367.5 U/ml (IQR 14.688-31.353) (p = .032). Both results were far above the median titer in naïve individuals after a full vaccination schedule 1974.5 U/ml (IQR 895-3455) (p  less then  .0001). Adverse events after vaccine injection were more frequent after the second dose of vaccine (mean 0.95; 95% confidence interval [CI] 0.75-1.14 vs. mean 1.91; 95% CI 1.63-2.19) (p  less then  .0001) and in exposed compared to naïve (mean 1.63; 95% CI 1.28-1.98 vs. mean 2.35; 95% CI 1.87-2.82) (p = .015). In SARS-CoV-2 naturally infected individuals a single mRNA vaccine dose seems sufficient to reach immunity. Modifying current dosing schedules would speed-up vaccination campaigns.Epidermal nerve fibre (ENF) density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear more clustered within the epidermis in subjects suffering from diabetic neuropathy compared to healthy subjects. Therefore, it is important to understand the spatial behaviour of ENFs in healthy and neuropathy subjects. By using confocal microscopy data , we study the spatial structure of epidermal nerves by regarding the nerve tree locations as realizations of marked point processes . The termination points of the fibres of a nerve tree are used to define a reactive territory which is taken as a mark for the nerve tree location. We study the differences in the spatial pattern of ENFs between healthy subjects and subjects suffering from mild diabetic neuropathy by using Ripley’s K function and the mark correlation function. In addition, we propose a marked sequential point process model for the nerve tree locations. Data are replicated point patterns, where we have several patterns from each subject and from each group.The WuXi Biologics’ Ultra-high Productivity platform (WuXiUP) technology is an innovative and integrated platform of continuous biomanufacturing. Through process intensification, the platform enables continuous manufacturing of almost any type of biologics and delivers processes with ultra-high productivity. In this paper, a new case study producing a monoclonal antibody (mAb) via the WuXiUP process was further optimized. Key process parameters like culture temperature, basal media, and perfusion rate were evaluated to ensure an enhanced and robust process. To improve process efficiency for downstream processing, a continuous dual-pore size hollow fiber cell separation and product harvest system were also designed to complement the increased harvest volume from upstream production. In this case study, a significant protein concentration increase and harvest volume reduction were achieved by the application of the new WuXiUP platform.The midwestern United States is a highly productive agricultural region, and extended crop-free periods in winter/spring can result in nitrogen (N) and phosphorus (P) losses to waterways that degrade downstream water quality. Planting winter cover crops can improve soil health while reducing nutrient leaching from farm fields during the fallow period. In this study, we used linear mixed effects models and multivariate statistics to determine the effect of cover crops on soil nutrients by comparing fields with cover crops (n = 9) versus those without (n = 6) in two Indiana agricultural watersheds the Shatto Ditch Watershed, which had >60% of croppable acres in winter cover crops, and the Kirkpatrick Ditch Watershed, which had ∼20%. We found that cover crops decreased soil nitrate-N by >50% and that the magnitude of reduction was related to the amount of cover crop biomass. In contrast, cover crops had variable effects on water extractable P and Mehlich III soil test P. Finally, cover crop biomass significantly increased soil N mineralization and nitrification rates, demonstrating that cover crops have the potential to supply bioavailable N to cash crop after termination. Our study showed that widespread implementation of winter cover crops holds considerable promise for reducing nutrient loss and improving soil health. The degree to which these results are generalizable across other systems depends on factors such as climate, soil characteristics, and past and current agronomic practices.Modification of alkyl glycosides, to alter their properties and widen the scope of potential applications, is of considerable interest. Here, we report the synthesis of new anionic alkyl glycosides with long carbohydrate chains, using two different approaches laccase/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidation of a long-carbohydrate-chain alkyl glycoside and cyclodextrin glucanotransferase (CGTase)-catalyzed elongation of anionic alkyl glycosides. The laccase/TEMPO oxidation of dodecyl β- d-maltooctaoside proceeded efficiently with the formation of aldehyde and acid products. However, depolymerization occurred to a large extent, limiting the product yield and purity. On the other hand, CGTase-catalyzed coupling/disproportionation reactions with α-cyclodextrin and dodecyl β- d-maltoside diuronic acid (DDM-2COOH) or octyl β- d-glucuronic acid (OG-COOH) as substrates gave high conversions, especially when the CGTase Toruzyme was used. It was found that pH had a strong influence on both the enzyme activity and the acceptor specificity. With non-ionic substrates (dodecyl β- d-maltoside and octyl β- d-glucoside), Toruzyme exhibited high catalytic activity at pH 5-6, but for the acidic substrates (DDM-2COOH and OG-COOH) the activity was highest at pH 4. This is most likely due to the enzyme favoring the protonated forms of DDM-2COOH and OG-COOH, which exist at lower pH (pKa about 3).Keratinase is an attractive industrial enzyme that can specifically catalyze keratin waste to obtain value-added products. A challenge to the application of keratinase is improving catalytic capacity to achieve efficient hydrolysis. In this study, we effectively expressed the keratinase gene from Bacillus licheniformis BBE11-1 in Bacillus subtilis WB600 based on pro-peptide engineering. Partial deletion of the pro-peptide sequence and the substitution of amino acid at the pro-peptide cleavage site (P1) suggested that the „chaperone effect” and „cleavage efficiency” of the pro-peptide determine the activity of the mature enzyme. Subsequently, seven target sites that can increase the activity of the mature enzyme by 16%-66% were obtained through the multiple sequence alignment of pro-peptides and site-directed mutation. We further performed combinatorial mutations at six sites based on the design principle of three-codon saturation mutations and obtained mutant 2-D12 (236.8 KU/mg) with a mature enzyme activity of 186% of the original (127.6 KU/mg). Finally, continuous fermentation was carried out in a 5-L bioreactor for 22 h, and the activity of the 2-D12 mature enzyme was increased to 391.6 KU/mg. Most importantly, 2-D12 could degrade more than 90% of feather waste into amino acids and peptides within 12 h with the aid of sulfite.This paper describes different flow management strategies for a connected purification process which includes two polishing steps, virus filtration