Understanding Staphylococcus aureus in hyperglycaemia: A review of virulence factor and metabolic adaptations.

Staphylococcus aureus is one of the most commonly detected bacteria in diabetic skin and soft tissue infections. The incidence and severity of skin and soft tissue infections are higher in patients with diabetes, indicating a potentiating mechanism of hyperglycaemia and infection. The goal of this review is to explore the metabolic and virulence factor adaptations of S. aureus under hyperglycaemic conditions. Primary data from identified studies were included and summarised in this paper. Understanding the nexus of hyperglycaemia, metabolism, and virulence factors provides insights into the complexity of diabetic skin and soft tissue infections attributed to S. aureus.

Exploring the Efficacy of Selected Allografts in Chronic Wound Healing: Evidence from Murine Models and Clinical Data for a Proposed Treatment Algorithm.

Significance: Chronic wounds can lead to poor outcomes for patients, with risks, including amputation and death. In the United States, chronic wounds affect 2.5% of the population and cost up to $28 billion per year in primary health care costs. Recent Advances: Allograft tissues (dermal, amnion, and amnion/chorion) have shown efficacy in improving healing of chronic, recalcitrant wounds in human patients, as evidenced by multiple clinical trials. Their mechanisms of actions have been relatively understudied, until recently. Research in murine models has shown that dermal allografts promote reepithelialization, amnion allografts promote granulation tissue formation and angiogenesis, and amnion/chorion allografts support all stages of wound healing. These findings confirm their effectiveness and illuminate their therapeutic mechanisms. Critical Issues: Despite the promise of allografts in chronic wound care, a gap exists in understanding which allografts are most effective during each wound healing stage. The variable efficacy among each type of allograft suggests a mechanistic approach toward a proposed clinical treatment algorithm, based on wound characteristics and patient's needs, may be beneficial. Future Directions: Recent advances in allografts provide a framework for further investigations into patient-specific allograft selection. This requires additional research to identify which allografts support the best outcomes during each stage of wound healing and in which wound types. Longitudinal human studies investigating the long-term impacts of allografts, particularly in the remodeling phase, are also essential to developing a deeper understanding of their role in sustained wound repair and recovery.

Modulation of ipsilateral motor evoked potentials during bimanual coordination tasks.

Introduction: Ipsilateral motor evoked potentials (iMEPs) are difficult to obtain in distal upper limb muscles of healthy participants but give a direct insight into the role of ipsilateral motor control. Methods: We tested a new high-intensity double pulse transcranial magnetic stimulation (TMS) protocol to elicit iMEPs in wrist extensor and flexor muscles during four different bimanual movements (cooperative-asymmetric, cooperative-symmetric, non-cooperative-asymmetric and non-cooperative-symmetric) in 16 participants. Results: Nine participants showed an iMEP in the wrist extensor in at least 20% of the trials in each of the conditions and were classified as iMEP+ participants. iMEP persistence was greater for cooperative (50.5 ± 28.8%) compared to non-cooperative (31.6 ± 22.1%) tasks but did not differ between asymmetric and symmetric tasks. Area and amplitude of iMEPs were also increased during cooperative (area = 5.41 ± 3.4 mV × ms; amplitude = 1.60 ± 1.09 mV) compared to non-cooperative (area = 3.89 ± 2.0 mV × ms; amplitude = 1.12 ± 0.56 mV) tasks and unaffected by task-symmetry. Discussion: The upregulation of iMEPs during common-goal cooperative tasks shows a functional relevance of ipsilateral motor control in bimanual movements. The paired-pulse TMS protocol is a reliable method to elicit iMEPs in healthy participants and can give new information about neural control of upper limb movements. With this work we contribute to the research field in two main aspects. First, we describe a reliable method to elicit ipsilateral motor evoked potentials in healthy participants which will be useful in further advancing research in the area of upper limb movements. Second, we add new insight into the motor control of bimanual movements. We were able to show an upregulation of bilateral control represented by increased ipsilateral motor evoked potentials in cooperative, object-oriented movements compared to separate bimanual tasks. This result might also have an impact on neurorehabilitation after stroke.

Intracortical facilitation and inhibition in human primary motor cortex during motor skill acquisition.

