Strategies for elimination of rubella in pregnancy and of congenital rubella syndrome in high and upper-middle income countries

Rubella infection generally leads to mild symptoms; otherwise, in pregnant women it can cause severe damages. The only way to prevent rubella is vaccine. Before the introduction of the vaccine, up to 4 babies in 1000 live births were born with CRS.This work aims to review the most important strategies for the elimination of CRS in upper and high-income countries.Papers were selected through a PubMed search up to January 2019, using keywords rubella, congenital rubella syndrome and epidemiology. Articles published in the last 12 years and referred to upper income and high-income countries in title or abstract were included.Sixty-five papers were selected dealing with one or more of the following strategies: increasing of rubella vaccination coverage in childbearing age women, males, immigrants; exploitation of all appropriate occasions; improving of rubella surveillance.Despite numerous suggestions and indications for valid strategies to eliminate rubella in pregnancy and congenital rubella syndrome, a practical application is often missing

Immune Response in Young Thoroughbred Racehorses under Training

Training has a great impact on the physiology of an athlete and, like all stressful stimuli, can trigger an innate immune response and inflammation, which is part of a wider coping strategy of the host to restore homeostasis. The Thoroughbred racehorse is a valid animal model to investigate these changes thanks to its homogeneous training and highly selected genetic background. The aim of this study was to investigate modifications of the innate immune response and inflammation in young untrained Thoroughbred racehorses during the first training season through haematological and molecular investigations. Twenty-nine Thoroughbred racehorses were followed during their incremental 3-month sprint exercise schedule. Blood collection was performed at time 0 (T0; before starting the intense training period), 30 days after T0 (T30), and 90 days after T0 (T90). Haematological parameters (red and white blood cells, haemoglobin, and platelets) were evaluated and haematocrit (HCT), mean corpuscular haemoglobin concentration (MCHC), and red cells width distribution + standard deviation (RDW-SD) were calculated. Moreover, via RT-qPCR, we investigated the expression of, Interleukin 1β (IL-1β), Interleukin 4 (IL-4) Interleukin 6 (IL-6), Interleukin 2 (IL-2), Interleukin 3 (IL-3), Interleukin 5 (IL-5) Interleukin 8 (IL-8), Trasformig Growth Factor β and α (TGF-β), Tumor necrosis factor α (TNF-α), and Interferon γ (IFN-γ)genes. Main corpuscular volume (MCV) showed a significant (p = 0.008) increase at T90. Main corpuscular haemoglobin (MCH) and haemoglobin concentration (MCHC) values were significantly augmented at both T30 (p < 0.001) and T90 (p < 0.001). Basophils were significant increased at T30 (p = 0.02) and eosinophils were significantly increased at T90 (p = 0.03). Significant differences in gene expression were found for all the genes under study, with the exception of IFN-γ and TNF-α. In particular, IL-2 (T30, p = 0.011; T90, p = 0.015), IL-4 (T30, p = 0.009; T90, p < 0.001), and IL-8 (T30, p < 0.001; T90, p < 0.001) genes were significantly upregulated at both T30 and T90 with respect to T0, TGF-β was intensely downregulated at T30 (p < 0.001), IL-5 gene expression was significantly decreased at T90 (p = 0.001), while IL-1β (p = 0.005) and IL-3 (p = 0.001) expression was strongly augmented at the same time. This study highlighted long-term adjustments of O2 transport capability that can be reasonably traced back to exercise adaptation. Moreover, the observed changes of granulocyte numbers and functions and inflammatory cytokine gene expression confirm a major role of the innate immune system in the response to the complex of stressful stimuli experienced during the training period