and tangential flow filtration. Connecting these unit operations avoids introducing large intermediate product pool vessels in small manufacturing facilities. However, a connected-downstream process requires an elaborate control strategy enabling multiple unit operations to function as a single unit. The key strategy to enable the connected-downstream process is a robust management of flow disparities among unit operations. During a typical ultrafiltration step, product concentration increases as mass is added to the retentate tank, leading to a permeate flux decline. In a connected-downstream process, the inlet stream is directly connected to the prior unit operation and any decrease in permeate flow rate could cause a flow disparity. Four different flow management approaches are proposed to manage potential flow disparities and their advantages and challenges are discussed. Bench-scale results of these strategies are presented and evaluated.Interdiffusion and chemical reactions contribute to tool wear in metal machining. Increased understanding of these processes, through characterisation of worn tools, can facilitate design of more resilient materials through chemical and diffusional passivation. However, the unknown reaction conditions, the large number of elements, and the formation of interspersed phases makes for a complex analysis. Here, we demonstrate the use of scanning transmission electron microscopy and energy dispersive X-ray spectroscopy for characterising the interaction layer between a titanium alloy and a cemented carbide tool. Principal component analysis is used to find chemical correlations and help separate signals from embedded phases. Crucially, we evaluate the required X-ray count statistics from simulated spectrum images and theory prior to the experiment. We find no indications of intermediate phases between the original WC and the metallic W interaction layer. Furthermore, we find enrichment of minor constituents in the titanium alloy closest to the tool which alter the solubility of out-diffusing species, suggesting strong interrelations between the diffusion processes.T follicular helper (Tfh) cells play an essential role in regulating the GC reaction and, consequently, the generation of high-affinity antibodies and memory B cells. Therefore, Tfh cells are critical for potent humoral immune responses against various pathogens and their dysregulation has been linked to autoimmunity and cancer. Tfh cell differentiation is a multistep process, in which cognate interactions with different APC types, costimulatory and coinhibitory pathways, as well as cytokines are involved. However, it is still not fully understood how a subset of activated CD4+ T cells begins to express the Tfh cell-defining chemokine receptor CXCR5 during the early stage of the immune response, how some CXCR5+ pre-Tfh cells enter the B-cell follicles and mature further into GC Tfh cells, and how Tfh cells are maintained in the memory compartment. In this review, we discuss recent advances on how antigen and cognate interactions are important for Tfh cell differentiation and long-term persistence of Tfh cell memory, and how this is relevant to the current understanding of COVID-19 pathogenesis and the development of potent SARS-CoV-2 vaccines.One year into the coronavirus disease 2019 (COVID-19) pandemic, diagnostic strategies, although central for contact tracing and other preventive measures, are still limited. To meet the global demand, lower cost and faster antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection are a convenient alternative to the gold standard reverse transcription-polymerase chain reaction (RT-PCR) assay. We tested laboratory-based RT-PCR RNA detection and two rapid antigen detection (RAD) tests, based on the immunochromatography test for nucleocapsid protein of SARS-CoV-2 (COVID-19 Ag ECO Test, ECO Diagnóstica, and Panbio COVID-19 Ag Rapid Test Abbott). Paired collection and testing were done in a small prospective open study in three clinical services in São Paulo, constituted of mostly symptomatic volunteers at collection (97%, 109/112) for a median of 4 days (interquartile range 3-6), ranging from 1 to 30. Among the 108 paired RT-PCR/RAD tests, results were concordant in 96.4% (101/108). The test’s performance was comparable, with an overall sensitivity of 87% and a specificity of 96%. These observations add to other data that suggest that antigen tests may provide reasonable sensitivity and specificity and deserve a role to improve testing strategies, especially in resource-limited settings.Hypobaric hypoxia at higher altitudes usually impairs cognitive function. Previous studies suggested that epigenetic modifications are the culprits for this condition. Here, we set out to determine how hypobaric hypoxia mediates epigenetic modifications and how this condition worsens neurodegeneration and memory loss in rats. In the current study, different duration of hypobaric hypoxia exposure showed a discrete pattern of histone acetyltransferases and histone deacetylases (HDACs) gene expression in the hippocampus when compared with control rat brains. The level of acetylation sites in histone H2A, H3 and H4 was significantly decreased under hypobaric hypoxia exposure compared to the control rat’s hippocampus. Additionally, inhibiting the HDAC family with sodium butyrate administration (1.2 g/kg body weight) attenuated neurodegeneration and memory loss in hypobaric hypoxia-exposed rats. Moreover, histone acetylation increased at the promoter regions of brain-derived neurotrophic factor (BDNF); thereby its protein expression was enhanced significantly in hypobaric hypoxia exposed rats treated with HDAC inhibitor compared with hypoxic rats. Thus, BDNF expression upregulated cAMP-response element binding protein (CREB) phosphorylation by stimulation of PI3K/GSK3β/CREB axis, which counteracts hypobaric hypoxia-induced spatial memory impairment. In conclusion, these results suggested that sodium butyrate is a novel therapeutic agent for the treatment of spatial memory loss associated with hypobaric hypoxia, and also further studies are warranted to explore specific HDAC inhibitors in this condition.Structuring is a parental response to young children’s behavior that may foster children’s attempts to use cognitive skills to engage in self-regulation. Using a rural, economically strained sample, parental structuring in response to 127 eighteen-month-olds’ negative emotion was observed during a home visit. Children’s distraction, a useful cognitive strategy when waiting for a reward, was assessed during a laboratory wait task at 18, 24, 36, and 48 months. More frequent parental structuring at child age 18 months predicted more developmental growth in children’s use of distraction between 18 and 48 months, in contrast with parental directives. Consistent with Kopp’s (1989) framework, parental structuring may capitalize on children’s cognitive development to play a unique role in fostering children’s self-regulation of negative emotion.

