Rapid Discrimination of Salmonella enterica Serovar Typhi from Other Serovars by MALDI-TOF Mass Spectrometry

Systemic infections caused by Salmonella enterica are an ongoing public health problem especially in Sub-Saharan Africa. Essentially typhoid fever is associated with high mortality particularly because of the increasing prevalence of multidrug-resistant strains. Thus, a rapid blood-culture based bacterial species diagnosis including an immediate sub-differentiation of the various serovars is mandatory. At present, MALDI-TOF based intact cell mass spectrometry (ICMS) advances to a widely used routine identification tool for bacteria and fungi. In this study, we investigated the appropriateness of ICMS to identify pathogenic bacteria derived from Sub-Saharan Africa and tested the potential of this technology to discriminate S. enterica subsp. enterica serovar Typhi (S. Typhi) from other serovars. Among blood culture isolates obtained from a study population suffering from febrile illness in Ghana, no major misidentifications were observed for the species identification process, but serovars of Salmonella enterica could not be distinguished using the commercially available Biotyper database. However, a detailed analysis of the mass spectra revealed several serovar-specific biomarker ions, allowing the discrimination of S. Typhi from others. In conclusion, ICMS is able to identify isolates from a sub-Saharan context and may facilitate the rapid discrimination of the clinically and epidemiologically important serovar S. Typhi and other non-S. Typhi serovars in future implementations

Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Down-Regulates IL-22R1 Expression through a Cis-Acting Element within the Promoter Region

Kaposi's sarcoma-associated herpesvirus (KSHV) is considered to be a necessary, but not sufficient, causal agent of Kaposi's sarcoma (KS). All forms of KS are characterized by the proliferation of spindle-shaped cells, and most (>90%) spindle cells from KS lesions are latently infected with KSHV. During KSHV latency, only a few viral genes are expressed. Among those latent genes, the ORF 73 gene encodes the latency-associated nuclear antigen (LANA), which is critical for the establishment and maintenance of the latent KSHV infection. Much evidence suggests that many cytokines can increase the frequency and aggressiveness of KS. In this study, a microarray analysis of KS and normal tissues revealed that multiple cytokines and cytokine receptors are regulated by KSHV latent infection. Of special interest, IL-22R1 transcript level was found to be down-regulated in the KS tissue. To study the possible regulation of IL-22R1 by LANA, the IL-22R1 promoter was constructed and found to contain a LANA-binding site (LBS). LANA was demonstrated to down-regulate IL-22R1 expression via direct binding to the LBS located within the IL-22R1 promoter region. Furthermore, KSHV latently infected cells showed an impaired response to IL-22 stimulation. These results suggest that LANA can regulate host factor expression by directly binding to a cis-acting element within the factor's promoter to benefit latent viral infection and suppression of the antiviral immune response

Sexual dimorphisms in adult human neural, mesoderm-derived, and neural crest-derived stem cells

Greiner J, Merten M, Kaltschmidt C, Kaltschmidt B. Sexual dimorphisms in adult human neural, mesoderm-derived, and neural crest-derived stem cells. FEBS letters. 2019;593(23):3338-3352.Sexual dimorphisms contribute, at least in part, to the severity and occurrence of a broad range of neurodegenerative, cardiovascular, and bone disorders. In addition to hormonal factors, increasing evidence suggests that stem cell‐intrinsic mechanisms account for sex‐specific differences in human physiology and pathology. Here, we discuss sex‐related intrinsic mechanisms in adult stem cell populations, namely mesoderm‐derived stem cells, neural stem cells (NSCs), and neural crest‐derived stem cells (NCSCs), and their implications for stem cell differentiation and regeneration. We particularly focus on sex‐specific differences in stem cell‐mediated bone regeneration, in neuronal development, and in NSC‐mediated neuroprotection. Moreover, we review our own recently published observations regarding the sex‐dependent role of NF‐κB‐p65 in neuroprotection of human NCSC‐derived neurons and sex differences in NCSC‐related disorders, so‐called neurocristopathies. These observations are in accordance with the increasing evidence pointing toward sex‐specific differences in neurocristopathies and degenerative diseases like Parkinson's disease or osteoporosis. All findings discussed here indicate that sex‐specific variability in stem cell biology may become a crucial parameter for the design of future treatment strategies

Response to chemotherapy in patients with recurrent rectal cancer in previously irradiated area

Tumor lesions in previously irradiated area may have a less favorable response to chemotherapy compared to tumor sites outside the radiation field. The aim of the present study was to evaluate the response to chemotherapy of locally recurrent rectal cancer (LRRC) within the previous radiation field compared to the response of distant metastases outside the radiation field. All patients with LRRC referred between 2000 and 2012 to our tertiary university hospital were reviewed. The response to chemotherapy of LRRC within previously irradiated area was compared to the response of synchronous distant metastases outside the radiation field according to the Response Evaluation Criteria in Solid Tumors (RECIST). Out of 363 cases with LRRC, 29 previously irradiated patients with distant metastases were treated with chemotherapy and eligible for analysis. Twenty-six patients (89 %) suffered a first recurrence and three patients (11 %) a second recurrence. These patients were followed with a median of 22 months (IQR, 9-40 months) and had a median survival of 33 months (IQR, 14-42). In 23 patients (79 %), the local recurrence showed stable disease, but the overall response rate of the local recurrences in the previously irradiated area was significantly lower than the response rate of distant metastases outside the radiation field (10 vs. 41 %,p = 0.034). Previously irradiated patients with LRRC have a lower response rate to chemotherapy of the local recurrence within the radiation field compared to the response rate of distant metastases outside the radiation field. This suggests that chemotherapy for local palliation may not have the desired effect