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BACKGROUND: Lung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCO2R) to achieve LDP targets. METHODS: An in silico clinical trial was conducted using a previously published mathematical model of patient-ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics. Ventilation and sedation were titrated according to a pre-defined algorithm in pressure support ventilation (PSV) and proportional assist ventilation (PAV+) modes, with or without adjunctive ECCO2R, and using ECCO2R alone (without ventilation or sedation). Random forest modelling was employed to identify patient-level factors associated with achieving targets. RESULTS: After titration, the proportion of patients achieving targets was lower in PAV+ vs. PSV (37% vs. 43%, odds ratio 0.78, 95% CI 0.73-0.85). Adjunctive ECCO2R substantially increased the probability of achieving targets in both PSV and PAV+ (85% vs. 84%). ECCO2R alone without ventilation or sedation achieved LDP targets in 9%. The main determinants of success without ECCO2R were lung compliance, ventilatory ratio, and strong ion difference. In silico trial results corresponded closely with the results obtained in a clinical trial of the LDP titration algorithm (n = 30). CONCLUSIONS: In this in silico trial, many patients required ECCO2R in combination with mechanical ventilation and sedation to achieve LDP targets. ECCO2R increased the probability of achieving LDP targets in patients with intermediate degrees of derangement in elastance and ventilatory ratio.

This study investigates a novel approach toward enhancing the efficacy of Lutetium-177 (Lu-177) radiopharmaceutical therapy by combining it with gold nanoparticles (AuNPs) in the HepG2 hepatic cancer cell line. Lu-177, known for its effective β radiation, also emits gamma rays at energies (113 keV and 208 keV) near the photoelectric absorption range, suggesting potential for targeted and localized radiation enhancement when used in conjunction with AuNPs. Thus, HepG2 cells were treated at two different activity levels (74 MBq and 148 MBq), with Lu-177 alone, with a combination of Lu-177 and AuNPs in two sizes (10 nm and 50 nm), while some received no treatment. Treatment efficacy was assessed by quantifying the radiation enhancement ratio (RER) and the apoptosis levels. The results reveal that combining Lu-177 with AuNPs significantly increases cell death and apoptosis compared to Lu-177 alone, with 10 nm AuNPs demonstrating superior effectiveness. Additionally, varying Lu-177 activity levels influenced the treatment outcomes, with higher activity levels further augmenting the therapeutic impact of combined therapy. These findings underscore the potential of utilizing Lu-177’s beta, but also gamma, emissions, traditionally considered non-therapeutic, for localized radiation enhancement when combined with AuNPs. This novel strategy leverages Lu-177 as an internal irradiator to exploit gamma radiation for a targeted therapeutic advantage without requiring nanoparticle functionalization. The study provides a promising approach to improving radionuclide therapy and sets the stage for future research aimed at optimizing cancer treatments through the combined use of Lu-177 and AuNPs.

Abstract Background Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. Methods This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by ‘static’ (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and ‘dynamic’ (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman’s correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. Results In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. Conclusions In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.

This study highlights the barriers that secondary teachers in Greece face dealing with the implementation of Environmental Education programs throughout a period of more than 30 years in the Greek educational system. Participants were 20 secondary teachers, emanating from various disciplines. Seven were "senior" teachers, having implemented EE projects before its official institutionalization, in 1990, and 13 were "junior", meaning that they implemented EE projects during the Decade of Education for Sustainable Development (2005-2014). In-depth, face-to-face, semi-structured interviews were used to identify teachers' views about the barriers they faced regarding changes or transformations in the realization of EE during the periods under focus. Collected data were subjected to grounded theory analysis and revealed that there were similarities and differences concerning the barriers encountered in the periods of study. Barriers are of structural, financial and economic nature as well as pedagogical and epistemological. These refer to the position of EE into the secondary schools and to the orientation of the school within the general educational system. Results indicate rather a restriction of EE into schools instead of expansion and flourishment following the international progress made, in theoretical and practical level, and the experience that have been gained worldwide after decades of practicing.

