Applying wet sieving fecal particle size measurement to frugivores: A case study of the eastern chimpanzee (Pan troglodytes schweinfurthii).
Fecal particle size (FPS) as quantified by wet sieving analysis is a measure of chewing efficiency relevant for the understanding of physiological adaptations and constraints in herbivores. FPS has not been investigated systematically in frugivores, and important methodological problems remain. In particular, food items that are not chewed may skew estimates of FPS. We address such methodological issues and also assess the influence of diet type and age on FPS in wild chimpanzees. About 130 fecal samples of 38 individual chimpanzees (aged from 1.3 to ∼55 years) from the Kanyawara community of Kibale National Park (Uganda) were collected during three fruit seasons and analyzed using standardized wet sieves (pores from 16 to 0.025 mm). The effects of using different sieve series and excluding large seeds were investigated. We also assessed the relationship between FPS and sex, age, and fruit season. The treatment of seeds during the sieving process had a large influence on the results. FPS was not influenced by chimpanzee sex or age, but was smaller during a fig season (0.88 ± 0.31 mm) than during two drupe-fruit seasons (1.68 ± 0.37 mm) (0.025-4 mm sieves, excluding seeds). The absence of an age effect on FPS suggests that dental senescence might be less critical in chimpanzees, or in frugivores in general, than in folivorous herbivores. To increase the value of FPS studies for understanding frugivore and hominoid dietary evolution we propose modifications to prior herbivore protocols.


On the power for linkage detection using a test based on scan statistics.
We analyze some aspects of scan statistics, which have been proposed to help for the detection of weak signals in genetic linkage analysis. We derive approximate expressions for the power of a test based on moving averages of the identity by descent allele sharing proportions for pairs of relatives at several contiguous markers. We confirm these approximate formulae by simulation. The results show that when there is a single trait-locus on a chromosome, the test based on the scan statistic is slightly less powerful than that based on the customary allele sharing statistic. On the other hand, if two genes having a moderate effect on a trait lie close to each other on the same chromosome, scan statistics improve power to detect linkage.


Feigning in adjudicative competence evaluations.
Competence to stand trial (adjudicative competence) is the most requested forensic psychiatric evaluation, with an estimated 60,000 referrals annually. The challenge of detecting feigned incompetence has not been systematically studied until the past decade. Estimates of feigned adjudicative incompetence vary from 8 to 21%. This article reviews techniques for detecting malingered psychosis and malingered cognitive impairment during competence evaluations. Specific techniques for assessing feigned adjudicative incompetence and estimating the malingerer's genuine abilities are discussed. A stepwise approach to suspected feigned adjudicative incompetence is proffered.


Baseline and annual repeat rounds of screening: implications for optimal regimens of screening.
Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. • Lung cancer aggressiveness varies considerably by cell type and nodule consistency. • Kaplan-Meier survival rates varied by cell type between 100% and 48%. • The percentages of lung cancers by cell type in screening rounds reflect screening biases. • Rank ordering by cell type survival is consistent with that by lead times. • Empirical evidence provides critical information for the regimen of screening.


Genomic profiling of multiple primary cancers including synchronous lung adenocarcinoma and bilateral malignant mesotheliomas: Identification of a novel BAP1 germline variant.
We report a case with a rare combination of synchronous lung adenocarcinoma and bilateral malignant pleural mesotheliomas in a 70-year-old male without asbestos exposure. He metachronously developed peritoneal malignant mesothelioma, intrahepatic cholangiocarcinoma, urothelial carcinoma of the bladder and prostatic adenocarcinoma. Immunohistochemistry revealed complete loss of BAP1 expression in all seven lesions. Targeted next generation sequencing using Todai OncoPanel identified a novel germline variant (c.1565_1566del, p.P522Rfs*14) of BAP1. Additionally, different nonsynonymous somatic mutations of BAP1 were identified in four lesions including lung adenocarcinoma, malignant pleural and peritoneal mesotheliomas, and bladder cancer. The remaining two lesions had different somatic mutations in genes other than BAP1. Multiple BAP1-deficient cancers that developed in a single patient suggest the newly identified germline variant of BAP1 gene to be pathogenic and this case expands the clinical spectrum of BAP1-tumor predisposition syndrome. Screening for BAP1 status is highly recommended in cases with a similar combination of cancers.


Discriminating the ecotoxicity due to metals and to low pH in acid mine drainage.
Several techniques have been developed to assess the ecotoxicity of contaminated watercourses. Most of these techniques involve chemical alterations of water samples, by diluting it or by adding chelating agents. These changes become particularly severe when assessing the toxicity of samples with very low pH and with high quantities of contaminants. Trying to overcome this problem, a novel toxicity test, specific for acid waters, was previously developed and field validated. The toxicity of acid samples is assessed using the survival time of Ceriodaphnia dubia. During this study, the novel test was applied to a field situation, where an aquatic system is seriously impacted with acid mine drainage. Its efficiency was tested and compared with two classical toxicity tests: the Microtox and the median lethal dilution with C. dubia. The survival time test was performed without adjusting pH and after adjusting pH to a fixed value (pH 2, 3, and 4). At pH 2 and 4 no acceptable results were obtained; at pH 3 it was possible to distinguish the toxicity due to pH from the toxicity due to other toxicants. The test conducted at local pH was able to discriminate toxicity sources only for highly contaminated samples. The toxicity evaluation of acid mine drainage samples was possible neither with the median lethal dilution test nor with Microtox.


Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-dependent pathway in non-small cell lung cancer cells.
Amphiregulin (AR) and insulin-like growth factor-1 (IGF1) are growth factors known to promote non-small cell lung cancer (NSCLC) survival. We have previously published that 1) AR and IGF1, secreted by H358 NSCLC cells, cooperate to protect those cells and H322 NSCLC cells from serum-starved apoptosis; 2) H358 cells resist Bax-induced apoptosis through an inhibition of Bax conformational change. We show here that the antiapoptotic activity of the AR/IGF1 combination is specifically abolished by the PKC inhibitors calphostin C and staurosporine, but not by the MAPK and phosphatidylinositol 3-kinase inhibitors PD98059 and wortmannin, suggesting the involvement of a PKC-dependent and MAPK- and phosphatidylinositol 3-kinase-independent survival pathway. The PKCdelta inhibitor rottlerin restores apoptosis induced by serum deprivation. In addition, phosphorylation of PKCdelta and PKCzeta/lambda, but not of PKCalpha/beta(II), increases in serum-starved H358 cells and in H322 cells treated with an AR/IGF1 combination and is blocked by calphostin C. The combination of AR and IGF1 increases p90(rsk) and Bad phosphorylation as well as inhibiting the conformational change of Bax by a PKC-dependent mechanism. Finally, PKCdelta, PKCzeta, or p90(rsk) small interfering RNAs block the antiapoptotic activity of AR/IGF1 combination but have no effect on partial apoptosis inhibition observed with each factor used alone. Constitutively active PKC expression inhibits serum deprivation-induced apoptosis, whereas a catalytically inactive form of p90(rsk) restores it. Thus, AR and IGF1 cooperate to prevent apoptosis by activating a specific PKC-p90(rsk)-dependent pathway, which leads to Bad and Bax inactivation. This signaling pathway is different to that used by single factor.


Spitz nevi in the classic histopathological pattern--lamb in wolf`s clothing.
Spitz nevus is a benign melanocytic lesion and also one of the main differential diagnosis of melanoma. A descriptive and retrospective study of surgical specimens from patients with a diagnosis of Spitz nevus was conducted at two institutions in Niterói - RJ. 32 cases were analyzed. The most frequent histological subtype was compound (60 %), with a predominance of epithelioid cells (17 cases - 53%). Pagetoid spread was observed in 21 cases (68%). Maturation of melanocytes was present in 13 cases (81%). Kamino bodies were found in eight cases (25%). Atypical melanocytes were present in 18 cases (56%). Mitoses were present in 11 cases (34%). Detailed knowledge of the classical form of Spitz nevi is essential for the differential diagnosis with melanoma. However, no single criterium is definitive in the differential diagnosis between Spitz nevus and melanoma.


