The immune response against Chlamydia suis genital tract infection partially protects against re-infection

International audienceThe aim of the present study was to reveal the characteristic features of genital Chlamydia suis infection and re-infection in female pigs by studying the immune response, pathological changes, replication of chlamydial bacteria in the genital tract and excretion of viable bacteria. Pigs were intravaginally infected and re-infected with C. suis strain S45, the type strain of this species. We demonstrated that S45 is pathogenic for the female urogenital tract. Chlamydia replication occurred throughout the urogenital tract, causing inflammation and pathology. Furthermore, genital infection elicited both cellular and humoral immune responses. Compared to the primo-infection of pigs with C. suis, re-infection was characterized by less severe macroscopic lesions and less chlamydial elementary bodies and inclusions in the urogenital tract. This indicates the development of a certain level of protection following the initial infection. Protective immunity against re-infection coincided with higher Chlamydia-specific IgG and IgA antibody titers in sera and vaginal secretions, higher proliferative responses of peripheral blood mononuclear cells (PBMC), higher percentages of blood B lymphocytes, monocytes and CD8+ T cells and upregulated production of IFN-γ and IL-10 by PBMC

The interRAI Acute Care instrument incorporated in an eHealth system for standardized and web-based geriatric assessment: strengths, weaknesses, opportunities and threats in the acute hospital setting

BACKGROUND: The interRAI Acute Care instrument is a multidimensional geriatric assessment system intended to determine a hospitalized older persons’ medical, psychosocial and functional capacity and needs. Its objective is to develop an overall plan for treatment and long-term follow-up based on a common set of standardized items that can be used in various care settings. A Belgian web-based software system (BelRAI-software) was developed to enable clinicians to interpret the output and to communicate the patients’ data across wards and care organizations. The purpose of the study is to evaluate the (dis)advantages of the implementation of the interRAI Acute Care instrument as a comprehensive geriatric assessment instrument in an acute hospital context. METHODS: In a cross-sectional multicenter study on four geriatric wards in three acute hospitals, trained clinical staff (nurses, occupational therapists, social workers, and geriatricians) assessed 410 inpatients in routine clinical practice. The BelRAI-system was evaluated by focus groups, observations, and questionnaires. The Strengths, Weaknesses, Opportunities and Threats were mapped (SWOT-analysis) and validated by the participants. RESULTS: The primary strengths of the BelRAI-system were a structured overview of the patients’ condition early after admission and the promotion of multidisciplinary assessment. Our study was a first attempt to transfer standardized data between home care organizations, nursing homes and hospitals and a way to centralize medical, allied health professionals and nursing data. With the BelRAI-software, privacy of data is guaranteed. Weaknesses are the time-consuming character of the process and the overlap with other assessment instruments or (electronic) registration forms. There is room for improving the user-friendliness and the efficiency of the software, which needs hospital-specific adaptations. Opportunities are a timely and systematic problem detection and continuity of care. An actual shortage of funding of personnel to coordinate the assessment process is the most important threat. CONCLUSION: The BelRAI-software allows standardized transmural information transfer and the centralization of medical, allied health professionals and nursing data. It is strictly secured and follows strict privacy regulations, allowing hospitals to optimize (transmural) communication and interaction. However, weaknesses and threats exist and must be tackled in order to promote large scale implementation

GATA-3 in Human T Cell Helper Type 2 Development

The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell–mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/− individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell–mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3+/+ controls. Concordant with these data, silencing of GATA-3 in GATA-3+/+ CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo

Chlamydia trachomatis L2c infection in a porcine model produced urogenital pathology and failed to induce protective immune responses against re-infection

The current study was designed to evaluate the pathogenesis, pathology and immune response of female genital tract infection with Chlamydia trachomatis L2c, the most recently discovered lymphogranuloma venereum strain, using a porcine model of sexually transmitted infections. Pigs were mock infected, infected once or infected and re-infected intravaginally, and samples were obtained for chlamydial culture, gross and microscopic pathology, and humoral and cell-mediated immunity. Intravaginal inoculation of pigs with this bacterium resulted in an infection that was confined to the urogenital tract, where inflammation and pathology were caused that resembled what is seen in human infection. Re-infection resulted in more severe gross pathology than primary infection, and chlamydial colonization of the urogenital tract was similar for primary infected and re- infected pigs. This indicates that primary infection failed to induce protective immune responses against re-infection. Indeed, the proliferative responses of mononuclear cells from blood and lymphoid tissues to C. trachomatis strain L2c were never statistically different among groups, suggesting that C. trachomatis-specific lymphocytes were not generated following infection or re-infection. Nevertheless, anti-chlamydial antibodies were elicited in sera and vaginal secretions after primary infection and re-infection, clearly resulting in a secondary systemic and mucosal antibody response. While primary infection did not protect against reinfection, the porcine model is relevant for evaluating immune and pathogenic responses for emerging and known C. trachomatis strains to advance drug and/or vaccine development in humans

Fetal sex determination in twin pregnancies using non-invasive prenatal testing

Non-invasive prenatal testing (NIPT) is accurate for fetal sex determination in singleton pregnancies, but its accuracy is not well established in twin pregnancies. Here, we present an accurate sex prediction model to discriminate fetal sex in both dichorionic diamniotic (DCDA) and monochorionic diamniotic/monochorionic monoamniotic (MCDA/MCMA) twin pregnancies. A retrospective analysis was performed using a total of 198 twin pregnancies with documented sex. The prediction was based on a multinomial logistic regression using the normalized frequency of X and Y chromosomes, and fetal fraction estimation. A second-step regression analysis was applied when one or both twins were predicted to be male. The model determines fetal sex with 100% sensitivity and specificity when both twins are female, and with 98% sensitivity and 95% specificity when a male is present. Since sex determination can be clinically important, implementing fetal sex determination in twins will improve overall twin pregnancies management

