Comparing the effects of continuous positive airway pressure via mask or helmet interface on oxygenation and pulmonary complications after major abdominal surgery: a randomized trial.

The risk of pulmonary complications is high after major abdominal surgery but may be reduced by prophylactic postoperative noninvasive ventilation using continuous positive airway pressure (CPAP). This study compared the effects of intermittent mask CPAP (ICPAP) and continuous helmet CPAP (HCPAP) on oxygenation and the risk of pulmonary complications following major abdominal surgery. Patients undergoing open abdominal aortic aneurysm repair or pancreaticoduodenectomy were randomized (1:1) to either postoperative ICPAP or HCPAP. Oxygenation was evaluated as the partial pressure of oxygen in arterial blood fraction of inspired oxygen ratio (PaO2/FIO2) at 6 h, 12 h, and 18 h postoperatively. Pulmonary complications were defined as X-ray verified pneumonia/atelectasis, clinical signs of pneumonia, or supplementary oxygen beyond postoperative day 3. Patient-reported comfort during CPAP treatment was also evaluated. In total, 96 patients (ICPAP, n = 48; HCPAP, n = 48) were included, and the type of surgical procedure were evenly distributed between the groups. Oxygenation did not differ between the groups by 6 h, 12 h, or 18 h postoperatively (p = 0.1, 0.08, and 0.67, respectively). Nor was there any difference in X-ray verified pneumonia/atelectasis (p = 0.40) or supplementary oxygen beyond postoperative day 3 (p = 0.53). Clinical signs of pneumonia tended to be more frequent in the ICPAP group (p = 0.06), yet the difference was not statistically significant. Comfort scores were similar in both groups (p = 0.43), although a sensation of claustrophobia during treatment was only experienced in the HCPAP group (11% vs. 0%, p = 0.03). Compared with ICPAP, using HCPAP was associated with similar oxygenation (i.e., PaO2/FIO2 ratio) and a similar risk of pulmonary complications. However, HCPAP treatment was associated with a higher sensation of claustrophobia.

KwARG: parsimonious reconstruction of ancestral recombination graphs with recurrent mutation.

MOTIVATION: The reconstruction of possible histories given a sample of genetic data in the presence of recombination and recurrent mutation is a challenging problem, but can provide key insights into the evolution of a population. We present KwARG, which implements a parsimony-based greedy heuristic algorithm for finding plausible genealogical histories (ancestral recombination graphs) that are minimal or near-minimal in the number of posited recombination and mutation events. RESULTS: Given an input dataset of aligned sequences, KwARG outputs a list of possible candidate solutions, each comprising a list of mutation and recombination events that could have generated the dataset; the relative proportion of recombinations and recurrent mutations in a solution can be controlled via specifying a set of 'cost' parameters. We demonstrate that the algorithm performs well when compared against existing methods. AVAILABILITY AND IMPLEMENTATION: The software is available at https://github.com/a-ignatieva/kwarg. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BACKGROUND: A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account. METHODS: Patients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR-proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered. RESULTS: Plasma MR-proANP decreased for patients undergoing gastroesophageal surgery (-9% [95% CI -3.2 to -15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR-proANP and fluid balance were correlated (r = .352 [95% CI 0.031-0.674], p < .001). In contrast, plasma MR-proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR-proANP and fluid balance, and no patient was fluid responsive. CONCLUSION: Plasma MR-proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

Concomitant full-thickness cartilage lesions do not affect patient-reported outcomes at minimum 10-year follow-up after ACL reconstruction.

