Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection. We aimed to determine pro-survival/anti-apoptotic protein networks involved in the stroma protection of leukemic cells. Proteomic profiling of cultured primary AML (n = 14) with Hs5 stroma cell line uncovered an up-regulation of energy-favorable metabolic proteins. Next, we modulated stroma-induced drug resistance with an epigenetic drug library, resulting in reduced apoptosis with histone deacetylase inhibitor (HDACi) treatment versus other epigenetic modifying compounds. Quantitative phosphoproteomic probing of this effect further revealed a metabolic-enriched phosphoproteome including significant up-regulation of acetyl-coenzyme A synthetase (ACSS2, S30) in leukemia-stroma HDACi treated cocultures compared with untreated monocultures. Validating these findings, we show ACSS2 substrate, acetate, promotes leukemic proliferation, ACSS2 knockout in leukemia cells inhibits leukemic proliferation and ACSS2 knockout in the stroma impairs leukemic metabolic fitness. Finally, we identify ACSS1/ACSS2-high expression AML subtype correlating with poor overall survival. Collectively, this study uncovers the leukemia-stroma phosphoproteome emphasizing a role for ACSS2 in mediating AML growth and drug resistance.

Complexities of modeling the bone marrow microenvironment to facilitate hematopoietic research.

Hematopoiesis occurs in the bone marrow (BM), within a specialized microenvironment referred to as the stem cell niche, where the hematopoietic stem cells (HSCs) reside and are regulated for quiescence, self-renewal and differentiation through intrinsic and extrinsic mechanisms. The BM contains at least two distinctive HSC-supportive niches: an endosteal osteoblastic niche that supports quiescence and self-renewal and a more vascular/perisinusoidal niche that promotes proliferation and differentiation. Both associate with supporting mesenchymal stromal cells. Within the more hypoxic osteoblastic niche, HSCs specifically interact with the osteoblasts that line the endosteal surface, which secrete several important HSC quiescence and maintenance regulatory factors. In vivo imaging indicates that the HSCs and progenitors located further away, in the vicinity of sinusoidal endothelial cells, are more proliferative. Here, HSCs interact with endothelial cells via specific cell adhesion molecules. Endothelial cells also secrete several factors important for HSC homeostasis and proliferation. In addition, HSCs and mesenchymal stromal cells are embedded within the extracellular matrix (ECM), an important network of proteins such as collagen, elastin, laminin, proteoglycans, vitronectin, and fibronectin. The ECM provides mechanical characteristics such as stiffness and elasticity important for cell behavior regulation. ECM proteins are also able to bind, sequester, display, and distribute growth factors across the BM, thus directly affecting stem cell fate and regulation of hematopoiesis. These important physical and chemical features of the BM require careful consideration when creating three-dimensional models of the BM.

Eligibility of a novel BW + technology and comparison of sensitivity and specificity of different imaging methods for radiological caries detection.

OBJECTIVES: Bitewing radiography is considered to be of high diagnostic value in caries detection, but owing to projections, lesions may remain undetected. The novel bitewing plus (BW +) technology enables scrolling through radiographs in different directions and angles. The present study aimed at comparing BW + with other 2D and 3D imaging methods in terms of sensitivity, specificity, and user reliability. MATERIALS AND METHODS: Five human cadavers were used in this study. In three cadavers, natural teeth were transplanted post-mortem. BW + , two-dimensional (digital sensors, imaging plates, 2D and 3D bitewing radiographs) and 3D methods (high and low dose CBCT) were taken. Carious lesions were evaluated on 96 teeth at three positions (mesial, distal, and occlusal) and scored according to their level of demineralization by ten observers, resulting in 35,799 possible lesions across all observers and settings. For reference, µCT scans of all teeth were performed. RESULTS: Overall, radiographic evaluations showed a high rate of false-negative diagnoses, with around 70% of lesions remaining undetected, especially enamel lesions. BW + showed the highest sensitivity for dentinal caries and had comparatively high specificity overall. CONCLUSIONS: Within the limits of the study, BW + showed great potential for added diagnostic value, especially for dentinal caries. However, the tradeoff of diagnostic benefit and radiation exposure must be considered according to each patient's age and risk.

