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Blood-culture overutilization is associated with increased cost and excessive antimicrobial use. We implemented an intervention in the adult intensive care unit (ICU), combining education based on the DISTRIBUTE algorithm and restriction to infectious diseases and ICU providers. Our intervention led to reduced blood-culture utilization without affecting safety metrics.

Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the β-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.

Current therapy against herpes simplex viruses (HSV) relies on the use of a few nucleoside antivirals such as acyclovir, famciclovir and valacyclovir. However, the current drugs are ineffective against latent and drug-resistant HSV infections. A series of amidinourea compounds, designed as analogues of the antiviral drug moroxydine, has been synthesized and evaluated as potential non-nucleoside anti-HSV agents. Three compounds showed micromolar activity against HSV-1 and low cytotoxicity, turning to be promising candidates for future optimization. Preliminary mode of action studies revealed that the new compounds act in an early stage of the HSV replication cycle, just after the viral attachment and the entry phase of the infection.

Devices for the endovascular embolization of intracranial aneurysms (ICAs) face limitations related to suboptimal rates of lasting complete occlusion. Incomplete occlusion frequently leads to residual flow within the aneurysm sac, which subsequently causes aneurysm recurrence needing surgical re-operation. An emerging method for improving the rates of complete occlusion both immediately after implant and in the longer run can be the fabrication of patient-specific materials for ICA embolization. Shape memory polymers (SMPs) are materials with great potential for this application, owing to their versatile and tunable shape memory properties that can be tailored to a patient’s aneurysm geometry and flow condition. In this review, we first present the state-of-the-art endovascular devices and their limitations in providing long-term complete occlusion. Then, we present methods for the fabrication of SMPs, the most prominent actuation methods for their shape recovery, and the potential of SMPs as endovascular devices for ICA embolization. Although SMPs are a promising alternative for the patient-specific treatment of ICAs, there are still limitations that need to be addressed for their application as an effective coil-free endovascular therapy.

The rainfall regime is changing in the Catalan territory, likely in most areas in the Mediterranean Basin. This variability, spatial and temporal, means that there may be periods of severe drought combined with periods of heavy rainfall and floods. In this way, the management of water resources is complicated and can produce a high impact on different social aspects. The high convective activity leads to investigating the relationship between the electric discharges and radar parameters (reflectivity, echo top, vertically integrated liquid, and accumulated rainfall). The correlation allows identifying some elements that may be significant in terms of changes in rainfall regimes. Besides, using several radar parameters apart from precipitation accumulation reveals interesting explicit patterns of the previously known. These patterns can help better understand the precipitation behavior and the changes associated with it.

Study Design: Retrospective, controlled study.Purpose: Dynamic fixation (topping-off technique) adjacent to a transforaminal lumbar interbody fusion (TLIF) level was developed to reduce the risk of adjacent segment disease (ASDi). This study was designed to compare the clinical and radiological outcomes between patients who underwent circumferential lumbar fusion (CLF) without the topping-off technique, CLF with dynamic rod constructs (DRC), and CLF with interspinous device (ISD).Overview of Literature: Lumbar fusion can result in the re-distribution of stress, increased mobility, and increased intradiscal pressure at adjacent levels, ultimately leading to adjacent segment degeneration (ASDe) and ASDi. Dynamic fixation techniques (topping-off techniques) adjacent to vertebral fusion have been developed to reduce the risk of ASDe and ASDi because they provide a transitional zone between a caudal rigid fused segment and cephalad-mobile unfused levels.Methods: A single-center, retrospective, controlled study was designed, including all patients who underwent CLF due to degenerative lumbar spinal disease in Hospital Clinic of Barcelona between 2012 and 2018. Three groups of patients were evaluated as per the type of topping-off technique used: CLF alone group, DRC group, and ISD group. Clinical and radiological outcomes were evaluated.Results: A total of 117 patients were enrolled in the study. Sixty patients (51.3%) underwent CLF without dynamic stabilization, 24 (20.5%) were treated with DRC as topping-off technique, and 33 (28.5%) were treated with an ISD. A total of 12 patients (20.0%) in the CLF alone group showed ASDi at the final follow-up, compared to 1 (4.2%) in the DRC group (p=0.097) and 2 (6.1%) in the ISD group (p=0.127). The Cox regression model identified a significantly decreased risk of ASDi when a topping-off technique (DRC or ISD) was used (hazard ratio, 0.154; 95% confidence interval, 0.31–0.77).Conclusions: Dynamic fixation adjacent to CLF was a safe and efficient procedure associated with improved clinical outcomes in patients with lumbar spine degenerative disease.

