Knowledge and Awareness of Postextraction Complications among Dental Seniors and Interns in Riyadh Province.
Postextraction complications are multifactorial. Taking proper medical and dental history, thorough planning, and a skillful dentist can help the prediction and reduction of these complications. This study aims to assess and compare the knowledge of senior students and interns regarding postextraction complications in government and private colleges in Riyadh Province. A random sampling technique was used to select a minimum of 250 participants for this study. A self-designed, close-ended questionnaire was disseminated through an online platform in a manner. Sixth-year (senior) dental students and interns were included in the study. Data were coded and entered into spreadsheet software and analyzed using Chi-square tests. More than half were dental interns (54.04%), and the rest were senior students (45.96%). Male participants comprised 52.57% of the total participants, whereas females were 47.43%. Most participants were from government colleges (53.31%), whereas 46.69% belonged to private colleges. Male interns from government colleges demonstrated the best knowledge among all the participants. In private colleges, females demonstrated better knowledge than males in both the senior and intern groups, and the difference was statistically significant. The difference in knowledge between participants from government and private colleges was found to be statistically significant (P = 0.001). Government colleges were found to demonstrate more complications than private colleges, and the difference was statistically significant (P = 0.003). Male interns from government colleges had the best knowledge about the postextraction complications among the candidates.


Affective disorder: studies with amine precursors.
The authors assessed the clinical antidepressant effects of L-tryptophan given alone and in combination with L-dopa in 12 patients with a diagnosis of primary affective disorder; Preliminary results did not demonstrate an antidepressant response when L-dopa was combined with L-tryptophan. Also, the results did not support the catecholamine or biogenic amine hypotheses of affective disorder.


The Overt Behaviour Scale-Self-Report (OBS-SR) for acquired brain injury: exploratory analysis of reliability and validity.
The objectives were to test the properties, via a psychometric study, of the Overt Behaviour Scale-Self-Report (OBS-SR), a version of the OBS-Adult Scale developed to provide a client perspective on challenging behaviours after acquired brain injury. Study sample 1 consisted of 37 patients with primary brain tumour (PBT) and a family-member informant. Sample 2 consisted of 34 clients with other acquired brain injury (mixed brain injury, MBI) and a service-provider informant. Participants completed the OBS-SR (at two time points), and the Awareness Questionnaire (AQ) and Mayo Portland Adaptability Inventory-III (MPAI-III) once; informants completed the OBS-Adult and AQ once only. PBT-informant dyads displayed "good" levels of agreement (ICC2,k = .74; OBS-SR global index). Although MBI-informant dyads displayed no agreement (ICC2,k = .22; OBS-SR global index), the sub-group (17/29) rated by clinicians as having moderate to good levels of awareness displayed "fair" agreement (ICC2,k = .58; OBS-SR global index). Convergent/divergent validity was demonstrated by significant correlations between OBS-SR subscales and MPAI-III subscales with behavioural content (coefficients in the range .36 -.61). Scores had good reliability across one week (ICC2,k = .69). The OBS-SR took approximately 15 minutes to complete. It was concluded that the OBS-SR demonstrated acceptable reliability and validity, providing a useful resource in understanding clients' perspectives about their behaviour.


The use of three-phase scintigraphy for diagnosing hemangiomas of the extremities. A clinical evaluation.
Five hemangiomas were found in four patients and were assessed by three-phase blood perfusion and blood-pool scintigraphy to determine the usefulness of this method for the imaging characteristics of different types of hemangiomas of the extremities. After injecting Tc-99m RBC or Tc-99m DTPA HSA, dynamic perfusion and early and delayed pool images were obtained and analyzed. The perfusion images of one cavernous hemangioma and two venous hemangiomas showed normal activity, but blood-pool imaging showed increased activity, whereas on perfusion imaging and early blood-pool imaging, another cavernous hemangioma showed a partial increase in activity in its periphery and on delayed blood-pool imaging, diffuse increase in activity. Further, the remaining hemangioma, a mixed-type hemangioma, showed, diffuse increase in activity on both perfusion and blood-pool imaging. Thus, three-phase scintigraphy was found useful in evaluating and achieving a diagnosis of a hemangioma of the extremities.


Morphological features and prognostic significance of tip variant of focal segmental glomerulosclerosis: Study of an Indian cohort.
Several attempts have been made to formulate a morphologic classification of focal segmental glomerulosclerosis (FSGS) variants with therapeutic and prognostic implications. Differences in study populations such as racial profile or therapy offered have hampered attempts to define prognostic variables in FSGS. Literature reveals conflicting results regarding the prognostic significance of tip variant of FSGS in different populations. To study the clinical and pathologic parameters in tip and not otherwise specified (NOS) variants of FSGS, in subjects from the Indian subcontinent with prognostic significance. First we performed a retrospective analysis of patients with biopsy proven primary FSGS, diagnosed between January 2004 and December 2008. Twenty cases of tip variant were encountered in adult population and similar numbers of adult cases of NOS variant were randomly selected. Renal biopsies were studied using light and immunofluorescence microscopy. Medical records for clinical data at presentation, biopsy and three monthly follow-up intervals were reviewed and compared between two groups. At presentation, clinical profiles for the two groups were similar; however, significant differences in histological parameters and clinical outcome in tip and NOS variant cases were noted. Interstitial fibrosis and tubular atrophy were significantly higher in NOS variant. Greater response rate to steroid therapy was observed in tip variant cases while higher proportion of NOS variant cases showed renal failure. Analysis of histological parameters is important in assessing the outcome of tip and NOS variants. Tip variant signifies a better prognostic subset for a population of Indian origin affected by FSGS.


Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.
To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [<12 years] and adolescents [12-17 years]). US adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5 kg/m(2)), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon β-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon β-1a to another DMT before the end of the observation period. This retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon β-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance.


An Attention-based Bidirectional LSTM Model for Continuous Cross-Subject Estimation of Knee Joint Angle during Running from sEMG Signals.
Accurate and robust estimation of joint kinematics via surface electromyogram (sEMG) signals provides a human-machine interaction (HMI)-based method that can be used to adequately control rehabilitation robots while performing complex movements, such as running, for motor function restoration in affected individuals. To this end, this paper proposes a deep learning-based model (AM-BiLSTM) that integrates a bidirectional long short-term memory (BiLSTM) network and an attention mechanism (AM) for robust estimation of joint kinematics. The proposed model was appraised using knee joint kinematic and sEMG signals collected from fourteen subjects who performed running at the speed of 2 m/s. The proposed model's generalizability was tested for both within- and cross-subject scenarios and compared with long short-term memory (LSTM) and multi-layer perceptron (MLP) networks in terms of normalized root-mean-square error and correlation coefficient metrics. Based on the statistical tests, the proposed AM-BiLSTM model significantly outperformed the LSTM and MLP methods in both within- and cross-subject scenarios (p<0.05) and achieved state-of-the-art performance.Clinical Relevance- The promising results of this study suggest that the AM-BiLSTM model has the potential for continuous cross-subject estimation of lower limb kinematics during running, which can be used to control sEMG-driven exoskeleton robots oriented towards rehabilitation training.


Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synovium.
Leukocyte infiltration into the rheumatoid arthritis (RA) synovium is a multistep process in which leukocytes leave the bloodstream and invade the synovial tissue (ST). Leukocyte transendothelial migration and adhesion to RA ST requires adhesion molecules on the surface of endothelial cells and RA ST fibroblasts. This study was undertaken to investigate the role of junctional adhesion molecule C (JAM-C) in mediating leukocyte recruitment and retention in the RA joint. Immunohistologic analysis was performed on RA, osteoarthritis (OA), and normal ST samples to quantify JAM-C expression. Fibroblast JAM-C expression was also analyzed using Western blotting, cell surface enzyme-linked immunosorbent assay, and immunofluorescence. To determine the role of JAM-C in leukocyte retention in the RA synovium, in vitro and in situ adhesion assays and RA ST fibroblast transmigration assays were performed. JAM-C was highly expressed by RA ST lining cells, and its expression was increased in OA ST and RA ST endothelial cells compared with normal ST endothelial cells. JAM-C was also expressed on the surface of OA ST and RA ST fibroblasts. Furthermore, we demonstrated that myeloid U937 cell adhesion to both OA ST and RA ST fibroblasts and to RA ST was dependent on JAM-C. U937 cell migration through an RA ST fibroblast monolayer was enhanced in the presence of neutralizing antibodies against JAM-C. Our results highlight the novel role of JAM-C in recruiting and retaining leukocytes in the RA synovium and suggest that targeting JAM-C may be important in combating inflammatory diseases such as RA.


Match Running Performance in Australian Football Is Related to Muscle Fiber Typology.
To examine the association between muscle fiber typology and match running performance in professional Australian football (AF) athletes. An observational time-motion analysis was performed on 23 professional AF athletes during 224 games throughout the 2020 competitive season. Athletes were categorized by position as hybrid, small, or tall. Athlete running performance was measured using Global Navigation Satellite System devices. Mean total match running performance and maximal mean intensity values were calculated for moving mean durations between 1 and 10 minutes for speed (in meters per minute), high-speed-running distance (HSR, >4.17 m·s-1), and acceleration (in meters per second squared), while intercept and slopes were calculated using power law. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and expressed as a carnosine aggregate z score (CAZ score) to estimate muscle fiber typology. Mixed linear models were used to determine the association between CAZ score and running performance. The mean (range) CAZ score was -0.60 (-1.89 to 1.25), indicating that most athletes possessed a greater estimated proportion of type I muscle fibers. A greater estimated proportion of type I fibers (ie, lower CAZ score) was associated with a larger accumulation of HSR (>4.17 m·s-1) and an increased ability to maintain HSR as the peak period duration increased. AF athletes with a greater estimated proportion of type I muscle fibers were associated with a greater capacity to accumulate distance running at high speeds, as well as a greater capacity to maintain higher output of HSR running during peak periods as duration increases.


