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Wrinkling has recently attracted an increasing interest by suggesting a number of unforeseeable applications in many emerging material science and engineering fields. If guided and somehow designed, wrinkles could be in fact used as an alternative printing way for realizing complex surface geometries and thus employed as an innovative bottom-up process in the fabrication of nano- and micro-devices. For these reasons, the prediction of wrinkles of films adhering on flat as well as on structured substrata is a challenging task, genesis and development of the phenomenon being not yet completely understood both when thin membranes are coupled with soft supports and in cases where the geometry of the surfaces are characterized by complex three-dimensional profiles. Here we investigate the experimental formation of new intriguing and somehow unforeseeable wrinkled patterns achieved on periodic structures, by showing prediction through a new hybrid analytical-numerical strategy capable to overcome some common obstacles encountered in modeling film wrinkling on flat and 3D-shaped substrata. The proposed approach, which drastically reduces the computational effort, furnishes a helpful way for predicting both qualitative and quantitative results in terms of wrinkling patterns, magnitude and wavelength, by also allowing to follow the onset of film instabilities and the progressive evolution of the phenomenon until its final stage. Keywords: Thin film, Wrinkling, PDMS substrates, Lithium niobate crystals, FEM simulations

Background: Pyro-electrohydrodynamic jetting (p-jet) has emerged recently as a promising technique for biosensing applications, through the concentration of highly diluted biomolecules in fluorescent spots at microscale. However, a great challenge still remains in optimizing the binding strategy for the sensing interface, enabling the detection of low abundance proteins through immunofluorescence protocols. Indeed, the surface of reaction can be functionalized with different chemical groups able to bind the target molecule with a strong interaction, prior to the p-jet spots decreasing the possibility to lose sensitivity after the common rinsing steps., Results: Here, we characterize the immobilization of a model protein, specifically the bovine serum albumin (BSA), in the concentrated p-jet spots to demonstrate the reliability of the technique for highly sensitive immunodetection assays. We first performed spectroscopic measurements on BSA deposited through pipette spots at relatively high concentrations and we achieved a higher efficiency in case of the covalent bond by using the carbonate buffer and the epoxy-based slides. We then tested the covalent setting in case of the p-jet spots with highly diluted samples of pre-labelled BSA. A significant concentration-dependent behavior of the signal was obtained down to picogram levels. Finally, an immunofluorescent protocol was settled with the p-jet spots and a Limit of the Detection (LOD) of 0. 27 pg/mL was reached., Significance: The demonstration here that the p-jet spots are compatible with immunodetection procedures and provide a LOD down to 0.27 pg/mL, launches the p-jet technique towards the development in future of a point-of-care (POC) diagnostic tool. This would become a major force in analytical chemical laboratories. The identification of highly diluted biomarkers from peripheral body fluids would help clinicians performing early diagnosis, overcoming the limitations of the traditional immunochemistry tests, such as the enzyme-linked immunosorbent assay (ELISA)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Studies about clinician acceptability of integrative palliative care interventions in the inpatient and outpatient cancer settings are limited. In this study, we examined clinician acceptability of a NIH-funded interdisciplinary PAlliative and Supportive Care inTervention (PACT) for older adults with acute myeloid leukemia (AML) and their care partners that transcends both inpatient and outpatient settings., Materials and Methods: Data was collected using semi-structured interviews with clinicians who were directly involved in PACT. The domains of the Theoretical Framework of Acceptability were used to guide the qualitative analysis., Results: The clinicians consisted of occupational therapists (37%), physical therapists (25%), registered nurses (25%), and a clinical rehabilitation manager (13%). Five themes were identified in the thematic analysis: (1) Emotions and affect towards the intervention, (2) Intervention coherence and self-efficacy, (3) Barriers, burden, and opportunity costs of delivering the intervention, (4) Usefulness and effectiveness of the intervention, and (5) Recommendations to improve intervention delivery., Discussion: All clinicians found the PACT intervention highly acceptable and expressed the positive impact of the intervention on job fulfillment and satisfaction. Our findings provide evidence to inform the delivery and implementation of future large scale integrative palliative care intervention trials., Competing Interests: Declaration of Competing Interest VC reports other from Oncology Nursing Foundation Research Doctoral (PhD) Academic Scholarship (2023-2024), other from UNC School of Nursing Glaxo Fellowship in Nursing (2023-2024), other from UNC School of Nursing Samuel B. Kellett Future Nursing Faculty Scholar (2022-2023), during the conduct of the study; other from Cassava Sciences, other from Bristol-Myers Squibb, other from Abcellera Biologics, other from In8bio, other from Pfizer, other from Aclarion, other from Viatris, other from Predictive Oncology, outside the submitted work. YC is a MaRS fellow at Duke University and is funded by GlaxoSmithKline outside the submitted work. MP reports receiving a salary from Select Medical., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Robotic-assisted surgery has improved the precision and accuracy of surgical movements with subsequent improved outcomes. However, it requires steep Trendelenburg positioning combined with pneumoperitoneum that negatively affects respiratory mechanics and increases the risk of postoperative respiratory complications. This narrative review summarises the state of the art in ventilatory management of these patients in terms of levels of positive end-expiratory pressure (PEEP), tidal volume, recruitment manoeuvres, and ventilation modes during both urological and gynaecological robotic-assisted surgery. A review of the literature was conducted using PubMed/MEDLINE; after completing abstract and full-text review, 31 articles were included. Although different levels of PEEP were often evaluated within a protective ventilation strategy, including higher levels of PEEP, lower tidal volume, and recruitment manoeuvres vs a conventional ventilation strategy, we conclude that the best PEEP in terms of lung mechanics, gas exchange, and ventilation distribution has not been defined, but moderate PEEP levels (4-8 cm H 2 O) could be associated with better outcomes than lower or highest levels. Recruitment manoeuvres improved intraoperative arterial oxygenation, end-expiratory lung volume and the distribution of ventilation to dependent (dorsal) lung regions. Pressure-controlled compared with volume-controlled ventilation showed lower peak airway pressures with both higher compliance and higher carbon dioxide clearance. We propose directions to optimise ventilatory management during robotic surgery in light of the current evidence., (Copyright © 2023. Published by Elsevier Ltd.)

