Search

This paper focuses on the integrated and multiscale archaeological analysis of the necropolis of Jebel Zebouzi in El Kef, Northern Tunisia, shedding light on the complex and diverse megalithic structures that characterize the region. North Africa features a vast array of pre-Roman funerary monuments, ranging from monumental tombs influenced by Punic and Roman-Hellenistic examples to autochthonous rock-cut chamber tombs known as haouanet. The landscape is further enriched with bazinas, chouchet, tumuli, and dolmens, in some cases forming extensive necropolises. Despite their visibility, the understanding of these structures remains limited. Early assumptions regarding their dating were challenged, suggesting a Late Bronze Age origin. After two centuries of research, there remains a significant hiatus in knowledge regarding the spatial arrangement, funerary traditions, and chronology of these megalithic necropolises. To bridge this gap, the research project described in this paper has employed cutting-edge techniques such as drone imagery, photogrammetry for documentation during remote and on-foot surveys. Together with selected excavations and bioarchaeological analysis, the goal is to reconstruct some of the necropolis’ stratigraphical and spatial configuration, offering insights into horizontal and vertical social complexity and the utilization of space. The study addresses hence the phenomenon of reuse and modification of these ancient monuments over time, raising questions about cultural appropriation, memory, history, and the negotiation of cultural identity. This comprehensive approach aims to contribute to the understanding of North African pre-Roman funerary practices and the cultural dynamics that shaped these megalithic landscapes.

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n = 42) and major NCD (n = 164) through DSM-5 criteria on 206 participants aged > 65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (β = −1.05, p < 0.0001) and minor NCD (β = −0.06, p < 0.01). In the fully adjusted multivariate regression model (sex–age–education–multimorbidity–depressive symptoms–antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (β = 0.09, p < 0.001). The effect of loneliness on IADL (β = −0.26, p < 0.0001) and ADL (β = −0.24, p < 0.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL: β = 0.26, p < 0.0001; ADL: β = 0.05, p = 0.01). Minor NCD displayed different levels of MMSE (β = 6.68, p < 0.001) but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

Abstract The late Middle Pleistocene, starting at around 300 ka, witnessed large-scale biological and cultural dynamics in hominin evolution across Africa including the onset of the Middle Stone Age that is closely associated with the evolution of our species—Homo sapiens. However, archaeological and geochronological data of its earliest appearance are scarce. Here we report on the late Middle Pleistocene sequence of Wadi Lazalim, in the Sahara of Southern Tunisia, which has yielded evidence for human occupations bracketed between ca. 300–130 ka. Wadi Lazalim contributes valuable information on the spread of early MSA technocomplexes across North Africa, that likely were an expression of large-scale diffusion processes.

Megalithic monuments are a distinctive archaeological feature of Saharan landscape, as indicated by different systematic research projects undertaken so far. Starting from a very low baseline of previous archaeological research, and as part of a comprehensive research programme focussed on northern Sahara, we launched in 2015 a territorial investigation of stone monuments of the pre-protohistory and early history of southern Tunisia. To do this, we selected a sample study area east and south-east of the Chott el Jérid depression (Kebili region) where to conduct field research. In this paper we present the research strategy adopted, planned to address some issues such as the poor state of preservation of the monuments or their uncertain chronology, also known from other parts of the Sahara. Our results, based on the combination of remote sensing analysis, field survey and selected excavations, highlight a dense occupation of this area of northern Sahara, where monumental buildings of possible funerary function tentatively trace back to the late pre-protohistory up to the roman age. The persistent use of the area across a long-time span corroborates its pivotal location in ancient trans-Saharan connection routes.

The abundant faunal remains from the Takarkori rock shelter in the Tadrart Acacus region of southwestern Libya are described. The material that covers the period between 10,200 to 4650 years cal BP illustrates the more humid environmental conditions in the Central Sahara during early and middle Holocene times. Particular attention is focussed on the aquatic fauna that shows marked diachronic changes related to increasing aridification. This is reflected in the decreasing amount of fish remains compared to mammals and, within the fish fauna, by changes through time in the proportion of the species and by a reduction of fish size. The aquatic fauna can, in addition, be used to formulate hypotheses about the former palaeohydrographical network. This is done by considering the possible location of pre-Holocene relic populations combined with observations on the topography and palaeohydrological settings of the Central Sahara.