Orientation of nonsense codons on the genetic map of the lac operon.
Intracodon recombination is used to orient the nonsense codons UGA, UAG, and UAA on the genetic map of the (lactose) lac operon of Escherichia coli. The 5'-end of these triplets is toward the operator end of the operon. A hypothesis is presented to explain the fact that the frequency of recombination between adjacent nucleotides is many times lower than expected.


Zinc fingers in Caenorhabditis elegans: finding families and probing pathways.
More than 3 percent of the protein sequences inferred from the Caenorhabditis elegans genome contain sequence motifs characteristic of zinc-binding structural domains, and of these more than half are believed to be sequence-specific DNA-binding proteins. The distribution of these zinc-binding domains among the genomes of various organisms offers insights into the role of zinc-binding proteins in evolution. In addition, the complete genome sequence of C. elegans provides an opportunity to analyze, and perhaps predict, pathways of transcriptional regulation.


Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients.
Several models have recently been developed to predict mismatch repair (MMR) gene mutations. Their comparative performance with clinical criteria or universal molecular screening in a population based colorectal cancer (CRC) cohort has not been assessed. All 1222 CRC from the EPICOLON cohort underwent tumour MMR testing with immunohistochemistry and microsatellite instability, and those with MMR deficiency (n = 91) underwent MLH1/MSH2 germline testing. Sensitivity, specificity and positive predictive value (PPV) of the PREMM(1,2) and the Barnetson models for identification of MLH1/MSH2 mutation carriers were evaluated and compared with the revised Bethesda guidelines (RBG), Amsterdam II criteria, and tumour analysis for MMR deficiency. Overall discriminative ability was quantified by the area under the ROC curve (AUC), and calibration was assessed by comparing the average predictions versus the observed prevalence. Both models had similar AUC (0.93 and 0.92, respectively). Sensitivity of the RBG and a PREMM(1,2) score > or =5% was 100% (95% CI 71% to 100%); a Barnetson score >0.5% missed one mutation carrier (sensitivity 87%, 95% CI 51% to 99%). PPVs of all three strategies were 2-3%. Presence of MMR deficiency increased specificity and PPV of predictive scores (97% and 21% for PREMM(1,2) score > or =5%, and 98% and 21% for Barnetson > or =0.5%, respectively). The PREMM(1,2) and the Barnetson models offer a quantitative systematic approach to select CRC patients for identification of MLH1/MSH2 mutation carriers with a similar performance to the RBG.


Water-induced morphology changes in BaO/gamma-Al2O3 NOx storage materials.
Exposure of NO(2)-saturated BaO/gamma-Al(2)O(3) NO(x) storage materials to H(2)O vapour results in the conversion of surface nitrates to Ba(NO(3))(2) crystallites, causing dramatic morphological changes in the Ba-containing phase, demonstrating a role for water in affecting the NO(x) storage/reduction properties of these materials.


Interlayer coupling and electric field tunable electronic properties and Schottky barrier in a graphene/bilayer-GaSe van der Waals heterostructure.
In this work, using density functional theory we investigated systematically the electronic properties and Schottky barrier modulation in a multilayer graphene/bilayer-GaSe heterostructure by varying the interlayer spacing and by applying an external electric field. At the equilibrium state, the graphene is bound to bilayer-GaSe by a weak van der Waals interaction with the interlayer distance d of 3.40 Å with the binding energy per carbon atom of -37.71 meV. The projected band structure of the graphene/bilayer-GaSe heterostructure appears as a combination of each band structure of graphene and bilayer-GaSe. Moreover, a tiny band gap of about 10 meV is opened at the Dirac point in the graphene/bilayer-GaSe heterostructure due to the sublattice symmetry breaking. The band gap opening in graphene makes it suitable for potential applications in nanoelectronic and optoelectronic devices. The graphene/bilayer-GaSe heterostructure forms an n-type Schottky contact with the Schottky barrier height of 0.72 eV at the equilibrium interlayer spacing. Furthermore, a transformation from the n-type to p-type Schottky contact could be performed by decreasing the interlayer distance or by applying an electric field. This transformation is observed when the interlayer distance is smaller than 3.30 Å, or when the applied positive external electric field is larger than 0.0125 V Å-1. These results are very important for designing new electronic Schottky devices based on graphene and other 2D semiconductors such as a graphene/bilayer-GaSe heterostructure.


Rapid, multiplexed microfluidic phage display.
The development of a method for high-throughput, automated proteomic screening could impact areas ranging from fundamental molecular interactions to the discovery of novel disease markers and therapeutic targets. Surface display techniques allow for efficient handling of large molecular libraries in small volumes. In particular, phage display has emerged as a powerful technology for selecting peptides and proteins with enhanced, target-specific binding affinities. Yet, the process becomes cumbersome and time-consuming when multiple targets are involved. Here we demonstrate for the first time a microfluidic chip capable of identifying high affinity phage-displayed peptides for multiple targets in just a single round and without the need for bacterial infection. The chip is shown to be able to yield well-established control consensus sequences while simultaneously identifying new sequences for clinically important targets. Indeed, the confined parameters of the device allow not only for highly controlled assay conditions but also introduce a significant time-reduction to the phage display process. We anticipate that this easily-fabricated, disposable device has the potential to impact areas ranging from fundamental studies of protein, peptide, and molecular interactions, to applications such as fully automated proteomic screening.


Association between muscle hydration measures acquired using bioelectrical impedance spectroscopy and magnetic resonance imaging in healthy and hemodialysis population.
Establishing the effect of fluctuating extracellular fluid (ECF) volume on muscle strength in people with end-stage renal disease (ESRD) on hemodialysis (HD) is essential, as inadequate hydration of the skeletal muscles impacts its strength and endurance. Bioelectrical impedance spectroscopy (BIS) has been a widely used method for estimating ECF volume of a limb or calf segment. Magnetic resonance imaging (MRI)-acquired transverse relaxation times (T2) has also been used for estimating ECF volumes of individual skeletal muscles. The purpose of this study was to determine the association between T2 (gold standard) of tibialis anterior (TA), medial (MG), and lateral gastrocnemius (LG), and soleus muscles and calf BIS ECF, in healthy and in people with ESRD/HD. Calf BIS and MRI measures were collected on two occasions before and after HD session in people with ESRD/HD and on a single occasion for the healthy participants. Linear regression analysis was used to establish the association between these measures. Thirty-two healthy and 22 participants on HD were recruited. The association between T2 of TA, LG, MG, and soleus muscles and ratio of calf BIS-acquired ECF and intracellular fluids (ICF) were: TA: β = 0.30, P > 0.05; LG: β = 0.37, P = 0.035; MG: β = 0.43, P = 0.014; soleus: β = 0.60, P < 0.001. For the HD group, calf ECF was significantly associated with T2 of TA (β = 0.44, P = 0.042), and medial gastrocnemius (β = 0.47, P = 0.027) following HD only. Hence BIS-acquired measures cannot be used to measure ECF volumes of a single muscle in the ESRD/HD population; however, BIS could be utilized to estimate ratio of ECF: ICF in healthy population for the LG, MG, and soleus muscles.


Knowledge-Infused Abstractive Summarization of Clinical Diagnostic Interviews: Framework Development Study.
In clinical diagnostic interviews, mental health professionals (MHPs) implement a care practice that involves asking open questions (eg, "What do you want from your life?" "What have you tried before to bring change in your life?") while listening empathetically to patients. During these interviews, MHPs attempted to build a trusting human-centered relationship while collecting data necessary for professional medical and psychiatric care. Often, because of the social stigma of mental health disorders, patient discomfort in discussing their presenting problem may add additional complexities and nuances to the language they use, that is, hidden signals among noisy content. Therefore, a focused, well-formed, and elaborative summary of clinical interviews is critical to MHPs in making informed decisions by enabling a more profound exploration of a patient's behavior, especially when it endangers life. The aim of this study is to propose an unsupervised, knowledge-infused abstractive summarization (KiAS) approach that generates summaries to enable MHPs to perform a well-informed follow-up with patients to improve the existing summarization methods built on frequency heuristics by creating more informative summaries. Our approach incorporated domain knowledge from the Patient Health Questionnaire-9 lexicon into an integer linear programming framework that optimizes linguistic quality and informativeness. We used 3 baseline approaches: extractive summarization using the SumBasic algorithm, abstractive summarization using integer linear programming without the infusion of knowledge, and abstraction over extractive summarization to evaluate the performance of KiAS. The capability of KiAS on the Distress Analysis Interview Corpus-Wizard of Oz data set was demonstrated through interpretable qualitative and quantitative evaluations. KiAS generates summaries (7 sentences on average) that capture informative questions and responses exchanged during long (58 sentences on average), ambiguous, and sparse clinical diagnostic interviews. The summaries generated using KiAS improved upon the 3 baselines by 23.3%, 4.4%, 2.5%, and 2.2% for thematic overlap, Flesch Reading Ease, contextual similarity, and Jensen Shannon divergence, respectively. On the Recall-Oriented Understudy for Gisting Evaluation-2 and Recall-Oriented Understudy for Gisting Evaluation-L metrics, KiAS showed an improvement of 61% and 49%, respectively. We validated the quality of the generated summaries through visual inspection and substantial interrater agreement from MHPs. Our collaborator MHPs observed the potential utility and significant impact of KiAS in leveraging valuable but voluminous communications that take place outside of normally scheduled clinical appointments. This study shows promise in generating semantically relevant summaries that will help MHPs make informed decisions about patient status.


[Medical scientific research with people: what the law does not regulate].
The 'Bill on Medical Scientific Research with Humans' fail to state clearly which research may and which research may not be carried out without previous approval from a review committee. This is a problem especially with regard to studies using human body material and studies involving questioning people to collect study data. For the sake of clarity in practice it would be advisable if researchers and review committees would observe the following rules: every planned research project which involves patients or other persons having to do or to undergo something for the special purpose of the study must be submitted by the researchers to a review committee. However, actual reviewing is only necessary in the case of studies which, in the review committee's opinion, entail a real health risk or cause significant physical inconvenience or mental stress. Research involving persons who are vulnerable with respect to self-determination, such as the mentally incompetent, should always be reviewed, even if it does not seriously threaten the subjects' physical or mental well-being.


