The purpose of this study was to compare the relative accuracy of magnetic resonance (MR) imaging (n = 26), endovaginal sonography (EVS) (n = 14), and hysterosalpingography (HSG) (n = 20) in the classification of müllerian duct anomalies in 26 patients. There were 24 cases of surgically proved anomaly, and two patients had normal uteri (one with a vaginal septum). MR imaging allowed diagnosis of 24 of 24 cases (accuracy, 100%), and EVS was correct in 11 of 12 cases (accuracy, 92%). HSG was correct in only four cases. In the diagnosis of septate uterus, MR imaging demonstrated a sensitivity and specificity of 100% and EVS demonstrated a sensitivity of 100% and a specificity of 80%. Both MR imaging and EVS demonstrated a sensitivity and specificity of 100% in distinguishing those anomalies that did not require surgery. The high accuracy of MR imaging and EVS permit noninvasive differentiation of uterine anomalies and can spare women diagnostic laparoscopy, promoting cost-effective diagnosis.

Tolerance to bacterial cell wall components including lipopolysaccharide (LPS) may represent an essential regulatory mechanism during bacterial infection. Two members of the Toll-like receptor (TLR) family, TLR2 and TLR4, recognize the specific pattern of bacterial cell wall components. TLR4 has been found to be responsible for LPS tolerance. However, the role of TLR2 in bacterial lipoprotein (BLP) tolerance and LPS tolerance is unclear. Pretreatment of human THP-1 monocytic cells with a synthetic bacterial lipopeptide induced tolerance to a second BLP challenge with diminished tumor necrosis factor-␣ and interleukin-6 production, termed BLP tolerance. Furthermore, BLP-tolerized THP-1 cells no longer responded to LPS stimulation, indicating a cross-tolerance to LPS. Induction of BLP tolerance was CD14-independent, as THP-1 cells that lack membranebound CD14 developed tolerance both in serum-free conditions and in the presence of a specific CD14 blocking monoclonal antibody (MEM-18). Pre-exposure of THP-1 cells to BLP suppressed mitogen-activated protein kinase phosphorylation and nuclear factor-B activation in response to subsequent BLP and LPS stimulation, which is comparable with that found in LPStolerized cells, indicating that BLP tolerance and LPS tolerance may share similar intracellular pathways. However, BLP strongly enhanced TLR2 expression in non-tolerized THP-1 cells, whereas LPS stimulation had no effect. Furthermore, a specific TLR2 blocking monoclonal antibody (2392) attenuated BLP-induced, but not LPS-induced, tumor necrosis factor-␣ and interleukin-6 production, indicating BLP rather than LPS as a ligand for TLR2 engagement and activation. More importantly, pretreatment of THP-1 cells with BLP strongly inhibited TLR2 activation in response to subsequent BLP stimulation. In contrast, LPS tolerance did not prevent BLPinduced TLR2 overexpression. These results demonstrate that BLP tolerance develops through downregulation of TLR2 expression.

Tolerance to bacterial cell wall components is an adaptive host response. Endotoxin/LPS tolerance is characterized by a survival advantage against subsequent lethal LPS challenge. However, it is uncertain whether LPS tolerance can afford protection against other septic challenges. In this study, we show that tolerance induced by bacterial lipoprotein (BLP) protects mice against not only BLP-induced lethality, but also LPS-, live bacteria-, and polymicrobial sepsis-induced lethality. In contrast, LPS tolerance offers no survival benefit against the latter two challenges. Furthermore, induction of BLP tolerance results in overexpression of complement receptor type 3 and FcγIII/IIR on neutrophils (polymorphonuclear neutrophils) and peritoneal macrophages, with increased bacterial recognition and bactericidal activity, whereas LPS-tolerized mice exhibit an impaired ability to ingest and to kill bacteria. These results indicate that BLP tolerance is a novel adaptive host response associated with a unique protective effect during septic shock.