IntroductionThe mechanisms of lung inflation and deflation are only partially known. Ventilatory strategies to support lung function rely upon the idea that lung alveoli are isotropic balloons that progressively inflate or deflate and that lung pressure/volume curves derive only by the interplay of critical opening pressures, critical closing pressures, lung history, and position of alveoli inside the lung. This notion has been recently challenged by subpleural microscopy, magnetic resonance, and computed tomography (CT). Phase-contrast synchrotron radiation CT (PC-SRCT) can yield in vivo images at resolutions higher than conventional CT.ObjectivesWe aimed to assess the numerosity (ASden) and the extension of the surface of airspaces (ASext) in healthy conditions at different volumes, during stepwise lung deflation, in concentric regions of the lung.MethodsThe study was conducted in seven anesthetized New Zealand rabbits. They underwent PC-SRCT scans (resolution of 47.7 μm) of the lung at five decreasing positive end expiratory pressure (PEEP) levels of 12, 9, 6, 3, and 0 cmH2O during end-expiratory holds. Three concentric regions of interest (ROIs) of the lung were studied: subpleural, mantellar, and core. The images were enhanced by phase contrast algorithms. ASden and ASext were computed by using the Image Processing Toolbox for MatLab. Statistical tests were used to assess any significant difference determined by PEEP or ROI on ASden and ASext.ResultsWhen reducing PEEP, in each ROI the ASden significantly decreased. Conversely, ASext variation was not significant except for the core ROI. In the latter, the angular coefficient of the regression line was significantly low.ConclusionThe main mechanism behind the decrease in lung volume at PEEP reduction is derecruitment. In our study involving lung regions laying on isogravitational planes and thus equally influenced by gravitational forces, airspace numerosity and extension of surface depend on the local mechanical properties of the lung.

Book review

The Pierres de Ben Barour, also known as trapping or tethering stones (TS), are stone artefacts with notches or grooves usually interpreted as hunting devices on the basis of rock art engravings. Though their presence is a peculiar feature of desert landscapes from the Sahara to the Arabian Peninsula, we know little about their age, context and function. Here we present a new approach to the study of these artefacts based on a large dataset (837 items) recorded in the Messak plateau (SW Libya). A statistically-based geoarchaeological survey carried out between 2007 and 2011 in Libya, alongside landscape and intra-site analyses of specific archaeological features (such as rock art, settlement and ceremonial contexts), reveal that these artefacts were used for a prolonged period, probably from the early Holocene. This was followed by a multifunctional use of these devices, particularly during the Pastoral Neolithic phase (ca. 6400-3000 cal BC), with the highest concentrations being found near ceremonial contexts related to cattle burials.

Purpose. To evaluate agreement between measured and intended distance of Keraring (Mediphacos, Belo Horizonte, Brazil) intracorneal ring segments from the anterior and posterior corneal surfaces. Methods. Twenty-six Keraring ICRS implanted in 24 keratoconic eyes were examined. The distance from the Keraring apex to the anterior corneal surface and the distance from the inner and the outer corners to the posterior corneal surface were measured 3 months postoperatively using spectral-domain optical coherence tomography. Agreement between measured distance and intended distance was assessed by calculating the absolute differences and 95% limits of agreement (95% LoA). Results. The mean absolute difference was significantly lower (p

Nous présentons les résultats préliminaires d'un projet Tuniso-Italien de collaboration scientifique dans le domaine des études environnementales et de la recherche préhistorique et anthropologique en Tunisie méridionale mené selon une approche interdisciplinaire qui comprend la géo-archéologie, la géochronologie, la géochimie, la palynologie, la paléoanthropologie et la génétique. La zone de recherche se trouve au sud du Chott el Jérid et ses environs. Il s’agit d’une zone caractérisée par la présence de l’un des méga lacs qui existaient dans le Sahara pendant les périodes humides à la fin du Quaternaire. La région est une zone charnière entre la Méditerranée et le Sahara, donc favorable à l’étude des diffusions culturelles et des déplacements humains à travers les différentes périodes et environnements.