PURPOSE: To compare patients with a concomitant full-thickness cartilage lesion and anterior cruciate ligament (ACL) injury to patients with an isolated ACL injury at 10-15 years post ACL reconstruction. METHODS: This is a longitudinal follow-up of a cohort of 89 patients that were identified in the Norwegian National Knee Ligament Registry and included in the index study in 2007. The study group consisted of 30 patients that underwent ACL reconstruction and had a concomitant, isolated full-thickness cartilage lesion (International Cartilage Repair Society [ICRS] grade 3-4). Each study patient was matched with two control patients who underwent ACL reconstruction but had no cartilage lesions (ICRS grade 1-4) (n = 59). At a median follow-up of 10.2 years (range 9.9-15.6), 65 patients (74%) completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), which was the main outcome measure, resulting in 23 pairs after matching. RESULTS: At a follow-up of 10-15 years after ACL reconstruction, no significant differences in KOOS were found between patients with a concomitant full-thickness cartilage lesion and patients without cartilage lesions. There was also no significant difference between the two groups when comparing the change over time in KOOS scores from preoperative to follow-up. Both groups showed significant improvement in all KOOS subscales from preoperative to follow-up, except for in the Symptoms subscale for the control group. The greatest improvement was in the QoL subscale for the study group. CONCLUSION: ACL-reconstructed patients with a full-thickness cartilage lesion did not report worse outcomes at 10-15 years after surgery compared with patients with an isolated ACL injury. Our findings support that there is no long-term negative effect of a concomitant cartilage lesion in an ACL-reconstructed knee. These findings should be considered when discussing treatment and informing about the expected long-term outcome after ACL reconstruction to patients with such combined injuries. LEVEL OF EVIDENCE: II.

Time to maximum indocyanine green fluorescence of gastric sentinel lymph nodes and feasibility of combined indocyanine green/sodium fluorescein gastric lymphography.

PURPOSE: Indocyanine green (ICG) and sodium fluorescein (SF) are fluorescent dyes used for sentinel lymph node mapping. In oncological gastric surgery, ICG lymphography has increased the number of resected lymph nodes. However, the optimal time to administer ICG is unclear, and both preoperative and intraoperative injections have been practised. As dye spillage will diminish lymphogram visibility, a second dye with different excitation and emission spectra may present a clinical alternative. We measured the time until maximum ICG fluorescence of gastric sentinel lymph nodes and investigated the feasibility of combined lymphography with two fluorescent dyes: ICG and SF. METHODS: Ten Danish Landrace/Yorkshire pigs were used in this study. After completion of the laparoscopic setup, ICG and then SF were endoscopically injected into the gastric submucosa. Lymphograms for both dyes were recorded, and the time until maximum ICG sentinel lymph node fluorescence was determined. RESULTS: The mean time until maximum ICG fluorescence of gastric sentinel lymph nodes was 50 s (± 12.5), and the fluorescent signal then remained stable until the end of the recorded period (45 min). A lymphogram showing both ICG and SF was acquired for eight of the ten pigs. CONCLUSIONS: Because of the short time until maximum ICG fluorescence of sentinel lymph nodes, intraoperative injections could be a sufficient alternative to preoperative injections for oncological gastric surgery. Combined ICG and SF lymphography was feasible and resulted in clear lymphograms with no interference between the two dyes. The ability to use multiple dyes during a surgical procedure offers the exciting prospect of simultaneously assessing perfusion and performing fluorescence lymphography.

Exploring healthcare students' interprofessional teamwork in primary care simulation scenarios: collaboration to create a shared treatment plan.

