Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

Background: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care.

Primary HSV-2 Infection Complicated by Radiculomyelitis in a Young Immunocompetent Female Patient with Inherited Chromosomally Integrated HHV-6: A Case Report.

Background: HSV-1, HSV-2 and VZV are alpha Herpesviruses, neurotropic viruses that are associated with various neurologic complications upon primary infection or reactivation. Cases of myelitis and radiculomyelitis are rare and appropriate etiologic diagnoses can be tricky.

Case Presentation: Here we describe the case of a young immunocompetent woman who developed painful and extended vesicular genital lesions, with subsequent radiculomyelitis.

Clinical sign and biomarker-based algorithm to identify bacterial pneumonia among outpatients with lower respiratory tract infection in Tanzania.

Background: Inappropriate antibiotics use in lower respiratory tract infections (LRTI) is a major contributor to resistance. We aimed to design an algorithm based on clinical signs and host biomarkers to identify bacterial community-acquired pneumonia (CAP) among patients with LRTI.

Methods: Participants with LRTI were selected in a prospective cohort of febrile (≥ 38 °C) adults presenting to outpatient clinics in Dar es Salaam.

Unexpected associations between respiratory viruses and bacteria with Pulmonary Function Testing in children suffering from Cystic Fibrosis (MUCOVIB study).

Background: Various bacterial and viral assemblages composing Cystic Fibrosis (CF) lung microbiota contribute to long-term lung function decline over time. Yet, the impact of individual microorganisms on pulmonary functions remains uncertain in children with CF.

Methods: As part of the 'Mucoviscidosis, respiratory VIruses, intracellular Bacteria and fastidious organisms'' project, children with CF were longitudinally followed in a Swiss multicentric study.

Prognosis of Laboratory-Confirmed Influenza and Respiratory Syncytial Virus in Acute Heart Failure.

Concomitant respiratory viral infections may influence clinical outcomes of acute decompensated heart failure (ADHF) but this association is based on indirect observation. The aim of this study was to evaluate the prevalence and impact of laboratory-confirmed influenza or respiratory syncytial virus (RSV) infection on outcomes in patients hospitalised for ADHF. Prospective cohort of patients hospitalised for ADHF with systematic influenza and RSV screening using real-time PCR on nasopharyngeal swabs.

Viral co-infections among SARS-CoV-2-infected children and infected adult household contacts.

We evaluated the rates of viral respiratory co-infections among SARS-CoV-2-infected children. Twelve percent of SARS-CoV-2-infected children had viral co-infection with one or more common respiratory viruses. This was significantly more frequent than among their SARS-CoV-2-infected adult household contacts (0%; p=0.

A community outbreak of Legionnaires' disease in Geneva, Switzerland, June to September 2017.

Purpose: Eight confirmed cases of Legionnaires’ disease were identified at the Geneva University Hospitals between 28 July 2017 and 02 August 2017, leading to a detailed outbreak investigation.

Methods: Legionnaires’ disease cases were defined according to Swiss and European (ELDSNet) consensus guidelines. An outbreak investigation task force was put in place.

Dengue fever in Dar es Salaam, Tanzania: clinical features and outcome in populations of black and non-black racial category.

Background: Although the incidence of dengue across Africa is high, severe dengue is reported infrequently. We describe the clinical features and the outcome of dengue according to raceduring an outbreak in Dar es Salaam, Tanzania that occurred in both native and expatriate populations.

Methods: Adults with confirmed dengue (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) were included between December 2013 and July 2014 in outpatient clinics.

Prognostic value of quickSOFA as a predictor of 28-day mortality among febrile adult patients presenting to emergency departments in Dar es Salaam, Tanzania.

Background: Quick Sequential Organ Failure Assessment (qSOFA) is a three-item clinical instrument for bedside identification of sepsis patients at risk of poor outcome. qSOFA could be a valuable triage tool in emergency departments of low-income countries, yet its performance in resource-limited settings remains unknown. The prognostic accuracy of qSOFA for 28-day all-cause mortality in febrile adults treated at the EDs in a low-income country was evaluated.

A new real-time RT-qPCR assay for the detection, subtyping and quantification of human respiratory syncytial viruses positive- and negative-sense RNAs.