Objectives: New targets and approaches are under investigation for the treatment of nonmuscle invasive bladder cancer (NMIBC). Preclinical data suggest cyclooxygenase-2 (COX-2) as a promising target. Celecoxib, a COX-2 selective inhibitor, inhibits tumor development and enhances survival, both in vitro and in vivo models of bladder cancer. Therefore, we conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC. Methods: Treatment with celecoxib was administered orally for 12 months and compared with a contemporary series of patients treated with intravesical mitomycin C (MMC), given weekly for 4 weeks and then monthly for 11 months. Primary endpoints were time to first recurrence and adverse events. Results: From 2003 through 2006, 58 patients were treated with celecoxib and compared with 66 patients receiving MMC. After a median follow up of 75 months, 49 patients were disease free, including 23 (34.85%) in the MMC group and 26 (44.8%) in the celecoxib group. Median disease-free interval was 67 months [95% confidence interval (CI) 35.8 to NA] versus 41 months (95% CI 27.1–67.1; log-rank p = 0.25) for patients treated with MMC and celecoxib, respectively. In the multivariate analysis, treatment was not found to be an independent predictor for recurrence [hazard ratio (HR) 0.76, 95% CI 0.47–1.22, p = 0.25). Overall, 45 AEs were recorded in 35/124 patients. There were no differences between the two groups. Conclusions: Our data support a clinical benefit of celecoxib and encourage future trials in which COX-2 inhibitors may be tested in selected patients with NMIBC.

Previous research has identified the antiquity and chronology of dairying practices as beginning in the Near East and its subsequent spread across Europe. In the Libyan Sahara, archaeological evidence, confirmed by the remarkable rock art depicting cattle herding, together with faunal evidence, also suggests an early inception of dairying practices in North Africa and the formation of an independent ‘secondary products’ economy by mobile pastoral groups. In this paper, we elaborate on the first unequivocal chemical evidence, based on the δ13C and Δ13C values of the major fatty acids of milk fat, for the adoption of dairying practices by prehistoric Saharan African people in the fifth millennium BC.

Cattle pastoralism is an important trait of African cultures. Ethnographic studies describe the central role played by domestic cattle within many societies, highlighting its social and ideological value well beyond its mere function as 'walking larder'. Historical depth of this African legacy has been repeatedly assessed in an archaeological perspective, mostly emphasizing a continental vision. Nevertheless, in-depth site-specific studies, with a few exceptions, are lacking. Despite the long tradition of a multi-disciplinary approach to the analysis of pastoral systems in Africa, rarely do early and middle Holocene archaeological contexts feature in the same area the combination of settlement, ceremonial and rock art features so as to be multi-dimensionally explored: the Messak plateau in the Libyan central Sahara represents an outstanding exception. Known for its rich Pleistocene occupation and abundant Holocene rock art, the region, through our research, has also shown to preserve the material evidence of a complex ritual dated to the Middle Pastoral (6080-5120 BP or 5200-3800 BC). This was centred on the frequent deposition in stone monuments of disarticulated animal remains, mostly cattle. Animal burials are known also from other African contexts, but regional extent of the phenomenon, state of preservation of monuments, and associated rock art make the Messak case unique. GIS analysis, excavation data, radiocarbon dating, zooarchaeological and isotopic (Sr, C, O) analyses of animal remains, and botanical information are used to explore this highly formalized ritual and the lifeways of a pastoral community in the Holocene Sahara.

In order to assess the risk associated with the transport of stock calves imported from France to Italy, information obtained from inspections carried out in Piedmont by competent authorities between 2001 and 2010 was considered. The inspections concerned 246 trucks transporting a total of 13,857 fattening calves. Based on the types of infringements recorded, several hazards related to animal welfare, such as overcrowding, tying by the horns and inappropriate mixing, were identified and characterized. The inspection of vehicles revealed hazards concerning partitions, bedding, decks, lighting, drinking and mechanical ventilation systems. A calculation was made of the incidence of these infringements and the consequent exposure of calves to such hazards and risk characterization was performed. The ranking shows overcrowding and the absence of partitions to be major risks in stock calf transportation from France to Italy. A logistic regression was adopted to evaluate the effect on the exposure to hazards of the only two variables recordable during the inspections: number of calves inside each vehicle and distance of the journey. The results showed a direct relationship between the number of calves per vehicle and exposure to overcrowding or to absence of partitions. The journey distance was found weakly and inversely related to exposure to the absence of partitions. The information obtained from the inspections provides not only a basis for evaluating the welfare of calves during transport but also an objective contribution to the assessment of the risks tied to their transportation.