The primary motor cortex (M1) is critical for movement execution, but its role in motor skill acquisition remains elusive. Here, we examine the role of M1 intracortical circuits during skill acquisition. Paired-pulse transcranial magnetic stimulation (TMS) paradigms of short-interval intracortical facilitation (SICF) and inhibition (SICI) were used to assess excitatory and inhibitory circuits, respectively. We hypothesised that intracortical facilitation and inhibition circuits in M1 would be modulated to support acquisition of a novel visuomotor skill. Twenty-two young, neurologically healthy adults trained with their nondominant hand on a skilled and non-skilled sequential visuomotor isometric finger abduction task. Electromyographic recordings were obtained from the nondominant first dorsal interosseous (FDI) muscle. Corticomotor excitability, SICF, and SICI were examined before, at the midway point, and after the 10-block motor training. SICI was assessed using adaptive threshold-hunting procedures. Task performance improved after the skilled, but not non-skilled, task training, which likely reflected the increase in movement speed during training. The amplitudes of late SICF peaks were modulated with skilled task training. There was no modulation of the early SICF peak, SICI, and corticomotor excitability with either task training. There was also no association between skill acquisition and SICF or SICI. The findings indicate that excitatory circuitries responsible for the generation of late SICF peaks, but not the early SICF peak, are modulated in motor skill acquisition for a sequential visuomotor isometric finger abduction task.

Predicting local material thickness from steady-state ultrasonic wavefield measurements using a convolutional neural network.

Acoustic steady-state excitation spatial spectroscopy (ASSESS) is a full-field, ultrasonic non-destructive evaluation (NDE) technique used to locate and characterize defects in plate-like structures. ASSESS generates a steady-state, single-tone ultrasonic excitation in a structure and a scanning laser Doppler Vibrometer (LDV) measures the resulting full-field surface velocity response. Traditional processing techniques for ASSESS data rely on wavenumber domain analysis. This paper presents the alternative use of a convolutional neural network (CNN), trained using simulated ASSESS data, to predict the local plate thickness at every pixel in the wavefield measurement directly. The defect detection accuracy of CNN-based thickness predictions are shown to improve for defects of greater size, and for defects with higher thickness reductions. The CNN demonstrates the ability to predict thickness accurately in regions where Lamb wave dispersion relations are complex or unknown, such as near the boundaries of a test specimen, so long as the CNN is trained on data that accounts for these regions. The CNN also shows generalizability to ASSESS experimental data, despite an entirely simulated training dataset.

Phylogenetics of Leptocereus (Cactaceae) on Hispaniola: clarifying species limits in the L. weingartianus complex and a new species from the Sierra de Bahoruco.

The Antillean genus Leptocereus represents an in-situ radiation among the Greater and Lesser Antilles of 19 currently recognized species. Extensive fieldwork carried out in the Dominican Republic over recent years has revealed that the species limits of Leptocereus of Hispaniola are more complex than previously thought. There are four currently recognized species that occur on the island, L. demissus, L. paniculatus, L. undulosus and L. weingartianus. We evaluate species limits in this group based on DNA sequence data and phylogenetic analysis, morphological characters and a survey of herbarium specimens from across Hispaniola. Based on our analyses, it is clear that at least five species occur on the island of Hispaniola, with the new species from Sierra de Bahoruco, L. velozianus, described here. We provide an identification key, distribution maps and photographic plates for all species on Hispaniola based on our own fieldwork and the study of herbarium specimens. The description of yet another species of Leptocereus on Hispaniola reiterates the importance of the poorly studied, but yet biodiverse, seasonally dry tropical forest in the Antilles.

Physiologic Analysis and Clinical Performance of the Ventilatory Ratio in Acute Respiratory Distress Syndrome.