Abstract Human herpes viruses (HHV) are ubiquitous and have been implicated in numerous long-term health conditions. Since the association between viral exposure and long-term health impacts is partially influenced by variation in human leukocyte antigen (HLA) genes, we evaluated in silico the binding affinities of 9 HHV envelope glycoproteins with 127 common HLA Class I and Class II molecules. The findings show substantial variability in HHV binding affinity across viruses, HLA Class, HLA genes, and HLA alleles. Specific findings were as follows: (1) the predicted binding affinities of HHVs were characterized by four distinct groupings—[HHV1, HHV2], [HHV3, HHV4, HHV5], [HHV6A], [HHV6B, HHV7, HHV8]—with relatively lower binding affinities for HHV1, HHV2, and HHV6a compared to other HHVs; (2) significantly higher binding affinity was found for HLA Class I relative to Class II; (3) analyses within each class demonstrated that alleles of the C gene (for Class I) and DRB1 gene (for Class II) had the highest binding affinities; and (4) for each virus, predicted binding affinity to specific alleles varied, with HHV6a having the lowest affinity for HHV-HLA complexes, and HHV3, HHV4, and HHV5 having the highest. Since HLA-antigen binding is the first step in initiating an immune response to foreign antigens, these relative differences in HHV binding affinities are likely to influence long-term health impacts such that the cells infected with viruses associated with higher binding affinities across common HLA alleles may be more reduced in numbers, thereby lowering the potential for long-term sequelae of their infections.

Abstract Background Spinal manipulation (SM) has been claimed to change anatomy, either in structure or position, and that these changes may be the cause of clinical improvements. The aim of this systematic review was to evaluate and synthesise the peer-reviewed literature on the current evidence of anatomical changes in response to SM. Methods The review was registered with PROSPERO (CRD42022304971) and reporting was guided by the standards of the PRISMA Statement. We searched Medline, Embase, CINAHL, AMED, Cochrane Library all databases, PEDro, and the Index to Chiropractic Literature from inception to 11 March 2022 and updated on 06 June 2023. Search terms included manipulation, adjustment, chiropractic, osteopathy, spine and spine-related structures. We included primary research studies that compared outcomes with and without SM regardless of study design. Manipulation was defined as high-velocity, low-amplitude thrust delivered by hand to the spine or directly related joints. Included studies objectively measured a potential change in an anatomical structure or in position. We developed a novel list of methodological quality items in addition to a short, customized list of risk of bias (RoB) items. We used quality and RoB items together to determine whether an article was credible or not credible. We sought differences in outcomes between SM and control groups for randomised controlled trials and crossover studies, and between pre- and post-SM outcomes for other study designs. We reported, in narrative form, whether there was a change or not. Results The search retrieved 19,572 articles and 20 of those were included for review. Study topics included vertebral position (n = 3) facet joint space (n = 5), spinal stiffness (n = 3), resting muscle thickness (n = 6), intervertebral disc pressure (n = 1), myofascial hysteresis (n = 1), and further damage to already damaged arteries (n = 1). Eight articles were considered credible. The credible articles indicated that lumbar facet joint space increased and spinal stiffness decreased but that the resting muscle thickness did not change. Conclusion We found few studies on this topic. However, there are two promising areas for future study: facet joint space and spinal stiffness. A research strategy should be developed with funding for high quality research centres.

Abstract To compare the effectiveness and safety of scleral buckling and pars plana vitrectomy in treating retinal detachment without posterior vitreous detachment. A total of 88 eyes of 83 patients with retinal detachment without prior posterior vitreous detachment were investigated retrospectively. Group A comprised patients who underwent scleral buckling (n = 47) and Group B (n = 36) patients who were treated with pars plana vitrectomy. Anatomical success, postoperative visual acuity, and ocular adverse events were evaluated. The primary and final anatomical success rate showed a nonsignificant difference (p = 0.465 and p = 0.37 respectively). No significant difference was observed in the reoperation rate or development of epiretinal membrane between the groups (p = 0.254 and p = 0.254 respectively). However, scleral buckling resulted in significantly better visual acuity at the last follow-up (0.12 ± 0.23) compared to pars plana vitrectomy (0.37 ± 0.46, p = 0.001). The incidence of cataract progression was also significantly higher in the pars plana vitrectomy group (46%) compared to the scleral buckling group (10%, p