Target gene-specific regulation of androgen receptor activity by p42/p44 mitogen-activated protein kinase.
Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapies, highlights the need to find alternate means to block AR activity. AR, a hormone-activated transcription factor, and its coactivators are phosphoproteins. Thus, we sought to determine whether inhibition of specific cell signaling pathways would reduce AR function. We found that short-term inhibition of p42/p44 MAPK activity either by a MAPK kinase inhibitor, U0126, or by depletion of kinase with small interfering RNA caused target gene-specific reductions in AR activity. AR enhances histone H3 acetylation of target genes that are sensitive to U0126 including prostate-specific antigen and TMPRSS2, but does not increase histone H3 acetylation of the U0126-resistant PMEPA1 gene. Thus, although AR induces transcription of many target genes, the molecular changes induced by AR at the chromatin level are target gene specific. Long-term treatment (24-48 h) with U0126 causes a G1 cell cycle arrest and reduces AR expression both through a decrease in AR mRNA and a reduction in AR protein stability. Thus, treatments that reduce p42/p44 MAPK activity in prostate cancer have the potential to reduce AR activity through a reduction in expression levels as well as by target gene-selective inhibition of AR function.


Heterogeneity of Loss Aversion in Pathological Gambling.
Pathological gambling (PG) is characterized by continual repeated gambling behavior despite negative consequences. PG is considered to be a disorder of altered decision-making under risk, and behavioral economics tools were utilized by studies on decision-making under risk. At the same time, PG was suggested to be a heterogeneous disorder in terms of personality traits as well as risk attitude. We aimed to examine the heterogeneity of PG in terms of loss aversion, which means that a loss is subjectively felt to be larger than the same amount of gain. Thirty-one male PG subjects and 26 male healthy control (HC) subjects underwent a behavioral economics task for estimation of loss aversion and personality traits assessment. Although loss aversion in PG subjects was not significantly different from that in HC subjects, distributions of loss aversion differed between PG and HC subjects. HC subjects were uniformly classified into three levels (low, middle, high) of loss aversion, whereas PG subjects were mostly classified into the two extremes, and few PG subjects were classified into the middle range. PG subjects with low and high loss aversion showed a significant difference in anxiety, excitement-seeking and craving intensity. Our study suggested that PG was a heterogeneous disorder in terms of loss aversion. This result might be useful for understanding cognitive and neurobiological mechanisms and the establishment of treatment strategies for PG.


Pulsatile Flow-Induced Fatigue-Resistant Photopolymerizable Hydrogels for the Treatment of Intracranial Aneurysms.
An alternative intracranial aneurysm embolic agent is emerging in the form of hydrogels due to their ability to be injected in liquid phase and solidify in situ. Hydrogels have the ability to fill an aneurysm sac more completely compared to solid implants such as those used in coil embolization. Recently, the feasibility to implement photopolymerizable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogels in vitro has been demonstrated for aneurysm application. Nonetheless, the physical and mechanical properties of such hydrogels require further characterization to evaluate their long-term integrity and stability to avoid implant compaction and aneurysm recurrence over time. To that end, molecular weight and polymer content of the hydrogels were tuned to match the elastic modulus and compliance of aneurysmal tissue while minimizing the swelling volume and pressure. The hydrogel precursor was injected and photopolymerized in an in vitro aneurysm model, designed by casting polydimethylsiloxane (PDMS) around 3D printed water-soluble sacrificial molds. The hydrogels were then exposed to a fatigue test under physiological pulsatile flow, inducing a combination of circumferential and shear stresses. The hydrogels withstood 5.5 million cycles and no significant weight loss of the implant was observed nor did the polymerized hydrogel protrude or migrate into the parent artery. Slight surface erosion defects of 2-10 μm in depth were observed after loading compared to 2 μm maximum for non-loaded hydrogels. These results show that our fine-tuned photopolymerized hydrogel is expected to withstand the physiological conditions of an in vivo implant study.


Shared medical appointments for weight loss: a systematic review.
Shared medical appointments (SMAs) may help mitigate some of the barriers for managing obesity in primary care. The primary aim of this systematic review was to measure the effect of weight loss SMAs. Systematic searches using keywords and Medical Subject Headings for overweight, obesity, and SMAs were conducted in the CENTRAL, Medline Complete, PsycINFO, Scopus, CINAHL, EMBASE, and Web of Science databases with no date limits. Risk of bias was assessed using the Effective Health Practice Project Quality Assessment Tool for Quantitative Studies. Fifteen studies involving weight loss SMAs in adults and children were identified. Six studies had controls. Inconsistency in reporting weight loss or weight change in controlled studies meant that data could not be pooled for meta-analysis. Results from individual studies indicated that SMAs can support adult patients to achieve significant weight loss. Women and older adults were more likely to take up SMA invitations. Results from the 5 studies involving children were less conclusive. Studies involving participants of a higher socioeconomic status tended to report lower attrition than studies involving participants who experienced disadvantage. These findings should be interpreted with caution as all but 1 included study was assessed as being weak in quality. Overall, SMAs may be of benefit to address obesity in primary care, particularly for women and older adults. Appropriately designed prospective and controlled studies are required to engage their target audience and to assess whether SMAs are superior to other weight loss options in primary care.


Central nervous system changes after radiation therapy and/or chemotherapy: correlation of CT and autopsy findings.
This is a restrospective correlative study of cranial computed tomography (CT) and autopsy findings in 50 patients after central nervous system radiation therapy and/or chemotherapy. Most patients had more than one posttherapy CT scan and all cases were autopsied. Twenty-six cases (52%) showed no posttherapy CT changes. In 18 cases (36%) enlargement of intracranial subarachnoid spaces and/or ventricles was seen on CT, but only two of these cases showed gross atrophy on postmortem examination; even in these, the cortex was histologically normal, suggesting that these CT changes may be reversible. In six cases a decrease in white-matter density was seen on CT. Two of these cases were histologically normal, two cases showed some white-matter rarefaction, one case contained multiple foci of white-matter and vessel well necrosis, and one case had progressive multifocal leukoencephalopathy.


Alkylsquarates as key intermediates for the rapid preparation of original drug-inspired compounds.
Many natural privileged scaffolds contain a basic nitrogen atom, which often is a key element of pharmacophore and a chemically reactive centre as well. In our ongoing research program devoted to the design of targeted libraries based on acidic templates, we developed methods to convert privileged basic compounds -like natural alkaloids or drugs into acidic compounds. This conversion led to a profound alteration of the pharmacophore, without changing the overall shape and lipophilicity of the molecule. We expect such modifications to generate unexpected biological activities. Recently, we focused on derivatives of squaric acid, a vinylogous carboxylic acid. Two series were studied. First we describe a new, selective parallel synthesis of squaramic acids from a dissymmetric diester (3-tert-butoxy-4-ethoxy-cyclobut-3-en-1,2-dione). This efficient procedure avoids the synthesis of the undesired squaramides. Secondly we describe a microplate parallel synthesis (15 micromol-scale) of squaric acid hydroxamate amides from a squaric hydroxamate ester.


Piercing of Consciousness as a Threshold-Crossing Operation.
Many decisions arise through an accumulation of evidence to a terminating threshold. The process, termed bounded evidence accumulation (or drift diffusion), provides a unified account of decision speed and accuracy, and it is supported by neurophysiology in human and animal models. In many situations, a decision maker may not communicate a decision immediately and yet feel that at some point she had made up her mind. We hypothesized that this occurs when an accumulation of evidence reaches a termination threshold, registered, subjectively, as an "aha" moment. We asked human participants to make perceptual decisions about the net direction of dynamic random dot motion. The difficulty and viewing duration were controlled by the experimenter. After indicating their choice, participants adjusted the setting of a clock to the moment they felt they had reached a decision. The subjective decision times (tSDs) were faster on trials with stronger (easier) motion, and they were well fit by a bounded drift-diffusion model. The fits to the tSDs alone furnished parameters that fully predicted the choices (accuracy) of four of the five participants. The quality of the prediction provides compelling evidence that these subjective reports correspond to the terminating process of a decision rather than a post hoc inference or arbitrary report. Thus, conscious awareness of having reached a decision appears to arise when the brain's representation of accumulated evidence reaches a threshold or bound. We propose that such a mechanism might play a more widespread role in the "piercing of consciousness" by non-conscious thought processes.