Human respiratory syncytial virus (RSV) is a major health problem and the main cause of hospitalization due to bronchiolitis. RSV is divided into two antigenic subgroups, RSV-A and -B that co-circulate worldwide. Rapid and sensitive detection is desirable for proper patient handling while assessment of viral load may help to evaluate disease severity and progression.

Ebola virus disease diagnosis by real-time RT-PCR: A comparative study of 11 different procedures.

Background: The diagnosis of Ebola virus disease relies on the detection of viral RNA in blood by real-time reverse-transcription PCR. While several of these assays were developed during the unprecedented 2013-2015 Ebola virus disease outbreak in West Africa, few were applied in the field.

Objectives: To compare technical performances and practical aspects of 11 Ebola virus real-time reverse-transcription PCR procedures.

Foxa1 and Foxa2 regulate α-cell differentiation, glucagon biosynthesis, and secretion.

The Forkhead box A transcription factors are major regulators of glucose homeostasis. They show both distinct and redundant roles during pancreas development and in adult mouse β-cells. In vivo ablation studies have revealed critical implications of Foxa1 on glucagon biosynthesis and requirement of Foxa2 in α-cell terminal differentiation.

Pax6 controls the expression of critical genes involved in pancreatic {alpha} cell differentiation and function.

The paired box homeodomain Pax6 is crucial for endocrine cell development and function and plays an essential role in glucose homeostasis. Indeed, mutations of Pax6 are associated with diabetic phenotype. Importantly, homozygous mutant mice for Pax6 are characterized by markedly decreased β and δ cells and absent α cells.

Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression.

Specific expression of the glucagon gene in the rat pancreas requires the presence of the G1 element localized at -100/-49 base pairs on the promoter. Although it is known that multiple transcription factors such as Pax-6, Cdx-2/3, c-Maf, Maf-B, and Brain-4 can activate the glucagon gene promoter through G1, their relative importance in vivo is unknown. We first studied the expression of Maf-B, c-Maf, and Cdx-2/3 in the developing and adult mouse pancreas.

The beta-cell specific transcription factor Nkx6.1 inhibits glucagon gene transcription by interfering with Pax6.

The transcription factor Nkx6.1 is required for the establishment of functional insulin-producing beta-cells in the endocrine pancreas. Overexpression of Nkx6.

Activin A decreases glucagon and arx gene expression in alpha-cell lines.

Activin A is a potent growth and differentiation factor involved in development, differentiation, and physiological functions of the endocrine pancreas; it increases insulin and pax4 gene expression in beta-cells and can induce transdifferentiation of the exocrine acinar cell line AR42J into insulin-producing cells. We show here that Activin A decreases glucagon gene expression in the alpha-cell lines InR1G9 and alphaTC1 in a dose- and time-dependent manner and that the effect is blocked by Follistatin. This effect is also observed in adult human islets.

The zinc finger-containing transcription factor Gata-4 is expressed in the developing endocrine pancreas and activates glucagon gene expression.

Gene inactivation studies have shown that members of the Gata family of transcription factors are critical for endoderm development throughout evolution. We show here that Gata-4 and/or Gata-6 are not only expressed in the adult exocrine pancreas but also in glucagonoma and insulinoma cell lines, whereas Gata-5 is restricted to the exocrine pancreas. During pancreas development, Gata-4 is expressed already at embryonic d 10.

Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1.

Neonatal diabetes mellitus can be transient or permanent. The severe form of permanent neonatal diabetes mellitus can be associated with pancreas agenesis. Normal pancreas development is controlled by a cascade of transcription factors, where insulin promoter factor 1 (IPF1) plays a crucial role.

Hepatic nuclear factor-3 (HNF-3 or Foxa2) regulates glucagon gene transcription by binding to the G1 and G2 promoter elements.

Glucagon gene expression in the endocrine pancreas is controlled by three islet-specific elements (G3, G2, and G4) and the alpha-cell-specific element G1. Two proteins interacting with G1 have previously been identified as Pax6 and Cdx2/3. We identify here the third yet uncharacterized complex on G1 as hepatocyte nuclear factor 3 (HNF-3)beta, a member of the HNF-3/forkhead transcription family, which plays an important role in the development of endoderm-related organs.