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (-308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Therapeutic drug monitoring (TDM) is a useful tool for optimising the use of anti-TNFα inhibitors in patients with inflammatory bowel diseases (IBDs). Recently, point-of-care methods for the quantification of drug levels and anti-drug antibodies (ADAs) have been developed to overcome the limitations of conventional enzyme-linked immunoabsorbent assays (ELISAs). Here, we evaluated the performance, interchangeability, and agreement between an automated ELISA-based immunoassay (CHORUS Promonitor) and the lateral flow assay (RIDA ® QUICK) for the quantification of infliximab (IFX, n = 65) and adalimumab (ADM, n = 58) plasma levels in IBD patients. Thirty-two samples for IFX and twenty-three samples for ADM that tested positively for the presence of ADAs were also used. Overall, data analysis showed a good agreement of ADM trough concentrations (R 2 = 0.75) between the two assays as well as for ADA measurement (K > 0.8). However, IFX levels highlighted a weak correlation (R 2 = 0.58) between the two kits, with the RIDA ® QUICK assay overestimating IFX plasma values by 30% when compared to the CHORUS Promonitor kit. Results from this study show that the two assays are not quantitatively and qualitatively interchangeable due to substantial discrepancies in some results. Accordingly, the same assay should be used for the longitudinal follow-up of IBD patients.

A 53-year-old man with granulomatosis with polyangiitis presented with fever and acute kidney injury with nephrotic-range proteinuria following the second dose of the mRNA COVID-19 vaccine. Renal biopsy revealed an unexpected immune complex-glomerulonephritis (IC-GN) without vasculitis. Further workup found the patient to have HIV that was unmasked following the treatment of IC-GN. This case report explores the possible relationship between COVID-19 vaccines and the immune response in the setting of chronic HIV., (Copyright © 2022 Baylor University Medical Center.)