Increasing evidence suggests systemic inflammation-caused skeletal muscle atrophy as a major clinical feature of cachexia. Triptolide obtained from Tripterygium wilfordii Hook F possesses potent anti-inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects and molecular mechanisms of triptolide on inflammation-induced skeletal muscle atrophy.

The effects of triptolide on skeletal muscle atrophy were investigated in LPS-treated C2C12 myotubes and C57BL/6 mice. Protein expressions and mRNA levels were analysed by western blot and qPCR, respectively. Skeletal muscle mass, volume and strength were measured by histological analysis, micro-CT and grip strength, respectively. Locomotor activity was measured using the open field test.

Triptolide (10-100 fM) up-regulated protein synthesis signals (IGF-1/p-IGF-1R/IRS-1/p-Akt/p-mTOR) and down-regulated protein degradation signal atrogin-1 in C2C12 myotubes. In LPS (100 ng·ml

)-treated C2C12 myotubes, triptolide up-regications for the discovery of novel agents for preventing muscle wasting.The pathogenesis of autoimmune complications triggered by SARS-CoV2 has not been completely elucidated. Here, we performed an analysis of the cellular immune status, cell ratios, and monocyte populations of patients with COVID-19 treated in the intensive care unit (ICU) (cohort 1, N = 23) and normal care unit (NCU) (cohort 2, n = 10) compared with control groups patients treated in ICU for noninfectious reasons (cohort 3, n = 30) and patients treated in NCU for infections other than COVID-19 (cohort 4, n = 21). Patients in cohort 1 presented significant differences in comparison with the other cohorts, including reduced frequencies of lymphocytes, reduced CD8+T-cell count, reduced percentage of activated and intermediate monocytes and an increased B/T8 cell ratio. Over time, patients in cohort 1 who died presented with lower counts of B, T, CD4+ T, CD8+ T-lymphocytes, NK cells, and activated monocytes. The B/T8 ratio was significantly lower in the group of survivors. In cohort 1, significantly higher levels of IgG1 and IgG3 were found, whereas cohort 3 presented higher levels of IgG3 compared to controls. Among many immune changes, an elevated B/T8-cell ratio and a reduced rate of activated monocytes were mainly observed in patients with severe COVID-19. Both parameters were associated with death in cohort 1.The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE). Here, we report the development of a mouse anti-mouse IL-12 vaccine and the production of monoclonal antibodies (mAbs) that do not react with p40 or p35 (in IL-35) but specifically recognize and functionally inhibit the IL-12 heterodimer. Using one of these mAbs, MM12A1.6, that strongly inhibited IFN-γ production and LPS-induced septic shock after viral infection, we demonstrate the critical role played by IL-12 in the rejection of male skin graft by female C57BL/6 syngeneic recipients and in the clearance of an immunogenic mastocytoma tumor variant by DBA/2 mice, but not in a parent to F1 immune aggression model nor in MOG-induced EAE, which was clearly prevented by anti-p40 mAb C17.8. Given this selective inhibition of IL-12, these mAbs provide new options for reassessing IL-12 function in vivo.

Leiomyosarcoma (LMS) is the most common soft tissue and uterine sarcoma, but no standard therapy is available for recurrent or metastatic LMS. TP53, p16/RB1, and PI3K/mTOR pathway dysregulations are recurrent events, and some LMS express estrogen receptor (ER) and/or progesterone receptor (PR). To characterize relationships between these pathway perturbations, the authors evaluated protein expression in soft tissue and uterine nonprimary leiomyosarcoma (np-LMS), including local recurrences and distant metastases.