The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry.
The UK military was continuously engaged in armed conflict in Iraq and Afghanistan between 2003 and 2014, resulting in 629 UK fatalities. Traumatic cardiac arrest (TCA) is a precursor to traumatic death, but data on military outcomes are limited. In order to better inform military treatment protocols, the aim of this study was to define the epidemiology of TCA in the military population with a particular focus on survival rates and injury patterns. A retrospective database analysis of the UK Joint Theatre Trauma Registry was undertaken. Patients who were transported to a UK deployed hospital between 2003 and 2014 and suffered TCA were included. Those patients injured by asphyxiation, electrocution, burns without other significant trauma and drowning were excluded. Data included mechanism of injury, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) for each body region and survival to deployed (Role 3) field hospital discharge. 424 TCA patients were identified during the study period; median age was 23 years, with a median ISS of 45. The most common mechanism of injury was explosive (55.7%), followed by gunshot wound (38.9%), road traffic collision (3.5%), crush (1.7%) and fall (0.2%). 45 patients (10.6% (95% CI 8.0% to 13.9%)) survived to deployed (Role 3) hospital discharge. The most prevalent body region with a severe to maximum AIS injury was the head, followed by the lower limbs, thorax and abdomen. Haemorrhage secondary to abdominal and lower limb injury was associated with survival; traumatic brain injury was associated with death. This study has shown that short-term survival from TCA in a military population is 10.6%. With appropriate and aggressive early management, although unlikely, survival is still potentially possible in military patients who suffer traumatic cardiac arrest.


Risk factors for overweight in five- to six-year-old Hispanic-American children: a pilot study.
The objective of this study was to determine the prevalence of and possible risk factors for overweight in a sample of 5- to 6-year-old Hispanic (predominantly Mexican American) children in Chicago, Illinois, to see if overweight is more common in more highly acculturated immigrant families. There were 250 kindergarten students (92% of those eligible) attending two public elementary schools serving primarily Mexican American neighborhoods measured for height and weight. Consenting mothers were interviewed (n = 80) and measured (n = 38). The interview tool covered demography, acculturation, infant and toddler feeding practices, current eating patterns and food preparation habits, physical activity, and psychosocial family characteristics. Overweight was conservatively defined as weight-for-height at or above the National Center for Health Statistics 95th percentile. The data were used to describe the prevalence of overweight. Overweight and nonoverweight children were compared on all survey variables using appropriate statistical tests, with significance set at.05. There were 23% of the total sample of children (n = 250) and 26% of the subsample of children (those whose mothers were interviewed) who were overweight. Analysis limited to children in the subsample explored risk factors. The median score on the Acculturation Scale was 4.0 (range 2.4 - 10.4) on a scale of 2.4 (entirely not acculturated) to 12 (fully acculturated). There was no significant association between overweight and Acculturation Scale score. Overweight children were more likely than those not overweight to watch television for more than 3 hours during weekend days (48% vs. 22%, P =.03). Overweight children were also more likely to consume sweetened beverages (powdered drinks, soda pop, atole) daily (67% vs. 39%, P =.03). There was a trend indicating that free access to food at home increased the risk of overweight (P = 0.06). No other family- or child-level variables were related to overweight. Only 40% of mothers with an overweight child correctly assessed these children as overweight. Approximately one quarter of the children in the study were overweight. Our hypothesis that their obesity was linked to acculturation was not confirmed. Longer hours of child television viewing on weekends and higher levels of sweetened beverage consumption were important behaviors associated with the occurrence of overweight. These data should be considered when designing future studies in this population.


The budgetary impact of genetic testing for hereditary breast cancer for the statutory health insurance.
Objectives: Potential opportunities and challenges of predictive genetic risk classification of healthy persons are currently discussed. However, the budgetary impact of rising demand is uncertain. This project aims to evaluate budgetary consequences of predictive genetic risk classification for statutory health insurance in Germany.Methods: A Markov model was developed in the form of a cohort simulation. It analyzes a population of female relatives of hereditary breast cancer patients. Mutation carriers are offered intensified screening, women with a BRCA1 or BRCA2 mutation can decide on prophylactic mastectomy and/or ovarectomy. The model considers the following scenarios: (a) steady demand for predictive genetic testing, and (b) rising demand. Most input parameters are based on data of the German Consortium for Hereditary Breast and Ovarian Cancer. The model contains 49 health states, starts in 2015, and runs for 10 years. Prices were evaluated from the perspective of statutory health insurance.Results: Steady demand leads to an expenditure of €49.8 million during the 10-year period. Rising demands lead to additional expenses of €125.5 million. The model reveals the genetic analysis to be the main cost driver while cost savings in treatment costs of breast and ovarian cancer are indicated.Conclusions: The results contribute to close the knowledge gap concerning the budgetary consequences due to genetic risk classification. A rising demand leads to additional costs especially due to costs for genetic analysis. The model indicates budget shifts with cost savings due to breast and ovarian cancer treatment in the scenario of rising demands.


High-mannose intercellular adhesion molecule-1 enhances CD16+ monocyte adhesion to the endothelium.
Human monocytes have been classified into three distinct groups, classical (anti-inflammatory; CD14+/CD16-), nonclassical (patrolling; CD14+/CD16++), and intermediate (proinflammatory; CD14++/CD16+). Adhesion of nonclassical/intermediate monocytes with the endothelium is important for innate immunity, and also vascular inflammatory disease. However, there is an incomplete understanding of the mechanisms that regulate CD16+ versus CD16- monocyte adhesion to the inflamed endothelium. Here, we tested the hypothesis that a high-mannose (HM) N-glycoform of intercellular adhesion molecule-1 (ICAM-1) on the endothelium mediates the selective recruitment of CD16+ monocytes. Using TNF-α treatment of human umbilical vein endothelial cells (HUVECs), and using proximity ligation assay for detecting proximity of specific N-glycans and ICAM-1, we show that TNF-α induces HM-ICAM-1 formation on the endothelial surface in a time-dependent manner. We next measured CD16- or CD16+ monocyte rolling and adhesion to TNF-α-treated HUVECs in which HM- or hybrid ICAM-1 N-glycoforms were generated using the α-mannosidase class I and II inhibitors, kifunensine and swainsonine, respectively. Expression of HM-ICAM-1 selectively enhanced CD16+ monocyte adhesion under flow with no effect on CD16- monocytes noted. CD16+ monocyte adhesion was abrogated by blocking either HM epitopes or ICAM-1. A critical role for HM-ICAM-1 in mediating CD16+ monocyte rolling and adhesion was confirmed using COS-1 cells engineered to express HM or complex ICAM-1 N-glycoforms. These data suggest that HM-ICAM-1 selectively recruits nonclassical/intermediate CD16+ monocytes to the activated endothelium.NEW & NOTEWORTHY Monocyte subsets have been associated with cardiovascular disease, yet it is unknown how different subsets are recruited to the endothelium. This study demonstrates the formation of distinct ICAM-1 N-glycoforms in the activated endothelium and reveals a key role for high mannose ICAM-1 in mediating proinflammatory CD16+ monocyte adhesion. Presented data identify roles for endothelial N-glycans in recruiting specific monocyte subsets during inflammation.


Involvement of YAP, TAZ and HSP90 in contact guidance and intercellular junction formation in corneal epithelial cells.
The extracellular environment possesses a rich milieu of biophysical and biochemical signaling cues that are simultaneously integrated by cells and influence cellular phenotype. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (WWTR1; TAZ), two important signaling molecules of the Hippo pathway, have been recently implicated as nuclear relays of cytoskeletal changes mediated by substratum rigidity and topography. These proteins intersect with other important intracellular signaling pathways (e.g. Wnt and TGFβ). In the cornea, epithelial cells adhere to the stroma through a 3-dimensional topography-rich basement membrane, with features in the nano-submicron size-scale that are capable of profoundly modulating a wide range of fundamental cell behaviors. The influences of substratum-topography, YAP/TAZ knockdown, and HSP90 inhibition on cell morphology, YAP/TAZ localization, and the expression of TGFβ2 and CTGF, were investigated. The results demonstrate (a) that knockdown of TAZ enhances contact guidance in a YAP dependent manner, (b) that CTGF is predominantly regulated by YAP and not TAZ, and (c) that TGFβ2 is regulated by both YAP and TAZ in these cells. Additionally, inhibition of HSP90 resulted in nuclear localization and subsequent transcriptional-activation of YAP, formation of cell-cell junctions and co-localization of E-cadherin and β-catenin at adherens junctions. Results presented in this study reflect the complexities underlying the molecular relationships between the cytoskeleton, growth factors, heat shock proteins, and co-activators of transcription that impact mechanotransduction. The data reveal the importance of YAP/TAZ on the cell behaviors, and gene and protein expression.


Study of the effects of antigammaglobulin factors on lymphocytes from patients with rheumatoid arthritis.
Previous work suggests that peripheral blood lymphocytes from patients with rheumatoid arthritis have altered reactivity. The purpose of this study has been to observe the behavior of cultures of lymphocytes from patients with rheumatoid arthritis when stimulated with autologous 19S rheumatoid factor and with rabbit serum against autologous IgG fraction. The peripheral blood lymphocytes (PBL) from 15 patients with classical rheumatoid arthritis were obtained by passage of the leukocyte-rich plasma through a polyamide fiber column. The purified lymphocytes were cultured with rheumatoid factor obtained from the same donor through Sephadex G-200 chromatography. In another set of experiments rheumatoid lymphocytes were stimulated with rabbit serum containing antibodies against the IgG fraction of the same patient obtained through DEAE chromatography. After five days the lymphocytes were examined for large cells plus cells in mitosis. A positive response was defined as an increase of 5% or more in the experimental tubes when compared with the cells cultured alone. Ten healthy normal subjects were used also as lymphocyte and serum donors. These lymphocytes were cultured alone and with rabbit serum, anti-autologous IgG. 80% of rheumatoid lymphocytes responded with an average of 37% of enlarging and dividing cells when stimulated by autologous RF. The same pannel of lymphocytes responded only with an average of 14% stimulation when cultured with rabbit serum anti-autologous IgG. The response to the 7S antigammaglobulin factor from rabbit in 7 normal PBL was similar to that of rheumatoid lymphocytes. There was some relation between activity of the RA and lymphocyte response to RF and rabbit antiserum. These results could explain the lymphoid infiltration and hyperplasia of patients with RA and, on the other hand, would support the idea that entrapment of RF by leukocytes ('RA cell') would be a protective mechanism.