Cardiotocography pattern: not always a true friend

: Fetal well-being in labor could be assessed trough cardiotocography (CTG). Some doubts have been raised about its unequivocal applicability. Pathological CTG is in most cases connected to fetal acidosis at birth, but other potential causes must be considered in the differential diagnosis. A 31-years-old G2P1 patient referred to our Department of Obstetrics and Gynecology for her scheduled post-term CTG at 40 weeks and 3 days of gestation. The pregnancy was uneventful. CTG was classified as suspicious, and after pharmacological induction, it switched as pathological: an emergency cesarean section was performed. Venous and arterial blood sample taken from the umbilical cord were normal. The next assessments revealed that Atrial Flutter (AFL) occurred at birth. Suspicious CTG is not always associated to neonatal asphyxia. Cardiotocography can help not only in the evaluation of fetal distress, but also in the assessment of global fetal cardiac activity. The presence of a fetal heart defect should be considered when CTG is suspicious

Cross-species infectivity of H3N8 influenza virus in an experimental infection in swine

Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool.We thank Jaime Maldonado and HIPRA (Spain) for the A/Swine/Spain/ 54008/2004 (H3N2) strain, Edward J. Dubovi and Cornell University for the A/Canine/NY/105447/08 (H3N8) IAV strain, T. M. Chambers and the University of Kentucky for the A/Equine/OH/1/03 (H3N8) IAV strain, and Hon Ip and the U.S. Geological Survey National Wildlife Health Center for the A/American black duck/Maine/44411-532/2008 (H3N8) and the A/Harbor Seal/New Hampshire/179629/2011 (H3N8) IAV strains. We thank Sergio López, David Solanes, Francisco X. Abad, Jordi Alberola, Jaume Martorell, and Eduard J. Cunilleras for help in providing different samples and during the experimental infections, as well as the personnel in Cat3 laboratories and the animal house. We thank Adolfo García-Sastre for providing materials and for support as the principal investigator of the NIAID-funded Center for Research in Influenza Pathogenesis (HHSN266200700010C). The research leading to these results received funding from the European Community’s Seventh Framework Programme (FP7, 2007-2013), the Research Infrastructures Action under grant FP7-228393 (a NADIR project), and projects AGL2010-22200-C02-01 and AGL2007-60274 of the Spanish Ministry of Science and Innovation

IMPACT OF PHYSICAL EXERCISE ON PSYCHOLOGICAL WELL-BEING AND PSYCHIATRIC DISORDERS

Background: Physical exercise is one of the major features of human health, as it is involved in several physiological processes and related to major benefits in reducing body fat, myocardial infarction, hypertension and insulin resistance risk. Physical exercise also plays a positive role in achieving psychological well-being that can be defined as a state of happiness and serenity, with low levels of distress, overall good physical and mental health and outlook and a good quality of life. Aim of the paper: To review the positive effects of physical activity on psychological well-being and its possible neurobiological underpinnings, as well as its impact on several neuropsychiatric disorders, such as depression, anxiety, eating disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, schizophrenia and some neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Methods: The PubMed, Scopus, Embase, PsycINFO and Google Scholar databases were searched for full text articles published in the latest thirty years on the benefits that physical activity exerts on psychological well-being. Objectives: This study aims to identify the common and differential elements of the DLD (SLI) and LD through a quantitative and qualitative analysis. Results: An impressive amount of data support the positive role of physical activity on psychological well-being and a large amount of research has focused on its beneficial effects in improving the symptoms of the main neuropsychiatric disorders, while highlighting its usefulness as an adjuvant option to psychopharmacological treatments and psychotherapy. In particular, exercise would deeply affect CNS morphology and function, through heterogeneous mechanisms including, amongst the others, the production of hormones, neurotransmitters and neurotrophins, the promotion of angiogenesis and neuroplasticity, and the regulation of gene expression. Conclusion: Literature indicates that the promotion of physical activity may work like an adjunctive and/or augmentation strategy to enhance drugs or psychological treatments, or even as an alternative option in major depression

Chemotherapy and palliative care near end-of life: Examining the appropriateness at a cancer institute for colorectal cancer patients