BACKGROUND: Primary care providers assume responsibility for patients with increasingly complex problems requiring interprofessional collaboration. Introducing interprofessional education in healthcare curricula prepares healthcare students for this reality. Solving simulation scenarios as an educational strategy is promoted to support interprofessional education in health care, and is mostly used in acute clinical situations. This paper aims to explore how healthcare students' actions influence interprofessional collaboration and treatment plan identification when they solve common, sub-acute patient scenarios in primary care situations. METHODS: Interaction analysis of video recordings from the simulation scenarios was performed with a focus on the students' joint actions; specifically how these actions unfold and how productive the students were in terms of developing treatment plans. RESULTS: We found variation in the groups' interactions, the paths they followed, and the quality of their knowledge output in their shared treatment plan. The groups with the capacity to collaborate and engage in sharing information, and explain and elaborate on concepts, were more successful in developing comprehensive treatment plans. Furthermore, these groups managed the duality of defining and solving the immediate problem and collaboratively preparing for future care. CONCLUSIONS: Analysis of the activities in our scenarios showed the students' potential to practice interprofessional collaboration. Our study illustrates that simulation of sub-acute scenarios in primary care is an underexplored but suitable arena to train communication and teamwork in complex situations. The simulation scenarios are also feasible for use on-site in an educational facility or in practice with minimal equipment and resources.

Development of a severe mesenteric traction syndrome during major abdominal surgery is associated with increased postoperative morbidity: Secondary data analysis on prospective cohorts.

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery. METHODS: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF1α, a stable metabolite of PGI2, were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC). RESULTS: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality. CONCLUSION: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.

Laser speckle contrast imaging for quantitative assessment of facial flushing during mesenteric traction syndrome in upper gastrointestinal surgery.

The mesenteric traction syndrome (MTS) is associated with prostacyclin (PGI2) facilitated systemic vasodilatation during surgery and is identified by facial flushing. We hypothesized that severe facial flushing would be related to the highest concentrations of plasma PGI2 and accordingly to the highest levels of skin blood flow measured by laser speckle contrast imaging (LSCI). Patients scheduled for major upper abdominal surgery were consecutively included. Within the first hour of the procedure, facial flushing was scored according to a standardized scale, and skin blood flow (LSPU) was continuously measured on the forehead and the cheeks by LSCI. Arterial blood samples for 6-keto-PGF1α (stable metabolite of PGI2) and hemodynamic variables were obtained at defined time points. Overall, 66 patients were included. After 15 min of surgery, patients with severe flushing demonstrated the highest plasma 6-keto-PGF1α concentration and the most significant decrease in systemic vascular resistance. Accordingly, the skin blood flow on the forehead (238 [201-372] to 562 LSPU [433-729]) and the cheeks (341 [239-355] to 624 LSPU [468-917]) increased and were significantly higher than for patients with moderate or no flushing (both, P = 0.04). A cut-off value for skin blood flow could be defined for both the cheeks and the forehead for patients with severe flushing vs. no flushing (425/456 LSPU, sensitivity 75/76% and specificity 80/85%). MTS is linked to an increase in facial skin blood flow during upper gastrointestinal surgery. By applying LSCI, it is possible to quantitatively register facial blood flow, and thereby provide an objective tool for intraoperative verification of MTS.

Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease.

INTRODUCTION: We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning. METHODS: Thirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2). RESULTS: At baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low PtO2 across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT). DISCUSSION: Our results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention.

Thoracic epidural analgesia reduces gastric microcirculation in the pig.

BACKGROUND: Thoracic epidural analgesia (TEA) is used for pain relief during and after abdominal surgery, but the effect of TEA on the splanchnic microcirculation remains debated. We evaluated whether TEA affects splanchnic microcirculation in the pig. METHODS: Splanchnic microcirculation was assessed in nine pigs prior to and 15 and 30 min after induction of TEA. Regional blood flow was assessed by neutron activated microspheres and changes in microcirculation by laser speckle contrast imaging (LSCI). RESULTS: As assessed by LSCI 15 min following TEA, gastric arteriolar flow decreased by 22 % at the antrum (p = 0.020) and by 19 % at the corpus (p = 0.029) of the stomach. In parallel, the microcirculation decreased by 19 % at the antrum (p = 0.015) and by 20 % at the corpus (p = 0.028). Reduced arteriolar flow and microcirculation at the antrum was confirmed by a reduction in microsphere assessed regional blood flow 30 min following induction of TEA (p = 0.048). These manifestations took place along with a drop in systolic blood pressure (p = 0.030), but with no significant change in mean arterial pressure, cardiac output, or heart rate. CONCLUSION: The results indicate that TEA may have an adverse effect on gastric arteriolar blood flow and microcirculation. LSCI is a non-touch technique and displays changes in blood flow in real-time and may be important for further evaluation of the concern regarding the effect of thoracic epidural anesthesia on gastric microcirculation in humans. TRIAL REGISTRATIONS: Not applicable, non-human study.