Background: The global burden of cervical cancer is concentrated in low-and middle-income countries (LMICs), with the greatest burden in Africa. Targeting limited resources to populations with the greatest need to maximize impact is essential. The objectives of this study were to geocode cervical cancer data from a population-based cancer registry in Kampala, Uganda, to create high-resolution disease maps for cervical cancer prevention and control planning, and to share lessons learned to optimize efforts in other low-resource settings., Methods: Kampala Cancer Registry records for cervical cancer diagnoses between 2008 and 2015 were updated to include geographies of residence at diagnosis. Population data by age and sex for 2014 was obtained from the Uganda Bureau of Statistics. Indirectly age-standardized incidence ratios were calculated for sub-counties and estimated continuously across the study area using parish level data., Results: Overall, among 1873 records, 89.6% included a valid sub-county and 89.2% included a valid parish name. Maps revealed specific areas of high cervical cancer incidence in the region, with significant variation within sub-counties, highlighting the importance of high-resolution spatial detail., Conclusions: Population-based cancer registry data and geospatial mapping can be used in low-resource settings to support cancer prevention and control efforts, and to create the potential for research examining geographic factors that influence cancer outcomes. It is essential to support LMIC cancer registries to maximize the benefits from the use of limited cancer control resources., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest Form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: Zika fever affects poor and vulnerable populations, presenting cycles observed in, at least 86 countries, with no vaccine prevention or treatment available. It is known that the genus Flavivirus causes Zika Virus (ZIKV), as Dengue and Yellow Fever, whose genetic material decodes, among other proteins, a series of non-structural (NS) proteins essential for viral replication, such as NS2B-NS3 protease. Additionally, chemical and biological systems are commonly studied using molecular modeling approaches allowing, among several other processes, to elucidate mechanisms of action, molecule reactivity and/or chemical properties and the design of new drugs. Thus, considering the in silico complexes between the biological target and the bioactive molecule, it is possible to understand better experimental results based on molecular properties, which are compared with the findings of the biological activity., Objective: Accordingly, this study aimed to present computational docking simulations of five previously reported active peptides against NS2B-NS3 protease of ZIKV and analyze some quantum chemical properties to identify the main contribution to improving the action., Methods: The compounds were described by Rut and coworkers (2017) and Hill and coworkers (2018), submitted to docking simulation in Gold software and quantum chemical properties calculations in Wavefunction Spartan software., Results: Total energy, electrophilicity index (ω) and energy gap (GAP) appeared to be the best properties to justify the peptide's biological activity. Moreover, the most promising compound (P1, Km 4.18 μM) had the best value of total energy (- 2763.04001 au), electrophilicity index (8.04 eV) and GAP (6.49 eV), indicating an energetically favorable molecule with good interaction with the target and, when compared to other peptides, presented moderate reactivity. P4 showed the highest electrophilicity index value (28.64 eV), which justified the interaction ability visualized in the docking simulation. However, its GAP value (4.24 eV) was the lowest in the series, suggesting high instability, possibly validating its low biological activity value (Km 19 uM). GAP was important to understand the chemical instability, and high values can promote damage to biological response., Conclusion: Furthermore, it was also noted that high electron affinity, related to the electrophilicity index, promoted electron-accepting characteristics, which was important to improve the biological activity of the peptides. A larger compound series must be studied to access features more precisely. However, these results have paramount importance in guiding future effort in this extremely-need health area., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Noninvasive continuous positive airway pressure (NIV-CPAP) is effective in patients with hypoxemic respiratory failure. Building evidence during the COVID-19 emergency reported that around 50% of patients in Italy treated with NIV-CPAP avoided the need for invasive mechanical ventilation. Standard NIV-CPAP systems operate at high gas flow rates responsible for noise generation and inadequate humidification. Furthermore, open-configuration systems require a high concentration of oxygen to deliver the desired FiO 2 . Concerns outlined the risk for aerosolization in the ambient air and the possible pressure drop in hospital supply pipes. A new NIV-CPAP system is proposed that includes automatic control of patient respiratory parameters. The system operates as a closed-loop breathing circuit that can be assembled, combining a sleep apnea machine with existing commercially available components. Analytical simulation of a breathing patient and simulation with a healthy volunteer at different FiO 2 were performed. Inspired and expired oxygen fraction and inspired and expired carbon dioxide pressure were recorded at different CPAP levels with different oxygen delivery. Among the main findings, we report (a) a significant (up to 30-fold) reduction in oxygen feeding compared to standard open high flow NIV-CPAP systems, to assure the same FiO 2 levels, and (b) a negligible production of the noise generated in ventilatory systems, and consequent minimization of patients' discomfort. The proposed NIV-CPAP circuit, reshaped in closed-loop configuration with the blower outside of the circuit, has the advantages of minimizing aerosol generation, environmental contamination, oxygen consumption, and noise to the patient. The system is easily adaptable and can be implemented using standard CPAP components., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Overweight and obesity have high prevalence worldwide and assessing the metabolomic profile is a useful approach to study their related metabolic processes. In this study, we assessed the metabolomic profile of 1391 subjects affected by overweight and obesity, enrolled in the frame of the SPHERE study, using a validated LC-MS/MS targeted metabolomic approach determining a total of 188 endogenous metabolites. Multivariable censored linear regression Tobit models, correcting for age, sex, and smoking habits, showed that 83 metabolites were significantly influenced by body mass index (BMI). Among compounds with the highest association, aromatic and branched chain amino acids (in particular tyrosine, valine, isoleucine, and phenylalanine) increased with the increment of BMI, while some glycerophospholipids decreased, in particular some lysophosphatidylcholines (as lysoPC a C18:2) and several acylalkylphosphatidylcholines (as PC ae C36:2, PC ae C34:3, PC ae C34:2, and PC ae C40:6). The results of this investigation show that several endogenous metabolites are influenced by BMI, confirming the evidence with the strength of a large number of subjects, highlighting differences among subjects with different classes of obesity and showing unreported associations between BMI and different phosphatidylcholines.

