The diagnostic criteria and the studied populations are very different from one study to another (Tables 5 and 6), these analyses suggest that both CMV and HSV are associated with increased mortality rates. This study strongly suggests that CMV reactivation in critically ill patients is associated with increased mortality. With respect to HSV infections, its impact on various outcome measures seems to be less important when compared to patients infected with CMV. However, only a trial evaluating the efficacy of an anti-viral treatment in ICU patients could demonstrate that CMV and/or HSV alter outcome.Author ContributionsConceived and designed the experiments: 12926553 YC LP SB BL. Performed the experiments: YC SB JMF SH BL AR CZ MM LP. Analyzed the data: YC LP SB. Wrote the paper: YC LP SJ DR.Impact of CMV and HSV on Ventilated Patients
Insulin-like Growth Factor-1 (IGF-1) is a potent peptide factor involved in a broad range of tissue processes including cell growth and survival, proliferation, differentiation and metabolism, but the molecular basis of these diverse functions is not well understood. In the adult mammal, IGF-1 is synthesized predominately in the liver, and acts as a systemic growth factor, playing important roles in both normal and neoplastic growth [1]. IGF-1 is also produced in extrahepatic MedChemExpress AKT inhibitor 2 tissues where it plays a predominantly autocrine/ paracrine role in local processes. Despite a significant reduction of serum IGF-1 peptide levels in mice where the Igf-1 gene was deleted conditionally in the liver, other parameters were largely normal, indicating that locally synthesized IGF-1 can support normal postnatal growth and development [2]. The diversity of IGF-1 actions may derive from the 14636-12-5 site existence of several different isoforms that differ from one another due to alternative splicing of the initial transcript [3,4]. The single copy Igf-1 gene locus encodes multiple pre-propeptide precursors in which the mature protein is flanked by variable N-terminal signal peptides and C-terminal extension (E) peptides. In the mouse, the Igf-1 gene encodes four main pre-propeptides, combining signal peptides (SP1 or SP2) with Ea or Eb extension peptides (Figure 1). As these pre-propeptides all undergo post-translational processing to generate the same mature 70 aa IGF-1 protein, the specific roles of E-peptides in IGF-1 biology remain unclear. One of the isolated E-peptides (Eb, renamed MGF) has been reported to increase the regenerative capability of skeletal muscle, play a neuroprotectiverole against ischemia, and facilitate the actions of IGF-1 to improve cardiac function and mobilize resident stem cell populations [5,6,7]. Other studies suggest 
that E-peptides are not required for IGF-1 secretion but increase cell entry of IGF-1 from the media [8]. Transgenic studies have shed further light on the role of Epeptides. IGF-1Ea propeptide provided as a muscle-specific transgene results in muscle hypertrophy and enhances regeneration after injury [9,10,11], reducing inflammation and fibrosis [12]. This phenotype is unaffected by the choice of N-terminal signal peptide [13] but is not recapitulated by a muscle-specific transgene encoding IGF-1 lacking an E-peptide moiety, which produces no local effects but instead significantly increases serum IGF-1 levels [14]. The dramatic phenotypes resulting from supplemental tissue-specific IGF-1Ea transgene expression in other tissues such as heart [15] and skin [16], with no increase in circulating IGF-1.The diagnostic criteria and the studied populations are very different from one study to another (Tables 5 and 6), these analyses suggest that both CMV and HSV are associated with increased mortality rates. This study strongly suggests that CMV reactivation in critically ill patients is associated with increased mortality. With respect to HSV infections, its impact on various outcome measures seems to be less important when compared to patients infected with CMV. However, only a trial evaluating the efficacy of an anti-viral treatment in ICU patients could demonstrate that CMV and/or HSV alter outcome.Author ContributionsConceived and designed the experiments: 12926553 YC LP SB BL. Performed the experiments: YC SB JMF SH BL AR CZ MM LP. Analyzed the data: YC LP SB. Wrote the paper: YC LP SJ DR.Impact of CMV and HSV on Ventilated Patients
Insulin-like Growth Factor-1 (IGF-1) is a potent peptide factor involved in a broad range of tissue processes including cell growth and survival, proliferation, differentiation and metabolism, but the molecular basis of these diverse functions is not well understood. In the adult mammal, IGF-1 is synthesized predominately in the liver, and acts as a systemic growth factor, playing important roles in both normal and neoplastic growth [1]. IGF-1 is also produced in extrahepatic tissues where it plays a predominantly autocrine/ paracrine role in local processes. Despite a significant reduction of serum IGF-1 peptide levels in mice where the Igf-1 gene was deleted conditionally in the liver, other parameters were largely normal, indicating that locally synthesized IGF-1 can support normal postnatal growth and development [2]. The diversity of IGF-1 actions may derive from the existence of several different isoforms that differ from one another due to alternative splicing of the initial transcript [3,4]. The single copy Igf-1 gene locus encodes multiple pre-propeptide precursors in which the mature protein is flanked by variable N-terminal signal peptides and C-terminal extension (E) peptides. In the mouse, the Igf-1 gene encodes four main pre-propeptides, combining signal peptides (SP1 or SP2) with Ea or Eb extension peptides (Figure 1). As these pre-propeptides all undergo post-translational processing to generate the same mature 70 aa IGF-1 protein, the specific roles of E-peptides in IGF-1 biology remain unclear. One of the isolated E-peptides (Eb, renamed MGF) has been reported to increase the regenerative capability of skeletal muscle, play a neuroprotectiverole against ischemia, and facilitate the actions of IGF-1 to improve cardiac function and mobilize resident stem cell populations [5,6,7]. Other studies suggest that E-peptides are not required for IGF-1 secretion but increase cell entry of IGF-1 from the media [8]. Transgenic studies have shed further light on the role of Epeptides. IGF-1Ea propeptide provided as a muscle-specific transgene results in muscle hypertrophy and enhances regeneration after injury [9,10,11], reducing inflammation and fibrosis [12]. This phenotype is unaffected by the choice of N-terminal signal peptide [13] but is not recapitulated by a muscle-specific transgene encoding IGF-1 lacking an E-peptide moiety, which produces no local effects but instead significantly increases serum IGF-1 levels [14]. The dramatic phenotypes resulting from supplemental tissue-specific IGF-1Ea transgene expression in other tissues such as heart [15] and 
skin [16], with no increase in circulating IGF-1.