Laser Speckle Contrast Imaging for Monitoring Changes in Microvascular Blood Flow.

BACKGROUND/AIMS: Microvascular blood flow is essential for healing and predicts surgical outcome. The aim of the current study was to investigate the relation between fluxes measured with the laser speckle contrast imaging (LSCI) technique and changes in absolute blood flow. In addition, we studied the reproducibility of the LSCI technique when assessing the intra-abdominal microcirculation of the pig. METHODS: During trial 1, a fish gill arch was mechanically perfused with heparinized fish blood under controlled stepwise-altered flow rates alongside mechanically induced movement artefacts. The microcirculation of the fish gill was simultaneously assessed with the LSCI technique. In trial 2, microcirculation was measured in the stomach, liver, and small intestine of 10 pigs by two observers. RESULTS: A linear correlation was observed between flux and volumetric flow. During conditions of no volumetric flow, the high recording speed with the LSCI technique registered the movement artefacts as flow signals. The LSCI measurements showed good correlation and agreement between the two observers when assessing microcirculation in the stomach, liver, and small intestine (r2 = 0.857, 0.956, and 0.946; coefficients of variation = 6.0, 3.2, and 6.4%, respectively). CONCLUSION: Due to the non-contact and real-time assessment over large areas, LSCI is a promising technique for the intraoperative assessment of intra-abdominal microcirculation. A linear correlation between flux and volumetric flow was found, in accordance with previous experimental studies. However, movement artefacts affect flux measurements, and the choice of the sampling speed must be made with care, depending on the given setting.

Aarhus Regenerative Orthopaedics Symposium (AROS).

The combination of modern interventional and preventive medicine has led to an epidemic of ageing. While this phenomenon is a positive consequence of an improved lifestyle and achievements in a society, the longer life expectancy is often accompanied by decline in quality of life due to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem.

Major Increase in Incidence of Pediatric ACL Reconstructions From 2005 to 2021: A Study From the Norwegian Knee Ligament Register.

BACKGROUND: The incidence of pediatric and adolescent anterior cruciate ligament reconstruction (ACLR) is increasing in several countries. It is uncertain whether this trend applies to countries that traditionally prefer an initial nonoperative treatment approach whenever possible, like Norway. Nationwide, long-term patient-reported outcomes and revision rates after ACLR in the pediatric population are also lacking. PURPOSE: To determine the incidence of pediatric ACLR in Norway since 2005, as well as to detect trends in surgical details and describe patient-reported outcomes up to 10 years after ACLR. STUDY DESIGN: Descriptive cohort study. METHODS: This study is based on prospectively collected data on girls ≤14 years and boys ≤16 years, registered in the Norwegian Knee Ligament Register at the time of their primary ACLR, between 2005 and 2021. The main outcome was the incidence of ACLR, adjusted to the corresponding population numbers for each year. The time trend was analyzed by comparing the mean of the first and last 3-year period (2005-2007 and 2019-2021). Patient-reported outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score preoperatively and at 2, 5, and 10 years postoperatively. RESULTS: A total of 1476 patients (1484 cases) were included, with a mean follow-up of 8.1 years (range, 1-17). The incidence of pediatric ACLRs per 100,000 population increased from 18 to 26, which corresponds to an increase of 40% for boys and 55% for girls. Concurrent meniscal procedures increased significantly from 45% to 62%, and the proportion of meniscal repairs increased from 19% to 43% when comparing the first and last time period. The mean Knee injury and Osteoarthritis Outcome Score values for the Sport and Recreation and Quality of Life subscales were between 72 and 75 at the 2-, 5- and 10-year follow-up. The 5-year revision rate was 9.9%. CONCLUSION: There was a major increase in incidence of pediatric ACLR in Norway during the study period. There was a shift in the approach to concomitant meniscal procedures from resection to repair, with more than a doubling of the proportion of meniscal repairs. Patient-reported outcomes revealed long-lasting reduced knee function.