Objectives: Type B aortic dissections are routinely treated with thoracic endovascular aortic repair (TEVAR). The timing for TEVAR remains controversial and might have an impact on the remodelling capacity of the aorta. This study analyses and compares aortic remodelling in acute (ABD) and chronic (CBD) type B aortic dissections after TEVAR., Methods: This retrospective study analysed the preoperative, postoperative and at least 1-year follow-up computed tomography of 53 TEVAR patients (36 ABD, 17 CBD) at a single institution between May 2005 and May 2016. The volumes of aortic lumen (AL), true lumen, false lumen (FL) and perfused FL were measured at the stent graft level (A), from the stent graft to the coeliac trunk (B) and from the coeliac trunk to the bifurcation (C). The absolute volumes, normalized volume changes and FL thrombosis rate of ABD and CBD patients were compared., Results: Absolute AL and FL of segment A were significantly larger in CBD patients compared to ABD patients preoperatively (AL: 354 ± 68 vs 255 ± 51 ml, P = 0.023, FL: 253 ± 56 vs 183 ± 35 ml, P = 0.028) until last follow-up (AL: 462 ± 52 vs 246 ± 52 ml, P = 0.003, FL: 268 ± 202 vs 91 ± 31 ml, P = 0.004). The true lumen in segment A increased more in ABD than in CBD patients preoperatively to postoperatively (112% vs 36% P < 0.001) and within the first year postoperatively (171% vs 80% P < 0.001). FL in segment A decreased more in ABD compared to CBD patients within the first year (-42% vs -13% P < 0.001) and thereafter (-50% vs +6% P = 0.002). In segments B and C, the FL thrombosis rate was higher in ABD than in CBD patients at all time points and significantly higher in segment A after the first year (91% vs 98% P = 0.035)., Conclusions: Aortic remodelling after TEVAR is significantly different in acute and chronic dissection patients. TEVAR promotes aortic remodelling in both acute and chronic dissections in terms of true lumen increase at stent graft level. Nevertheless, significant AL reduction by FL shrinkage is primarily found in ABD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The design of compounds with directed action to a defined organ or tissue is a very promising approach, since it can decrease considerably the toxicity of the drug/bioactive compound. For this reason, this kind of strategy has been greatly important in the scientific community. Dendrimers, on the other hand, comprise extremely organized macromolecules with many peripheral functionalities, stepwise controlled synthesis, and defined size. These nanocomposites present several biological applications, demonstrating their efficiency to act in the pharmaceutical field. Considering that, the main purpose of this review was describing the potential of dendrons and dendrimers as drug targeting, applying different targeting groups. This application has been demonstrated through interesting examples from the literature considering the last ten years of publications.

Objective: To comprehensively evaluate and compare utilization, outcomes, and especially costs of transfemoral (TF), transapical (TA), and transaortic (TAO) transcatheter aortic valve replacement (TAVR)., Methods: All Medicare fee-for-service patients undergoing TF (n = 4065), TA (n = 691), or TAO (n = 274) TAVR between January 1, 2011, and November 30, 2012, were identified using Health Care Procedure Classification Codes present on Medicare claims. Hospital charges from Medicare claims were converted to costs using hospital-specific Medicare cost-to-charge ratios., Results: TA and TAO patients were similar in age, race, and common comorbidities. Compared with TF patients, TA and TAO patients were more likely to be female and to have peripheral vascular disease, chronic lung disease, and renal failure. Thirty-day mortality rates were higher among TA and TAO patients than among TF patients (TA, 9.6%; TAO, 8.0%; TF, 5.0%; P < .001). Adjusted mortality beyond 1 year did not differ by access. TA patients were more likely to require cardiopulmonary bypass (CPB). Increased adjusted mortality was associated with CPB (hazard ratio, 2.13; P < .01) and increased 30-day cost ($62,000 [interquartile range (IQR)], $45,100-$86,400 versus $48,800 [IQR, $38,100-$62,900]; P < .01). Cost at 30 days was lowest for TF ($48,600) compared with TA ($49,800; P < .01) and TAO ($53,200; P = .03)., Conclusions: For patients ineligible to receive TF TAVR, TAO and TA approaches offer similar clinical outcomes at similar cost with acceptable operative and 1-year survival, except for higher rates of CPB use in TA patients. CPB was associated with worse survival and increased costs., (Copyright © 2017. Published by Elsevier Inc.)

Oat protoplasts are a useful and convenient system to study transient expression using whole cells. Nucleic acid can rapidly be introduced into live cells, and, depending on the assay, results can be collected the same day. Compared to plant tissue, oat cell suspension cultures provide a simple, high yielding, and consistent means to isolate protoplasts. Here, we describe how to generate an oat cell suspension culture from callus grown on solidified medium, and how to maintain the oat cells in cell suspension culture for protoplast preparation. Following the culturing procedure, we describe how to isolate oat protoplasts from cell suspension culture by enzymatic digestion of the cell walls and to transiently express nucleic acid (DNA or RNA) into the cells by electroporation.