Marmoset spermatogenesis: organizational similarities to the human.
The common marmoset (Callithrix jacchus), a small New World primate of high fecundity, is widely used in reproductive research. The aim of the present study was to determine the organization of the germ cells within the seminiferous epithelium, the duration of the spermatogenic cycle and the number of spermatogonial mitoses. Antibodies to cAMP response element modulator (CREM) and proliferating nuclear cell antigen (PCNA) and a cRNA directed against protamine P2 and morphological criteria were used to discriminate between stages of the spermatogenic cycle. Plastic sections were used to document the cell associations present in each of the nine stages of spermatogenesis. Up to five such stages could be observed within individual cross-sections of seminiferous tubules. Based on the pattern of incorporation of bromodeoxyuridine the length of the spermatogenic cycle was estimated to be 10 days and the duration of spermatogenesis to be 37 days. Four mitotic divisions were noted in spermatogonia. It is concluded that the organization of spermatogenesis in the marmoset has similarities to the human ('helical') and this makes the marmoset a suitable model for studies relevant to human testicular function.


The regulated exocytosis of enlargeosomes is mediated by a SNARE machinery that includes VAMP4.
The mechanisms governing the fast, regulated exocytosis of enlargeosomes have been unknown, except for the participation of annexin-2 in a pre-fusion step. We investigated whether any SNAREs are involved. In PC12-27 cells, which are enlargeosome-rich, the expressed SNAREs exhibited various distributions (trans-Golgi network, scattered puncta, plasma membrane); however, only VAMP4 was colocalized in discrete puncta with the enlargeosome marker desmoyokin. The exocytosis of the organelle, revealed by capacitance increases and by surface appearance of desmoyokin, was largely inhibited by microinjection of anti-VAMP4, anti-syntaxin-6 and anti-SNAP23 antibodies, by incubation with botulinum toxin E, and by transfection of VAMP4 and syntaxin-6 siRNAs. Microinjection of the antibodies anti-VAMP7, anti-VAMP8 and anti-syntaxin-4, and transfection with the VAMP8 siRNA were ineffective. Inhibition of enlargeosome exocytosis by VAMP4 siRNA also occurred in a cell type that was competent for neurosecretion, SH-SY5Y. Moreover, in cells expressing a VAMP4-GFP construct, enlargeosome exocytosis and surface appearance of fluorescence occurred concomitantly, and many ensuing surface patches were co-labelled by GFP and desmoyokin. VAMP4, an R-SNARE that has never been shown to participate in regulated exocytoses, therefore appears to be harboured in the membrane of enlargeosomes and to be a member of the machinery mediating their regulated exocytosis. Syntaxin-6 and SNAP23 appear also to be needed for the process to occur; however, the mechanism of their participation, whether direct or indirect, remains undefined.


Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress.
Protection of mitochondrial proteins from glycation by endogenous dicarbonyl compounds, methylglyoxal and glyoxal, was found recently to prevent increased formation of reactive oxygen species and oxidative and nitrosative damage to the proteome during aging and produce life extension in the nematode Caenorhabditis elegans. This suggests that dicarbonyl glycation damage to the mitochondrial proteome may be a preceding event to mitochondrial dysfunction leading to oxidative stress. Future research will address the functional charges in mitochondrial proteins that are the targets for dicarbonyl glycation.


Case-control study on infant mortality in Southern Brazil.
To identify risk factors associated with infant mortality and, more specifically, with neonatal mortality. A case-control study was carried out in the municipality of Caxias do Sul, Southern Brazil. Characteristics of prenatal care and causes of mortality were assessed for all live births in the 2001-2002 period with a completed live-birth certificate and whose mothers lived in the municipality. Cases were defined as all deaths within the first year of life. As controls, there were selected the two children born immediately after each case in the same hospital, who were of the same sex, and did not die within their first year of life. Multivariate analysis was performed using conditional logistic regression. There was a reduction in infant mortality, the greatest reduction was observed in the post-neonatal period. The variables gestational age (<36 weeks), birth weight (<2,500 g), and 5-minute Apgar (<6) remained in the final model of the multivariate analysis, after adjustment. Perinatal conditions comprise almost the totality of neonatal deaths, and the majority of deaths occur at delivery. The challenge for reducing infant mortality rate in the city is to reduce the mortality by perinatal conditions in the neonatal period.


Cost containment in cardiac surgery: results with a critical pathway for coronary bypass surgery at the New York hospital-Cornell Medical Center.
A multidisciplinary project was undertaken at The New York Hospital-Cornell Medical Center to develop critical pathways for open-heart surgery to help reduce cost, shorten hospital length of stay (LOS), and streamline patient care. A critical pathway for elective coronary artery bypass grafting instituted on March 1, 1995, was developed through a cooperative effort involving surgeons, anesthesiologists, nurses, social workers, physical therapists, nutritionists, and patient case managers. Prospective data collected on consecutive patients forming a critical pathway group (n = 114) over a 6-month period were compared with retrospective data on consecutive patients forming a cohort group (n = 382) who underwent elective coronary artery bypass grafting in 1994. The critical pathway group of patients experienced a significantly shorter total hospital LOS (7.7 +/- 2.3 days vs 11.1 +/- 6 days, p < 0.0001) and shorter intensive care unit LOS (1.5 +/- 0.9 days vs 2.0 +/- 2.8 days, p < 0.0001). Direct costs were computed by use of hospital charges multiplied by the Medicare cost-to-charge ratio. Mean hospital direct cost (ancillary resources) was $1181 lower in the critical pathway group when compared with the control group (p < 0.0001). The postoperative mortality and readmission rates were similar for the two groups of patients. The ongoing analysis of cost, LOSs, and outcomes has made possible a process of continuous quality improvement on the cardiothoracic service in which further areas for improvement are identified and studied. The use of a critical pathway for elective coronary artery bypass grafting at our institution significantly reduced hospital LOS and direct costs while maintaining the overall quality of patient care.


[Assessment of kidney function with 99mTc-pyrophosphate during the scintigraphy of the joints in rheumatoid arthritis patients].
Diagnostic potentialities of investigation of the kidneys using 99mTc-pyrophosphate were studied in 34 patients with rheumatoid arthritis (RA) for articular scintigraphy. The results obtained were compared with those of radionuclide renography with 131I-hippuran and excretory urography. A possibility of investigation of the kidneys with 99mTc-pyrophosphate for the assessment of parenchyma function and kidney urodynamics was shown. Taking into account a high prevalence of nephropathy in RA patients, dynamic renal scintigraphy and clearance registration were recommended at the first stage of articular scintigraphy with 99mTc-pyrophosphate in order to obtain information on the anatomotopographic site and accumulation-evacuatory function of the kidneys.


Asymmetrical natural hybridization varies among hybrid swarms between two diploid Rhododendron species.
The extent to which hybridization leads to gene flow between plant species depends on the structure of hybrid populations. However, if this varies between locations, species barriers might prove permeable in some locations but not in others. To assess possible variation in hybrid population structure, the magnitude and direction of natural hybridization between two Chinese endemic species, Rhododendron spiciferum and Rhododendron spinuliferum , were evaluated. Thirteen nuclear microsatellite markers were employed to characterize 566 individuals collected from 15 non-allopatric populations and nine allopatric parental populations. Chloroplast DNA (cpDNA) sequences were obtained from a subset of samples. Genetic structure and direction of gene flow was determined using a combination of STRUCTURE and NEWHYBRIDS analysis. Nuclear analysis revealed that parental taxa formed two genetically distinct clusters and hybrids shared the genetic background of both parents and did not form a separate genetic lineage. Overall, hybrid swarms were dominated by early- and later-generation hybrids, with a significantly higher proportion of hybrids (59·6 %) possessing >50 % R. spiciferum-like nuclear germplasm. The cpDNA analysis further indicated that a significantly greater proportion of hybrids (61·1 %) possessed the R. spiciferum cpDNA haplotype. Gene flow between R. spiciferum and R. spinuliferum was found to be bidirectional in 14 of the 15 hybrid swarms and asymmetrical in six hybrid swarms. Asymmetrical gene flow was evident for only nuclear DNA (nDNA) in two populations, for only cpDNA in three populations, and for both nDNA and cpDNA in one population. Collectively, the variation in genetic structure found among the 15 hybrid swarms suggests that introgression rather than hybrid speciation is a more likely outcome of hybridization between these hybridizing taxa.