Is online-only learning as effective as blended learning? A longitudinal study comparing undergraduate students' performance in oral radiology.

INTRODUCTION: Blended learning seems to be an effective teaching concept in oral radiology. During the COVID-19 pandemic, blended learning shifted towards online-only learning. The aim of the present study was to compare the effectiveness of pandemic online-only and pre-pandemic blended learning in three consecutive oral radiology courses (C1, C2 and C3) and to examine whether additional video-based e-learning modules (VBLMs) had a positive impact on undergraduate students' performance during pandemic semesters. MATERIALS AND METHODS: Data from 205 undergraduate dental students participating either in a blended learning or an online-only learning concept were analysed. Pre-pandemic blended learning comprised face-to-face seminars and access to an oral radiology platform (ORP). Pandemic online-only learning comprised online seminars, access to the ORP and additional VBLMs (two VBLMs for C1, four VBLMs for C2 and six VBLMs for C3). Through standardised e-exams at the beginning and end of each semester, performance in final exams and knowledge gain were compared between the two groups. RESULTS: No significant differences in scores in final exams (p = .11) and knowledge gain (p = .18) were found when comparing the pre-pandemic and pandemic groups. On course level, however, students receiving a lower number of VBLMs performed significantly worse in final exams (C1: p < .01, C2: p = .02) and showed inferior knowledge gain (C2: p < .01) during the pandemic. CONCLUSIONS: Within the limitations of the study, the present investigation confirmed that pandemic online-only learning involving VBLMs might be as effective as pre-pandemic blended learning.

Is there any sustained effect of the coronavirus disease 2019 pandemic? - A controlled trial comparing pre- and post-pandemic oral radiology courses.

PURPOSE/OBJECTIVES: Due to the coronavirus disease 2019 (COVID-19) pandemic, undergraduate education shifted towards online-only formats from April 2020 until July 2021. Previous research indicated a negative effect on students' competence development, and it remains unclear whether blended learning concepts could provide compensation. Therefore, the present study aimed to compare pre- to post-pandemic students' performance in standardized baseline (BL) and final exams (FE), as well as the associated knowledge gain (KG) in three consecutive undergraduate blended learning-based oral radiology courses (C1-3). METHODS: Ninety-four students participated during two pre-pandemic semesters (October 17-July 18), and ninety-eight students during two post-pandemic semesters (October 21-July 22). Before the pandemic, conventional face-to-face lectures were combined with an oral radiology platform. Two years into the COVID-19 pandemic, additional video-based e-learning modules were adopted from the pandemic online-only curriculum. In each semester, skills and KG were assessed by conducting standardized BL and FE. Students' performance in BL, FE, and the associated KG during pre-pandemic semesters was compared to post-pandemic semesters. RESULTS: In post-pandemic courses, students showed significantly lower BL scores, whereas KG was significantly higher in post- compared to pre-pandemic semesters (27.42% vs. 10.64%, p < 0.001, respectively). FE scores in C1 significantly improved from pre- to post-pandemic semesters. CONCLUSIONS: Within the limitations of our study, the lower BL scores confirmed the negative effect of the pandemic on competence development. Blended learning concepts seem to compensate for this effect and enable students to return to pre-pandemic levels. Future studies are needed to assess the additional impact of video-based e-learning modules.

Revisiting the effect of text complexity on Continuous Discourse Tracking using synthetic speech: Old tricks with new dogs.

Continuous Discourse Tracking (CDT) is a functional test of speech perceptual ability, which has been criticised on account of the procedural variation inherent in the method. This study sought to reduce this variation by using synthetic speech, which was subsequently vocoded to simulate listening with a cochlear implant. We also assessed the complexity of three text excerpts with auditory (n = 10) and written Cloze tests (n = 10). These same passages were used in an auditory-only CDT experiment (n = 12) performed with the synthetic-vocoded material. Mean tracking rates were lower, and the number of blockages was higher for the most difficult text as determined by the Cloze results. We also noted some anomalous realisations from the speech synthesis, but these were unlikely to have contributed to the differences in tracking rates that were observed for text complexity. These results show that Cloze testing is suitable to predict text complexity for CDT performed with synthesised speech. Furthermore, they indicate that the use of text-speech synthesis is viable and may be a useful addition to rehabilitation where functional measures are used to assess communication aptitude.