Abstract Several viruses have been implicated in breast cancer, including human herpes virus 4 (HHV4), human herpes virus 5 (HHV5), human papilloma virus (HPV), human JC polyoma virus (JCV), human endogenous retrovirus group K (HERVK), bovine leukemia virus (BLV) and mouse mammary tumor virus (MMTV). Human leukocyte antigen (HLA) is involved in virus elimination and has been shown to influence breast cancer protection/susceptibility. Here we investigated the hypothesis that the contribution of a virus to development of breast cancer would depend on the presence of the virus, which, in turn, would be inversely related to the success of its elimination. For that purpose, we estimated in silico predicted binding affinities (PBA) of proteins of the 7 viruses above to 127 common HLA alleles (69 Class I [HLA-I] and 58 Class II HLA-II]) and investigated the association of these binding affinities to the breast cancer—HLA (BC-HLA) immunogenetic profile of the same alleles. Using hierarchical tree clustering, we found that, for HLA-I, viruses BLV, JCV and MMTV were grouped with the BC-HLA, whereas, for HLA-II, viruses BLV, HERVK, HPV, JCV, and MMTV were grouped with BC-HLA. Finally, for both HLA classes, the average PBAs of the viruses grouped with the BC-HLA profile were significantly lower than those of the other, non BC-HLA associated viruses. Assuming that low PBAs are likely associated with slower viral elimination, these findings support the hypothesis that a defective/slower elimination and, hence, longer persistence and inefficient/delayed production of antibodies against them underlies the observed association of the low-PBA group with breast cancer.

Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance.

Abstract Background Musculoskeletal conditions are the leading contributor to global disability and health burden. Manual therapy (MT) interventions are commonly recommended in clinical guidelines and used in the management of musculoskeletal conditions. Traditional systems of manual therapy (TMT), including physiotherapy, osteopathy, chiropractic, and soft tissue therapy have been built on principles such as clinician-centred assessment, patho-anatomical reasoning, and technique specificity. These historical principles are not supported by current evidence. However, data from clinical trials support the clinical and cost effectiveness of manual therapy as an intervention for musculoskeletal conditions, when used as part of a package of care. Purpose The purpose of this paper is to propose a modern evidence-guided framework for the teaching and practice of MT which avoids reference to and reliance on the outdated principles of TMT. This framework is based on three fundamental humanistic dimensions common in all aspects of healthcare: safety, comfort, and efficiency. These practical elements are contextualised by positive communication, a collaborative context, and person-centred care. The framework facilitates best-practice, reasoning, and communication and is exemplified here with two case studies. Methods A literature review stimulated by a new method of teaching manual therapy, reflecting contemporary evidence, being trialled at a United Kingdom education institute. A group of experienced, internationally-based academics, clinicians, and researchers from across the spectrum of manual therapy was convened. Perspectives were elicited through reviews of contemporary literature and discussions in an iterative process. Public presentations were made to multidisciplinary groups and feedback was incorporated. Consensus was achieved through repeated discussion of relevant elements. Conclusions Manual therapy interventions should include both passive and active, person-empowering interventions such as exercise, education, and lifestyle adaptations. These should be delivered in a contextualised healing environment with a well-developed person-practitioner therapeutic alliance. Teaching manual therapy should follow this model.