Both 1,25(OH)(2)D(3) and other VDR agonists significantly reduce the pro-inflammatory response to antigen challenge in CF airway epithelial cells. VDR agonists have significant therapeutic potential in CF.

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Background Sublethal doses of endotoxin (lipopolysaccharide; LPS) induce tolerance in vivo and in vitro, and protect against the lethal effects of a further LPS challenge. Tolerance is characterized by diminished production of tumour necrosis factor (TNF) α. Bacterial lipoprotein (BLP), another bacterial wall component, might induce tolerance against its own lethal effects as well as those of endotoxin. Methods Ninety male MF‐1 mice (mean(s.d.) weight 18(2) g) were randomized into three groups (n = 30 per group). Mice in group 1 received a single BLP‐tolerant dose (10 mg kg−1) by intraperitoneal injection, whereas mice in group 2 received a second BLP‐tolerant dose (10 mg kg−1) after 24 h. Following induction of tolerance, all mice were challenged with high doses of LPS 45 mg kg−1, BLP 45 mg kg−1 or a combination of LPS 30 mg kg−1 plus BLP 30 mg kg−1. Mice in group 3 were treated with a high dose of the above agents only. Mortality was assessed at 24 and 48 h. Macrophages were isolated from mice and pretreated in vitro with culture medium alone or culture medium containing LPS 10 ng ml−1 or BLP 10 ng ml−1 for 24 h. The cells were then stimulated with high doses (100–1000 ng ml−1) of LPS, BLP or LPS plus BLP for 6 h. The cell culture supernatants were collected and TNF‐α levels were determined using enzyme‐linked immunosorbent assay. Results BLP‐induced tolerance significantly improved survival compared with that of mice without tolerance (P < 0·05). In vitro, pretreatment of murine macrophages with BLP significantly attenuated LPS, BLP and LPS plus BLP stimulation‐induced TNF‐α production. Mortality rate LPS 45 mg kg−1 BLP 45 mg kg−1 LPS 30 mg kg−1 + BLP 30 mg kg−1 24 h 48 h 24 h 48 h 24 h 48 h No tolerance808060606080Single tolerance40*40*0*0*0*0*Repeat tolerance20*30*0*0*0*0* Conclusion BLP mimics LPS in the development of the systemic inflammatory response syndrome. Furthermore, BLP is capable of inducing tolerance, both in vivo and in vitro, which subsequently prevents BLP‐ and LPS plus BLP‐induced death. © 2000 British Journal of Surgery Society Ltd

Background An important consequence of population ageing has been the increasing number of older adults who live alone. According to TILDA data, older adults with the lowest levels of education tend to experience most social isolation and there is a strong association between living alone and loneliness. We sought to compare the cohort of patients open to the Integrated Care for Older Persons (ICPOP) team in a University Teaching Hospital serving a community area of approx. 300,000 population, to this national dataset. Methods A convenience sample of 174 patients who underwent comprehensive geriatric assessment via domiciliary visit between July 2021-May 2022 by was analysed. Data was anonymised and analysis was performed using SPSS v.27. Results The average age was 81.5 (±8.1) with 63% women in the sample. Eighty-five older adults i.e. 49% of the sample either lived alone or spent more than 21 hours alone per 24-hour period. Compared to those who live with someone, those who lived alone had higher rates of likely depression as determined by Geriatric Depression Score (6.6 vs 4.8 p=0.007). They were also likely to have less educational attainment, as determined by years spent in full time education (11.81 vs 10.42 42 p= 0.0016) and those living alone had overall less central heating in their homes than those not living alone (64/85 vs 81/89 p=0.0109). There were no significant differences in the rates of polypharmacy, falls, dementia and home ownership between groups. There were higher levels of frailty in the group living with someone than those living alone as determined by Clinical Frailty Scale (6.14 vs 5.23 p&lt;0.001). Conclusion A high proportion of patients seen by our ICPOP team live alone and have complex care needs that require an innovative, multidisciplinary approach. Financial vulnerability in this group is likely to compound isolation and loneliness.