Background: There is growing interest in aortic valve-sparing and valve repair operations, but the ideal operation and timing of intervention in these generally younger patients undergoing operations for aortic insufficiency (AI) and dilated ascending aorta remains controversial., Methods: Root replacements at a single institution from 2002 to 2014 were reviewed. Inclusion criteria were age younger than 70 and presence of moderate or greater aortic insufficiency (AI), with or without aortic aneurysm. Of 1,425 root replacements, 220 patients were considered in the final analysis., Results: Moderate AI was present in 87 patients and severe AI in 133 patients. The 30-day mortality was 0% in moderate AI patients and 2% (n = 3) in severe AI patients (p = 0.3). Freedom from reoperation was 95% at 10 years. Severe preoperative AI was associated with worse long-term survival compared with moderate AI (hazard ratio, 2.6; p = 0.04). Patients undergoing root replacement with moderate AI had similar survival compared with the age- and gender-matched United States population (log-rank p = 0.93), whereas patients with severe AI had significantly worse survival (log-rank p = 0.02). Other multivariable predictors of decreased long-term survival were age (hazard ratio, 1.1; p = 0.01) and preoperative renal failure (hazard ratio, 6.9; p < 0.01)., Conclusions: Elective root replacement operations in patients younger than 70 are associated with low rates of mortality and reoperation, which should be considered the benchmark operation for aortic valve-sparing or repair operations in similar patients. Worse survival was associated with severe AI and older age, suggesting earlier intervention may be an appropriate therapeutic strategy in selected patients., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic lower back pain (CLBP) is problematic in older veterans. Spinal manipulative therapy (SMT) is commonly utilized for CLBP in older adults, yet there are few randomized placebo-controlled trials evaluating SMT., Methods: The purpose of the study was to compare the effectiveness of SMT to a sham intervention on pain (Visual Analogue Scale, SF-36 pain subscale), disability (Oswestry Disability Index), and physical function (SF-36 subscale, Timed Up and Go) by performing a randomized placebo-controlled trial at 2 Veteran Affairs Clinics., Results: Older veterans (≥ 65 years of age) who were naive to chiropractic were recruited. A total of 136 were included in the study with 69 being randomly assigned to SMT and 67 to sham intervention. Patients were treated 2 times per week for 4 weeks assessing outcomes at baseline, 5, and 12 weeks postbaseline. Both groups demonstrated significant decrease in pain and disability at 5 and 12 weeks. At 12 weeks, there was no significant difference in pain and a statistically significant decline in disability scores in the SMT group when compared to the sham intervention group. There were no significant differences in adverse events between the groups., Conclusions: The SMT did not result in greater improvement in pain when compared to our sham intervention; however, SMT did demonstrate a slightly greater improvement in disability at 12 weeks. The fact that patients in both groups showed improvements suggests the presence of a nonspecific therapeutic effect.

Background: Spinal Manipulative Therapy (SMT) and Active Exercise Therapy (AET) have both demonstrated efficacy in the treatment of Chronic Lower Back Pain (CLBP). A Clinical Prediction Rule (CPR) for responsiveness to SMT has been validated in a heterogeneous lower back pain population; however there is a need to evaluate this CPR specifically for patients with CLBP, which is a significant source of disability., Methods: We conducted a randomized controlled trial (RCT) in Veteran Affairs and civilian outpatient clinics evaluating a modification of the original CPR (mCPR) in CLBP, eliminating acute low back pain and altering the specific types of SMT to improve generalizability. We enrolled and followed 181 patients with CLBP from 2007 to 2010. Patients were randomized by status on the mCPR to undergo either SMT or AET twice a week for four weeks. Providers and statisticians were blinded as to mCPR status. We collected outcome measures at 5, 12 and 24-weeks post baseline. We tested our study hypotheses by a general linear model repeated measures procedure following a univariate analysis of covariance approach. Outcome measures included, Visual Analogue Scale, Bodily pain subscale of SF-36 and the Oswestry Disability Index, Patient Satisfaction and Patient Expectation., Results: Of the 89 AET patients, 69 (78%) completed the study and of the 92 SMT patients, 76 (83%) completed the study. As hypothesized, we found main effects of time where the SMT and AET groups showed significant improvements in pain and disability from baseline. There were no differences in treatment outcomes between groups in response to the treatment, given the lack of significant treatment x time interactions. The mCPR x treatment x time interactions were not significant. The differences in outcomes between treatment groups were the same for positive and negative on the mCPR groups, thus our second hypothesis was not supported., Conclusions: We found no evidence that a modification of the original CPR can be used to discriminate CLBP patients that would benefit more from SMT. Further studies are needed to further clarify the patient characteristics that moderate treatment responsiveness to specific interventions for CLBP., Trial Registration: ISRCTN30511490.

Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control. Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89 macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%. Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of percentages reported in the literature.