Abstract Respiratory drive is defined as the intensity of respiratory centers output during the breath and is primarily affected by cortical and chemical feedback mechanisms. During the involuntary act of breathing, chemical feedback, primarily mediated through CO2, is the main determinant of respiratory drive. Respiratory drive travels through neural pathways to respiratory muscles, which execute the breathing process and generate inspiratory flow (inspiratory flow-generation pathway). In a healthy state, inspiratory flow-generation pathway is intact, and thus respiratory drive is satisfied by the rate of volume increase, expressed by mean inspiratory flow, which in turn determines tidal volume. In this review, we will explain the pathophysiology of altered respiratory drive by analyzing the respiratory centers response to arterial partial pressure of CO2 (PaCO2) changes. Both high and low respiratory drive have been associated with several adverse effects in critically ill patients. Hence, it is crucial to understand what alters the respiratory drive. Changes in respiratory drive can be explained by simultaneously considering the (1) ventilatory demands, as dictated by respiratory centers activity to CO2 (brain curve); (2) actual ventilatory response to CO2 (ventilation curve); and (3) metabolic hyperbola. During critical illness, multiple mechanisms affect the brain and ventilation curves, as well as metabolic hyperbola, leading to considerable alterations in respiratory drive. In critically ill patients the inspiratory flow-generation pathway is invariably compromised at various levels. Consequently, mean inspiratory flow and tidal volume do not correspond to respiratory drive, and at a given PaCO2, the actual ventilation is less than ventilatory demands, creating a dissociation between brain and ventilation curves. Since the metabolic hyperbola is one of the two variables that determine PaCO2 (the other being the ventilation curve), its upward or downward movements increase or decrease respiratory drive, respectively. Mechanical ventilation indirectly influences respiratory drive by modifying PaCO2 levels through alterations in various parameters of the ventilation curve and metabolic hyperbola. Understanding the diverse factors that modulate respiratory drive at the bedside could enhance clinical assessment and the management of both the patient and the ventilator.

Objective: Host immunogenetics (Human Leukocyte Antigen, HLA) play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes hinge on the successful binding of epitopes of melanoma antigens to HLA Class I molecules for an effective engagement of cytotoxic CD8+ lymphocytes and subsequent elimination of the cancerous cell. This study evaluated the binding affinity and immunogenicity of HLA Class I to melanoma tumor antigens to identify alleles best suited to facilitate elimination of melanoma antigens. Methods: In this study, we used freely available software tools to determine in silico the binding affinity and immunogenicity of 2462 reported HLA Class I alleles to all linear nonamer epitopes of 11 known antigens expressed in melanoma tumors (TRP2, S100, Tyrosinase, TRP1, PMEL(17), MAGE1, MAGE4, CTA, BAGE, GAGE/SSX2, Melan). Results: We identified the following 9 HLA Class I alleles with very high immunogenicity and binding affinity against all 11 melanoma antigens: A*02:14, B*07:10, B*35:10, B*40:10, B*40:12, B*44:10, C*07:11, and C*07:13, and C*07:14. Conclusion: These 9 HLA alleles possess the potential to aid in the elimination of melanoma both by themselves and by enhancing the beneficial effect of immune checkpoint inhibitors.

Abstract Background Lung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCO2R) to achieve LDP targets. Methods An in silico clinical trial was conducted using a previously published mathematical model of patient–ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics. Ventilation and sedation were titrated according to a pre-defined algorithm in pressure support ventilation (PSV) and proportional assist ventilation (PAV+) modes, with or without adjunctive ECCO2R, and using ECCO2R alone (without ventilation or sedation). Random forest modelling was employed to identify patient-level factors associated with achieving targets. Results After titration, the proportion of patients achieving targets was lower in PAV+ vs. PSV (37% vs. 43%, odds ratio 0.78, 95% CI 0.73–0.85). Adjunctive ECCO2R substantially increased the probability of achieving targets in both PSV and PAV+ (85% vs. 84%). ECCO2R alone without ventilation or sedation achieved LDP targets in 9%. The main determinants of success without ECCO2R were lung compliance, ventilatory ratio, and strong ion difference. In silico trial results corresponded closely with the results obtained in a clinical trial of the LDP titration algorithm (n = 30). Conclusions In this in silico trial, many patients required ECCO2R in combination with mechanical ventilation and sedation to achieve LDP targets. ECCO2R increased the probability of achieving LDP targets in patients with intermediate degrees of derangement in elastance and ventilatory ratio.