S-Adenosylmethionine regulates apoptosis and autophagy in MCF-7 breast cancer cells through the modulation of specific microRNAs.
To get insight into the molecular mechanisms underlying the anti-tumor activity of S-adenosyl-l-methionine (AdoMet), we analyzed AdoMet-induced modulation of microRNAs (miRNAs) expression profile in MCF-7 breast cell line and its correlation with cancer-related biological pathways. MiRNA expression profiling was performed using a TaqMan MiRNA Array, following 500 µM AdoMet-treatment. The results were confirmed by Quantitative real-time PCR analysis. MCF-7 were transfected with miR-34a, miR-34c and miR-486-5p, mimics and inhibitors in presence or not of 500 µM AdoMet for 72 h. Apoptosis and autophagy were analyzed by flow cytometry and the modulation of the main antiproliferative signaling pathways were evaluated by Western blotting. The potential mRNA targets for each miRNA were identified by the TargetScan miRNA target prediction software. Twenty-eight microRNAs resulted differentially expressed in AdoMet-treated MCF-7 cells compared to control cells. Among them, miRNA-34a and miRNA-34c were up-regulated while miRNA-486-5p was down-regulated. Moreover, we confirmed the ability of AdoMet to regulate these miRNAs in MDA-MB 231 breast cancer cell line. We demonstrate that, in MCF7 cells, the combination of either miR-34a or miR-34c mimic with AdoMet greatly potentiated the pro-apoptotic effect of AdoMet, by a caspase-dependent mechanism and activates p53 acetylation by inhibiting SIRT1 and HDAC1 expression. We also showed that miR-486-5p inhibitor induces autophagy and enhances AdoMet-induced autophagic process by increasing PTEN expression and by inhibiting AKT signaling. Our findings provide the first evidence that AdoMet can regulate miRNA expression in MCF-7 increasing our knowledge on the molecular basis of the antitumor effect of the sulfonium compound and suggest the use of AdoMet as an attractive miRNA-mediated chemopreventive and therapeutic strategy in breast cancer.


[Diagnostics and therapy of depression in the general practice].
Depressive disorders are commonly encountered by primary care practitioners. Some four million people in Germany suffer from depression. This disease, which is life-threatening primarily due to the suicide risk, is still often not recognized and, consequently, undertreated. Once diagnosed, depression can be treated successfully with antidepressants, cognitive behavior therapy/interpersonal psychotherapy or a combination of both. Newer, selective drugs are preferred when choosing a suitable antidepressant due to their better tolerability and lower toxicity. A synopsis of the diagnosis and therapeutic algorithm of depressive disorders as well as recommendations for referrals to a specialist or hospital for the primary care physician are provided.


Practice variability in the management of complex febrile seizures by pediatric emergency physicians and fellows.
Febrile seizures are the most common type of childhood seizure and are categorized as simple or complex. Complex febrile seizures (CFSs) are defined as events that are focal, prolonged (> 15 minutes), or recurrent. The management of CFS is poorly defined. The objective of this study was to determine the degree of variability in the emergency department evaluation of children with CFSs. An online survey questionnaire was developed and sent to physicians identified via the listserv of the emergency medicine section of the American Academy of Pediatrics and the pediatric emergency medicine discussion list. The questionnaire consisted of five hypothetical case vignettes describing children under 5 years of age presenting with a CFS. Following review of the first four vignettes, participants were asked if they would (1) obtain blood and urine for evaluation; (2) perform a lumbar puncture; (3) perform neurologic imaging while the child was in the emergency department; (4) admit the child to the hospital; or (5) discharge with follow-up as an outpatient, with either the primary care provider or a neurologist. The final vignette determined if antiepileptic medication would be prescribed by the physician on discharge. Of the 353 physicians who participated, 293 (83%) were pediatric emergency medicine attending physicians and 60 (17%) were pediatric emergency medicine fellows. Overall, 54% of participants indicated that they would obtain blood for evaluation, 62% would obtain urine, 34% would perform a lumbar puncture, and 36% would perform neurologic imaging. The overall hypothetical admission rate for the case vignettes was 42%. This study indicates that extensive variability exists in the emergency department approach to patients with CFS. Our findings suggest that optimal management for CFS remains unclear and support the potential benefit of future prospective studies on this subject.


Angular Deformities of the Knee in Children Treated with Guided Growth.
The guided growth technique is an alternative to corrective osteotomy for treating angular deformities of the extremities. It has the advantage of being minimally invasive and is effective in a growing child. This study reports on the outcome of guided growth technique using a plate in correcting knee angular deformities. We conducted a retrospective study of children with angular deformity of the knee treated by the guided growth technique from January 2010 to December 2015 in a tertiary centre. The guided growth technique was done using either the flexible titanium plate (8-plate) or the 2-hole reconstruction plate. Correction of deformity was assessed on radiographs by evaluating the mechanical axis deviation and tibiofemoral angle. The implants were removed once deformity correction was achieved. A total of 17 patients (27 knees) were evaluated. Twenty-two knees (81.5%) achieved complete correction of the deformity. The median age was 4.0 (interquartile range 3.0-6.0) years and the median Body Mass Index (BMI) was 26.0 (25.0-28.0). There were 7 unilateral and 10 bilateral deformities with different pathologies (14 tibia vara, 3 genu valgus). The median rate of correction was 0.71° per month. One patient (1 knee) had screw pull-out and two patients (4 knees) had broken screws in the proximal tibia. Three patients (5 knees) failed to achieve complete correction and were subsequently treated with corrective osteotomies. Out of five patients (8 knees) who were followed-up for at least 12 months after removal of hardware, two had rebound deformities. No permanent growth retardation occurred in our patients. Our outcome for guided growth to correct knee angular deformity was similar to other studies. Guided growth is safe to perform in children below 12 years old and has good outcome in idiopathic genu valgus and Langeskiold II for tibia vara. Patients should be observed for recurrence until skeletal maturity following implant removal.


Isotopic disequilibrium of uranium: alpha-recoil damage and preferential solution effects.
Preferential loss of uranium-234 relative to uranium-238 from rocks into solutions has long been attributed to recoiling alpha-emitting nuclei. Direct evidence has been obtained for two mechanisms, first, recoil ejection from grains, and now release by natural etching of alpha-recoil tracks. The observations have implications for radon emanation and for the storage of alpha-emitting radioactive waste.


Early breastfeeding practices: Descriptive analysis of recent Demographic and Health Surveys.
The aim of this study was to describe early breastfeeding practices (initiation within 1 hr of birth, no prelacteal feeding, and a combination of both-"optimal" early breastfeeding) according to childbirth location in low- and middle-income countries. Using data from the most recent Demographic and Health Survey (2000-2013) for 57 countries, we extracted information on the most recent birth for women aged 15-49 with a live birth in the preceding 24 months. Childbirth setting was self-reported by location (home or facility) and subtype (home delivery with or without a skilled birth attendant; public or private facility). We produced overall world and four region-level summary statistics by applying national population adjusted survey weights. Overall, 39% of children were breastfed within 1 hr of birth (region range 31-60%), 49% received no prelacteal feeding (41-65%), and 28% benefited from optimal early breastfeeding (21-46%). In South/Southeast Asia and Sub-Saharan Africa, early breastfeeding outcomes were more favourable for facility births compared to home births; trends were less consistent in Latin America and Middle East/Europe. Among home deliveries, there was a higher prevalence of positive breastfeeding practices for births with a skilled birth attendant across all regions other than Latin America. For facility births, breastfeeding practices were more favourable among those taking place in the public sector. This study is the most comprehensive assessment to date of early breastfeeding practices by childbirth location. Our results suggest that skilled delivery care-particularly care delivered in public sector facilities-appears positively correlated with favourable breastfeeding practices.