Abnormal hyoid conformation in French Bulldogs: case report and computed tomographic anatomical comparison.
Brachycephalic obstructive airway syndrome (BOAS) is common in brachycephalic breeds and comprises multiple anatomic characteristics. Computed tomography (CT) is increasingly used in the preoperative assessment of dogs presenting with BOAS. We describe the case of a French Bulldog with a presumed congenital hyoid malformation and anatomic comparison of hyoid morphology between French Bulldogs and mesaticephalic dogs using CT. Skull CT studies of French Bulldogs and mesaticephalic dogs presenting to two referral hospitals between 2013 and 2020 were collected. The degree of curvature of the basihyoid bone and the relative ventrodorsal thickness (RVD) were determined using a novel measurement technique. A circle of best fit was applied to the inside arc of the basihyoid bone, and the radius and sector angle within the basihyoid bone were recorded. The RVD was defined by the ventrodorsal thickness divided by the width in the frontal plane. The basihyoid bone of French Bulldogs had a greater mean ± SD RVD of 0.23 ± 0.04 compared to 0.16 ± 0.03 in mesaticephalic dogs (P < 0.01). The sector angle was also greater in French Bulldogs, measuring 144.08 ± 20.88° compared to 103.94 ± 16.49° in mesaticephalic dogs (P < 0.01). This case of hyoid malformation in a French Bulldog reports a rarely documented condition that complicated the management of BOAS. Comparative assessment of hyoid conformation revealed more acute curvature and greater RVD in French Bulldogs than in mesaticephalic dogs. This may represent an additional distorted anatomic component of brachycephalic skull morphology.


Vision anomalies of Indian school children: the Lame Deer study.
The occurrence of vision anomalies among American Indian school children is measured for an entire school population, according to grade (pre-kindergarten through 12). The anomalies are identified, classified in three major groups (myopes, astigmats, all other), and each group is compared to Caucasian school children. Some conclusions and recommendations are made concerning the vision care needs of Amerind school children.


[Neurotransmitter mechanism of the tropoxin effect in comparison with other antimigraine preparations].
The results of experiments on cats showed that tropoxin produces no adreno- and cholinoblocking action and possesses no antihistamine properties. A comparative study of the antiserotonin cerebrovascular effect of tropoxin and some other well-known antimigraine drugs showed that tropoxin not only attenuates cerebrovascular constriction response to serotonin, but distorts these reactions so as to reduce the tone of cerebral vessels. An analogous antiserotonin activity was also observed for methysergide, dihydroergotamine, nicergoline, and (to a lower extent) tolfenamic acid, while propranolol inhibited serotonin reactions only in 50% of cases. The 5HT2 receptor blocker ketanserin significantly reduces the cerebrovascular effects of serotonin, while the 5HT3 receptor blocker tropisetron shows no such activity.


Mediterranean-Style Diet Improves Systolic Blood Pressure and Arterial Stiffness in Older Adults.
We aimed to determine the effect of a Mediterranean-style diet, tailored to meet dietary recommendations for older adults, on blood pressure and arterial stiffness. In 12 months, randomized controlled trial (NU-AGE [New Dietary Strategies Addressing the Specific Needs of Elderly Population for Healthy Aging in Europe]), blood pressure was measured in 1294 healthy participants, aged 65 to 79 years, recruited from 5 European centers, and arterial stiffness in a subset of 225 participants. The intervention group received individually tailored standardized dietary advice and commercially available foods to increase adherence to a Mediterranean diet. The control group continued on their habitual diet and was provided with current national dietary guidance. In the 1142 participants who completed the trial (88.2%), after 1 year the intervention resulted in a significant reduction in systolic blood pressure (-5.5 mm Hg; 95% CI, -10.7 to -0.4; P=0.03), which was evident in males (-9.2 mm Hg, P=0.02) but not females (-3.1 mm Hg, P=0.37). The -1.7 mm Hg (95% CI, -4.3 to 0.9) decrease in diastolic pressure after intervention did not reach statistical significance. In a subset (n=225), augmentation index, a measure of arterial stiffness, was improved following intervention (-12.4; 95% CI, -24.4 to -0.5; P=0.04) with no change in pulse wave velocity. The intervention also resulted in an increase in 24-hour urinary potassium (8.8 mmol/L; 95% CI, 0.7-16.9; P=0.03) and in male participants (52%) a reduction in pulse pressure (-6.1 mm Hg; 95% CI, -12.0 to -0.2; P=0.04) and 24-hour urinary sodium (-27.1 mmol/L; 95% CI, -53.3 to -1.0; P=0.04). In conclusion, a Mediterranean-style diet is effective in improving cardiovascular health with clinically relevant reductions in blood pressure and arterial stiffness. Clinical Trial Registration- URL: http://www.clinicialtrials.gov . Unique identifier: NCT01754012.


The Comprehensive Geriatric Assessment and the multidimensional approach. A new look at the older patient with gastroenterological disorders.
The Comprehensive Geriatric Assessment (CGA) is a multidimensional, usually interdisciplinary, diagnostic process intended to determine an elderly person's medical, psychosocial, and functional capacity and problems with the objective of developing an overall plan for treatment and short- and long-term follow-up. The potential usefulness of the CGA in evaluating treatment and follow-up of older patients with gastroenterological disorders is unknown. In the paper we reported the efficacy of a Multidimensional-Prognostic Index (MPI), calculated from information collected by a standardized CGA, in predicting mortality risk in older patients hospitalized with upper gastrointestinal bleeding and liver cirrhosis. Patients underwent a CGA that included six standardized scales, i.e. Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Short-Portable Mental Status Questionnaire (SPMSQ), Mini-Nutritional Assessment (MNA), Exton-Smith Score (ESS) and Comorbity Index Rating Scale (CIRS), as well as information on medication history and cohabitation, for a total of 63 items. The MPI was calculated from the integrated total scores and expressed as MPI 1=low risk, MPI 2=moderate risk and MPI 3=severe risk of mortality. Higher MPI values were significantly associated with higher short- and long-term mortality in older patients with both upper gastrointestinal bleeding and liver cirrhosis. A close agreement was found between the estimated mortality by MPI and the observed mortality. Moreover, MPI seems to have a greater discriminatory power than organ-specific prognostic indices such as Rockall and Blatchford scores (in upper gastrointestinal bleeding patients) and Child-Plugh score (in liver cirrhosis patients). All these findings support the concept that a multidimensional approach may be appropriate for the evaluation of older patients with gastroenterological disorders, like it has been reported for patients with other pathological conditions.


Rapidly increasing prevalence of overweight and obesity in older Ghanaian adults from 2007-2015: Evidence from WHO-SAGE Waves 1 & 2.
Studies on changes in the prevalence and determinants of obesity in older adults living in sub-Saharan Africa are scarce. We examined recent changes in obesity prevalence and associated factors for older adults in Ghana between 2007/08 and 2014/15. Data on adults aged 50 years and older in Ghana were drawn from the WHO SAGE 2007/08 (Wave 1; n = 4158) and 2014/15 (Wave 2; n = 1663). The weighted prevalence of obesity, overweight, normal weight and underweight, and of high central adiposity were compared in 2007/08 and 2014/15. Multinomial and binomial logistic regressions were used to examine whether the determinants of weight status based on objectively measured body mass index and waist circumference changed between the two time periods. The prevalence of overweight (2007/08 = 19.6%, 95% CI: 18.0-21.4%; 2014/15 = 24.5%, 95% CI: 21.7-27.5%) and obesity (2007/08 = 10.2%, 95% CI: 8.9-11.7%; 2014/15 = 15.0%, 95% CI: 12.6-17.7%) was higher in 2014/15 than 2007/08 and more than half of the population had high central adiposity (2007/08 = 57.7%, 95% CI: 55.4-60.1%; 2014/15 = 66.9%, 95% CI: 63.7-70.0%) in both study periods. While the prevalence of overweight increased in both sexes, obesity prevalence was 16% lower in males and 55% higher in females comparing 2007/08 to 2014/15. Female sex, urban residence, and high household wealth were associated with higher odds of overweight/obesity and high central adiposity. Those aged 70+ years had lower odds of obesity in both study waves. In 2014/15, females who did not meet the recommended physical activity were more likely to be obese. Over the 7-year period between the surveys, the prevalence of underweight decreased and overweight increased in both sexes, while obesity decreased in males but increased in females. The difference in obesity prevalence may point to differential impacts of past initiatives to reduce overweight and obesity, potential high-risk groups in Ghana, and the need to increase surveillance.


Lumbosacral radioculopathy: review of 100 consecutive cases.
Of 100 consecutive patients with acute lumbosacral radiculopathy who were treated conservatively and the majority of whom were followed for at least 5 years, only 5% had to undergo laminectomy and diskectomy. Conservative management included complete bed rest for 2 to 3 weeks, with occasional use of anti-inflammatory drugs, and support of the lumbosacral spine, at first with a corset and later with vigorous abdominal strengthening exercises. Repeated electromyography was of value in assessing clinical weakness, providing objective guidance to management. It is concluded that in only rare instances is surgery indicated for lumbosacral radiculopathy secondary to disk derangement.