Abstract Introduction and objectives Thoracic ultrasound (TUS) has been established as a powerful diagnostic and monitoring tool in the Intensive Care Unit (ICU). However, studies outside the critical care setting are scarce. The aim of this study was to investigate the value of TUS for hospitalized or ambulatory community patients. Materials and methods This was a retrospective study conducted from 2016 to 2020 in the TUS clinic at Heraklion University Hospital. TUS examination was performed using a standard ultrasound machine (EUB HITACHI 8500), and a high-frequency microconvex probe (5–8 MHz). Patients had been referred by their primary physician to address a range of different questions. The various respiratory system entities were characterised according to internationally established criteria. Results 762 TUS studies were performed on 526 patients due to underlying malignancy (n = 376), unexplained symptoms/signs (n = 53), pregnancy related issues (n = 42), evaluation of abnormal findings in X-ray (n = 165), recent surgery/trauma (n = 23), recent onset respiratory failure (n = 12), acute respiratory infection (n = 66) and underlying non-malignant disease (n = 25). Pleural effusion was the commonest pathologic entity (n = 610), followed by consolidation (n = 269), diaphragmatic dysfunction/paradox (n = 174) and interstitial syndrome (n = 53). Discrepancies between chest X-ray and ultrasonographic findings were demonstrated in 96 cases. The TUS findings guided invasive therapeutic management in 448 cases and non-invasive management in 43 cases, while follow-up monitoring was decided in 271 cases. Conclusions This study showed that TUS can identify the most common respiratory pathologic entities encountered in hospitalized and community ambulatory patients, and is especially useful in guiding the decision making process in a diverse group of patients.

Orthoimages are a common product used as a base in CAD software for vectorization purposes. In fact, vectorization of orthoimages constitutes a tedious and labour-intensive process which should be supervised by experts e.g. architects, chemical engineers etc. On the one hand, deep learning algorithms are used extensively nowadays achieving high quality results. On the other hand, deep learning algorithms require a huge amount of manually annotated data to be trained on, which is a very difficult process especially at pixel level applications like semantic segmentation and instance segmentation. However, the transformation of 2D CAD drawings into a suitable deep learning dataset (CAD2DLD) is underexplored ignoring a large source of data, created by experts. In this effort, the InCAD algorithm is proposed, which aims to automatically create 2D vector drawings using the YOLOv8 instance segmentation algorithm which was trained on CAD2DLD data. Additionally, a methodology for transforming 2D CAD drawings into a suitable deep learning dataset for instance segmentation, is presented. Finally, the proposed workflow is evaluated on the creation of 2D vector drawings of stones of a fortification wall achieving promising results (78.34 mIoU).

Edge detection is supported by extensive research and is part of different photogrammetric and computer vision tasks across numerous application areas. While 2D edge detection may achieve high accuracy results from several automated methods, the automation of edge detection in 3D space remains a challenge. Existing methods are often computationally demanding and heavily parameterized, leading to a lack of adaptability. In real-world applications 3D edges, representing the object boundaries and break lines, are crucial, particularly in fields such as computer vision, robotics and architecture. In this context, we present a method that automates 3D edge detection in 3D point clouds exploiting the normal vectors’ direction differences to detect finite edges, which are further pruned and grouped to edge segments and fitted to indicate the presence of a 3D edge.

Objective: The first COVID-19 pandemic wave was a period of reduced surgical activity and redistribution of resources to only those with late stage or critical presentations. This Vascular and Endovascular Research Network COVID-19 Vascular Service (COVER) study aimed to describe the six-month outcomes of patients who underwent open surgery and or endovascular interventions for major vascular conditions during this period. Methods: In this international, multicentre, prospective, observational study, centres recruited consecutive patients undergoing vascular procedures over a 12-week period. The study opened in March 2020 and closed to recruitment in August 2020. Patient demographics, procedure details, and post-operative outcomes were collected on a secure online database. The reported outcomes at 30 days and six months were post-operative complications, re-interventions, and all cause in-hospital mortality rate. Multivariable logistic regression was used to assess factors associated with six-month mortality rate. Results: Data were collected on 3 150 vascular procedures, including 1 380 lower limb revascularisations, 609 amputations, 403 aortic, 289 carotid, and 469 other vascular interventions. The median age was 68 years (interquartile range 59, 76), 73.5% were men, and 1.7% had confirmed COVID-19 disease. The cumulative all cause in-hospital, 30-day, and six-month mortality rates were 9.1%, 10.4%, and 12.8%, respectively. The six-month mortality rate was 32.1% (95% CI 24.2–40.8%) in patients with confirmed COVID-19 compared with 12.0% (95% CI 10.8–13.2%) in those without. After adjustment, confirmed COVID-19 was associated with a three times higher odds of six-month death (adjusted OR 3.25, 95% CI 2.18–4.83). Increasing ASA grade (3–5 vs. 1–2), frailty scores 4–9, diabetes mellitus, and urgent and or immediate procedures were also independently associated with increased odds of death by six months, while statin use had a protective effect. Conclusion: During the first wave of the pandemic, the six-month mortality rate after vascular and endovascular procedures was higher compared with historic pre-pandemic studies and associated with COVID-19 disease.