Overcoming BCR::ABL1 dependent and independent survival mechanisms in chronic myeloid leukaemia using a multi-kinase targeting approach.

BACKGROUND: Despite improved patient outcome using tyrosine kinase inhibitors (TKIs), chronic myeloid leukaemia (CML) patients require life-long treatment due to leukaemic stem cell (LSC) persistence. LSCs reside in the bone marrow (BM) niche, which they modify to their advantage. The BM provides oncogene-independent signals to aid LSC cell survival and quiescence. The bone-morphogenetic pathway (BMP) is one pathway identified to be highly deregulated in CML, with high levels of BMP ligands detected in the BM, accompanied by CML stem and progenitor cells overexpressing BMP type 1 receptors- activin-like kinases (ALKs), especially in TKI resistant patients. Saracatinib (SC), a SRC/ABL1 dual inhibitor, inhibits the growth of CML cells resistant to the TKI imatinib (IM). Recent studies indicate that SC is also a potent ALK inhibitor and BMP antagonist. Here we investigate the efficacy of SC in overcoming CML BCR::ABL1 dependent and independent signals mediated by the BM niche both in 2D and 3D culture. METHODS: CML cells (K562 cell line and CML CD34+ primary cells) were treated with single or combination treatments of: IM, SC and the BMP receptors inhibitor dorsomorphin (DOR), with or without BMP4 stimulation in 2D (suspension) and 3D co-culture on HS5 stroma cell line and mesenchymal stem cells in AggreWell and microfluidic devices. Flow cytometry was performed to investigate apoptosis, cell cycle progression and proliferation, alongside colony assays following treatment. Proteins changes were validated by immunoblotting and transcriptional changes by Fluidigm multiplex qPCR. RESULTS: By targeting the BMP pathway, using specific inhibitors against ALKs in combination with SRC and ABL TKIs, we show an increase in apoptosis, altered cell cycle regulation, fewer cell divisions, and reduced numbers of CD34+ cells. Impairment of long-term proliferation and differentiation potential after combinatorial treatment also occurred. CONCLUSION: BMP signalling pathway is important for CML cell survival. Targeting SRC, ABL and ALK kinases is more effective than ABL inhibition alone, the combination efficacy importantly being demonstrated in both 2D and 3D cell cultures highlighting the need for combinatorial therapies in contrast to standard of care single agents. Our study provides justification to target multiple kinases in CML to combat LSC persistence.

Blood is made in the spongy inner most section of the bone, called the bone marrow. The bone marrow is where normal blood stem cells live that are responsible for producing the different blood cell types; white blood cells (fight infections), red blood cells (carrying oxygen around the body), platelets (blood clotting) and other cells which support this process. Chronic myeloid leukaemia (CML) is a type of blood cancer that starts in the bone marrow. CML occurs when a normal blood stem cell becomes damaged, forming a leukaemia stem cell (LSC), leading to blood cancer. LSCs multiply and generate many faulty cancerous white blood cells that do not work properly. Patients are treated with a drug called imatinib, which reduces the number of cancerous cells circulating in the body. In many cases, this treatment is not enough to cure the disease because the bone marrow protects the LSCs from the drug meaning patients must remain on long term treatment. This work has discovered one of the ways in which the bone marrow protects LSCs from treatments and has used this knowledge to test new drugs that stop this protection. Our findings show that by combining two drugs, one that overcomes this protection and one that directly targets the cancerous cells, we can destroy more of the LSCs. These findings are a step closer towards a cure for CML and could improve treatment for patients in the future. Video Abstract.

Autoclaving-induced dimensional changes of three-dimensional printed surgical guides: An in vitro study.