Literature focused on quantifying or reducing patient harm in anaesthesia uses a variety of labels and definitions to represent patient safety-related events, such as 'medication errors', 'adverse events', and 'critical incidents'. This review extracts and compares definitions of patient safety-related terminology in anaesthesia to examine the scope of this variability and inconsistencies. A structured review was performed in which 36 of the 769 articles reviewed met the inclusion criteria. Similar terms were grouped into six categories by similarities in keyword choice (Adverse Event, Critical Incident, Medication Error, Error, Near Miss, and Harm) and their definitions were broken down into three base components to allow for comparison. Our analysis found that the Medication Error category, which encompasses the greatest number of terms, had widely variant definitions which represent fundamentally different concepts. Definitions of terms within the other categories consistently represented relatively similar concepts, though key variations in wording remain. This inconsistency in terminology can lead to problems with synthesising, interpreting, and overall sensemaking in relation to anaesthesia medication safety. Guidance towards how 'medication errors' should be defined is provided, yet a definition will have little impact on the future of patient safety without organisations and journals taking the lead to promote, publish, and standardise definitions., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Venetoclax is a selective BCL-2 inhibitor with clinical activity in relapsed/refractory multiple myeloma (RRMM). Combinations of venetoclax with agents that have complementary mechanisms of action may improve venetoclax efficacy in RRMM. This study evaluated venetoclax with pomalidomide and dexamethasone (VenPd) in RRMM., Patients and Methods: This phase II open label study (NCT03567616) evaluated VenPd in patients with RRMM who had received ≥ 1 prior therapy and were refractory to lenalidomide. Venetoclax was administered orally daily for days 1 to 28, pomalidomide was administered orally daily for days 1 to 21, and dexamethasone was administered weekly for each 28-day cycle. The primary objective was to characterize the safety and tolerability of VenPd. The secondary objectives were to evaluate the efficacy and pharmacokinetics. The study was terminated early due to partial clinical hold and decision to pursue biomarker driven strategy., Results: Eight patients were enrolled. Patients had a median age of 67.5 years. All patients received 400 mg venetoclax; 4 patients experienced dose-limiting toxicities and the dose was not escalated. All patients had a grade ≥ 3 adverse event, and the most common was neutropenia (n = 6); cytopenias were the most prevalent adverse events. Five patients (63%) had a confirmed response, and the median duration of response was 12.9 months. The median progression-free survival was 10.5 months., Conclusions: Given the limited enrollment, no clear safety or efficacy conclusions about VenPd can be drawn. Preliminary safety data, particularly the occurrence of cytopenias, can be used to guide dosing strategies for future combinations of venetoclax with immunomodulatory agents., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bedside measures of patient effort are essential to properly titrate the level of pressure support ventilation. We investigated whether the tidal swing in oesophageal (ΔPes) and transdiaphragmatic pressure (ΔPdi), and ultrasonographic changes in diaphragm (TFdi) and parasternal intercostal (TFic) thickening are reliable estimates of respiratory effort. The effect of diaphragm dysfunction was also considered., Methods: Twenty-one critically ill patients were enrolled: age 73 (14) yr, BMI 27 (7) kg m -2 , and Pao 2 /Fio 2 33.3 (9.2) kPa. A three-level pressure support trial was performed: baseline, 25% (PS-medium), and 50% reduction (PS-low). We recorded the oesophageal and transdiaphragmatic pressure-time products (PTPs), work of breathing (WOB), and diaphragm and intercostal ultrasonography. Diaphragm dysfunction was defined by the Gilbert index., Results: Pressure support was 9.0 (1.6) cm H 2 O at baseline, 6.7 (1.3) (PS-medium), and 4.4 (1.0) (PS-low). ΔPes was significantly associated with the oesophageal PTP (R 2 =0.868; P<0.001) and the WOB (R 2 =0.683; P<0.001). ΔPdi was significantly associated with the transdiaphragmatic PTP (R 2 =0.820; P<0.001). TFdi was only weakly correlated with the oesophageal PTP (R 2 =0.326; P<0.001), and the correlation improved after excluding patients with diaphragm dysfunction (R 2 =0.887; P<0.001). TFdi was higher and TFic lower in patients without diaphragm dysfunction: 33.6 (18.2)% vs 13.2 (9.2)% and 2.1 (1.7)% vs 12.7 (9.1)%; P<0.0001., Conclusions: ΔPes and ΔPdi are adequate estimates of inspiratory effort. Diaphragm ultrasonography is a reliable indicator of inspiratory effort in the absence of diaphragm dysfunction. Additional measurement of parasternal intercostal thickening may discriminate a low inspiratory effort or a high effort in the presence of a dysfunctional diaphragm., (Copyright © 2020. Published by Elsevier Ltd.)

