: The aim of this study was to examine how hospital patient-safety procedures affect the job satisfaction of hospital nurses. Additionally, we investigated the association between perceived autonomy and hospital patient-safety procedures and job satisfaction. BACKGROUND: Recently, measures for patient safety have been recognized as an essential requirement in hospitals. Hospital patient-safety procedures may enhance the job satisfaction of nurses by improving the quality of their work. However, such procedures may also decrease their job satisfaction by imposing excessive stress on nurses because they cannot make mistakes. METHODS: The participants included 537 nurses at 10 private hospitals in Japan (The surveys were collected from March to July 2012). Factors related to hospital patient-safety procedures were demonstrated using factor analysis, and the associations between these factors and nurses' self-perceived autonomy and job satisfaction were examined using structural equation modelling. FINDINGS: Five factors regarding hospital patient-safety procedures were extracted. Additionally, structural equation modelling revealed statistically significant associations between these factors and the nurses' self-perceived autonomy and job satisfaction. The findings showed that nurses' perceived autonomy of the workplace enhanced their job satisfaction and that their perceptions of hospital patient-safety procedures promoted their job satisfaction. However, some styles of chief nurses' leadership regarding patient safety restrict nurses' independent and autonomous decision-making and actions, resulting in a lowering of job satisfaction. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study demonstrated that hospital patient-safety procedures have ambiguous effects on nurses' job satisfaction. In particular, chief nurses' leadership relating to patient safety can have a positive or negative effect on nurses' job satisfaction. The findings indicated that hospital managers should demonstrate positive attitudes to improve patient safety for nurses' job satisfaction. In addition, policymakers in the hospitals should consider that chief nurses' leadership styles may reduce autonomy and suppress nurses' job satisfaction.

A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism.

Foxp3(+) regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3(+) T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-beta can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103(+) mesenteric lymph node dendritic cells (DCs) that induce the development of Foxp3(+) T reg cells. Importantly, promotion of T reg cell responses by CD103(+) DCs is dependent on TGF-beta and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.

Anaesthetic Management of Pulmonary Metastasectomy in a Patient Infected with Novel Corona Virus SARS-CoV-2.

Prioritisation of individual patients for thoracic surgeries gained importance during the current COVID-19 pandemic to ensure optimal utilisation of resources. We report a 76-year-old-male patient who presented to a tertiary care hospital in Muscat, Oman, 2020, with bilateral pulmonary metastasis. The patient underwent an urgent pulmonary metastasectomy with successful anaesthesia management in an elderly patient despite him testing positive for COVID-19 twice via real-time reverse transcription-polymerase chain reaction. At the 3-month follow-up some pulmonary abnormalities persisted but the patient was recovering well. This report discusses the rationale to perform surgery in this case and highlights the precautions taken for reducing aerosol generation during the various stages of anaesthesia.

Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells.

Intestinal CD103(+) DC promote the differentiation of Foxp3(+) Treg from naïve CD4(+) T cells through mechanisms involving TGF-beta and the dietary metabolite, retinoic acid (RA). In this study, we have analysed whether the specialised features of CD103(+) DC are conserved in colitis. Our results show that inflammation dampens the tolerogenic properties of MLN CD103(+) DC, which is associated with lower expression of tgfbeta2 and aldh1a2. Accordingly, CD103(+) DC taken from colitic mice are impaired in their ability to induce Foxp3(+) Treg and instead favour the emergence of IFN-gamma-producing CD4(+) T cells compared with their steady-state counterparts. BrdU-labelling studies and analysis of ontogeny markers show that CD103(+) DC from steady-state and colitic settings retain similar subset composition and developmental pathways. These results indicate that MLN CD103(+) DC are not hard-wired to promote tolerance but can adapt to environmental conditions. The inflammatory properties of MLN CD103(+) DC in colitic mice may reflect defective gut tolerogenic conditioning or altered migratory pathways and raise the possibility that migratory DC populations contribute to the pathogenesis of inflammatory bowel disease.

Engineering responses to pandemics.

Focusing on pandemic influenza, this chapter approaches the planning for and response to such a major worldwide health event as a complex engineering systems problem. Action-oriented analysis of pandemics requires a broad inclusion of academic disciplines since no one domain can cover a significant fraction of the problem. Numerous research papers and action plans have treated pandemics as purely medical happenings, focusing on hospitals, health care professionals, creation and distribution of vaccines and anti-virals, etc. But human behavior with regard to hygiene and social distancing constitutes a first-order partial brake or control of the spread and intensity of infection. Such behavioral options are "non-pharmaceutical interventions." (NPIs) The chapter employs simple mathematical models to study alternative controls of infection, addressing a well-known parameter in epidemiology, R0, the "reproductive number," defined as the mean number of new infections generated by an index case. Values of R0 greater than 1.0 usually indicate that the infection begins with exponential growth, the generation-to-generation growth rate being R0. R0 is broken down into constituent parts related to the frequency and intensity of human contacts, both partially under our control. It is suggested that any numerical value for R0 has little meaning outside the social context to which it pertains. Difference equation models are then employed to study the effects of heterogeneity of population social contact rates, the analysis showing that the disease tends to be driven by high frequency individuals. Related analyses show the futility of trying geographically to isolate the disease. Finally, the models are operated under a variety of assumptions related to social distancing and changes in hygienic behavior. The results are promising in terms of potentially reducing the total impact of the pandemic.