Linking habitat selection and predation risk to spatial variation in survival.
A central assumption underlying the study of habitat selection is that selected habitats confer enhanced fitness. Unfortunately, this assumption is rarely tested, and in some systems, gradients of predation risk may more accurately characterize spatial variation in vital rates than gradients described by habitat selection studies. Here, we separately measured spatial patterns of both resource selection and predation risk and tested their relationships with a key demographic trait, adult female survival, for a threatened ungulate, woodland caribou (Rangifer tarandus caribou Gmelin). We also evaluated whether exposure to gradients in both predation risk and resource selection value was manifested temporally through instantaneous or seasonal effects on survival outcomes. We used Cox proportional hazards spatial survival modelling to assess the relative support for 5 selection- and risk-based definitions of habitat quality, as quantified by woodland caribou adult female survival. These hypotheses included scenarios in which selection ideally mirrored survival, risk entirely drove survival, non-ideal selection correlated with survival but with additive risk effects, an ecological trap with maladaptive selection and a non-spatial effect of annual variation in weather. Indeed, we found positive relationships between the predicted values of a resource selection function (RSF) and survival, yet subsequently incorporating an additional negative effect of predation risk greatly improved models further. This revealed a positive, but non-ideal relationship between selection and survival. Gradients in these covariates were also shown to affect individual survival probability at multiple temporal scales. Exposure to increased predation risk had a relatively instantaneous effect on survival outcomes, whereas variation in habitat suitability predicted by an RSF had both instantaneous and longer-term seasonal effects on survival. Predation risk was an additive source of hazard beyond that detected through selection alone, and woodland caribou selection thus was shown to be non-ideal. Furthermore, by combining spatial adult female survival models with herd-specific estimates of recruitment in matrix population models, we estimated a spatially explicit landscape of population growth predictions for this endangered species.


Echocardiography in acute limb ischaemia.
In a retrospective study carried out over a 5-year period, 88 patients with acute limb ischaemia underwent echocardiography. Of this group, 74 were thought to have an embolic cause of ischaemia on either operative or arteriographic findings. Two-dimensional echocardiography detected a cardiac source in 30 patients (sensitivity 41%, specificity 100%). Clinical examination on admission correctly indicated an embolic source in 36 patients (sensitivity 49%, specificity 36%). The combination of echocardiography and clinical examination detected an embolic source in 60 of 74 (81%) patients. In this study echocardiography complemented clinical examination in the diagnosis of a cardiac source of acute limb ischaemia.


Determination of global phase shifts between interferograms by use of an energy-minimum algorithm.
A new algorithm for precise determination of the global phase shift between two interferograms is introduced. First we calculate the frame difference between the first and the second interferogram; the difference is multiplied by a properly chosen test phase factor, and then we implement a two-dimensional Fourier transform of the frame difference and calculate the energy of the first positive (or negative) diffraction order. An iterative approach is used for the test phase to ensure that the minimum energy is obtained, and then the correct phase shift value is found. This method is called the energy-minimum Fourier transform method, which is accurate and noise insensitive compared with the single-point Fourier transform method. Both the theoretical analysis and experimental results are given.


Solute concentration-dependent contact angle hysteresis and evaporation stains.
The presence of nonvolatile solutes in a liquid drop on a solid surface can affect the wetting properties. Depending on the surface-activity of the solutes, the extent of contact angle hysteresis (CAH) can vary with their concentration and the pattern of the evaporation stain is altered accordingly. In this work, four types of concentration-dependent CAH and evaporation stains are identified for a water drop containing polymeric additives on polycarbonate. For polymers without surface-activity such as dextran, advancing and receding contact angles (θa and θr) are independent of solute concentrations, and a concentrated stain is observed in the vicinity of the drop center after complete evaporation. For polymers with weak surface-activity such as poly(ethylene glycol) (PEG), both θa and θr are decreased by solute addition, and the stain pattern varies with increasing PEG concentration, including a concentrated stain and a mountain-like island. For polymers with intermediate surface-activity such as sodium polystyrenesulfonate (NaPSS), θa descends slightly, but θr decreases significantly after the addition of a substantial amount of NaPSS, and a ring-like stain pattern is observed. Moreover, the size of the ring stain can be controlled by NaPSS concentration. For polymers with strong surface-activity such as poly(vinylpyrrolidone) (PVP), θa remains essentially a constant, but θr is significantly lowered after the addition of a small amount of PVP, and the typical ring-like stain is seen.


Is it possible that we can increase the lymph node number in cases with rectum tumor receiving neoadjuvant therapy?
Though the recommended sampled lymph node number in colorectal carcinomas is at least 12, due to shrinkage after preoperative neoadjuvant chemoradiotherapy (NCRT), it can be difficult to attain that number. Our aim is to increase the lymph node number by applying alcohol fixation on the formalin-fixed resection materials of the patients that received or not received neoadjuvant therapy and to evaluate the changes in staging due to obtained lymph nodes. Non-randomized controlled trial. Lymph node dissection was performed in the resection materials with rectum tumor which were formalin- and afterwards, alcohol-fixed. The number of lymph nodes obtained by both of the methods and status of metastasis were evaluated statistically. Of the total 76 rectal tumors, 57 had and 19 had not received NCRT. The number of lymph node was adequate in 89.5% cases with no NCRT and in 63.2% cases with NCRT. While no change was observed after the alcohol fixation in the cases fulfilling adequacy criterion among those with no NCRT (p = 1.000), the adequacy rate increased from 63.2% to 87.7% in those with NCRT (p < 0.001). Although statistically insignificant, there was a change in pN stage in eight cases. In three of them, the stage varied from pN0 to pN1c, and in five cases, from pN1a to pN1b. Using solutions as alcohol during fixation might facilitate the identification of metastatic lymph nodes, might change the stage of the disease and therefore, might affect the patient-based therapy.


Expert nurse response to workforce recommendations made by The Coronavirus Commission For Safety And Quality In Nursing Homes.
COVID-19 has exposed the longstanding internal problems in nursing homes and the weak structures and policies that are meant to protect residents. The Centers for Medicare and Medicaid Services convened the Coronavirus Commission for Safety and Quality in NHs in April, 2020 to address this situation by recommending steps to improve infection prevention and control, safety procedures, and the quality of life of residents in nursing homes. The authors of this paper respond to the Final Report of the Commission and put forth additional recommendations to federal policymakers for meaningful nursing home reform: 1) ensuring 24/7 registered nurse (RN) coverage and adequate compensation to maintain total staffing levels that are based on residents' care needs; 2) ensuring RNs have geriatric nursing and leadership competencies; 3) increasing efforts to recruit and retain the NH workforce, particularly RNs; and 4) supporting care delivery models that strengthen the role of the RN for quality resident-centered care.


Noble gas isotopes reveal degassing-derived eruptions at Deception Island (Antarctica): implications for the current high levels of volcanic activity.
Deception Island is one of the most active volcanoes in Antarctica with more than twenty explosive eruptions in the past two centuries. Any future volcanic eruption(s) is a serious concern for scientists and tourists, will be detrimental to marine ecosystems and could have an impact to global oceanographic processes. Currently, it is not possible to carry-out low and high frequency volcanic gas monitoring at Deception Island because of the arduous climatic conditions and its remote location. Helium, neon and argon isotopes measured in olivine samples of the main eruptive events (pre-, syn- and post caldera) offer insights into the processes governing its volcanic history. Our results show that: (i) ascending primitive magmas outgassed volatiles with a MORB-like helium isotopic signature (3He/4He ratio); and (ii) variations in the He isotope ratio, as well as intensive degassing evidenced by fractionated 4He/40Ar* values, occurred before the beginning of the main eruptive episodes. Our results show how the pre-eruptive noble gas signals of volcanic activity is an important step toward a better understanding of the magmatic dynamics and has the potential to improve eruption forecasting.


Synthesis of mono- and 1,3-diaminocalix[4]arenes via Ullmann-type amination and amidation of 1,3-bistriflate esters of calix[4]arenes.
Practical methods are described for the preparation of monoamines 4 and 1,3-diamines 5, bearing one or two amino group(s) instead of the hydroxy group(s) at the 28-position or at both the 26- and 28-positions of p-tert-butylcalix[4]arene (1a) and p-tert-butylthiacalix[4]arene (1b), via the Ullmann-type amination or amidation. Thus, the copper-catalyzed or mediated amination of the 1,3-bistriflate ester (2a) of 1a with benzylamine affords either mono(benzylamino) triflate 7a or 1,3-bis(benzylamine) 8 in a high yield, depending on the reaction conditions. On the other hand, the 1,3-bistriflate ester (2b) of 1b resists disubstitution and produces, under stoichiometric conditions, mono(benzylamino) triflate 7b. The disubstitution of 2b is achieved by amidation with tosylamide, giving 1,3-bis(tosylamide) 17b. The hydrogenolysis of the benzylamino moiety of 7a, followed by the hydrolysis of the Tf moiety, affords monoamine 4a, while the hydrogenolysis of 8 affords 1,3-diamine 5a. The amino moiety of 7b can be deprotected under acidic conditions to give, after hydrolysis, monoamine 4b. The hydrolysis of 17b affords 1,3-diamine 5b. The overall yields of compounds 4a, 4b, 5a, and 5b are 72%, 45%, 78%, and 24%, respectively, based on commercially available compounds 1 and are much higher than the ones previously reported in the literature.