TP53, RB1, p16, and PTEN expression aberrations were determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) from 227 np-LMS and a comparison group of 262 primary leiomyosarcomas (p-LMS). Thirty-five of the np-LMS had a matched p-LMS specimen in the TMAs. Correlative studies included differentiation scoring, ER and PR IHC, and CDKN2A/p16 fluorescence in situ hybridization.

Dysregulation of TP53, p16/RB1, and PTEN was demonstrated in 90%, 95%, and 41% of np-LMS, respectively. PTEN inactivation was more common in soft tissue np-LMS than uterine np-LMS (55% vs 31%; P = .0005). Moderate-strong ER expression was more common in uterine np-LMS than soft tissue np-LMS (50% vs 7%; P < .0001). Co-inactivation of TP53 and RB1 was found in 81% of np-LMS and was common in both soft tissue and uterine np-LMS (90% and 74%, respectively). RB1, p16, and PTEN aberrations were nearly always conserved in p-LMS and np-LMS from the same patients.

These studies show that nearly all np-LMS have TP53 and/or RB1 aberrations. Therefore, therapies targeting cell cycle and DNA damage checkpoint vulnerabilities should be prioritized for evaluations in LMS.

These studies show that nearly all np-LMS have TP53 and/or RB1 aberrations. Therefore, therapies targeting cell cycle and DNA damage checkpoint vulnerabilities should be prioritized for evaluations in LMS.

To investigate the aetiology of acute-onset binocular diplopia (AOBD) in neurological units and identify the key diagnostic procedures in this setting.

Clinico-demographic data from patients hospitalized for AOBD from 2008 to 2019 were retrospectively reviewed. AOBD due to an underlying neurological disorder known to cause diplopia was addressed as secondary diplopia. Ophthalmoparesis plus was defined when subtle neurological signs/symptoms other than ophthalmoparesis were detected during neurological examination.

A total of 171 patients (mean age 57.6years) were included in the study. A total of 89 subjects (52%) had an oculomotor disturbance consistent with sixth nerve palsy, and 42 (24.6%) showed multiple oculomotor nerve involvement. The most common cause of AOBD was presumed to be microvascular in 56 patients (32.7%), while a secondary aetiology was identified in 102 (59.6%). Ophthalmoparesis plus and multiple oculomotor nerve involvement significantly predicted a secondary aetiology in multivariabderlying disease cannot be excluded. Brain MRI was found to perform well in all clinical scenarios, and it should be always considered when managing AOBD.Compositional data are common in many fields, both as outcomes and predictor variables. The inventory of models for the case when both the outcome and predictor variables are compositional is limited, and the existing models are often difficult to interpret in the compositional space, due to their use of complex log-ratio transformations. We develop a transformation-free linear regression model where the expected value of the compositional outcome is expressed as a single Markov transition from the compositional predictor. Our approach is based on estimating equations thereby not requiring complete specification of data likelihood and is robust to different data-generating mechanisms. Our model is simple to interpret, allows for 0s and 1s in both the compositional outcome and covariates, and subsumes several interesting subcases of interest. We also develop permutation tests for linear independence and equality of effect sizes of two components of the predictor. Finally, we show that despite its simplicity, our model accurately captures the relationship between compositional data using two datasets from education and medical research.Phylogenetic comparative methods are often used to test functional relationships between traits. However, million-year macroevolutionary observational datasets cannot definitively prove causal links between traits-correlation does not equal causation and experimental manipulation over such timescales is impossible. Although this caveat is widely understood, it is less appreciated that different phylogenetic approaches imply different causal assumptions about the functional relationships of traits. To make meaningful inferences, it is critical that our statistical methods make biologically reasonable assumptions. Here we illustrate the importance of causal reasoning in comparative biology by examining a recent study by Avaria-Llautureo et al (2019). that tested for the evolutionary coupling of metabolic rate and body temperature across endotherms and found that these traits were unlinked through evolutionary time and that body temperatures were, on average, higher in the early Cenozoic than they are today. We argue that the causal assumptions embedded into their models made it impossible for them to test the relevant functional and evolutionary hypotheses. We reanalyze their data using more biologically appropriate models and find support for the exact opposite conclusions, corroborating previous evidence from physiology and paleontology. We highlight the vital need for causal thinking, even when experiments are impossible.Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P less then 0·001) and in LATAIE, consanguineous parents (P less then 0·001) were more common. In CHAI patients the rates of granulomas (P less then 0·001), malignancies (P = 0·001), atope of transplanted CHAI and LATAIE patients.Myeloid-derived suppressor cells (MDSCs) are important regulators of immune processes during sepsis in mice. However, confirming these observations in humans has been challenging due to the lack of defined preparation protocols and phenotyping schemes for MDSC subsets. Thus, it remains unclear how MDSCs are involved in acute sepsis and whether they have a role in the long-term complications seen in survivors. Here, we combined comprehensive flow cytometry phenotyping with unsupervised clustering using self-organizing maps to identify the three recently defined human MDSC subsets in blood from severe sepsis patients, long-term sepsis survivors, and age-matched controls. We demonstrated the expansion of monocytic M-MDSCs and polymorphonuclear PMN-MDSCs, but not early-stage (e)-MDSCs during acute sepsis. High levels of PMN-MDSCs were also present in long-term survivors many months after discharge, suggesting a possible role in sepsis-related complications. Altogether, by employing unsupervised clustering of flow cytometric data we have confirmed the likely involvement of human MDSC subsets in acute sepsis, and revealed their expansion in sepsis survivors at late time points. The application of this strategy in future studies and in the clinical/diagnostic context would enable rapid progress toward a full understanding of the roles of MDSC in sepsis and other inflammatory conditions.Glycosylation is a critical quality attribute of therapeutic monoclonal antibodies (mAbs). The glycan pattern can have a large impact on the immunological functions, serum half-life and stability. The medium components and cultivation parameters are known to potentially influence the glycosylation profile. Mathematical modelling provides a strategy for rational design and control of the upstream bioprocess. However, the kinetic models usually contain a very large number of unknown parameters, which limit their practical applications. In this article, we consider the metabolic network of N-linked glycosylation as a Bayesian network (BN) and calculate the fluxes of the glycosylation process as joint probability using the culture parameters as inputs. The modelling approach is validated with data of different Chinese hamster ovary cell cultures in pseudo perfusion, perfusion, and fed batch cultures, all showing very good predictive capacities. In cases where a large number of cultivation parameters is available, it is shown here that principal components analysis can efficiently be employed for a dimension reduction of the inputs compared to Pearson correlation analysis and feature importance by decision tree. The present study demonstrates that BN model can be a powerful tool in upstream process and medium development for glycoprotein productions.