Mortality, intensive care treatment, and cost evaluation: Role of a polymerase chain reaction assay in patients with sepsis.
Objective We examined whether patients with a positive SeptiFast (SF) assay (LightCycler SeptiFast; Roche Diagnostics, Basel, Switzerland) developed higher long-term mortality, a more difficult course of treatment, and a higher antimicrobial treatment cost than patients with a negative SF assay. Methods We performed a post-hoc analysis of data collected in a 1-year prospective interventional study of adults with severe sepsis and septic shock. In addition to the standard treatment, an additional 5 ml of blood was obtained for an SF assay, and the antimicrobial treatment was changed according to the SF results. Results We included 57 patients, and the SF assay was positive (SF+) in 10 (17.5%) and negative (SF-) in 47 (82.5%) patients. A trend toward a higher 6-month, 1-year, and 2-year mortality rate was observed in the SF+ group. In the SF+ group, we observed a significantly greater need for second-line vasopressor therapy, a higher initial procalcitonin concentration, and higher maximum C-reactive protein and lactate concentrations. We found no significant differences in cost of antimicrobial treatment between the SF+ and SF- groups. Conclusions We observed a trend toward higher long-term mortality and a more difficult course of treatment but no difference in the cost of antimicrobial treatment.


Evaluation of biochemical parameters in platelet concentrates stored in glucose solution.
Therapeutic storage of platelet concentrate is a challenging problem for Transfusion Medicine, so that many studies have been carried out with the aim of improving the duration of storage of platelet concentrates. Little attention, however, has been given to the most appropriate biochemical methods for evaluating the quality of the stored platelet concentrates. [corrected] Platelet concentrates (n=10) were saved under gentle stirring at 22 masculineC for a total period of 8 days. Glucose 0.5% (w/v) was added either at the beginning of storage (time 0) or on the fifth day of storage. One millilitre of each concentrate was withdrawn at time 0 and after 5, 6, 7 and 8 days of storage for microbiological culture, evaluation of pH, lactate dehydrogenase (LDH), mean platelet volume, platelet haematocrit and analysis of metabolites of energy pathways (high energy phosphate derivatives, nucleosides, oxypurines and antioxidants) by high performance liquid chromatography. The addition of glucose 0.5% on day 5 did not produce significant differences in metabolites of energy pathways with respect to control platelet concentrates, whereas when the glucose was added at the beginning of storage (time 0) there was a recovery of ATP, GTP and a decrease of energetic catabolism, demonstrating a beneficial effect on energy metabolism. The changes in LDH values did not parallel those of the metabolites: indeed, only on day 7 of storage did the platelet concentrates treated with glucose on day 5 have significantly lower levels of this enzyme than those found in the other concentrates. The improvements produced by addition of glucose at time 0 were confirmed by morphological analyses (mean platelet volume, platelet haematocrit), and the pH. The metabolic profile of glucose-enriched plasma concentrates on the fifth day of storage, and the different time course of increased LDH concentration, could represent valid parameters to interpret platelet vitality in the successive days of storage. These preliminary data also indicate that glucose might be a good additive for a new storage formulation.


Ultrastructural and immunohistochemical studies on Trichomonas vaginalis adhering to and phagocytizing genitourinary epithelial cells.
Trichomonas vaginalis (T. vaginalis) belongs to a common sexually transmitted disease pathogen causing genitourinary trichomoniasis in both sexes. We investigated the pathogenetic mechanism of genitourinary trichomoniasis. Cultured T. vaginalis bodies were injected into the vaginas of rats, or incubated with genitourinary epithelial cells of female subjects, male subjects, and sperm. The ultrastructural and microscopic changes were observed via transmission and scanning electron microscopy and through microscopic histochemistry. Groups of T. vaginalis adhered to PAS positive columnar cells at the surface of stratified epithelium in the middle and upper portions of the vaginas. They also traversed under these cells. The parasites were shown to be PAS, cathepsin D, and actin positive, and they could release hydrolase into the cytoplasm of adhered epithelial cells. In the amebiform T. vaginalis, microfilaments were arranged into reticular formation. Similar phenomena were found during the interaction of T. vaginalis with host cells, both in vitro and in vivo. Usually several protozoa adhered to an epithelial cell and formed polymorphic pseudopodia or surface invaginations to surround and phagocytize the microvilli or other parts of the epithelial cytoplasm. Adhesion and phagocytosis of sperm by the protozoa occurred at 15 - 30 minutes of incubation. Digestion of sperm was found at 45 - 75 minutes and was complete at 90 - 105 minutes. T. vaginalis tends to parasitize at the fornix of the vagina, because this is the site where columnar cells are rich in mucinogen granules and their microvilli are helpful for adhesion and nibbling. T. vaginalis possesses some invading and attacking abilities. Shape change, canalization, encystation, phagocytosis, digestion, the cell coat, cytoskeleton, and lysosome all play important roles in the process of adhesion. They have two methods of phagocytosis: nibbling and ingestion. Genitourinary epithelium may be injured directly by the digestive action of hydrolases, phagocytosis, and the mechanical action of pseudopodia.


[The use of the upper septal approach during the performance of operations on the left atrioventricular valve].
The upper septal access to left atrioventricular valve (LAVV) was applied while the operation conduction, using the heart-lung apparatus, in 7 patients. Excellent exposition of all the parts of the LAVV ring and of subvalvular apparatus was achieved in all observations. There were no observed significant rhythm disorders and other complications due to the access chosen.


Validation of an open source, remote web-based eye-tracking method (WebGazer) for research in early childhood.
Measuring eye movements remotely via the participant's webcam promises to be an attractive methodological addition to in-person eye-tracking in the lab. However, there is a lack of systematic research comparing remote web-based eye-tracking with in-lab eye-tracking in young children. We report a multi-lab study that compared these two measures in an anticipatory looking task with toddlers using WebGazer.js and jsPsych. Results of our remotely tested sample of 18-27-month-old toddlers (N = 125) revealed that web-based eye-tracking successfully captured goal-based action predictions, although the proportion of the goal-directed anticipatory looking was lower compared to the in-lab sample (N = 70). As expected, attrition rate was substantially higher in the web-based (42%) than the in-lab sample (10%). Excluding trials based on visual inspection of the match of time-locked gaze coordinates and the participant's webcam video overlayed on the stimuli was an important preprocessing step to reduce noise in the data. We discuss the use of this remote web-based method in comparison with other current methodological innovations. Our study demonstrates that remote web-based eye-tracking can be a useful tool for testing toddlers, facilitating recruitment of larger and more diverse samples; a caveat to consider is the larger drop-out rate.


Validation of a platinum bioelectrode model for preclinical electrical and biological performance evaluation.
High throughput testing of clinically representative Pt electrodes requires an inexpensive, efficient method of production. The aim of this study was to develop a facile platinum (Pt) model electrode (PME) and assess its production process, stability, and reproducibility. In this study a new model electrode was developed using representative substrates and dimensions as state-of-the-art electrode arrays used for neural stimulation. It was found that the PME is a highly reproducible robust system with similar electrochemical performance but with lower variability than other neural prosthetic arrays.Clinical Relevance- As an estimate these novel model electrodes cost 300 times less than a cochlear implant, can be manufactured in a tenth of the time and with a less than 10% failure rate. It is expected that model electrodes with low variability of electrical properties will significantly improve preclinical validation testing of electrochemical stimulation, surface modifications, and coatings.


Practice Current: How do you manage mild cognitive impairment?
Mild cognitive impairment (MCI) is characterized by evidence of cognitive impairment with minimal disruption of instrumental activities of daily living and carries a substantial risk of progression of dementia. Whereas current guidelines support a relatively minimalistic workup to identify reversible or structural causes, the field has witnessed the rapid development of various sophisticated imaging, biomarker, and genetic investigations in the past few years. The role of these investigations in routine practice is uncertain. Similarly, although there are no approved treatments for MCI, neurologists may experience uncertainty about using cholinesterase inhibitors or other medications or supplements that have been studied in MCI with limited success, particularly when patients or families are keen to try pharmacologic options. Given these uncertainties, and the paucity of high-quality data in the literature, we sought expert opinion from around the globe on how to investigate and treat patients with MCI. Similar questions were posed to the rest of our readership in an online survey, the preliminary results of which are also presented.


Dimensionality of a scale of adjustment to unemployment.
Many of today's unemployed are middle managers or midcareer professionals who lost their jobs through no fault of their own. This study examined psychological effects of unemployment on 178 professionals using an adaptation of Kaufman's adjustment to unemployment scale. Analysis indicated two factors, negative affect (which includes anxiety, burden, irritation, resentment, and anomie; alpha = .69) and general affect (self-esteem, depression, and life satisfaction; alpha = .73). Implications for the study of unemployed professionals are discussed.


Evaluation of living liver donors using contrast enhanced multidetector CT - The radiologists impact on donor selection.
Living donor liver transplantation (LDLT) is a valuable and legitimate treatment for patients with end-stage liver disease. Computed tomography (CT) has proven to be an important tool in the process of donor evaluation. The purpose of this study was to evaluate the significance of CT in the donor selection process. Between May 1999 and October 2010 170 candidate donors underwent biphasic CT. We retrospectively reviewed the results of the CT and liver volumetry, and assessed reasons for rejection. 89 candidates underwent partial liver resection (52.4%). Based on the results of liver CT and volumetry 22 candidates were excluded as donors (31% of the cases). Reasons included fatty liver (n = 9), vascular anatomical variants (n = 4), incidental finding of hemangioma and focal nodular hyperplasia (n = 1) and small (n = 5) or large for size (n = 5) graft volume. CT based imaging of the liver in combination with dedicated software plays a key role in the process of evaluation of candidates for LDLT. It may account for up to 1/3 of the contraindications for LDLT.