RATIONALE: Pulmonary dead space fraction (Vd/Vt) is an independent predictor of mortality in acute respiratory distress syndrome (ARDS). Yet, it is seldom used in practice. The ventilatory ratio is a simple bedside index that can be calculated using routinely measured respiratory variables and is a measure of impaired ventilation. Ventilatory ratio is defined as [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5). OBJECTIVES: To determine the relation of ventilatory ratio with Vd/Vt in ARDS. METHODS: First, in a single-center, prospective observational study of ARDS, we tested the association of Vd/Vt with ventilatory ratio. With in-hospital mortality as the primary outcome and ventilator-free days as the secondary outcome, we tested the role of ventilatory ratio as an outcome predictor. The findings from this study were further verified in secondary analyses of two NHLBI ARDS Network randomized controlled trials. MEASUREMENTS AND MAIN RESULTS: Ventilatory ratio positively correlated with Vd/Vt. Ordinal groups of ventilatory ratio had significantly higher Vd/Vt. Ventilatory ratio was independently associated with increased risk of mortality after adjusting for PaO2/FiO2, and positive end-expiratory pressure (odds ratio, 1.51; P = 0.024) and after adjusting for Acute Physiologic Assessment and Chronic Health Evaluation II score (odds ratio, 1.59; P = 0.04). These findings were further replicated in secondary analyses of two separate NHLBI randomized controlled trials. CONCLUSIONS: Ventilatory ratio correlates well with Vd/Vt in ARDS, and higher values at baseline are associated with increased risk of adverse outcomes. These results are promising for the use of ventilatory ratio as a simple bedside index of impaired ventilation in ARDS.

Pulmonary mechanics and gas exchange characteristics in uncommon etiologies of acute respiratory distress syndrome.

BACKGROUND: Common causes of acute respiratory distress syndrome (ARDS) include pneumonia, aspiration, non-pulmonary sepsis and trauma. Little is known about pulmonary mechanics and gas exchange in less-common etiologies of ARDS, which comprises 12-23% of cases. Our hospital's ARDS quality assurance database contained a substantial number of these cases. This descriptive study examines the pulmonary mechanics, and gas exchange characteristics of this diverse cohort of ARDS subjects. METHODS: Between March 2010 and April 2017 we identified 94 subjects with less common etiologies of ARDS who had dead space fraction (VD/VT) and respiratory system compliance (CRS) measured within 24 hours of ARDS onset; 86 of whom did not have sepsis as a co-diagnosis. There were 18 identifiable sources of ARDS. For descriptive purposes these were subsumed under 10 etiologic categories: pancreatitis (n=16), hemorrhagic shock/reperfusion injury (n=9), transfusion-associated acute lung injury (TRALI) (n=3), drug overdose (n=13), inhalation injury (n=10), idiopathic (n=10), neurogenic (n=8), pulmonary toxicity (n=3), hyper-immune response (n=4), hepatic failure (n=7), and 3 other cases: 2 cutaneous burns and one case of malaria. VD/VT was measured using the Enghoff-Bohr equation. Arterial blood gases were drawn simultaneously with mixed expired CO2 using volumetric capnography and standard pulmonary mechanics measurements. Data are expressed as median (IQR). Comparisons between groups used Kruskal-Wallis and Dunn's post-tests, Mann-Whitney tests or Fisher exact tests. RESULTS: The majority of less common ARDS were from indirect sources (79%) with 9% attributed to direct causes and 11% idiopathic. Because of the small sample sizes, there were no differences in pulmonary mechanics or gas exchange between subgroups classified as indirect, direct and idiopathic, or between subgroups sharing common lung injury mechanisms. Nevertheless, salient trends were apparent particularly in CRS and VD/VT. CRS was most severely reduced in the toxicity subgroup and least impaired in the idiopathic subgroup [18 (11 to 22), and 40 (30 to 43) mL/cmH2O respectively]. VD/VT was extraordinarily high in the hepatic failure subgroup and lowest in pancreatitis [0.78 (0.57 to 0.79) and 0.54 (0.47 to 0.65) respectively]. There was less distinction in oxygenation as median values for all subgroups met moderate ARDS criteria. For the entire cohort, only VD/VT was statistically different between non-survivors and survivors: 0.66 (0.57 to 0.78) vs. 0.59 (0.51 to 0.68), P=0.012. CONCLUSIONS: Within a diverse cohort having less common presentations of ARDS, there was apparent variability in the distribution of CRS, VD/VT compared to differences oxygenation dysfunction. Elevated pulmonary dead space still identified patients with higher mortality, as is the case with more common causes of ARDS.

Lung Injury Etiology and Other Factors Influencing the Relationship Between Dead-Space Fraction and Mortality in ARDS.