Wildland fuel distribution and characteristics are critical components for the development of a national integrated wildfire management strategy. This study presents a methodological framework for the mapping of fuels in Mediterranean ecosystems in the different levels of a new fuel hierarchical classification scheme, using a spectral–spatial approach based on Sentinel-2 timeseries and auxiliary thematic maps. Furthermore, in the context of this research, a novel approach is proposed for separating Mediterranean shrubland vegetation into three broad height categories, using Sentinel-2 images, landscape variables, and climatic data. Two areas in Greece, namely Attica and Euboea, with major wildfire events over the past 3 years were selected as the study areas. The mapping methodology was designed to consist of three complementary mapping processes, each for the identification of specific types of fuels (i.e., urban, agricultural, and vegetation). The results are validated in a two-step approach for different levels of the classification scheme. The results for the first level display an overall accuracy of 88% and kappa of 0.84, while for the second level, overall accuracy was 71.64% and kappa was 0.68. Our research demonstrates the capacity to map fuel types with promising accuracy at different depths, highlighting a viable method that can be potentially exploited for the large-scale fuel mapping of Mediterranean biomes at a national level.

Background: One of the common complications after total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). The differential diagnosis should include allergies to implant components or cement constituents, for which the clinical manifestation may mimic an infection. An allergic skin reaction to suture material after TKA mimicking acute PJI has to date never been described in the literature. Case report: We present a case of acute allergic skin reaction to polydioxanone suture material (Stratafix™, Ethicon, Johnson & Johnson) initially suspected to be acute PJI one week after TKA. The patient was treated with debridement, extensive synovectomy, irrigation and implant retention followed by antibiotic therapy. The bacteriological analysis was negative and the histological examination of the excised wound showed Wells-type eosinophilic cellulitis. The definitive diagnosis was an allergic reaction to sutures mimicking an acute PJI. Conclusion: An allergic skin reaction to suture material mimicking acute PJI has an extremely low incidence and therefore has been barely described. The different clinical presentations complicate diagnosis and treatment decisions, particularly in acute settings. The formal diagnosis is made by histopathological analysis of wound tissue in the presence of negative microbiological cultures. We may consider wound biopsy during or before surgical revision as an additional tool in PIJ strategy work-up.

Identification of early influences on cognitive decline is of paramount importance in order to stem the impacts of decrements in cognitive functioning and to potentially intervene. Thus, here we focused on 132 healthy adult women (age range 26-98 years) to (a) determine whether factors circulating in serum may exert neurotoxic effects in vitro, (b) evaluate associations between serum neurotoxicity and cognitive performance, and (c) assess the influence of human herpes virus (HHV) seroprevalence and other factors on apoptosis and cognitive performance. The results documented that the addition of serum from healthy adult women to neural cell cultures resulted in apoptosis, indicating the presence of circulating neurotoxic factors in the serum. Furthermore, apoptosis increased with age, and was associated with decreased cognitive performance. Stepwise regression evaluating the influence of 6 HHVs on apoptosis and cognitive function revealed that only HHV5 (cytomegalovirus; CMV) seropositivity was significantly associated with apoptosis and cognitive decline, controlling for age. These findings document neurotoxic effects of serum from healthy women across the adult lifespan and suggest a unique detrimental influence associated with CMV seropositivity.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Historically, two COPD phenotypes have been described: chronic bronchitis and emphysema. Although these phenotypes may provide additional characterization of the pathophysiology of the disease, they are not extensive enough to reflect the heterogeneity of COPD and do not provide granular categorization that indicates specific treatment, perhaps with the exception of adding inhaled glucocorticoids (ICS) in patients with chronic bronchitis. In this review, we describe COPD phenotypes that provide prognostication and/or indicate specific treatment. We also describe COPD-like phenotypes that do not necessarily meet the current diagnostic criteria for COPD but provide additional prognostication and may be the targets for future clinical trials.