To investigate the efficacy and safety of adjunctive cenobamate for treatment of uncontrolled focal seizures.

We performed a systematic search of Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE and Google Scholar to identify eligible studies. We included randomized placebo-controlled trials (RCTs) for uncontrolled focal seizures. We calculated the risk ratio (RR) of ≥50%, ≥75% and 100% reduction in seizure frequency from baseline, as well as dropout and serious adverse events related to treatment. Quality of included trials was assessed using the Cochrane Collaboration’s tool.

Two RCTs with a total of 658 patients were included. A significantly larger proportion of patients allocated to cenobamate achieved 50% seizure reduction (RR 2.06, 95% CI 1.70-2.51, p<0.001) as compared to placebo, subgroup analysis demonstrated that the most effective dose was at 400mg (RR 2.28, 95% CI 1.57-3.32, p<0.001). Patients achieving seizure-freedom during the treatment period were 14.9% with cenue, headache and nausea. Nevertheless, majority of them were mild to moderate in severity.

Advanced age is associated with increased susceptibility to acute adverse effects of propofol. The present study aimed to describe patterns of propofol dosing for induction of general anesthesia before endotracheal intubation in a nationwide sample of older adults presenting for surgery.

Retrospective observational study using the Multicenter Perioperative Outcomes Group data set.

Thirty-six institutions across the United States.

A total of 350,766 patients aged over 65 years who received propofol for general anesthetic induction and endotracheal intubation between 2014 and 2018.

None.

Total induction bolus dose of propofol administered.

The mean (SD) weight-adjusted propofol dose was 1.7 (0.6) mg/kg. The mean prevalent propofol induction dose exceeded the upper bound of what has been described as the typical geriatric dose requirement across every age category examined. The percent of patients receiving propofol induction doses above the described typical geriatric range was 64.8% (95% CI 64.6-tice. Widespread variability in induction dose administration remains incompletely explained by known patient variables. The nature and clinical consequences of these unexplained dosing decisions remain important topics for further study. Observed discordance between expected and actual induction dosing raises the question of whether there should be reconsideration of widespread provider practice or, alternatively, whether what is published as the typical propofol induction dose range should be revisited.In recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This review presents the most recent insights into how cell intrinsic FA metabolism controls DC and macrophage function, as well as the current evidence of the importance of various exogenous FAs (such as polyunsaturated FAs and their oxidation products-prostaglandins, leukotrienes, and proresolving lipid mediators) in affecting DC and macrophage biology, by modulating their metabolic properties. Finally, we explore whether targeted modulation of FA metabolism of myeloid cells to steer their function could hold promise in therapeutic settings.

In general anaesthesia practice a fresh gas flow (FGF) of ≥0.5L/min is usually applied. Automated gas delivery devices are developed to reduce volatile anaesthetic consumption by limiting gas flow. This study aimed to compare desflurane consumption between automated gas control devices compared to conventional low flow anaesthesia in the Flow-I and Aisys anaesthesia machines, and to compare desflurane consumption between the two automated gas delivery devices. We hypothesised that desflurane consumption would be lower with automated gas delivery compared to conventional low flow anaesthesia, and that desflurane consumption could differ between the different gas delivery devices.

We allocated 160 patients undergoing robot-assisted laparoscopic surgery into four groups, Flow-I with automated gas control, Flow-i with conventional low-flow(1 L/min), Aisys with end tidal gas control and Aisys with conventional low flow. Patients were maintained at minimum alveolar concentration (MAC) 0.7-0.8. Desflurane consumption was recorded after 9, 30 and 60minutes of anaesthesia.

After 60minutes, compared to conventional low flow anaesthesia, automated gas delivery systems reduced desflurane consumption from 25.8 to 15.2mL for the Aisys machine (P<.001) and from 22.1 to 16.8mL for the Flow-I (P<.001). Time to MAC 0.7 and stable FGF was shorter with Aisys endtidal control compared to Flow-I automated gas control.