BACKGROUND: In ARDS, elevated pulmonary dead-space fraction (VD/VT) is a particularly strong indicator of mortality risk. Whether the magnitude of VD/VT is modified by the underlying etiology of ARDS and whether this influences the strength of its association with mortality remains unknown. We sought to elucidate the impact of ARDS etiology on VD/VT and also to determine whether ARDS severity, as classified by the Berlin definition, has correspondence with changes in VD/VT. METHODS: This single-center, retrospective, observational study (2010-2016) measured VD/VT in 685 subjects with ARDS as part of clinical management with lung-protective ventilation. Volumetric capnography was used to measure VD/VT with 99% of measurements occurring within 48 h of ARDS onset. Demographic information as well as illness severity scores and pulmonary mechanics data also were collected. Multivariate logistic regression modeling was done to assess the strength of association between VD/VT and mortality. RESULTS: VD/VT was elevated across etiologies, with aspiration and pneumonia having significantly higher VD/VT than non-pulmonary sepsis or trauma. Differences in the magnitude of VD/VT across etiologies did not necessarily correspond with mortality between etiologies. However, within each etiology grouping, VD/VT was significantly elevated in non-survivors versus survivors. The same results were found in both moderate and severe (but not mild) ARDS using the Berlin definition. In the final adjusted model, the strongest mortality risk was VD/VT, wherein the risk of death increased by 22% for every 0.05 increase in VD/VT. CONCLUSIONS: VD/VT magnitude varies by ARDS etiology, as does mortality. Only in mild ARDS does VD/VT fail to distinguish non-survivors from survivors. Nonetheless, VD/VT has the strongest association with mortality risk in those with ARDS.

Severity of Hypoxemia and Other Factors That Influence the Response to Aerosolized Prostacyclin in ARDS.

BACKGROUND: ARDS is characterized by decreased functional residual capacity (FRC), heterogeneous lung injury, and severe hypoxemia. Tidal ventilation is preferentially distributed to ventilated alveoli. Aerosolized prostaglandin I2 exploits this pathophysiology by inducing local vasodilation, thereby increasing ventilation-perfusion matching and reducing hypoxemia. Therefore, aerosolized prostaglandin I2 efficacy may depend upon FRC. Both PaO2 /FIO2 and compliance of the respiratory system (CRS) are indirect signifiers of FRC and thus may partly determine the response to aerosolized prostaglandin I2. METHODS: We reviewed the records of 208 ARDS subjects who received aerosolized prostaglandin I2 and had arterial blood gases done before and after the initiation of therapy, without other ventilator manipulations. Subjects were grouped according to baseline PaO2 /FIO2 (lowest: < 60, intermediate: 60-90, highest: > 90 mm Hg) and CRS (< 20, 20-29, 30-39, and ≥ 40 mL/cm H2O) and by other factors, such as sepsis. Comparisons were analyzed by paired t tests, or Kruskal-Wallis and Dunn post-tests. Multivariate logistic regression modeling was done to determine which of 18 clinically relevant factors were most predictive for responding to aerosolized prostaglandin I2. α was set at .05. RESULTS: Mean PaO2 /FIO2 increased by 33 mm Hg (42%) upon initiation of prostaglandin I2, with a responder rate of 62%. PaO2 /FIO2 increased significantly in all oxygenation groups. The highest baseline PaO2 /FIO2 group had the greatest improvement and responder rate (51 ± 63 mm Hg, and 82%). In addition, those with sepsis had a smaller improvement in PaO2 /FIO2 compared with those without sepsis (18 ± 35 vs 40 ± 55 mm Hg, P = .002). Both PaO2 /FIO2 and responder rate increased as CRS improved, but between-group improvements were not as consistent. In the final model, the only factors that predicted a positive response to aerosolized prostaglandin I2 were baseline PaO2 /FIO2 (odds ratio 1.10 [1.004-1.205], P = .042) and CRS (odds ratio 1.04 [1.01-1.08], P = .02). CONCLUSIONS: Aerosolized prostaglandin I2 improves oxygenation in approximately 60% of ARDS cases. A favorable response was most strongly associated with baseline PaO2 /FIO2 and CRS.