Background: We recently showed in a pig model of ex vivo lung perfusion (EVLP) that lung edema correlates with glucose consumption. We investigated whether salbutamol, a β-adrenergic receptor agonist known to upregulate fluid transport in the lung, modulates glucose concentration in the perfusate during EVLP., Methods: Lungs from domestic pigs underwent normothermic EVLP. At the end of controlled reperfusion, lungs were ventilated and perfused for 60 minutes, then randomized to salbutamol (β-Agonist) infusion or placebo (Control) for 180 minutes. Functional parameters were assessed., Results: In the β-Agonist group, glucose concentration decreased over time more than corresponding Control values (analysis of variance [ANOVA], p = 0.05). Mean pulmonary artery pressure (mPAP) was 16 ± 1 mm Hg in the β-Agonist group vs 21 ± 1 mm Hg in the Controls (ANOVA p < 0.05). Baseline mPAP was correlated with the drop of mPAP after the β-agonist infusion (R(2) = 0.856, p < 0.05). Dynamic compliance dropped from 51 ± 10 to 31 ± 6 ml/cm H(2)O in the β-Agonist group and from 60 ± 4 to 21 ± 3 ml/cm H(2)O in the Control group (ANOVA, p < 0.05 β-agonist vs Control). The Δ partial pressure of oxygen/fraction of inspired oxygen was 418 ± 15 and 393 ± 12 mm Hg in the β-Agonist and Control groups, respectively (t-test p = 0.106)., Conclusions: Glucose concentration in the perfusate was affected by salbutamol. Salbutamol was associated with lower pulmonary pressures and better lung mechanics. These data suggest a possible role for salbutamol as a pharmacologic adjunct during EVLP before transplantation., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Sequences of the lacSZ operon of 29 Streptococcus thermophilus strains from different dairy products were determined. Differences in sequence among the strains were detected within LacS more often than in the LacZ gene. The sequences were aligned and compared and it was possible to gather the strains into three groups of similarity on the basis of the LacS gene sequence. The dairy environment of origin did not seem to be related to the lacSZ operon sequence and thus to the similarity shown. Nucleotide variability was investigated and a total of 139 nucleotide changes were found in the LacS gene while 40 nucleotide changes were found in the sequences of the LacZ gene. Moreover, the influence of the nucleotide changes on the amino acid sequence of the LacS transporter and of the beta-galactosidase enzyme were discussed. Sequence variability within the region upstream from the LacS gene was used to develop group-specific PCR systems capable of distinguishing S. thermophilus at the strain level. A strain-specific primer set was designed allowing the specific detection of 11 out of 29 strains of S. thermophilus. Moreover, LacS-PCR-SSCP analysis of the 29 strains provided 2 different profiles, whereas 4 strain-specific profiles were detected by LacS-PCR-DGGE, indicating the potential to use these techniques for profiling and monitoring population of strains of S. thermophilus in food products. The results are discussed with reference to the potential of these PCR methods for ascertaining strain dominance and starter fitness in dairy processes.