The Risk of Selection Bias in a Clinical Multi-Center Cohort Study. Results from the Norwegian Cognitive Impairment After Stroke (Nor-COAST) Study.
The Norwegian Cognitive Impairment After Stroke (Nor-COAST) study aimed to estimate the prevalence and incidence of neurocognitive disorder in an unselected stroke cohort. The aim of the present study was to investigate whether selection bias occurred by comparing baseline characteristics from participants with non-participants in Nor-COAST. Nor-COAST is a prospective cohort multi-center study, recruiting participants from five Norwegian hospitals. Patients with the diagnosis of acute stroke were screened for inclusion. Baseline data from the participants recruited between May 2015 and March 2017 were compared to corresponding data from those not participating in Nor-COAST but registered in the Norwegian Stroke Registry. Regression analysis was used to assess whether age, stroke severity, sex and stroke subtype were independently associated with inclusion in the study. Out of 2505 available patients, 815 (32.5%) were included in Nor-COAST. There were no differences between participants and non-participants with respect to age (mean (SD) age 73.5 (11.7) versus 74.2 (14.5) years) or sex (44.8% versus 46.9% women). A significantly larger proportion of the participants were independent prior to stroke (87% versus 78%), had mild strokes (69% versus 55%) and suffered from cerebral infarction (90% versus 84%). The regression analysis showed decreased odds ratio (OR) of being included for those with higher degree of pre-stroke dependency (OR 0.895, 95% CI 0.825 to 0.971, p=0.007) and a more severe stroke (OR 0.952, 95% CI 0.939 to 0.966, p<0.001). The participants in Nor-COAST had a better pre-stroke health condition and milder strokes compared to non-participants. However, the participants should be regarded as representative of the majority of the stroke population which suffers from mild strokes. Nevertheless, baseline information for non-participants should be available also in future clinical studies to make it easier to identify which part of the stroke population the results can be generalized to.


Comparison of Visual Analog Scale Scores in Pain Assessment during Pulpotomy using Different Injection Materials in Children Aged 6 to 8 and 8 to 10 Years.
Proper anesthesia and pain management during treatment are most important concerns in dentistry for people of all ages, especially children. This study compared the success rate of lidocaine block with articaine buccal infiltration during anesthesia of the primary mandibular second molars in children aged 6 to 8 and 8 to 10 years. The present clinical trial was conducted on 40 children aged 6 to 8 and 8 to 10 years who were referred to the Department of Pediatrics of the Faculty of Dentistry at Shahid Sadoughi University of Medical Sciences in Yazd (Islamic Republic of Iran) and needed to be treated with pulpotomy on both primary mandibular second molars. The patients were randomly divided into two groups. At the first session, a group received articaine buccal infiltration and the other group experienced inferior alveolar nerve (IAN) block. At the next visit, this trend was reversed. Visual analog scale (VAS) was used to evaluate the pain during pulpotomy. Data were analyzed by Statistical Package for the Social Sciences (version 17) software using Mann-Whitney test. According to the results of this test, the pain during pulpotomy was significantly lower in the articaine group (p < 0.001). Articaine buccal infiltration can be employed for pulpotomy treatment in primary mandibular second molars. This research will eliminate block injection of lidocaine in children and utilize infiltration of articaine for pulpotomy treatment of mandibular teeth, hence preventing lingual nerve damage and prolonging paresthesia of IAN, lip, and cheek bite due to IAN block anesthesia.


Using average cost methods to estimate encounter-level costs for medical-surgical stays in the VA.
The U.S. Department of Veterans Affairs (VA) maintains discharge abstracts, but these do not include cost information. This article describes the methods the authors used to estimate the costs of VA medical-surgical hospitalizations in fiscal years 1998 to 2000. They estimated a cost regression with 1996 Medicare data restricted to veterans receiving VA care in an earlier year. The regression accounted for approximately 74 percent of the variance in cost-adjusted charges, and it proved to be robust to outliers and the year of input data. The beta coefficients from the cost regression were used to impute costs of VA medical-surgical hospital discharges. The estimated aggregate costs were reconciled with VA budget allocations. In addition to the direct medical costs, their cost estimates include indirect costs and physician services; both of these were allocated in proportion to direct costs. They discuss the method's limitations and application in other health care systems.


Patterns of pancreatic resection differ between patients with familial and sporadic pancreatic cancer.
Although the increased risk of developing pancreatic cancer (PC) in families with a strong history of the disease is well known, characteristics and outcomes of patients with familial PC is not described well. This study aims to evaluate outcomes following resection in patients with familial PC. We studied 208 patients who underwent resection of PC from 2000 to 2007 and had prospectively completed family history questionnaires for the Biospecimen Resource for Pancreas Research at our institution. We compared clinical characteristics and outcomes of familial and sporadic PC patients. Familial (N = 15) and sporadic PC patients (N = 193) did not have significantly different demographics, pre-operative CA19-9, pre-operative weight loss, R0 status, or T-staging (all p ≥ 0.05). Familial PC patients had lower pre-operative total serum bilirubin concentrations (p = 0.03) and lesions outside of the pancreatic head more frequently (p = 0.02) than sporadic PC patients. There was no difference in survival at 2 years between familial and sporadic PC patients (p = 0.52). Familial PC patients appear to develop tumors outside of the pancreatic head more frequently than sporadic PC patients. This difference in tumor distribution may be due to a broader area of cancer susceptibility within the pancreas for familial PC patients.


Factors affecting phosphorus and calcium digestibility in diets for growing-finishing pigs.
In two experiments, we investigated various factors that affect the estimation of the apparent total tract digestibility (ATTD) of DM, Ca, and total P in diets for growing-finishing pigs. In Exp. 1, the effects of age, housing, and calculation method (indicator [Cr2O3] vs 10-d total collection) were determined. Eighteen barrows and gilts (40 to 95 kg BW) were housed in six pens, and ATTD was estimated using the indicator method. Twelve barrows were housed in metabolic crates, and ATTD was estimated using both calculation methods. Dietary treatments were 1) a tapioca-soybean-barley-based diet, 2) Diet 1 supplemented with 400 FTU microbial phytase/kg of diet, and 3) a corn-soybean meal-based diet: In Exp. 2, six barrows (95 to 120 kg BW) were fed a phytase-deficient diet to investigate the effects of coprophagy (40 g fresh feces/kg of diet) and movement. Pigs were fed at 2.8 times maintenance requirement (418 kJ ME/BW.75); water supply was 2.5 L/kg of feed. The ATTD increased as BW increased. Phytase enhanced total P ATTD by an average of 18.1 percentage units. The ATTD of DM was higher and the ATTD of Ca and total P (P < .001) were lower in pigs housed in pens than in pigs housed in metabolic crates. Fecal consumption and movement led to numerical increases in Ca (P = .217) and total P (P = .103) ATTD. Estimates of Ca and total P ATTD using pigs in metabolic crates are lower than estimates in practice.


Amphiphilic porphyrins for second harmonic generation imaging.
Amphiphilic donor-acceptor meso-ethynyl porphyrins with polar pyridinium electron-acceptor head groups and hydrophobic dialkyl-aniline electron donors have high molecular hyperpolarizabilities (as measured by hyper-Rayleigh scattering) and high affinities for biological membranes. When bound to water droplets in dodecane, or to the plasma membranes of living cells, they can be used for second harmonic generation (SHG) microscopy; an incident light of wavelength 840 nm generates a strong frequency-doubled signal at 420 nm. Copper(II) and nickel(II) porphyrin complexes give similar SHG signals to those of the free-base porphyrins, while exhibiting no detectable two-photon excited fluorescence.


Controversies in the treatment of cancer of the breast.
There are many important controversial areas in the management of breast cancer. This chapter focuses on adjuvant hormonal and chemotherapy for early-stage breast cancer. Standard care for node-positive premenopausal women is chemotherapy. However, there are still unanswered questions revolving around the administration of the treatment such as optimal timing, treatment duration, specific drugs, and dose intensity. Also, the questions of adjuvant chemotherapy for postmenopausal women, adjuvant endocrine therapy, and therapy for node-negative women are reviewed.


Internet of Unmanned Aerial Vehicles: QoS Provisioning in Aerial Ad-Hoc Networks.
Aerial ad-hoc networks have the potential to enable smart services while maintaining communication between the ground system and unmanned aerial vehicles (UAV). Previous research has focused on enabling aerial data-centric smart services while integrating the benefits of aerial objects such as UAVs in hostile and non-hostile environments. Quality of service (QoS) provisioning in UAV-assisted communication is a challenging research theme in aerial ad-hoc networks environments. Literature on aerial ad hoc networks lacks cooperative service-oriented modeling for distributed network environments, relying on costly static base station-oriented centralized network environments. Towards this end, this paper proposes a quality of service provisioning framework for a UAV-assisted aerial ad hoc network environment (QSPU) focusing on reliable aerial communication. The UAV's aerial mobility and service parameters are modelled considering highly dynamic aerial ad-hoc environments. UAV-centric mobility models are utilized to develop a complete aerial routing framework. A comparative performance evaluation demonstrates the benefits of the proposed aerial communication framework. It is evident that QSPU outperforms the state-of-the-art techniques in terms of a number of service-oriented performance metrics in a UAV-assisted aerial ad-hoc network environment.


Cultural adaptation in HPV vaccine intervention among racial and ethical minority population: a systematic literature review.
Racial and ethnic minorities in the United States face higher risks of human papillomavirus (HPV) and are less likely to benefit from HPV vaccines. Effective HPV vaccine promotion efforts need to acknowledge and adapt to the cultural characteristics of these minority groups. This systematic review examines and evaluates the cultural adaptations in the HPV vaccine intervention studies conducted in racial and ethnic minority communities in the United States. We searched five databases and identified 26 peer-reviewed English-language journal articles published between 2010 and 2019. These articles were analyzed using Healey et al.'s (2017) cultural adaptation framework for community health interventions. Almost all of these interventions involved some cultural adaptation. However, there is a lack of use of theories in guiding intervention design, lack of systematic, planned cultural adaptations and insufficient in-depth understanding of the targeted population's cultural characteristics associated with their HPV-related attitudes, beliefs and behaviors. Future intervention studies should identify specific cultural characteristics related to vaccine attitudes and behaviors to create more targeted cultural adaptations in HPV vaccine promotion.


Bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF induce oxidative stress and biomacromolecular damage in human granulosa KGN cells.
Bisphenol A (BPA) is gradually being replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), due to its toxic, endocrine disrupting and possible carcinogenic effects. Although these bisphenols are widely used to produce a variety of everyday household items, the effects of BPA and its analogues on oxidative stress and cellular energy metabolism of the female reproductive system are still poorly understood. The aim of this study was to evaluate the oxidative stress, biomacromolecular damage and changes in calcium ion (Ca2+) levels induced by BPA and its substitutes on KGN cells, which are maintain physiological characteristics of ovarian granulosa cells. We have observed that BPA and BPAF significantly reduced the viability of KGN cells, while BPS and BPF exhibited a slight toxic effect on the cells. The levels of intracellular ROS production and antioxidant capacity were significantly increased and decreased, respectively, in KGN cells after treatment with high concentrations of BPA and its analogues. In addition, we found that the damage to biomacromolecules, which are the main targets of oxidative stress was significantly increased after treatment with BPA, BPS, BPF, and BPAF. The intracellular Ca2+ levels in KGN cells were significantly increased after exposure to high concentrations of BPA and BPAF, respectively. These results suggest that BPA and its analogues may play different roles in regulating the biologic functions of granulosa cells and the process of ovarian follicular development.


Effects of dietary proteins on the intestinal synthesis and transport of cholesterol and apolipoprotein A-I in rats.
Feeding a low-fat diet free of cholesterol to rats resulted in a low level of serum cholesterol and apolipoprotein A-1 (apoA-I) when dietary protein was soybean protein as compared to casein. Since the small intestine is an important synthetic site for lipoproteins, the effects of dietary protein sources on the intestinal synthesis in vitro of cholesterol and apoA-I and the concentration of these components in the mesenteric lymph were studied. In rats fed a 1% fat diet, the apoA-I concentration in the lymph and the de novo synthesis of apoA-I in the small intestine segment were both low for animals fed a soybean protein diet as compared to a casein diet. The intestinal hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity was high in animals fed soybean protein, whereas the lymph cholesterol level was comparable. Even in rats fed a 5% fat diet, concentrations of serum cholesterol and apoA-I and lymphatic apoA-I were again significantly low for rats fed vegetable protein. These results indicate that the intestine plays an important role in the dietary protein-dependent regulation of serum cholesterol and apoA-I levels.


Transcriptomic Variation of Amphiprion Percula (Lacepède, 1802) in Response to Infection with Cryptocaryon Irritans Brown, 1951.
Cryptocaryon irritans (Brown 1951) frequently infect the Pomacentridae fishes causing severe economic losses. However, the anti-C. irritans' molecular mechanism in these fishes remains largely unknown. To address this issue, we conducted RNA-Seq for C. irrtians-infected gills of the clownfish Amphiprion percula (Lacepède 1802) at the early (day 1) and late (day 3) stages of infection. A total of 1655 differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs showed a vast genetic variation related to the following aspects: ECM-receptor interaction, P13K-Akt signalling, cytokine-cytokine receptor interaction, and endocytosis. During the early phase of infection, key genes involved in ATP production, energy homeostasis, and stress control were abruptly increased. In the late phase, however, acute response molecules of the peripheral nervous system (synaptic transmission and local immunity), metabolic system triggering glycogen synthesis, energy maintenance, and osmoregulation were found to be critical. The highest number of upregulated genes (URGs) recovered during the early phase was included under the 'biological process' category, which primarily functions as response to stimuli, signalling, and biological regulation. In the late phase, most of the URGs were related to gene regulation and immune system processes under 'molecular function' category. The immune-related URGs of early infection include major histocompatibility complex (MHC) class-II molecules apparently triggering CD4+ T-cell-activated Th responses, and that of late infection include MHC class-1 molecules for the possible culmination of CD8+ T-cell triggered cytotoxicity. The high level of genic single nucleotide polymorphisms (SNPs) identified during the late phase of infection is likely to influence their susceptibility to secondary infection. In summary, the identified DEGs and their related metabolic and immune-related pathways and the SNPs may provide new insights into coordinating the immunological events and improving resistance in Pomacentridae fishes against C. irritans.


Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine.
The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. A total of 351 healthy subjects were primed with PHiD-CV at either 3 and 5 or 3, 4 and 5 months of age followed in all subjects by a booster dose at 11 to 12 months of age. Serotype-specific pneumococcal responses were measured by 22F-inhibition ELISA and opsonophagocytic assays 1 month following primary and booster vaccinations. Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77.6%, respectively). Opsonophagocytic activity (OPA) could be measured in 74.4% to 100% and 88.9% to 100% of the subjects after the 2-dose or 3-dose priming, respectively, except for serotype 1 (60.8% and 62.9%, respectively). In both groups, robust increases in ELISA antibodies and OPA titers were observed for all serotypes after the booster dose. Higher postprimary and postbooster ELISA antibody levels and OPA titers were observed for most serotypes following the 3+1 schedule. PHiD-CV was immunogenic in both schedules, but further effectiveness data are needed to fully understand the public health benefit to be expected from these schedules in terms of prevention against invasive and mucosal infections.


The fine structure and immunological labeling of the achromatic mitotic apparatus after disruption of cell membranes.
After treatment of HeLa and L cells with vinblastine sulfate the material of microtubules (tubulin) was reorganized into (a) large paracrystals (PC) of tightly packed tubules; (b) smaller aggregates of tubules with greater diameter whose walls are constituted from well defined, helically arranged morphological subunits; and (c) microtubules associated with helices of polyribosomes of uniform size. All of these structures survived disruption of cellular membranes by means of a nonionic detergent. Following a thorough stripping of membranes there remained a subcellular fraction sedimenting at 1,500 g for 15 min, in which were contained nuclei, centrioles, and the above mentioned microtubular elements, maintained as a complex of organelles by an interconnecting network of 80 A microfibrils. As a result of membrane disruption it was possible to localize precisely in the electron microscope the binding of ferritin antibody conjugates. Specific labeling at the surface of PC and microtubule aggregates could be demonstrated. This result was substantiated by means of the immunoperoxidase method of labeling the PC. A concentrated deposit of ferritin was also found in the vicinity of centrioles and related structures, the annuli of the nuclear pore complex and the annulate lamellae. However, the specificity of the label on these organelles remains questionable because ferritin, albeit in lower concentration, was also present on them in control preparations reacted with preimmune sera.


Mixed-method estimation of population-level HIV viral suppression rate in the Western Cape, South Africa.
There are few population-wide data on viral suppression (VS) that can be used to monitor programmatic targets in sub-Saharan Africa. We describe how routinely collected viral load (VL) data from antiretroviral therapy (ART) programmes can be extrapolated to estimate population VS and validate this using a combination of empiric and model-based estimates. VL test results from were matched using a record linkage algorithm to obtain linked results for individuals. Test-level and individual-level VS rates were based on test VL values <1000 cps/mL, and individual VL <1000 cps/mL in a calendar year, respectively. We calculated population VS among people living with HIV (PLWH) in the province by combining census-derived midyear population estimates, HIV prevalence estimates and individual level VS estimates from routine VL data. Approximately 1.9 million VL test results between 2008 and 2018 were analysed. Among individuals in care, VS increased from 85.5% in 2008 to 90% in 2018. Population VS among all PLWH in the province increased from 12.2% in 2008 to 51.0% in 2017. The estimates derived from this method are comparable to those from other published studies. Sensitivity analyses showed that the results are robust to variations in linkage method, but sensitive to the extreme combinations of assumed VL testing coverage and population HIV prevalence. While validation of this method in other settings is required, this approach provides a simple, robust method for estimating population VS using routine data from ART services that can be employed by national programmes in high-burden settings.


What is the role of the central nervous system in mineralocorticoid hypertension?
The importance of the central nervous system (CNS) in the development of mineralocorticoid hypertension has been well documented. Type I receptors in adrenalectomized rats are concentrated in the hippocampus, amygdala, lateral septum, and hypothalamus, particularly in the periventricular regions, areas known to be or suspected of being important in the regulation of ACTH release, arousal, fluid and fluid osmolality equilibrium, and the maintenance of normal blood pressure. In the rat, ablation of the AV3V area and central, but not peripheral, sympathectomy prevent the development of DOCA-salt hypertension. The continuous intracerebroventricular (icv) infusion of aldosterone in rats or dogs at doses which do not affect the blood pressure when administered subcutaneously (sc) produces significant increases in resting blood pressure. In rats this effect is dose dependent, blocked by the concomitant icv infusion of prorenone, an aldosterone antagonist, and enhanced, but not completely dependent upon renal mass reduction and excess salt consumption. The icv infusion of RU28318, a selective mineralocorticoid antagonist, at doses which are ineffective when administered sc, inhibits the development of hypertension produced by the sc infusion of aldosterone or deoxycorticosterone, as well as that produced by the oral administration of a licorice derivative and of a high salt diet in the Dahl S/JR rat. It is assumed that this effect is mediated through the mineralocorticoid receptor because it is inhibited by mineralocorticoid antagonists and because the icv infusion of RU26988, a selective glucocorticoid agonist, has no effect. The concomitant icv infusion of corticosterone, which is thought to be the primary ligand of the brain mineralocorticoid receptor, antagonizes the effect of icv infusion of aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)


The function of PML in p53-dependent apoptosis.
The PML gene of acute promyelocytic leukaemia (APL) encodes a growth- and tumour-suppresor protein that is essential for several apoptotic signals. The mechanisms by which PML exerts its pro-apoptotic function are still unknown. Here we show that PML acts as a transcriptional co-activator with p53. PML physically interacts with p53 both in vitro and in vivo and co-localizes with p53 in the PML nuclear body (PML-NB). The co-activatory role of PML depends on its ability to localize in the PML-NB. p53-dependent, DNA-damage-induced apoptosis, transcriptional activation by p53, the DNA-binding ability of p53, and the induction of p53 target genes such as Bax and p21 upon gamma-irradiation are all impaired in PML-/- primary cells. These results define a new PML-dependent, p53-regulatory pathway for apoptosis and shed new light on the function of PML in tumour suppression.