Long-range electron transfer across molecule-nanocrystalline semiconductor interfaces using tripodal sensitizers.
Four tripodal sensitizers, Ru(bpy)(2)(Ad-tripod-phen)(2+) (1), Ru(bpy)(2)(Ad-tripod-bpy)(2+) (2), Ru(bpy)(2)(C-tripod-phen)(2+) (3), and Ru(bpy)(2)(C-tripod-bpy)(2+) (4) (where bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline, and Ad-tripod-bpy (phen) and C-tripod-bpy (phen) are tripod-shaped bpy (phen) ligands based on 1,3,5,7-tetraphenyladamantane and tetraphenylmethane, respectively), have been synthesized and characterized. The tripodal sensitizers consist of a rigid-rod arm linked to a Ru(II)-polypyridine complex at one end and three COOR groups on the other end that bind to metal oxide nanoparticle surfaces. The excited-state and redox properties of solvated and surface-bound 1-4 have been studied at room temperature. The absorption spectra, emission spectra, and electrochemical properties of 1-4 in acetonitrile solution are preserved when 1-4 are bound to nanocrystalline (anatase) TiO(2) or colloidal ZrO(2) mesoporous films. This behavior is indicative of weak electronic coupling between TiO(2) and the sensitizer. The kinetics for excited-state decay are exponential for 1-4 in solution and are nonexponential when 1-4 are bound to ZrO(2) or TiO(2). Efficient and rapid (k(cs) > 10(8) s(-)(1)) excited-state electron injection is observed for 1-4/TiO(2). The recombination of the injected electron with the oxidized Ru(III) center is well described by a second-order kinetic model with rate constants that are independent of the sensitizer. The sensitizers bound to TiO(2) were reversibly oxidized electrochemically with an apparent diffusion coefficient approximately 1 x 10(-11) cm(2) s(-)(1).


[The Cochrane Collaboration and the practice of evidence-based cardiology].
Evidence-based Cardiology (EBC) permits a rational and updated clinical approach to patients. The EBC practice needs credible, independent and scientifically solid information, but the sheer volume of the medical bibliography precludes individual solutions: we have too much information and what is relevant is sunk within what is irrelevant or useless. Selection, critical appraisal and synthesis of the best scientific evidence constitutes the basis of EBC. The Cochrane Collaboration is the best source of independent, updated and valid information: through published systematic reviews, the evidence is available in the format of CD-ROM, and can serve as the basis for a modern, efficient and rational cardiological practice.


The Effect of Three Different Meditation Exercises on Hypertension: A Network Meta-Analysis.
We aimed to use the pairwise and network meta-analysis to estimate the effects of different meditation exercises on the control of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved from PubMed and Embase up to June 2016, which are published in English and reported on meditation exercise for hypertensive patients. Risks of bias assessment of the included studies were assessed by Cochrane Collaboration Recommendations and network meta-analysis was performed by ADDIS. Mean difference (MD) and its 95% confidence interval (CI) were used as the effect size. A number of 19 RCTs were included in this study. Results of pairwise comparisons indicated that meditation exercise could significantly decrease the SBP and DBP, compared with other interventions (MD = -7.10, 95% CI: -10.82 to -3.39; MD = -4.02, 95% CI: -6.12 to -1.92). With good consistence and convergence, network meta-analysis showed that there were no significant differences between meditation and other interventions on SBP. For DBP, Qigong was significantly lower than "no intervention" (MD = -11.73, 95% CI: -19.85 to -3.69). Qigong may be the optimal exercise way in lowering SBP and DBP of hypertensive patients, but a detailed long-term clinical research should be needed in the future.


Circulatory changes in muscle and skin arteries in primary hypertension.
This review deals with circulatory adjustments occurring in the limb arteries of hypertensive patients. Measurements of regional blood flow are mandatory, because conclusions drawn from calculated total peripheral resistance often are not applicable to local vascular beds. Limb arteries, which can be followed by easy and noninvasive methods, often are the first choice for study of regional circulation. In this discussion, a few historic studies are cited first; next, the data available on skeletal muscle (forearm and calf) and skin (finger) circulation are reviewed, to show that flow through both muscle and skin is increased in mild and moderate hypertension, while there is a trend to lower values in more severe hypertension. Our own data are derived from 51 untreated patients showing mild to moderate hypertension, matched to 23 normotensive subjects. Flow is measured simultaneously with an ECG-triggered venous occlusion plethysmograph at calf and finger. At rest, calf and finger blood flows are significantly higher and calculated resistance is lower in hypertensive subjects; during reactive hyperemia, blood flow remains higher in hypertensive subjects but calculated resistance increases up to values that are higher, compared to normotensive control subjects; these data are compatible with structural changes in the vascular wall.


Molecular and genetic analysis of the transferred DNA regions of the root-inducing plasmid of Agrobacterium rhizogenes.
The T-DNA regions of the root-inducing (Ri) plasmid pRiA4b of Agrobacterium rhizogenes were characterized. Two regions, designated TL-DNA and TR-DNA, were found to be integrated and stably maintained in the plant genome. The TL-DNA spanned a 15- to 20-kilobase region of pRiA4b and was separated from the TR-DNA region by at least 15 kilobases of nonintegrated plasmid DNA. The TR-DNA region also spanned a 15- to 20-kilobase region of pRiA4b and included a region of homology to the tms morphogenic loci of the tumor-inducing (Ti) plasmid of Agrobacterium tumefaciens. Eighteen deletions and 95 transposon insertions were generated in the T-DNA regions and tested for alterations in virulence. Insertions into four loci in the TL-DNA affected the morphology of root formation of Kalanchoë diagremontiana leaves and stems, but had no visible effects on other host plants. Insertions into two loci (tms-1 and tms-2) in the TR-DNA eliminated virulence symptoms on all plants tested, with the exception of K. diagremontiana stems, where sparse root formation occurred. Complementation experiments with Ri and Ti plasmid T-DNA mutations indicate that the tms genes of the two plasmids serve similar functions and suggest a functional relationship between one or more genes of the TL-DNA and the cytokinin synthesis locus tmr of the Ti plasmid.


Recent technological developments: in situ histopathological interrogation of surgical tissues and resection margins.
The tumour margin is an important surgical concept significantly affecting patient morbidity and mortality. We aimed in this prospective study to apply the microendoscope on tissue margins from patients undergoing surgery for oral cancer in vivo and ex vivo and compare it to the gold standard "paraffin wax", inter-observer agreement was measured; also to present the surgical pathologist with a practical guide to the every day use of the microendoscope both in the clinical and surgical fields. Forty patients undergoing resection of oral squamous cell carcinoma were recruited. The surgical margin was first marked by the operator followed by microendoscopic assessment. Biopsies were taken from areas suggestive of close or positive margins after microendoscopic examination. These histological samples were later scrutinized formally and the resection margins revisited accordingly when necessary. Using the microendoscope we report our experience in the determination of surgical margins at operation and later comparison with frozen section and paraffin section margins "gold standard". We were able to obtain a sensitivity of 95% and a specificity of 90%. Inter-observer Kappa scores comparing the microendoscope with formal histological analysis of normal and abnormal mucosa were 0.85. The advantage of this technique is that a large area of mucosa can be sampled and any histomorphological changes can be visualized in real time allowing the operator to make important informed decisions with regards the intra-operative resection margin at the time of the surgery.