Purpose: The main purpose of this review is to address some concerns regarding the accurate and timely diagnosis of lysosomal storage disorders (LSD)., Methods: Using their experience in diagnosing LSD in more than 2500 individuals, the authors highlight several diagnostic difficulties and solutions and review the latest methods for early diagnosis and treatment., Results: While "classic" patients can be accurately diagnosed using relatively simple methods in an experienced laboratory, atypical patients require more detailed studies. With a few exceptions, almost all LSD can be diagnosed in leukocytes or plasma. Methods for screening all newborns without a family history of a LSD have been proposed, but such screening may require a large amount of effort for little gain., Conclusions: With effective therapy becoming available for some LSD, early diagnosis is critically important. If the goal is to prevent serious complications related to the nervous and skeletal systems, earlier diagnosis is potentially advantageous. Accurate prognosis and assessing the need for aggressive therapy in newly diagnosed patients are problems that need further study.

Postnatal CD34(+) cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assays. Hypothetically, CD34(+)KDR(+) cells may comprise hemangioblasts bipotent for both lineages. This hypothesis is consistent with 2 series of experiments. In the first series, in clonogenic culture permissive for hematopoietic and endothelial cell growth, CD34(+)KDR(+) cells generate large hemato-endothelial (Hem-End) colonies (5% of seeded cells), whereas CD34(+)KDR(-) cells do not. Limiting-dilution analysis indicates that Hem-End colonies are clonally generated by single hemangioblasts. Sibling cells generated by a hemangioblast, replated in unicellular culture, produce either hematopoietic or Hem-End colonies, depending on the specific culture conditions. Identification of endothelial cells was based on the expression of VE-cadherin and endothelial markers and with lack of CD45 and hematopoietic molecules, as evaluated by immunofluorescence, immunocytochemistry, and reverse transcription-polymerase chain reaction. Furthermore, endothelial cells were functionally identified using low-density lipoprotein (LDL) uptake and tube-formation assays. In the second series, to evaluate the self-renewal capacity of hemangioblasts, single CD34(+)KDR(+) cells were grown in 3-month extended long-term culture (ELTC) through 3 serial culture rounds-that is, blast cells generated in unicellular ELTC were reseeded for a subsequent round of unicellular ELTC. After 9 months, 10% blasts from tertiary ELTC functioned as hemangioblasts and generated macroscopic Hem-End colonies in clonogenic culture. These studies identified postnatal hemangioblasts in a CD34(+)KDR(+) cell subset, endowed with long-term proliferative potential and bilineage differentiation capacity. Although exceedingly rare, hemangioblasts may represent the lifetime source/reservoir for primitive hematopoietic and endothelial progenitors.

Studies were carried out on the microbiological and physico-chemical changes which occurred during the ripening of five batches of Naples-type salami, manufactured without starter cultures. Salami were sampled internally and externally, and the following microbial groups were studied: lactic acid bacteria, Micrococcaceae and yeasts. The results obtained indicated that lactobacilli constituted the predominant flora, both on the surface and in the interior of the pieces throughout the ripening period. Micrococcaceae and yeasts were also found in considerable number in both locations. Characterisation of 191 lactic isolates indicated that the salami microflora was dominated by homofermentative lactobacilli; approximately 63% of them could be identified as Lactobacillus sake; 40% showing the traits of a racemase negative variant of this species, once referred to Lactobacillus bavaricus. Yeast population mainly comprised Debaryomyces strains. All the colonies grown on mannitol salt and Kranep agar were catalase-positive cocci; novobiocin-resistant staphylococci were the only Micrococcaceae found. The API Staph identification system did not prove to be reliable: 82% of the isolates remained unidentified. To achieve improved characterisation, cluster analysis was subsequently performed on this group, corroborating the existence of a fairly homogeneous group representing an intermediate variety between Staphylococcus xylosus and Staphylococcus saprophyticus that was isolated during the whole ripening process.