Metal mining and birth defects : a case-control study in Lubumbashi, Democratic Republic of the Congo

Background Widespread environmental contamination caused by mining of copper and cobalt has led to concerns about the possible association between birth defects and exposure to several toxic metals in southern Katanga, Democratic Republic of the Congo (DRC). We therefore aimed to assess the possible contribution of parental and antenatal exposure to trace metals to the occurrence of visible birth defects among neonates. Methods We did a case-control study between March 1, 2013, and Feb 28, 2015, in Lubumbashi, DRC. We included newborns with visible birth defects (cases) and healthy neonates born in the same maternity ward (controls). Mothers were interviewed about potentially relevant exposures, including their partners' jobs. Various trace metals were measured by inductively coupled plasma mass spectrometry in maternal urine, maternal blood, umbilical cord blood, placental tissue, and surface dust at home. Multivariable logistic regression analyses were done to calculate adjusted odds ratios and their 95% CIs (CI). Findings Our study included 138 neonates with visible birth defects (about 0.1% of the 133 662 births in Lubumbashi during the study period) and 108 control neonates. Potential confounders were similarly distributed between cases and controls. Vitamin consumption during pregnancy was associated with a lower risk of birth defects (adjusted odds ratio 0.2, 95% CI 0.1-0.5). Mothers having paid jobs outside the home (2.8, 1.2-6.9) and fathers having mining-related jobs (5.5, 1.2-25.0) were associated with a higher risk of birth defects. We found no associations for trace metal concentrations in biological samples, except for a doubling of manganese (Mn; 1.7, 1.1-2.7) and zinc (Zn; 1.6, 0.9-2.8) in cord blood. In a separate model including placentas, a doubling of Mn at the fetal side of the placenta was associated with an increased risk of birth defects (3.3, 1.2-8.0), as was a doubling of cord blood Zn (5.3, 1.6-16.6). Interpretation To our knowledge, this is the first study of the effects of mining-related pollution on newborns in sub-Saharan Africa. Paternal occupational mining exposure was the factor most strongly associated with birth defects. Because neither Mn nor Zn are mined in Lubumbashi, the mechanism of the association between their increased prenatal concentrations and birth defects is unclear

Unplanned readmission prevention by a geriatric emergency network for transitional care (URGENT): a prospective before-after study

URGENT is a comprehensive geriatric assessment (CGA) based nurse-led care model in the emergency department (ED) with geriatric follow-up after ED discharge aiming to prevent unplanned ED readmissions. Methods A quasi-experimental study (sequential design with two cohorts) was conducted in the ED of University Hospitals Leuven (Belgium). Dutch-speaking, community-dwelling ED patients aged 70 years or older were eligible for enrolment. Patients in the control cohort received usual care. Patient in the intervention cohort received the URGENT care model. A geriatric emergency nurse conducted CGA and interdisciplinary care planning among older patients identified as at risk for adverse events (e.g. unplanned ED readmission, functional decline) with the interRAI ED Screener (c) and clinical judgement of ED staff. Case manager follow-up was offered to at risk patients without hospitalization after index ED visit. For inpatients, geriatric follow-up was guaranteed on an acute geriatric ward or by the inpatient geriatric consultation team on a non-geriatric ward if considered necessary. Primary outcome was unplanned 90-day ED readmission. Secondary outcomes were ED length of stay (LOS), hospitalization rate, in-hospital LOS, 90-day higher level of care, 90-day functional decline and 90-day post-hospitalization mortality. Results Almost half of intervention patients (404/886 = 45.6%) were categorized at risk. These received on average seven advices. Adherence rate to advices on the ED, during hospitalization and in community care was 86.1, 74.6 and 34.1%, respectively. One out of four at risk patients without hospitalization after index ED visit accepted case manager follow-up. Unplanned ED readmission occurred in 170 of 768 (22.1%) control patients and in 205 of 857 (23.9%) intervention patients (p = .11). The intervention group had shorter ED LOS (12.7 h versus 19.1 h in the control group; p < .001), but higher rate of hospitalization (70.0% versus 67.0% in the control group; p = .003)

Predicting hospitalisation-associated functional decline in older patients admitted to a cardiac care unit with cardiovascular disease: a prospective cohort study

Up to one in three of older patients who are hospitalised develop functional decline, which is associated with sustained disability, institutionalisation and death. This study developed and validated a clinical prediction model that identifies patients who are at risk for functional decline during hospitalisation. The predictive value of the model was compared against three models that were developed for patients admitted to a general medical ward.; A prospective cohort study was performed on two cardiac care units between September 2016 and June 2017. Patients aged 75 years or older were recruited on admission if they were admitted for non-surgical treatment of an acute cardiovascular disease. Hospitalisation-associated functional decline was defined as any decrease on the Katz Index of Activities of Daily Living between hospital admission and discharge. Predictors were selected based on a review of the literature and a prediction score chart was developed based on a multivariate logistic regression model.; A total of 189 patients were recruited and 33% developed functional decline during hospitalisation. A score chart was developed with five predictors that were measured on hospital admission: mobility impairment = 9 points, cognitive impairment = 7 points, loss of appetite = 6 points, depressive symptoms = 5 points, use of physical restraints or having an indwelling urinary catheter = 5 points. The score chart of the developed model demonstrated good calibration and discriminated adequately (C-index = 0.75, 95% CI (0.68-0.83) and better between patients with and without functional decline (chi; 2; = 12.8, p = 0.005) than the three previously developed models (range of C-index = 0.65-0.68).; Functional decline is a prevalent complication and can be adequately predicted on hospital admission. A score chart can be used in clinical practice to identify patients who could benefit from preventive interventions. Independent external validation is needed