[Pigmented villonodular synovitis with polyarticular presentation].
Pigmented villonodular synovitis (PSV) rarely involves more than one joint, and its occurrence in children is uncommon. One case of PSV with polyarticular involvement in a child is presented, and the differential diagnoses with other polyarthritis are offered. Synovial biopsy of both knees at different ages showed the presence of PSV in a fourteen years old boy with a nine years history of painless swelling of wrist, knees and ankles. Painless polyarticular swelling with few inflammatory signs, negative acute-phase laboratory tests, normal synovial fluid, periarticular soft tissue swelling on plain films and a mandatory synovial biopsy are the diagnostic clues of this rare presentation.


Length-tension relationship of the external anal sphincter muscle: implications for the anal canal function.
The length at which a muscle operates in vivo (operational length) and the length at which it generates maximal force (optimal length) may be quite different. We studied active and passive length-tension characteristics of external anal sphincter (EAS) in vivo and in vitro to determine the optimal and operational length of rabbit EAS. For the in vitro studies, rings of EAS (n = 4) were prepared and studied in a muscle bath under isometric conditions. For in vivo studies, female rabbits (n = 19) were anesthetized and anal canal pressure was recorded by use of a sleeve sensor placed in the custom-designed catheter holders of 4.5-, 6-, and 9-mm diameters. Measurements were obtained at rest and during EAS electrical stimulation. Sarcomere length of EAS muscle was measured by laser diffraction technique with no probe and three probes in the anal canal. In vitro studies revealed 2,054 mN/cm(2) active tension at optimal length. In vivo studies revealed a probe size-dependent increase in anal canal pressure and tension. Maximal increase in anal canal tension with stimulation was recorded with the 9-mm probe. Increases in anal canal tension with increase in probe size were completely abolished by pancuronium bromide. EAS muscle sarcomere length without and with 9-mm probe in the anal canal were 2.11 +/- 0.08 and 2.99 +/- 0.07 microm, respectively. Optimal sarcomere length, based on the thin filament length measured by thin filament analysis, is 2.44 +/- 0.10 microm. These data show that the operational length of EAS is significantly shorter than its optimal length. Our findings provide insight into EAS function and we propose the possibility of increasing anal canal pressure by surgical manipulation of the EAS sarcomere length.


Evaluation and management of recurrent anterior shoulder instability.
To present an organized approach to the assessment and treatment of symptomatic recurrent anterior shoulder instability. Knowledge of the relevant pathology and pathomechanics serves as an excellent foundation for the clinical examination, rehabilitation, and if necessary, surgical intervention for shoulder instability. An algorithm is presented for the initial evaluation of shoulder instability, ie, history, physical examination, and diagnostic studies, followed by modes of treatment such as rehabilitation, modification of biomechanics, and surgical treatment (arthroscopic versus open). Early identification of shoulder instability allows for the timely introduction of treatment principles that may obviate more invasive operative procedures.


[Professional training in biology: its relationships with animal experimentation and environmental protection].
With reference to the controversy regarding animal experimentation, this article questions the relationship with the professional training in universities. The considerations voiced in the paper are based on data gathered from interviews with students and professors of Biological Science courses at two different universities in São Paulo. These data reveal that the use of animals is not seen as an ethical problem by most of the people interviewed and, also, that there exists a high degree of unfamiliarity with the laws, principles and techniques recommended for animal experimentation. It is also suggested that this situation springs from a class orientation and predominance of a technician tendency geared toward professionalization, which in turn is subordinated to market demands, in university teaching.


Myotonia congenita. A histochemical and ultrastructural study in the goat: comparison with abnormalities found in human myotonia dystrophica.
Muscle biopsy specimens from the myotonic goat, an animal model of heritable myotonia, were examined histochemically and by electron microscopy. After Periodic acid-Schiff (PAS) staining with diastase digestion, there was increased PAS-positive material within myotonic goat fibers, as compared with those of normal goats. Myotonic muscle stained with alizarin red S, a histochemical stain for calcium, also had an increased staining reaction when compared with muscle from normal goats. Several ultrastructural abnormalities were found in myotonic goat muscle using routine osmium and uranyl acetate staining. These included increased density of the t-tubules, electron-dense material within t-tubules, proliferation and dilatation of sarcotubular elements, and abnormal mitochondria in the myotonic biopsy specimens. To further study muscle ultrastructure, ruthenium red and lanthanum were used as electron microscopic stains with specificity for membranes. There was increased density of the sarcolemma and t-tubules in myotonic muscle stained with ruthenium red as compared to normal, and lanthanum produced a darker staining reaction of the myotonic goat sarcolemma. The histochemical and ultrastructural differences between normal and myotonic goat muscle were interpreted to be consistent with a morphologic basis for the abnormal contraction-relaxation properties characteristic of myotonia.


Necrotizing fasciitis with no mortality or limb loss.
Necrotizing fasciitis is a potentially lethal invasive soft tissue infection. Early aggressive antibiotic therapy and surgical debridement have been the hallmark of successful therapy. It is commonly held that delays in surgical debridement significantly increase the mortality rate and rate of limb loss. A mortality rate of 20 per cent or greater has been reported throughout the last 80 years. We recently reviewed the cases of 20 consecutive patients admitted to our hospital in various stages of necrotizing fasciitis progression. Treatment of all 20 patients consisted of antibiotic therapy and surgical debridement, with frequent follow-up serial debridement. Topical negative pressure was achieved with the use of the Vacuum Assisted Closure system. An aggressive surgical approach, (including the frequency of debridement, appropriate antibiotic utilization, and use of the Vacuum Assisted Closure system), significantly impacted our results, despite delays in treatment and progression of the infection.


Sensors for Fetal Hypoxia and Metabolic Acidosis: A Review.
This article reviews existing clinical practices and sensor research undertaken to monitor fetal well-being during labour. Current clinical practices that include fetal heart rate monitoring and fetal scalp blood sampling are shown to be either inadequate or time-consuming. Monitoring of lactate in blood is identified as a potential alternative for intrapartum fetal monitoring due to its ability to distinguish between different types of acidosis. A literature review from a medical and technical perspective is presented to identify the current advancements in the field of lactate sensors for this application. It is concluded that a less invasive and a more continuous monitoring device is required to fulfill the clinical needs of intrapartum fetal monitoring. Potential specifications for such a system are also presented in this paper.


Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.
We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.


Revisiting the Jewish Ethical Approach Toward Perimortem Cesarean Section in Light of Emerging Medical Evidence.
Maternal cardiac arrest during gestation constitutes a devastating event. Training and anticipant preparedness for prompt action in such cases may save the lives of both the woman and her fetus. To address a previous Jewish guideline that a woman in advanced pregnancy should not undergo any medical procedure to save the fetus until her condition is stabilized. Current evidence on perimortal cesarean section shows that immediate section during resuscitation provides restoration of the integrity of the mother's vascular compartment and increases her probability of survival. We analyzed Jewish scriptures from the Talmud and verdicts of the oral law and revealed that the Jewish ethical approach toward late gestational resuscitation was discouraged since it may jeopardize the mother. We discuss the pertinent Jewish principles and their application in light of emerging scientific literature on this topic. An example case that led to an early perimortem cesarean delivery and brought about a gratifying, albeit only partially satisfying outcome, is presented, albeit with only a partially satisfying outcome. The arguments that were raised are relevant to such cases and suggest that previous judgments should be reconsidered. The Jewish perspective can guide medical personnel to modify and adapt the concrete rules to diverse clinical scenarios in light of current medical knowledge. With scientific data showing that both mother and fetus can prosper from immediate surgical extrication of the baby during resuscitation of the advanced pregnant woman, these morals should dictate training and practice in urgent perimortal cesarean sections whenever feasible.


Altered sensitivity of chronic diabetic rat heart to calcium.
An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.