OBJECTIVES: Surgical guides are frequently used for dental implant placement. The aim of this study was to evaluate the impact of the 3D printing process itself and subsequent steam autoclaving on the dimensional stability of five different resin/printer combinations (RPCs). MATERIALS AND METHODS: Fifty identical surgical guides (10 per group) were produced consisting of five RPCs. Half of the guides (5 per group) were steam autoclaved with cycle 1 (121°C, 1 bar, 20.5 min) and the other half with cycle 2 (134°C, 2 bar, 5.5 min). All guides were scanned with a structured-light (SL) 3D scanner before (T0) and after (T1) autoclaving. Linear measurements along the x-, y-, and z-axes were performed at landmarks on the original STL file and on SL scans at T0 and T1, respectively. Wilcoxon signed-rank test, Kruskal-Wallis test, and linear mixed-effects models were performed, depending on the analysis. RESULTS: Three-dimensional printing was associated with significant dimensional alterations for all RPCs. Steam autoclaving using cycle 1 was associated with significant shrinkage in x- (1 RPC), y- (2 RPCs), and z-direction (2 RPCs), while cycle 2 was also associated with shrinkage in x- (2 RPCs), y- (1 RPC), and z-direction (1 RPC). One resin did not present any dimensional changes independently of the cycle. CONCLUSIONS: The majority of the guides presented minor but significant shrinkage due to 3D printing itself and both steam autoclaving cycles, the extent varied between different RPCs. Whether these changes compromise implant placement accuracy remains to be investigated.

BH3 mimetics in combination with nilotinib or ponatinib represent a promising therapeutic strategy in blast phase chronic myeloid leukemia.

Dysregulation of the BCL-2 family is implicated in protecting chronic myeloid leukemia (CML) cells from intracellular damage and BCR::ABL1-inhibition with tyrosine kinase inhibitors (TKIs) and may be a viable therapeutic target in blast phase (BP-)CML, for which treatment options are limited. BH3 mimetics, a class of small molecule inhibitors with high-specificity against the prosurvival members of the BCL-2 family, have displayed clinical promise in the treatment of chronic lymphocytic and acute myeloid leukemia as single agents and in combination with standard-of-care therapies. Here we present the first comparison of inhibition of BCL-2 prosurvival proteins BCL-2, BCL-xL and MCL-1 in combination with a second or third generation TKI, crucially with comparisons drawn between myeloid and lymphoid BP-CML samples. Co-treatment of four BP-CML cell lines with the TKIs nilotinib or ponatinib and either BCL-2 (venetoclax), MCL-1 (S63845) or BCL-xL (A-1331852) inhibitors resulted in a synergistic reduction in cell viability and increase in phosphatidylserine (PS) presentation. Nilotinib with BH3 mimetic combinations in myeloid BP-CML patient samples triggered increased induction of apoptosis over nilotinib alone, and a reduction in colony-forming capacity and CD34+ fraction, while this was not the case for lymphoid BP-CML samples tested. While some heterogeneity in apoptotic response was observed between cell lines and BP-CML patient samples, the combination of BCL-xL and BCR::ABL1 inhibition was consistently effective in inducing substantial apoptosis. Further, while BH3 mimetics showed little efficacy as single agents, dual-inhibition of BCL-2 prosurvival proteins dramatically induced apoptosis in all cell lines tested and in myeloid BP-CML patient samples compared to healthy donor samples. Gene expression and protein level analysis suggests a protective upregulation of alternative BCL-2 prosurvival proteins in response to BH3 mimetic single-treatment in BP-CML. Our results suggest that BH3 mimetics represent an interesting avenue for further exploration in myeloid BP-CML, for which alternative treatment options are desperately sought.

Standardized assessment of bone micromorphometry around teeth following orthodontic tooth movement : A µCT split-mouth study in mice.

PURPOSE: Volumetric quantitative analyses of bone micromorphometry changes following orthodontic tooth movements are hardly standardizable. The present study aimed at validating and applying a novel microcomputed tomography (CT)-based approach that enables the segmentation of teeth and definition of a standardized volume of interest (VOI) around the roots to assess local bone micromorphometry. METHODS: The jaws of 3 untreated and 14 orthodontically treated mice (protraction of the upper right molar for 11 days with 0.5 N; untreated left upper molar) were scanned with a micro-CT. The first molars and the alveolar bone were segmented, and a standardized VOI was defined around the teeth. The bone volume per total volume (BV/TV) was assessed within the VOI, and BV/TV values were compared between contralateral sites in both untreated (method validation) and treated animals (method application). RESULTS: The intraclass correlation coefficient of 0.99 revealed high reliability of the method. In the untreated animals, Bland-Altman analysis confirmed comparable BV/TV fractions (mean difference: -1.93, critical difference: 1.91, Wilcoxon: p = 0.03). In the orthodontically treated animals, BV/TV values were significantly lower at the test compared to the control site (test: 33.23% ± 5.74%, control: 41.33% ± 4.91%, Wilcoxon: p < 0.001). CONCLUSION: Within the limits of the study, the novel approach demonstrated the applicability to evaluate bone micromorphometry around teeth subjected to orthodontic treatment.