Introduction: Autologous cell suspension (ACS)-based therapy represents a highly promising approach for burns and chronic wounds. However, existing technologies have not achieved the desired clinical success due to several limitations. To overcome practical and cost-associated obstacles of existing ACS methods, we have established a novel methodology for rapid, enzymatic disaggregation of human skin cells and their isolation using a procedure that requires no specialist laboratory instrumentation and is performed at room temperature.Methods: Cells were isolated using enzymatic disaggregation of split-thickness human skin followed by several filtration steps for isolation of cell populations, and cell viability was determined. Individual population recovery was confirmed in appropriate culture medium types, and the presence of epidermal stem cells (EpSCs) within keratinocyte sub-populations was defined by flow cytometry via detection of CD49 and CD71. Positive mediators of wound healing secreted by ACS-derived cultures established on a collagen-based wound-bed mimic were detected by proteome arrays and quantified by ELISA, and the role of such mediators was determined by cell proliferation assays. The effect of ACS-derived conditioned-medium on myofibroblasts was investigated using an in-vitro model of myofibroblast differentiation via detection of α-SMA using immunoblotting and immunofluorescence microscopy.Results: Our methodology permitted efficient recovery of keratinocytes, fibroblasts and melanocytes, which remained viable upon long-term culture. ACS-derivatives comprised sub-populations with the CD49-high/CD71-low expression profile known to demarcate EpSCs. Via secretion of mitogenic factors and wound healing-enhancing mediators, the ACS secretome accelerated keratinocyte proliferation and markedly curtailed cytodifferentiation of myofibroblasts, the latter being key mediators of fibrosis and scarring.Discussion: The systematic characterisation of the cell types within our ACS isolates provided evidence for their superior cell viability and the presence of EpSCs that are critical drivers of wound healing. We defined the biological properties of ACS-derived keratinocytes, which include ability to secrete positive mediators of wound healing as well as suppression of myofibroblast cytodifferentiation. Thus, our study provides several lines of evidence that the established ACS isolates comprise highly-viable cell populations which can physically support wound healing and possess biological properties that have the potential to enhance not only the speed but also the quality of wound healing.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

Post-bariatric hypoglycemia (PBH) is an increasingly recognized complication after metabolic bariatric surgery (MBS). The aim of this study is to investigate potential factors associated with PBH. A cohort of 24 patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) ≥40 kg/m2 who underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) was retrospectively investigated for PBH at 12 months. PBH was defined as postprandial glucose at 120 min below 60 mg/dL. Questionnaires based on the Edinburgh hypoglycemia scale were filled out by the participants. Glycemic parameters and gastrointestinal (GI) hormones were also investigated. Based on the questionnaires, five patients presented more than four symptoms that were highly indicative of PBH at 12 months. According to glucose values at 120 min, one patient experienced PBH at 6 months and four patients experienced it at 12 months. Postprandial insulin values at 30 min and 6 months seem to be a strong predictor for PBH (p < 0.001). GLP-1 and glucagon values were not significantly associated with PBH. PBH can affect patients with T2DM after MBS, reaching the edge of hypoglycemia. Postprandial insulin levels at 30 min and 6 months might predict the occurrence of PBH at 12 months, but this requires further validation with a larger sample size.

We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson χ2 = 7.08, p = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans (p = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth “concomitant” and “hybrid” regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.

Vaccination against Bacillus anthracis is the best preventive measure against the development of deadly anthrax disease in the event of exposure to anthrax either as a bioweapon or in its naturally occurring form. Anthrax vaccines, however, have historically been plagued with controversy, particularly related to their safety. Fortunately, recent improvements in anthrax vaccines have been shown to confer protection with reduced short-term safety concerns, although questions about long-term safety remain. Here, we (a) review recent and ongoing advances in anthrax vaccine development, (b) emphasize the need for thorough characterization of current (and future) vaccines, (c) bring to focus the importance of host immunogenetics as the ultimate determinant of successful antibody production and protection, and (d) discuss the need for the systematic, active, and targeted monitoring of vaccine recipients for possible Chronic Multisymptom Illness (CMI).