Nonlinear layered lattice model and generalized solitary waves in imperfectly bonded structures.

We study nonlinear waves in a two-layered imperfectly bonded structure using a nonlinear lattice model. The key element of the model is an anharmonic chain of oscillating dipoles, which can be viewed as a basic lattice analog of a one-dimensional macroscopic waveguide. Long nonlinear longitudinal waves in a layered lattice with a soft middle (or bonding) layer are governed by a system of coupled Boussinesq-type equations. For this system we find conservation laws and show that pure solitary waves, which exist in a single equation and can exist in the coupled system in the symmetric case, are structurally unstable and are replaced with generalized solitary waves.

Fission of a longitudinal strain solitary wave in a delaminated bar.

The aim of the paper is to show that splitting of a waveguide leads to fission of bulk solitons in solids. We study the dynamics of a longitudinal bulk solitary wave in a delaminated, symmetric layered elastic bar. First, we consider a two-layered bar and assume that there is a perfect interface when x<0 and complete debonding (splitting) when x>0 , where the axis Ox is directed along the bar. We derive the so-called doubly dispersive equation (DDE) for a long nonlinear longitudinal bulk wave propagating in an elastic bar of rectangular cross section. We formulate the problem for a delaminated two-layered bar in terms of the DDE with piecewise constant coefficients, subject to continuity of longitudinal displacement and normal stress across the "jump" at x=0 . We find the weakly nonlinear solution to the problem and consider the case of an incident solitary wave. The solution describes both the reflected and transmitted waves in the far field, as well as the diffraction in the near field (in the vicinity of the jump). We generalize the solution to the case of a symmetric n -layered bar. We show that delamination can lead to the fission of an incident solitary wave, and obtain explicit formulas for the number, amplitudes, velocities, and positions of the secondary solitary waves propagating in each layer of the split waveguide. We establish that generally there is a higher-order reflected wave even when the leading order reflected wave is absent.

[Clinical significance of serial monitoring of short-latency somatosensory evoked potential in head injury with special reference to intracranial hypertension].

Short-latency somatosensory evoked potential (SEP) was serially monitored in head-injured patients and its clinical significance was evaluated in relation to auditory brain stem response (ABR), prognosis and other parameters such as intracranial pressure (ICP). SEP, ABR, and ICP were monitored serially and automatically in 16 patients with acute head injury. Glasgow Coma Scale (GCS) score was equal to or less than 8 in 14 cases. High dose barbiturate therapy was performed in 7 cases and intracranial hematoma was removed operatively in 14 cases. SEP was recorded from C3'or C4'-Fz leads on the lesion side following stimulation of the contralateral median nerve, and the difference between the two potentials (N20, N13) defined as central conduction time (CCT) was followed at a basic time interval of 10-20 min. The patients were divided into 3 groups according to N20 finding and the prognosis of each group was analyzed. The final outcome (assessed 6 months after injury) was graded according to Glasgow Outcome Scale as follows: good (good recovery, moderate disability), poor (severe disability, persistent vegetative state), death (death). Three patients with no CCT change showed good recovery (table, 11). Out of 7 patients with no N20 on admission, 5 died due to severely increased ICP and the prognosis for the other 2 cases was poor. The last group consisted of 6 patients in whom CCT varied during hospitalization. In 3 out of these 6 cases N20 finally disappeared due to increased ICP and they died in the acute stage.(ABSTRACT TRUNCATED AT 250 WORDS)

A quantitative survey of the literature on poliovirus infection and immunity.

OBJECTIVE: To examine forces that drive vaccination policy to eradicate wild- and vaccine-derived poliovirus, and to focus on the efficacy of vaccines to support decision-making and further research. METHODS: We searched PubMed and Ovid databases for English-language publications, without date restrictions. We also collected references from major reviews on polio vaccine immunogenicity or protection. We conducted a meta-analysis of human immunity to polio infections using multiple non-linear regression, and built a database from a broad (but not systematic) set of polio vaccine studies (46 studies, >10000 subjects). RESULTS: The outcome was an immunological model representative of many different datasets. Parameters measured immunogenicity to both humoral and mucosal immune compartments for Salk and Sabin vaccines. The immunity model was more highly correlated with the data than a simpler per-dose efficacy model. CONCLUSIONS: The model offers new insights for immunization policy. We measured the mucosal immunogenicity of IPV to a precision that is useful in decision-making for end-game polio immunization policies.

The molecular pathogenesis of endotoxic shock and organ failure.

Sepsis is still associated with a high mortality rate. Septic shock and sequential multiple organ failure have a strong correlation with poor outcome. Lipopolysaccharide (LPS) plays a pivotal role in the initiation of host responses to Gram-negative infection. A number of mediators, such as cytokines, nitric oxide and eicosanoids, are responsible for most of the manifestations caused by LPS, and circulatory failure, leukocyte-induced tissue injury and coagulation disorder appear to be critical determinants in the development of sequential organ failure. Although several anti-LPS or anti-cytokine clinical trials have been attempted, none of them has so far been successful.