Three different approaches (whole-cell protein profiles, DNA fingerprinting combined with pulsed-field gel electrophoresis and analysis of rDNA genes) were used to characterize thirty-one strains of Lactobacillus delbrueckii subsp. bulgaricus from different dairy products, and three type strains belonging to L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. lactis and L. delbrueckii subsp. bulgaricus. Moreover, the number and different forms of rrn operons in L. delbrueckii and its subspecies were defined. At the strain typing level, Notl macrorestriction analysis permitted grouping of the 32 strains of L. delbrueckii subsp. bulgaricus into 23 restriction patterns, providing a high degree of discriminatory power. Among whole-cell protein profiles, PCR analysis of rDNA genes and ribotyping, the latter method seemed to be the most reliable approach to characterizing the subspecies belonging to L. delbrueckii. Ribotyping combined with enzymes such as HindIII and EcoRI showed that at least six rrn operons were present in L. delbrueckii and its subspecies; two forms of rrn operons were present in the subspecies lactis and bulgaricus and four forms were present in the subspecies delbrueckii.

We compare here the results of electrophysiological measurements on proximal tubular cells performed on rat kidney in vivo and on isolated rabbit and rat tubules in vitro. Based on different effects of carbonic anhydrase inhibitors in the in vivo and in vitro preparation, we conclude that NaHCO3 cotransport across the basolateral cell membrane functions as Na(+)-CO3(2-)-HCO3- cotransport in vivo, but as Na(+)-HCO3(-)-HCO3- cotransport in the classical in vitro preparation. The former, but not the latter, transport mode is characterized by generation of local disequilibrium pH/CO3(2-) concentrations that oppose fluxes if membrane-bound carbonic anhydrase is inhibited. In support of this conclusion, we find that overall transport functions with a HCO3- to Na+ stoichiometry of 3:1 in vivo (since each transported CO3(2-) eventually generates 2 HCO3- ions), but 2:1 in vitro. This has been deduced from various measurements, among them super-Nernstian and reverse nernstian, potential responses to changing ion concentrations which are characteristic of obligatorily coupled cation-anion cotransporters, but are not known in classical electrochemistry. The different transport modes in vivo and in vitro suggest that isolated proximal tubules have functional deficits compared to proximal tubules in vivo.

Reduced glutathione (GSH) has been hypothesized to play a role in the rescue of cells from apoptosis, by buffering an endogenously induced oxidative stress. We correlated GSH levels and apoptosis in U937 human monocytic cells induced to apoptosis by different agents. All treatments led to depletion of GSH concomitant with the onset of apoptosis. The loss was due to extrusion of GSH outside the cell, while GSSG was not accumulated in the apoptosing cells, nor was it found in the extracellular medium. Modulation of intracellular GSH level did not influence the overall extent of apoptosis. We conclude that glutathione loss in apoptosis is not necessarily preceded by an oxidative stress, and that GSH depletion alone is not sufficient to lead cells to apoptosis.

Twenty strains of Streptococcus thermophilus were classified into five different types characterized by ribotyping after DNA digestion with HindIII and hybridization with cDNA from 16S-23S rDNA of Escherichia coli. Ribotyping after digestion with HaeIII and XhoI enabled the same strains to be gathered into three groups as a consequence of the reduced influence of the flanking sequences within the analysis of rRNA operons. Amplified rDNA restriction analysis clearly confirmed the discrimination of these three different ribotypes, producing evidence to suggest that subtaxa are to be recognized within this species.

DNA of 33 strains of Streptococcus thermophilus (7 isolated from natural whey cultures utilized as starter, 25 from commercial yogurts and 1 reference strain) was analysed by restriction endonuclease digestion and both conventional and pulsed-field agarose gel electrophoresis. The restriction patterns after digestion of total DNA with HindIII, EcoRI and BamHI enabled 10 different groups to be distinguished by conventional electrophoresis. Digesting genomic DNA with SmaI or NotI and separating it by pulsed-field gel electrophoresis, the 33 strains could be classified into 5 groups. The same result was obtained after digestion with HaeIII and conventional electrophoresis. The 33 isolates could be divided into 13 groups when diversities among patterns obtained after both the first and second method were considered. A combination of the two techniques turned out to be the most reliable methodological approach for characterizing strains of S. thermophilus for scientific, industrial and legal purposes.