Bandpass sorting of heterogeneous cells using a single surface acoustic wave transducer pair.

Separation and sorting of biological entities (viruses, bacteria, and cells) is a critical step in any microfluidic lab-on-a-chip device. Acoustofluidics platforms have demonstrated their ability to use physical characteristics of cells to perform label-free separation. Bandpass-type sorting methods of medium-sized entities from a mixture have been presented using acoustic techniques; however, they require multiple transducers, lack support for various target populations, can be sensitive to flow variations, or have not been verified for continuous flow sorting of biological cells. To our knowledge, this paper presents the first acoustic bandpass method that overcomes all these limitations and presents an inherently reconfigurable technique with a single transducer pair for stable continuous flow sorting of blood cells. The sorting method is first demonstrated for polystyrene particles of sizes 6, 10, and 14.5 µm in diameter with measured purity and efficiency coefficients above 75 ± 6% and 85 ± 9%, respectively. The sorting strategy was further validated in the separation of red blood cells from white blood cells and 1 µm polystyrene particles with 78 ± 8% efficiency and 74 ± 6% purity, respectively, at a flow rate of at least 1 µl/min, enabling to process finger prick blood samples within minutes.

Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML.

Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.

Efficacy of orthodontic mini implants for en masse retraction in the maxilla: a systematic review and meta-analysis.

BACKGROUND/AIM: Retraction of the upper incisors/canines requires maximum anchorage. The aim of the present study was to analyze the efficacy of mini implants in comparison to conventional devices in patients with need for en masse retraction of the front teeth in the upper jaw. MATERIAL AND METHODS: An electronic search of PubMed, Web of Science, and EMBASE and hand searching were performed. Relevant articles were assessed, and data were extracted for statistical analysis. A random effects model, weighted mean differences (WMD), and 95% confidence intervals (CI) were computed for horizontal and vertical anchorage loss at the first molars in the analyzed patient treatments. RESULTS: A total of seven RCTs employing direct anchorage through implants in the alveolar ridge were finally considered for qualitative and quantitative analysis, and further five publications were considered for the qualitative analysis only (three studies: indirect anchorage through implant in the mid-palate, two studies: direct/indirect anchorage in the alveolar ridge). In the control groups, anchorage was achieved through transpalatal arches, headgear, Nance buttons, intrusion arches, and differential moments. WMD [95% CI, p] in anchorage loss between test and control groups amounted to - 2.79 mm [- 3.56 to - 2.03 mm, p < 0.001] in the horizontal and - 1.76 mm [- 2.56 to - 0.97, p < 0.001] favoring skeletal anchorage over control measures. The qualitative analysis revealed that minor anchorage loss can be associated with indirect anchorage, whereas anchorage gain was commonly associated with direct anchorage. Implant failures were comparable for both anchorage modalities (direct 9.9%, indirect 8.6%). CONCLUSION: Within its limitations, the meta-analysis revealed that maximum anchorage en masse retraction can be achieved by orthodontic mini implants and direct anchorage; however, the ideal implant location (palate versus alveolar ridge) and the beneficial effect of direct over indirect anchorage needs to be further evaluated.

Chronic myeloid leukaemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal.

Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is deregulated in CML, with altered expression and response to the BMP ligands shown to impact on LSC expansion and behaviour. In this study, we determined whether alterations in the BMP pathway gene signature had any predictive value for therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2 trial and correlating the data to treatment response using the 18-month follow-up data. There was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response. Therapeutic targeting of CML cells using BMP receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI), indicate a synergistic mode of action. Furthermore, dual treatment resulted in altered cell cycle gene transcription and irreversible cell cycle arrest, along with increased apoptosis compared to single agents. Targeting CML CD34+ cells with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34+ cells and colony formation when compared to normal donor CD34+ cells, both in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC) model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso-endodermal differentiation. These findings indicate that transformed stem cells may be more reliant on BMP signalling than normal stem cells. These changes offer a therapeutic window in CML, with intervention using BMP inhibitors in combination with TKI having the potential to target LSC self-renewal and improve long-term outcome for patients.

Animal-Assisted Interventions for Children with Attention Deficit/Hyperactivity Disorder: A Theoretical Review and Consideration of Future Research Directions.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders and is characterized by core symptoms of inattention, impulsivity, and hyperactivity. Given the limitations of the existing treatment strategies, it seems necessary to consider the further exploration of alternative treatment approaches. In this review, the application and complementary use of animal-assisted interventions to the treatment of ADHD were discussed. Several mechanisms including calming, socializing, motivating, and cognitive effects of animal-assisted interventions were explored. Since studies directly investigating these effects on ADHD are scarce, so each of them were examined in terms of how it could benefit the treatment of ADHD. These effects can have a positive effect on several core symptoms of ADHD.

Hybrid laparoscopic versus open pylorus-preserving pancreatoduodenectomy: retrospective matched case comparison in 80 patients.

PURPOSE: We compared the outcome of hybrid laparoscopic pylorus-preserving pancreatoduodenectomy (lapPPPD) and open PPPD (oPPPD) in a retrospective case-matched study. METHODS: Patients operated from 2010 to 2013 by lapPPPD were matched 1:1 for age, sex, histopathology, American Society of Anesthesiologists category and body mass index to oPPPD patients operated from 1996 to 2013. RESULTS: Patients eligible for lapPPPD are a risk group due to a high rate of soft pancreata. Complication rate and mortality were comparable to oPPPD. There was a significantly reduced transfusion requirement and a trend towards shorter operation time, less delayed gastric emptying, and reduced hospital stay. The main reason for conversion was portal venous tumor adhesion. Patient selection changed and operation time and hospital stay decreased with the surgeons' experience. CONCLUSION: In selected patients, a hybrid laparoscopic technique of pancreatoduodenectomy is feasible with complication rates comparable to the open procedure. There seem to be advantages in terms of transfusion requirement, operation time, and hospital stay.

The effects of a confectionery snack on attention in young boys.

The relationship between consumption of a confectionery snack after an overnight fast and cognitive function was examined using a variety of cognitive tasks, including spatial memory, verbal memory, attention, visual perception and short-term memory, in a sample of 21 boys, ages 9-12 years. Performance on the vigilance attention task was significantly improved when the participants consumed a confectionery snack compared to consumption of a noncalorie snack. Participants had significantly higher hit rates and significantly lower miss rates after the confectionery snack. In addition, false alarm rates increased as a function of time for the placebo condition and decreased for the confectionery condition. Thus, the confectionery snack enhanced ability to stay on task for an extended period of time, enabling the children to more accurately identify target information, as well as correctly reject nontarget information. Analysis of the types of errors made also revealed that when the children were in the confectionery condition they were less likely to make more glaring errors. No significant differences were found in tests of digit span, verbal memory, spatial memory or visual perception.

Effects of hot and cold temperature exposure on performance: a meta-analytic review.

A meta-analysis to mathematically summarize the effect of hot and cold temperature exposure on performance was completed. The results from 515 effect sizes calculated from 22 original studies suggest that hot and cold temperatures negatively impact performance on a wide range of cognitive-related tasks. More specifically, hot temperatures of 90 degrees F (32.22 degrees C) Web Bulb Globe Temperature Index or above and cold temperatures of 50 degrees F (10 degrees C) or less resulted in the greatest decrement in performance in comparison to neutral temperature conditions (14.88% decrement and 13.91% decrement, respectively). Furthermore, the duration of exposure to the experimental temperature, the duration of exposure to the experimental temperature prior to the task onset, the type of task and the duration of the task had differential effects on performance. The current results indicate that hot and cold temperature exposure have a negative impact on performance and that other variables (e.g., length of exposure to the temperature or task duration) may modify this relationship.