Frnakenstein: multiple target inverse RNA folding.

BACKGROUND: RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. RESULTS: In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. CONCLUSIONS: Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are real structures, while no deterioration was observed for predicted structures. Design for two structure targets is considerably more difficult, but far from impossible, demonstrating the feasibility of automated design of artificial riboswitches. The Python implementation is available at http://www.stats.ox.ac.uk/research/genome/software/frnakenstein.

Reconstructing the ancestral germ line methylation state of young repeats.

One of the key objectives of comparative genomics is the characterization of the forces that shape genomes over the course of evolution. In the last decades, evidence has been accumulated that for vertebrate genomes also epigenetic modifications have to be considered in this context. Especially, the elevated mutation frequency of 5-methylcytosine (5mC) is assumed to facilitate the depletion of CpG dinucleotides in species that exhibit global DNA methylation. For instance, the underrepresentation of CpG dinucleotides in many mammalian genomes is attributed to this effect, which is only neutralized in so-called CpG islands (CGIs) that are preferentially unmethylated and thus partially protected from rapid CpG decay. For primate-specific CpG-rich transposable elements from the ALU family, it is unclear whether their elevated CpG frequency is caused by their small age or by the absence of DNA methylation. In consequence, these elements are often misclassified in CGI annotations. We present a method for the estimation of germ line methylation from pairwise ancestral-descendant alignments. The approach is validated in a simulation study and tested on DNA repeats from the AluSx family. We conclude that a predicted unmethylated state in the germ line is highly correlated with epigenetic activity of the respective genomic region. Thus, CpG-rich repeats can be facilitated as in silico probes for the epigenetic potential of their genomic neighborhood.

A preliminary simulation-based qualitative study of healthcare students' experiences of interprofessional primary care scenarios.

BACKGROUND: Introducing interprofessional education (IPE) in healthcare curricula can prepare students for healthcare practices that have become increasingly complex. The use of simulation is promoted to support IPE. This study explores healthcare students' experiences of participating in common, sub-acute patient scenarios that routinely occur in clinical practice in primary care. More specifically, it looks at how sub-acute patient scenarios from primary care can help develop interprofessional collaborative competence. METHODS: Medical students (N = 10), master's students in advanced geriatric nursing (N = 8) and bachelor's students in nursing (N = 9) participated in the simulations. The students were in their last or second-to-last year of education. We conducted five semi-structured focus group interviews with the participants' directly after the simulation training to elicit experiences related to the scenarios, the simulation and interprofessional collaboration. The transcripts were analysed using systematic text condensation. To supplement the focus group interviews, the students also completed the interprofessional collaborative competency attainment survey (ICCAS), which measures the students' self-assessed interprofessional competence. RESULTS: Three main themes emerged from the analysis of the focus group interviews: realism, uncertainty and reflection. The students emphasised the importance of authentic and recognisable scenarios. They said the vague and unspecific patient symptoms created uncertainty in the situation, making it difficult to understand the patient's diagnosis. Despite that uncertainty, they described the experience as positive. Further, the students expressed that the simulation increased their confidence in interprofessional collaboration and prepared them for future work. The results from the ICCAS questionnaire showed that the students reported a subjective positive change in their interprofessional competence after participating in the scenarios. CONCLUSIONS: This study showed that simulation-based IPE with sub-acute primary care scenarios contributes to develop interprofessional collaborative competence in healthcare education. Sub-acute scenarios can supplement the more common approaches with acute care scenarios and aid in developing the collaborative competence required to work in healthcare teams.