Kinesin-related KIP3 of Saccharomyces cerevisiae is required for a distinct step in nuclear migration.
Spindle orientation and nuclear migration are crucial events in cell growth and differentiation of many eukaryotes. Here we show that KIP3, the sixth and final kinesin-related gene in Saccharomyces cerevisiae, is required for migration of the nucleus to the bud site in preparation for mitosis. The position of the nucleus in the cell and the orientation of the mitotic spindle was examined by microscopy of fixed cells and by time-lapse microscopy of individual live cells. Mutations in KIP3 and in the dynein heavy chain gene defined two distinct phases of nuclear migration: a KIP3-dependent movement of the nucleus toward the incipient bud site and a dynein-dependent translocation of the nucleus through the bud neck during anaphase. Loss of KIP3 function disrupts the unidirectional movement of the nucleus toward the bud and mitotic spindle orientation, causing large oscillations in nuclear position. The oscillatory motions sometimes brought the nucleus in close proximity to the bud neck, possibly accounting for the viability of a kip3 null mutant. The kip3 null mutant exhibits normal translocation of the nucleus through the neck and normal spindle pole separation kinetics during anaphase. Simultaneous loss of KIP3 and kinesin-related KAR3 function, or of KIP3 and dynein function, is lethal but does not block any additional detectable movement. This suggests that the lethality is due to the combination of sequential and possibly overlapping defects. Epitope-tagged Kip3p localizes to astral and central spindle microtubules and is also present throughout the cytoplasm and nucleus.


Molecular modeling studies of the DNA-topoisomerase I ternary cleavable complex with camptothecin.
The present studies provide a three-dimensional model for the postulated ternary cleavable complex of topoisomerase I (top1), DNA, and camptothecin (CPT). Molecular simulations were done using the AMBER force field. The results suggest that a ternary cleavable complex might be stabilized by several hydrogen bonds in the binding site. In this proposed "drug-stacking" model, CPT is pseudointercalated in the top1-linked DNA cleavage site and interacts with the protein near its catalytic tyrosine through hydrogen bonding and stacking. The structural model is consistent with the following experimental observations: (i) the N3 position of the 5' terminal purine of the cleaved DNA strand is readily alkylated by 7-chloromethyl 10,11-methylenedioxy CPT; (ii) CPT generally tolerates substituents at positions 7, 9, and 10 but is inactivated by additions at position 12; (iii) 10,11-methylenedioxy (MDO) CPT is much more potent than 10,11-dimethoxy (DMO) CPT; (iv) the lactone portion of CPT is essential for top1 inhibitory activity; (v) 20S derivatives of CPT are much more potent than the 20R analogues; (vi) a catalytic tyrosine hydroxyl in top1 covalently links to the 3' terminal base, T, of the cleaved DNA strand; and (vii) top1 mutation Asn722Ser leads to CPT resistance. A total of 18 camptothecin derivatives with different DNA cleavage potencies were docked into the hypothetical cleavable complex binding site to test and refine the model. These studies provide insight into a possible mechanism of top1 inhibition by CPT derivatives and suggest rational approaches for the design of new CPT derivatives.


Evaluating the decision accuracy and speed of clinical data visualizations.
Clinicians face an increasing volume of biomedical data. Assessing the efficacy of systems that enable accurate and timely clinical decision making merits corresponding attention. This paper discusses the multiple-reader multiple-case (MRMC) experimental design and linear mixed models as means of assessing and comparing decision accuracy and latency (time) for decision tasks in which clinician readers must interpret visual displays of data. These tools can assess and compare decision accuracy and latency (time). These experimental and statistical techniques, used extensively in radiology imaging studies, offer a number of practical and analytic advantages over more traditional quantitative methods such as percent-correct measurements and ANOVAs, and are recommended for their statistical efficiency and generalizability. An example analysis using readily available, free, and commercial statistical software is provided as an appendix. While these techniques are not appropriate for all evaluation questions, they can provide a valuable addition to the evaluative toolkit of medical informatics research.


Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.
A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively). These findings are important for the development of an accurate system for interpretation of INSTI resistance and the rational design of next-generation INSTIs.


First-principles calculations of angle-resolved and spin-resolved photoemission spectra of Cr(110) surfaces at the 2p-3d Cr resonance.
A first principles approach for spin- and angle-resolved resonant photoemission is developed within multiple scattering theory and applied to a Cr(110) surface at the 2p-3d resonance. The resonant photocurrent from this nonferromagnetic system is found to be strongly spin polarized by circularly polarized light, in agreement with experiments on antiferromagnetic and magnetically disordered systems. By comparing the antiferromagnetic and Pauli-paramagnetic phases of Cr, we explicitly show that the spin polarization of the photocurrent is independent of the existence of local magnetic moments, solving a long-standing debate on the origin of such polarization. New spin polarization effects are predicted for the paramagnetic phase even with unpolarized light, opening new directions for full mapping of spin interactions in macroscopically nonmagnetic or nanostructured systems.


Developing a communitywide electronic health record disease registry in primary care practices: lessons learned from the Western new york beacon community.
Disease registries, as part of electronic health records (EHRs), have shown promise in improving care and outcomes. However, little is known about how best to implement them across communities, especially in communities that are not highly integrated. The Western New York (WNY) primary care community consists largely of independent practices using at least 20 different EHR products. This paper discusses the processes undertaken to develop a communitywide EHR disease registry in WNY, improvements it engendered, barriers overcome, and the lessons learned. HEALTHeLINK, under the Office of the National Coordinator for Health Information Technology Beacon Community Initiative, reached out to 98 primary care practices in the WNY region to establish EHR-based diabetes registries. Working with practices, community partners, and vendors, registry specifications were created. The registry was piloted with practices using one local vendor's EHR product and then rolled out to other practices, including five other EHR products. Using identified and de-identified registry datasets, quality benchmarking within and between practices and population health management were undertaken. From 2011 to 2013, the WNY Beacon Community assisted 98 practices (344 providers) serving over 50,000 adult diabetic patients. A major focus was on EHR registry development across diverse systems, and overcoming the challenges this presented. The Beacon diabetes registry was implemented at 85 of the 98 targeted practices. Of these registries, 65 met the criteria described in a later section for quality benchmarking and population health management purposes. Practices received quarterly benchmark reports summarizing their performance on key diabetes quality metrics and were compared to community practice averages. Practices used their registries for population health management by identifying and targeting patients in need of follow-up or specific diabetes-related care. The creation of the registry infrastructure required unified registry technical specifications as well as close collaboration between all parties involved. The WNY experience showed that a useful disease registry can be established in a community largely consisting of numerous disparate primary care practices. This laid the groundwork for the future use of EHR data for a variety of purposes in the community. The methods used and lessons learned through this endeavor may benefit other communities in a similar position, with several disconnected EHRs, to establish unified registries.


Repeated open endotracheal suctioning causes gradual desaturation but does not exacerbate lung injury compared to closed endotracheal suctioning in a rabbit model of ARDS.
Although endotracheal suctioning induces alveolar derecruitment during mechanical ventilation, it is not clear whether repeated endotracheal suctioning exacerbates lung injuries. The present study aimed to determine whether repeated open endotracheal suctioning (OS) exacerbates lung injury compared to closed endotracheal suctioning (CS) during mechanical ventilation in an animal model of acute respiratory distress syndrome (ARDS). Briefly, thirty six Japanese white rabbits were initially ventilated in pressure-controlled mode with a constant tidal volume (6 mL/kg). Then, lung injury was induced by repeated saline lavage. The rabbits were divided into four groups, namely: a) OS; b) CS; c) control with ARDS only; d) and healthy control (HC) without ARDS. Animals in all the groups were then ventilated with positive end expiratory pressure (PEEP) at 10 cm H2O. CS was performed using 6 French-closed suctioning catheters connected to endotracheal tube under the following conditions: a) a suctioning time and pressure of 10 sec and 140 mm Hg, respectively; and b) a suction depth of 2 cm (length of adapter) plus tracheal tube. OS was performed using the same conditions described for CS, except the ventilator was disconnected from the animals. Each endotracheal suctioning was performed at an interval of 30 min. PaO2/FIO2 (P/F) ratio for CS, control and HC groups remained at >400 for 6 hours, whereas that of the OS group progressively declined to 300 (p < 0.05), with each suctioning. However, no difference was observed either in lung injury score (histology) or in the expression pattern of inflammatory cytokines (tumor necrosis factor-α and interleukin-6) after 6 hours between the OS and CS groups in the circulatory as well as the pulmonary tissues. Progressive arterial desaturation under conditions of repeated endotracheal suctioning is greater in OS than in CS time-dependently. However, OS does not exacerbate lung injury during mechanical ventilation when observed over a longer time span (6 hours) of repeated endotracheal suctioning, based on morphological and molecular analysis.


Cellular pathogenesis of Duchenne muscular dystrophy: progressive myofibre degeneration, chronic inflammation, reactive myofibrosis and satellite cell dysfunction.
Duchenne muscular dystrophy is a highly progressive muscle wasting disease of early childhood and characterized by complex pathophysiological and histopathological changes in the voluntary contractile system, including myonecrosis, chronic inflammation, fat substitution and reactive myofibrosis. The continued loss of functional myofibres and replacement with non-contractile cells, as well as extensive tissue scarring and decline in tissue elasticity, leads to severe skeletal muscle weakness. In addition, dystrophic muscles exhibit a greatly diminished regenerative capacity to counteract the ongoing process of fibre degeneration. In normal muscle tissues, an abundant stem cell pool consisting of satellite cells that are localized between the sarcolemma and basal lamina, provides a rich source for the production of activated myogenic progenitor cells that are involved in efficient myofibre repair and tissue regeneration. Interestingly, the self-renewal of satellite cells for maintaining an essential pool of stem cells in matured skeletal muscles is increased in dystrophin-deficient fibres. However, satellite cell hyperplasia does not result in efficient recovery of dystrophic muscles due to impaired asymmetric cell divisions. The lack of expression of the full-length dystrophin isoform Dp427-M, which is due to primary defects in the DMD gene, appears to affect key regulators of satellite cell polarity causing a reduced differentiation of myogenic progenitors, which are essential for myofibre regeneration. This review outlines the complexity of dystrophinopathy and describes the importance of the pathophysiological role of satellite cell dysfunction. A brief discussion of the bioanalytical usefulness of single cell proteomics for future studies of satellite cell biology is provided.