Under clinical conditions, we found a reduction in desflurane consumption when using automated gas delivery devices compared to conventional low flow anaesthesia. Both devices were reliable in use.

Under clinical conditions, we found a reduction in desflurane consumption when using automated gas delivery devices compared to conventional low flow anaesthesia. Both devices were reliable in use.Scrubbed team members leaving the OR while x-rays are taken Key words radiation source exposure, x-ray, distance and shielding, radiation protection devices, inverse square law. Cleaning radiation protection garments and devices Key words radiation protection, cleaning reusable garments, eyewear, lead aprons, shielding devices. Implementing radiation precautions for pregnant health care workers Key words scatter radiation, shielding, dosimeter, pregnant health care worker, protective garment. Protecting patients from radiation exposure Key words scatter radiation, radiation protection devices, radiation shielding, radiation protection drapes, patient exposure. Wearing x-ray aprons that fit correctly Key words body size, radiation protection garment sizing, x-ray, lead aprons, anthropomorphic phantom.Working in health care can be physically stressful. The perioperative setting, which is largely concealed from other health care workers and the general public, places unique physical demands on its workers. Perioperative personnel are responsible for a variety of physical tasks, including moving and positioning patients, holding extremities, and moving equipment and supplies. As the nursing workforce ages, the physical demands of the perioperative environment may affect the development of musculoskeletal disorders in older nurses. The purpose of this article is to review published research and describe the ergonomic challenges of working in the OR. There currently is a paucity of literature on the effects of ergonomic risk factors on perioperative nurses in the United States. This article also provides some recommendations for perioperative staff members and leaders that may assist them with creating and maintaining a healthy and safe work environment.The RN circulator role includes maintaining situational awareness and mitigating risks to patient safety in the OR. Flow disruptions-deviations that threaten the safe and efficient flow of surgery-may contribute to the occurrence of errors and negatively affect safety for patients and health care providers. We used an existing data set to explore the effects of flow disruptions on the RN circulator. To create the data set, doctoral-level human factors students observed 24 cardiac surgery procedures and recorded the types and durations of disruptions. We used a human factors taxonomy to classify the flow disruptions. Of the 1,470 events observed, interruptions were most prevalent (66.67%), followed by coordination issues (15.37%) and communication breakdowns (8.37%). Layout (7.21%), equipment (1.77%), and usability (0.61%) issues accounted for the remainder of the disruptions. Perioperative leaders should work with staff members to minimize workflow disruptions and provide support for identifying and documenting flow disruptions.In today’s perioperative setting, staff members are potentially exposed to a variety of safety and environmental concerns. As health care organizations implement measures to provide safe environments for perioperative team members, organizational leaders must pivot away from antiquated mindsets and responses and other hierarchical models of leadership. Foundational to creating and fostering safe environments is providing an atmosphere in which staff members, regardless of their role, are empowered to speak up for safety. This article defines a just culture; explores the critical elements of a just culture, including psychological safety, leader and staff member responsibilities, and staff member empowerment; and provides tools and resources that may be beneficial for leaders who are creating a just culture for staff safety in the perioperative setting.Twin-to-twin transfusion syndrome (TTTS) is a condition that results in unbalanced blood flow between two fetuses. Patients diagnosed with TTTS can experience maternal or fetal morbidity and mortality. Depending on the severity of TTTS, laser ablation of placental anastomoses may be the most effective treatment. The preferred treatment method requires percutaneous entry to the uterus; however, some patient circumstances (eg, placenta location) require a laparoscopic-assisted procedure. During the preoperative appointments, clinicians assess the condition of the fetuses and patients may participate in genetic counseling. Intraoperative care involves an interdisciplinary team that may include a pediatric general surgeon, maternal-fetal medicine specialists, an RN circulator, a scrub person, and an anesthesia professional. Perioperative nurses should have knowledge of the pathophysiology of TTTS, including its natural progression. They also should understand preoperative and intraoperative patient care requirements to provide safe and effective care for patients undergoing laparoscopic-assisted fetoscopic placental laser photocoagulation procedures.Surgical site infections (SSIs) negatively affect patients and health care organizations. We conducted a descriptive, correlational study at two hospitals that provide care to rural patients in one Midwestern state. The study purposes were to describe types of organisms causing reportable organ/space SSIs that occurred within 30 days of an open or a laparoscopic abdominal surgery (N = 20), and commonalities in patient- and care-related factors to provide baseline information for site-level prevention efforts for quality improvement. We identified Escherichia coli in almost half of the SSI cases (n = 9, 45%). Common patient-related factors included ethnicity, smoking, and dirty or contaminated wounds. Common care-related factors included longer surgery times (> 60 minutes), unplanned surgeries, and procedures that involved the colon or small bowel. Personnel can use site-level data to monitor prevalent types of organisms causing SSIs, enabling an evidence-based, interdisciplinary approach to develop and test methods to enhance prevention.Operating rooms are dynamic places with a lot of movement and people working as a concerted team. Operating room traffic can be necessary (eg, retrieving an unusual supply) or unnecessary (eg, a social visit). This quality improvement project aimed to reduce the amount of OR traffic to only necessary traffic and reduce the surgical site infection rates for the orthopedic ORs in a northern California community hospital. There were three principle interventions door signs discouraging traffic, staff member relief in batches, and preference card review for accuracy. During the six-week post-intervention period, there were no reported surgical site infections for orthopedic procedures, and the standardized infection ratio decreased from 1.75 to 0 in 10 weeks. Operating room traffic decreased after implementation by 46.9%. The number of door openings per minute decreased from 1.96 per minute to 1.04 per minute at the project’s conclusion. Staff members’ awareness of OR traffic increased.