With great interest, we read the study of Dr Khabbazi et al1 regarding treatment adherence in patients with inflammatory rheumatic diseases during the COVID-19 pandemic in the East Azarbaijan province of Iran. They conducted telephone interviews to 1324 patients and inquired about treatment adherence behaviours during 2 weeks from July 2020. Of the 858 patients included in the final analysis, non-adherence was reported by 6.5% of the patients (defined by the group as ≥20% change in the dose or frequency of medications). In accordance to previous studies,2 this work demonstrates that a small percentage of patients were non-adherent to their treatment and with a lower frequency than the one reported in our Latin American sample population (15.1%).3 The principal pattern of non-adherence was the complete discontinuation of medications (58.9%), and the most common reason (62.5%, n=35) was the fear of the immunosuppressive effects of therapy.

Complex I (proton-pumping NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain and a significant source of reactive oxygen species (ROS). We hypothesized that during energy conversion by complex I, electron transfer onto ubiquinone triggers the concerted rearrangement of three protein loops of subunits ND1, ND3, and 49-kDa thereby generating the power-stoke driving proton pumping. Here we show that fixing loop TMH1-2 ND3 to the nearby subunit PSST via a disulfide bridge introduced by site-directed mutagenesis reversibly disengages proton pumping without impairing ubiquinone reduction, inhibitor binding or the Active/Deactive transition. The X-ray structure of mutant complex I indicates that the disulfide bridge immobilizes but does not displace the tip of loop TMH1-2 ND3 . We conclude that movement of loop TMH1-2 ND3 located at the ubiquinone-binding pocket is required to drive proton pumping corroborating one of the central predictions of our model for the mechanism of energy conversion by complex I proposed earlier. Proton pumping of mitochondrial complex I depends on the reduction of ubiquinone but the molecular mechanism of energy conversion is unclear. Here, the authors provide structural and biochemical evidence showing that movement of loop TMH1-2 in complex I subunit ND3 is required to drive proton pumping.

On examination, extensive areas of alopecia were observed on the majority of the scalp, with no visible follicular openings, along with erosions and tense bullae on the left side of the scalp and periocular area. Brunsting-Perry Pemphigoid (BPP) Histology revealed subepidermal blisters, dermal scar changes due to dermal fibrosis with absence of hair follicles, and inflammatory infiltrates containing neutrophils and eosinophils. Discussion Cicatricial alopecia refers to a group of disorders that cause permanent hair loss due to the destruction of hair follicles.

The purpose of this study was to determine the influence of krill meal (KM) inclusion at various levels (0%, 2.5%, 5%) in plant-based and animal-based feeds, that were fishmeal (FM) and fish oil (FO) free, on Atlantic salmon growth. A FM/FO feed containing 0% KM was the control. Using a 2 × 3 factorial approach, diets were randomly assigned to one of 28 0.5 m3 flow-through tanks (n = 4 tanks per diet) initially stocked with 60 fish (148.4 ± 12.9 g; 23.6 ± 0.8 cm; condition factor (K) = 1.16 ± 0.08) each. Salmon were fed for 90 days using automatic feeders ad libitum. On day 45, stocking densities were reduced to 45 fish per tank by the random removal of 15 individuals to remove any potential of density affecting growth through the trial end. Water temperature, oxygen saturation, pH, and salinity throughout the trial were 11.8 °C, 103.5%, 7.38, and 32.0 g L−1, respectively. Fish fed plant-based feed without KM were lighter (p < 0.05) than all other groups at day 45 and 90, but those fed a plant-based feed with KM had comparable growth and feed intake compared to that of fish fed the control diet. Irrespective of the presence of KM, animal-based feeds achieved comparable weight growth (p > 0.05) to the control and 5% KM plant-based groups, with KM increasing feed intake (p < 0.05). Between day 45 and 90, feed conversion ratios increased in all groups except the control and 0% KM plant-based group, while specific growth rates (SGRs) decreased for all except the 0% KM plant-based diet. Between-group differences (p < 0.05) were also noted for the thermal growth coefficient. No differences were recorded in visceral or intestinal weight, and whole-body lipid levels were identical, proportional for all groups. Although differences (p < 0.05) were apparent in the concentrations of individual fillet fatty acids between groups, a 75 g serving size of any treatment would be sufficient to exceed daily intake recommendations for EPA + DHA. This trial determined that benefit, in terms of feed intake and growth performance, was gained when KM was added to plant-based feeds. However, no such advantage was observed when KM was used with animal-based feeds.