A Variety of Mouse PYHIN Proteins Restrict Murine and Human Retroviruses.

PYHIN proteins are only found in mammals and play key roles in the defense against bacterial and viral pathogens. The corresponding gene locus shows variable deletion and expansion ranging from 0 genes in bats, over 1 in cows, and 4 in humans to a maximum of 13 in mice. While initially thought to act as cytosolic immune sensors that recognize foreign DNA, increasing evidence suggests that PYHIN proteins also inhibit viral pathogens by more direct mechanisms. Here, we examined the ability of all 13 murine PYHIN proteins to inhibit HIV-1 and murine leukemia virus (MLV). We show that overexpression of p203, p204, p205, p208, p209, p210, p211, and p212 strongly inhibits production of infectious HIV-1; p202, p207, and p213 had no significant effects, while p206 and p214 showed intermediate phenotypes. The inhibitory effects on infectious HIV-1 production correlated significantly with the suppression of reporter gene expression by a proviral Moloney MLV-eGFP construct and HIV-1 and Friend MLV LTR luciferase reporter constructs. Altogether, our data show that the antiretroviral activity of PYHIN proteins is conserved between men and mice and further support the key role of nuclear PYHIN proteins in innate antiviral immunity.

Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay.

Objective: Hospital-acquired pressure ulcers are an important indicator of the quality of care. Most pressure ulcers are avoidable with a robust protocol for prevention, but prevention activities often have a low priority for senior management because the true costs to the hospital are not visible. Our aim was to raise awareness of the value of pressure ulcer prevention by estimating the excess length of inpatient stay associated with hospital-acquired pressure ulcers, and by assessing whether additional costs are covered by increased reimbursement. Methods: National activity data for hospitals in Germany are available through the InEK Data Browser. Data were extracted covering discharges from German hospitals between January 1 and December 31, 2021. Cases were selected according to the presence of a pressure ulcer diagnosis using ICD-10-GM codes L89.0-L89.3. Information was extracted for the ten most common German Diagnosis-Related Group (G-DRG) codes in patients with a secondary pressure ulcer diagnosis on mean length of stay and average reimbursement. Ulcer-associated excess length of stay was estimated by comparing cases within the same G-DRG with and without a pressure ulcer diagnosis. Results: Mean length of stay was higher in patients with a pressure ulcer than in patients with no ulcer by between 1.9 (all ages) and 2.4 days (patients aged ≥65) per case. In patients aged ≥65 years, 22.1% of cases with a pressure ulcer had a length of stay above the norm for the DRG. In the German system length of stay above the norm is not normally reimbursed. Excess length of stay between 1.9 and 2.4 days leads to a potential cost to a hospital of between 1,633€ and 2,074€ per case. Conclusion: Hospital-acquired pressure ulcers represent an important source of cost for a hospital which highlights the potential value of effective prevention.

Assessing Implementation of Helping Babies Breathe Program Through Observing Immediate Care of Neonates at Time of Delivery.

Background: Training in neonatal resuscitation has been shown to reduce deaths related to intrapartum asphyxia. Helping Babies Breathe (HBB) is a simulation-based program focusing on training healthcare providers (HCPs) in immediate neonatal care including stimulation, initiating bag mask ventilation (BMV) in the absence of breathing by 1 min of life, and delayed (30-60 s after birth) umbilical cord clamping (DCC). Data on implementation of HBB posttraining are limited. Objective: To determine time from birth to spontaneous breathing, cord clamping, and initiation of BMV in a setting where the majority of HCPs are HBB trained. Methods: Two research nurses observed deliveries conducted in two referral hospitals. Timing included the onset of breathing, cord clamping, and initiation of BMV. Deliveries were grouped according to the mode of delivery. Results: In total, 496 neonates were observed; 410 (82.7%) neonates cried or had spontaneous breathing (median time 17 s) soon after birth, 25/86 (29%) of neonates not breathing responded to stimulation, 61 (12.3%) neonates required BMV, and 2 (0.4%) neonates required chest compression and/or adrenalin. Neonates delivered by cesarean section (CS) took longer to initiate first breath than those delivered vaginally (median time 19 vs. 14 s; p = 0.009). Complete data were available in 58/61 (95%) neonates receiving BMV, which was initiated in 54/58 (93%) cases within 60 s of life (the "Golden Minute"). Median time to cord clamping was 74 s, with 414 (83.5%) and 313 (63.0%) having cord clamped at ≥ 30 and ≥ 60 s, respectively. Factors associated with BMV were CS delivery [odds ratio (OR) 29.9; 95% CI 3.37-229], low birth weight (LBW) (birthweight < 2,500 g) (OR 2.47; 95% CI 1.93-5.91), and 1 min Apgar score < 7 (OR 149; 95% CI 49.3-5,021). DCC (≥ 60 s) was less likely following CS delivery (OR 0.14; 95% CI 0.02-0.99) and being LBW (OR 0.43; 95% CI 0.24-0.77). Conclusion: Approximately 83% of neonates initiated spontaneous breathing soon after birth and 29% of neonates not breathing responded to physical stimulation. BMV was initiated within the Golden Minute in most neonates, but under two-thirds had DCC (≥60 s). HBB implementation followed guidelines, suggesting that knowledge and skills taught from HBB are retained and applied by HCP.

Endogenous TRIM5α Function Is Regulated by SUMOylation and Nuclear Sequestration for Efficient Innate Sensing in Dendritic Cells.

During retroviral infection, viral capsids are subject to restriction by the cellular factor TRIM5α. Here, we show that dendritic cells (DCs) derived from human and non-human primate species lack efficient TRIM5α-mediated retroviral restriction. In DCs, endogenous TRIM5α accumulates in nuclear bodies (NB) that partly co-localize with Cajal bodies in a SUMOylation-dependent manner. Nuclear sequestration of TRIM5α allowed potent induction of type I interferon (IFN) responses during infection, mediated by sensing of reverse transcribed DNA by cGAS. Overexpression of TRIM5α or treatment with the SUMOylation inhibitor ginkgolic acid (GA) resulted in enforced cytoplasmic TRIM5α expression and restored efficient viral restriction but abrogated type I IFN production following infection. Our results suggest that there is an evolutionary trade-off specific to DCs in which restriction is minimized to maximize sensing. TRIM5α regulation via SUMOylation-dependent nuclear sequestration adds to our understanding of how restriction factors are regulated.