Shared decision-making is advocated as a key component of patient-centred care and associated with many benefits that improve patient outcomes. However, shared decision-making is not yet embedded in clinical practice and confronts many barriers that hinder its implementation especially in countries of the World Health Organization (WHO) Eastern Mediterranean Region.

We conducted a systematic review to identify and understand factors influencing shared decision-making in the Region.

We searched PsycINFO, CINAHL, PubMed, Medline, Scopus and Saudi Digital Library for articles published between January 1997 and February 2019. Studies conducted in the Region that reported barriers, facilitators, experiences, expectations and attitudes to shared decision-making were included. The Mixed Methods Appraisal Tool (MMAT) was used to assess the methodological quality of the studies in this review.

Of the 1813 initial articles retrieved, 19 eligible articles were identified. The main factors that emerged were grouped under three broad themes participant factors (patients/families and physicians); consultation factors (relationship between participants, engaging patients, evaluating preferences, introducing options, providing information, and decision making); and healthcare system factors (organizational characteristics, time constraints, continuity of care, and healthcare resources).

There is growing interest in shared decision-making in several countries in the Region. However, there are many existing barriers that hinder the implementation of shared decision-making. These need to be addressed before shared decision-making can be fully adopted in these countries.

There is growing interest in shared decision-making in several countries in the Region. However, there are many existing barriers that hinder the implementation of shared decision-making. These need to be addressed before shared decision-making can be fully adopted in these countries.

There is currently a growing concern to conduct health-related quality of life (HRQOL) studies among people with epilepsy in low- and middle-income countries, as most data have been derived from high-income countries in North America and Europe.

To translate, adapt and validate the Moroccan Arabic version of the QOL Inventory in Epilepsy-31 (MA-QOLIE-31) to evaluate HRQOL predictors in the Moroccan population with epilepsy.

Adaptation and validation of QOLIE-31 were performed in July 2018 among 118 patients with epilepsy in the Fez-Meknes region. The test was translated, adapted and validated into Arabic according to the Streiner & Norman recommendations. Acceptability, reliability, central tendency and validity of the QOLIE-31 were assessed.

The acceptability and reproducibility were satisfactory and the internal consistency was strong (Cronbach α = 0.993). The mean (standard deviation) global score of QOL in the MA-QOLIE-31 was 68 (22.16). The scores in the subscales were 51 (36.88) for seizures worry, 48.86 (25.44) for overall QOL, 45.60 (26.73) for well-being, 41.28 (25.37) for energy and fatigue, 47.55 (28.33) for cognitive function, 66.83 (39.49) for medication effects and 52.44 (30.26) for social functioning.

The global score of QOL in Moroccan patients with epilepsy is similar to that in patients in low and middle- income countries. MA-QOLIE-31 will facilitate further studies in HRQOL in Morocco and Arabic-speaking countries.

The global score of QOL in Moroccan patients with epilepsy is similar to that in patients in low and middle- income countries. MA-QOLIE-31 will facilitate further studies in HRQOL in Morocco and Arabic-speaking countries.

Tuberculosis (TB) is a major health problem worldwide. Raising awareness of various aspects of the disease among patients who have TB is important to help in control and prevention.

This was a quasi-experimental study, pre- and post-test, designed to evaluate the effect of an educational intervention on awareness among patients with pulmonary TB.

A structured questionnaire covering various facts about pulmonary TB was used in the pre-intervention phase for 150 TB patients who were being followed-up in a major hospital in Sudan (r = 0.80). The same questionnaire was reused after the patients underwent an educational awareness programme.

There were more males (74%) than females. Mean age was 36.5 years. Most patients (86.6%) had some education, however, their knowledge about aspects of TB was generally poor prior to the intervention. This included the nature of the causative organism, modes of transmission and measures needed for the control and prevention. Post-intervention, there was significant improvement in all aspects of knowledge tested (P < 0.007).

Although the diagnosis of TB in the participants was confirmed and they were on regular clinical follow-up, their knowledge about various aspects of TB was poor prior to the educational intervention. There is a need for more effort towards raising awareness among patients with TB about their disease while on treatment. This is important to help control and prevent the disease.

Although the diagnosis of TB in the participants was confirmed and they were on regular clinical follow-up, their knowledge about various aspects of TB was poor prior to the educational intervention. There is a need for more effort towards raising awareness among patients with TB about their disease while on treatment. This is important to help control and prevent the disease.

There is little evidence about salt intake and its food sources in the Iranian population, especially in children and adolescents.

To investigate salt intake and dietary sources in Isfahan, Islamic Republic of Iran.