Background: Appropriate cessation of chemotherapy and timely referral of patients to hospice services are crucial for the quality of care near death. We investigated the quality of care in our Cancer Institute in very advanced metastatic colorectal cancer patients treated in real life. Patients and Methods: We performed a retrospective analysis of electronic medical data of patients with metastatic colorectal cancer who were candidates for chemotherapy during the study period (1 January 2007-30 June 2014) and died before 31 December 2014. Quality-of-cancer-care indicators were calculated for the overuse of chemotherapy and referral to hospice. Predictive factors of chemotherapy discontinuation and hospice referral in end-of life care were investigated using parametric and nonparametric methods. Results: Of the 365 patients who died before 31 December 2014, 26 (7.1%) received chemotherapy in the last 14 days of life and 36 (9.8%) started a new chemotherapy regimen in the last 30 days of life. Factors associated with the overuse of chemotherapy were being < 70 years of age for both indicators and not having received advanced chemotherapy treatments for the former indicator. The majority of patients (74.7%) had access to hospice services, of whom only a small percentage (7.2%) accessed them very near to death. Conclusions: According to the criteria used, our Institute provides a good quality of cancer care for dying colorectal cancer patients, measured by the use of chemotherapy and referral to hospice in their last days of life

Insulin-like Growth Factor-1 Receptor (IGF-1R) expression on Circulating Tumor Cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial

Purpose To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. Methods CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. Results Seventy-two out of 126 randomized patients were evaluated: 57% had >= 1 IGF-1R positive CTC and 37.5% >= 4 IGF-1R negative cells; 42% had CTC count >= 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. Conclusion Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. Clinical trial registration: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26)

PYRROLO[1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) induce apoptosis in K562 cells

BACKGROUND: The objective of this study was to gain insight into the molecular mechanism of induced cell death (apoptosis) by PYRROLO [1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) series compounds, using human (K562) cells as a model. METHODS: We focused our attention on some members of the PBTDs family to test their potential apoptotic activity in K562 cells. Important apoptotic activity was demonstrated, as evidenced by the concentration and percentage of cell death quantified by measuring PI-uptake by flow cytometry, and DNA fragmentation analyzed by agarose gel electrophoresis, generating a characteristic ladder pattern of discontinuous DNA fragments. The expression of Bcl-2 family was tested using western blotting and transfection method. RESULTS: PBTDs-mediated suppression of K562 cell proliferation was induced by apoptosis characterized by the appearance of DNA fragmentation and was associated with the poly(ADP-ribose)polymerase (PARP) cleavage. PBTD-1 and -3 treatment resulted in caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. Furthermore, we used K562/vector and K562/bcl-2 cells, which were generated by transfection of the cDNA of the Bcl-2 gene. As compared with K562/vector, K562/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment with 10 muM PBTD-1 and -3 for 24 h produced morphological features of apoptosis and DNA fragmentation in K562/vector cells, respectively. In contrast, PBTD-1 and -3-induced caspase-3 activation and apoptosis were inhibited in K562/Bcl-2. Furthermore, Bcl-2 overexpressing cells exhibited less cytocrome c release during PBTDs-induced apoptosis. CONCLUSION: These results indicate that PBTDs effectively induce apoptosis of K562 leukemia cells through the activation of caspase cascades. In addition, these findings indicate that Bcl-2 inhibits PBTD-1 and -3 induced-apoptosis via a mechanism that interferes with cytocrome c release, and the activity of caspase-3, which is involved in the execution of apoptosis

All-trans retinoic acid (ATRA) in non-promyelocytic acute myeloid leukemia (AML): results of combination of ATRA with low-dose Ara-C in three elderly patients with NPM1-mutated AML unfit for intensive chemotherapy and review of the literature

Based upon the clinical behavior of three patients, we suggest that the combination of low-dose Ara-C and all-trans retinoic acid may potentially be effective in some elderly patients, unfit for intensive chemotherapy, affected with NPM1-mutated acute myeloid leukemia without FLT3 mutations, warranting perspective clinical studies in these selected patients