Surgical helmets can be converted into efficient disinfectable powered air-purifying respirators.

BACKGROUND: Filtering facepiece respirators often fail to provide sufficient protection due to a poor fit. Powered air-purifying respirators (PAPRs) are not designed for healthcare personnel, and are challenging to disinfect. Surgical helmets (SH) are available in many United States hospitals but do not provide respiratory protection. Several modifications to SH have been suggested, but none are sufficiently compliant with safety and efficiency standards. The purpose of this investigation was the development of a filter adaptor, which converts SHs into efficient, safe, and disinfectable PAPRs. METHODS: Four critical features were investigated close to regulatory requirements: total inward leakage of particles, CO2 concentrations, intra-helmet differential pressure, and automated disinfection. RESULTS: The average total inward leakage in the 2 independent tests were 0.005% and 0.01%. CO2 concentrations were lower than in the original SH. The modification generates a positive differential pressure. The filter's performance was not compromised after 50 cycles in a sterilization machine. DISCUSSION: The modified SH provides several hundred times better protection than FFP-3 masks. CONCLUSIONS: Surgical helmets can be modified into safe, efficient, and disinfectable PAPRs, suitable for HCP and the operating room in particular. They can play a role in the preparedness for upcoming events requiring efficient respiratory protection.

Capillary function progressively deteriorates in prodromal Alzheimer's disease: A longitudinal MRI perfusion study.

Cardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream ß-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified a semaphorin-plexin signaling pathway that operates in gastric G cells to inhibit gastrin expression on a transcriptional level, thereby limiting food-stimulated gastrin release and gastric acid secretion. Using a systematic siRNA screening approach combined with biochemical, cell biology, and in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin signal transduction, which suppresses gastrin expression through inactivation of the small GTPase R-Ras. Moreover, we show that Rasal1 is pathophysiologically relevant for the pathogenesis of peptic ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs), a main risk factor of peptic ulcers in humans. Last, we show that application of recombinant semaphorin 4D alleviates peptic ulcer disease in mice in vivo, demonstrating that this signaling pathway can be harnessed pharmacologically. This study unravels a mode of G cell regulation that is functionally important in gastric homeostasis and disease.

Fixation of Acute Chondral Fractures in Adolescent Knees.

OBJECTIVES: Chondral fractures are focal cartilage lesions without osseous attachment, most commonly seen in adolescent knees. They have limited capacity for intrinsic healing and traditional treatment has been removal of loose fragments. However, case reports of successful healing after fixation indicate that repair of the joint surface is possible. We wanted to evaluate the outcome in a cohort of patients who underwent fixation of acute chondral fractures in the knee. DESIGN: Patients treated with fixation of a chondral fracture in the knee at our institution were invited to participate in a follow-up study. The mechanism of injury, fragment properties and complications were registered. Patients completed KOOS (Knee Injury and Osteoarthritis Outcome Score) and Lysholm questionnaires and performed a validated single leg hop test. Magnetic resonance imaging (MRI) was used to assess healing of the defect and the quality of the cartilage. RESULTS: Ten patients with a median age at surgery of 15 years (12-17 years) and median follow-up of 5 years (2-9 years) were assessed. The lesions were located on the patella (n = 7), the trochlea (n = 2), and the lateral femoral condyle (n = 1). Median lesion size was 250 mm2 (1.9-6.0 cm2) All patients were treated within 2 months of injury (4-58 days). All patients returned to preinjury level of sports and MRI showed retained fragments that integrated well with surrounding cartilage at follow-up. Mean Lysholm score at follow-up was 90 (73-100). CONCLUSION: Fixation of traumatic chondral-only fragments using bioabsorbable implants may result in successful healing in adolescent patients and should be considered a treatment option in acute injuries.