This was a cross-sectional survey conducted in 2014-2015. We randomly selected 1384 adults (50.3% female, 49.7% male) aged > 18 years [mean 37.9 (10.6) years], and 786 children and adolescents (50.9% male, 49.1% female) aged 6-18 years [mean 12.5 (3.4) years]. All participants underwent a dietary assessment for salt intake, using a validated food frequency questionnaire.

The total salt intake was 10.9 (3.4) g/day in adults and 10.3 (2.9) g/day in children and adolescents. Added salt was the primary source of salt intake, followed by bread and cheese in both groups. Salt intake was related significantly to being younger, male, a smoker, less educated and physically active in the adult group. In children and adolescents, it was significantly associated with increasing age, male sex, low physical activity and parents’ education level (all P < 0.05).

Salt intake in Isfahan was more than twice that recommended by the World Health Organization. The main source of sodium was added salt, followed bread and cheese. Future national studies are warranted to assess the dietary salt intake and its main sources in different provinces in the Islamic Republic of Iran.

Salt intake in Isfahan was more than twice that recommended by the World Health Organization. The main source of sodium was added salt, followed bread and cheese. Future national studies are warranted to assess the dietary salt intake and its main sources in different provinces in the Islamic Republic of Iran.

Despite a remarkable reduction in the occurrence of many micronutrient deficiencies in most countries, vitamin D deficiency has remained a global problem. Age-adjusted disability-adjusted life years lost due to cardiovascular disease in the Eastern Mediterranean Region, including in the Islamic Republic of Iran, are higher than the global average.

To assess the effects of latitude and season on vitamin D status in the Iranian population and the association between vitamin D status and certain cardiometabolic risk factors.

A sample of 1111 participants aged 19-65 years was randomly selected from 6 regions with latitudes ranging from 29º.0 N to 37.5º N. All anthropometric and biochemical assessments were performed twice a year, summer and winter during 2013 to 2014.

Overall mean 25(OH)D concentration was 26.9 [standard deviation (SD) 17.8] nmol/L in winter and 43.4 (SD 32.9 nmol/L in summer (P < 0.001). Poor vitamin D status was noticeable in both seasons (90.1% and 69.2%, respectively). Being male (B, 7.6; 95% CI 4.3 to 10.8; P < 0.001) and living at a latitude higher than 33 ° were positive predictors, and serum 25(OH)D concentration in winter (B, -0.2; 95% CI -2.9 to -0.11; P < 0.001) was a negative predictor of changes of 25(OH)D concentrations.

We found a high prevalence of suboptimal vitamin D status in Iranian adults throughout the year, irrespective of latitude and season. Improvement of mean circulating 25(OH)D concentrations in the community to 50+ nmol/L through a fortification programme is likely to engender healthy cardiometabolic changes.

We found a high prevalence of suboptimal vitamin D status in Iranian adults throughout the year, irrespective of latitude and season. Improvement of mean circulating 25(OH)D concentrations in the community to 50+ nmol/L through a fortification programme is likely to engender healthy cardiometabolic changes.

Depressive disorders in elderly people can affect their cognitive and physical abilities and nutritional status.

This study aimed to determine the prevalence of depressive disorders in older Palestinians and its relationship with nutritional, functional and cognitive status.

A cross-sectional study was conducted among Palestinians > 60 years living in Hebron, West Bank from September 2017 to March 2018. An interview-based questionnaire was used to obtain information on sociodemographic characteristics, nutritional habits, anthropometric measurements, cognitive function (using the Montreal cognitive assessment tool), and functional status (using activities of daily living and instrumental activities of daily living scales). The presence of depressive symptoms was determined using the geriatric depression scale a score ≥ 5 indicated depressive symptoms.

A total of 291 participants were included in the study. Mean age was 70.4 (SD 7.0) years, range 60-100. The prevalence of depressive symptoms was 51.9%. Depression was significantly associated with marital status (being single), low educational and income level, unemployment, and inability to write and make calculations. The presence of depressive disorders was also significantly associated with lower scores on the instrumental activities of daily living scale and the Montreal cognitive assessment tool, and with hypercholesterolaemia, chewing and swallowing difficulties and lack of appetite.

A considerable percentage of older Palestinian adults had depressive symptoms. There is a need to screen and treat depressive symptoms among older Palestinian adults to prevent their progression to severe mental health problems.

A considerable percentage of older Palestinian adults had depressive symptoms. There is a need to screen and treat depressive symptoms among older Palestinian adults to prevent their progression to severe mental health problems.

Lack of diagnosis and reporting of child maltreatment are important problems worldwide.

This study aimed to assess the knowledge, attitude and practice of physicians in Alexandria University teaching hospitals about the diagnosis and reporting of child maltreatment cases.

A descriptive cross-sectional study was conducted at three hospitals. All physicians working regularly in emergency units were invited to complete a self-administered questionnaire. Data collected included sociodemographic characteristics, knowledge of and formal training on child maltreatment, attitude to dealing with child maltreatment, and experience of child maltreatment cases and reporting behaviour.

A total of 90 physicians were included in the study. Only 11% correctly identified all the signs of child maltreatment and 29% correctly answered all questions on the social indicators of maltreatment. Only 41% of the participants had a good knowledge score (≥ 75%) on child maltreatment. Longer work experience (P = 0.019) and older age (P = 0.