Parents' Consumer Preferences for Early Childhood Behavioral Intervention in Primary Care.
Early childhood parenting interventions are increasingly delivered in primary care, but parental engagement with those interventions is often suboptimal. We sought to better understand parents' preferences for the content and delivery method of behavioral health guidance in pediatric primary care and to determine the relationship of those preferences with demographic characteristics, child behavior problems, and parenting style. Participants were 396 parents of young children recruited from primary care offices. We collected measures of parental preferences (including behavioral topics, intervention strategies, and methods of delivery) for behavioral intervention in primary care, child behavior symptoms, parenting style, and demographic characteristics. Descriptive statistics were used to identify parents' most preferred behavioral topics and intervention delivery methods. We used a hierarchical regression approach to determine whether parenting style predicted parents' preferences beyond demographic and child-level factors. Nearly all parents (96%) endorsed a behavioral topic (e.g., aggression) as important. Most preferred to receive intervention during routine medical appointments. Child behavior problems correlated with parents' overall interest in behavioral guidance, but clinically significant symptoms did not differentiate interest in any single topic. Socioeconomic factors and negative parenting practices predicted some parental preferences. Notably, lax parenting generally predicted higher interest in behavioral intervention, whereas hostile and physically controlling parenting predicted lower interest. Most parents are interested in behavioral guidance as part of primary care, but their preferences for the content and delivery of that guidance vary by known socioeconomic, child, and parenting risk factors. Tailoring intervention to parents' preferences may increase engagement with available interventions.


Evolution of a distinct genomic domain in Drosophila: comparative analysis of the dot chromosome in Drosophila melanogaster and Drosophila virilis.
The distal arm of the fourth ("dot") chromosome of Drosophila melanogaster is unusual in that it exhibits an amalgamation of heterochromatic properties (e.g., dense packaging, late replication) and euchromatic properties (e.g., gene density similar to euchromatic domains, replication during polytenization). To examine the evolution of this unusual domain, we undertook a comparative study by generating high-quality sequence data and manually curating gene models for the dot chromosome of D. virilis (Tucson strain 15010-1051.88). Our analysis shows that the dot chromosomes of D. melanogaster and D. virilis have higher repeat density, larger gene size, lower codon bias, and a higher rate of gene rearrangement compared to a reference euchromatic domain. Analysis of eight "wanderer" genes (present in a euchromatic chromosome arm in one species and on the dot chromosome in the other) shows that their characteristics are similar to other genes in the same domain, which suggests that these characteristics are features of the domain and are not required for these genes to function. Comparison of this strain of D. virilis with the strain sequenced by the Drosophila 12 Genomes Consortium (Tucson strain 15010-1051.87) indicates that most genes on the dot are under weak purifying selection. Collectively, despite the heterochromatin-like properties of this domain, genes on the dot evolve to maintain function while being responsive to changes in their local environment.


Tumor-Targeting Cholesterol-Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing.
Probing endogenous molecular profiles is of fundamental importance to understand cellular function and processes. Despite the promise of programmable nucleic-acid-based aptasensors across the breadth of biomolecular detection, target-responsive aptasensors enabling intracellular detection are as of yet infrequently realized. Several challenges remain, including the difficulties in quantification/normalization of quencher-based intensiometric signals, stability issues of the probe architecture, and complex sensor operations often necessitating extensive structural modeling. Here, the biomimetic crystallization-empowered self-assembly of a tumor-targetable DNA-inorganic hybrid nanocomposite aptasensor is presented, which enables Förster resonance energy transfer (FRET)-based quantitative interpretation of changes in the cellular target abundance. Leveraging the design programmability and high-throughput fabrication of rolling circle amplification-driven DNA nanoarchitecture, this designer platform offers a method to self-assemble a robust nanosensor from a multifunctionality-encoded template that includes a cell-targeting aptamer, a ratiometric aptasensor, and a cholesterol-decorating element. Taking prostate cancer cells and intracellular adenosine triphosphate molecules as a model system, a synergistic effect in the targeted delivery by cholesterol and aptamers, and the feasibility of quantitative intracellular aptasensing are demonstrated. It is envisioned that this approach provides a highly generalizable strategy across wide-ranging target systems toward a biologically deliverable nanosensor that enables quantitative monitoring of the abundance of endogenous biomolecules.


Computational modeling of interventions for developmental disorders.
We evaluate the potential of connectionist models of developmental disorders to offer insights into the efficacy of interventions. Based on a range of computational simulation results, we assess factors that influence the effectiveness of interventions for reading, language, and other cognitive developmental disorders. The analysis provides a level of mechanistic detail that is generally lacking in behavioral approaches to intervention. We review an extended program of modeling work in four sections. In the first, we consider long-term outcomes and the possibility of compensated outcomes and resolution of early delays. In the second section, we address methods to remediate atypical development in a single network. In the third section, we address interventions to encourage compensation via alternative pathways. In the final section, we consider the key issue of individual differences in response to intervention. Together with advances in understanding the neural basis of developmental disorders and neural responses to training, formal computational approaches can spur theoretical progress to narrow the gap between the theory and practice of intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Treatment patterns and associated costs with Parkinson's disease levodopa induced dyskinesia.
This study examined the treatment patterns, direct healthcare costs and predictors of treatment costs associated with levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). This retrospective cohort study followed PD patients for 1-year pre- and post-onset of LID, using a large US health insurance claims database from January 1, 2004 to December 31, 2008. Patients with LID were matched to patients without LID based on propensity scores to control for potential selection bias. Descriptive statistics and bootstrap techniques were employed to assess patient demographic and clinical characteristics and costs incurred. Factors influencing treatment costs were analyzed using a generalized linear model with log-link function and gamma distribution. Costs were adjusted to 2009 prices. After patients developed LID, their total treatment costs were increased from $18,645 during the 12 months preceding LID onset to $26,439 for the 12-month period subsequent to LID onset (incremental costs of $7795: P<0.001). PD-related costs increased from $3917 to $8110 (incremental costs of $4194: p<0.001) LID events, medical resource utilization, higher levodopa dosage, and use of alternative PD medications were associated with increases in total treatment costs. Few changes in medication treatment patterns were noted following the initial LID, with only slight increases in levodopa dosage and few additions of alternative agents. In the United States, PD patients with LID impose a significant economic burden when compared to patients without LID. Currently available, treatment strategies for dyskinesia should be used more frequently in PD management, and new treatment strategies should be considered as they may lower healthcare costs.


[Properties of the chorioamnios zone inducing premature membranes rupture].
Premature membrane rupture (PMR) is one of the most serious public health problems in the world, ocurring in 10% of all pregnancies. PMR has important adverse effects on maternofetal morbidity-mortality, as it has been estimated that it accounts on the whole for 70% and 40% of neonatal morbidity and mortality, respectively. PMR treatment is empirical, as its aetiology is unknown and its physiopathogenic description has just been initiated. This work analyzes the possibility of documenting functional differences in human chorio-amnios, comparing the zone where rupture most frequently occurs in PMR with some other distant chorio-amnionic zones and with equivalent zones of fetal membranes obtained from nine month pregnancies which have not undergone labor. The membrane zone which was nearest to the cervical os was identified and marked to be analyzed later for extracellular matrix metalloprotease (MMP) activity, histology and topographical MMP distribution. The MMP expression was quantitatively determined in explant culture media from membrane fragments using specific immuno-enzymatic essays (ELISA) and zymography. In addition, immuno-histochemistry methods were used to reveal MMP expression in the different tissues. This methods allowed us to show the existence of a decreasing MMP activity gradient, with the greatest value corresponding to the zone nearest to the cervical os in the membranes obtained from PMR cases. In membranes obtained from cesarean operations no characteristic pattern was documented and values were always lower than those obtained for PMR tissues. We conclude that there is a chorio-amnionic zone in which connective tissue degradation is specifically induced and which coincides with the membrane zone in contact with the cervical os.


Arabidopsis AHP2, AHP3, and AHP5 histidine phosphotransfer proteins function as redundant negative regulators of drought stress response.
Cytokinin is an essential phytohormone controlling various biological processes, including environmental stress responses. In Arabidopsis, although the cytokinin (CK)-related phosphorelay--consisting of three histidine kinases, five histidine phosphotransfer proteins (AHPs), and a number of response regulators--has been known to be important for stress responses, the AHPs required for CK signaling during drought stress remain elusive. Here, we report that three Arabidopsis AHPs, namely AHP2, AHP3, and AHP5, control responses to drought stress in negative and redundant manner. Loss of function of these three AHP genes resulted in a strong drought-tolerant phenotype that was associated with the stimulation of protective mechanisms. Specifically, cell membrane integrity was improved as well as an increased sensitivity to abscisic acid (ABA) was observed rather than an alteration in ABA-mediated stomatal closure and density. Consistent with their negative regulatory functions, all three AHP genes' expression was down-regulated by dehydration, which most likely resulted from a stress-induced reduction of endogenous CK levels. Furthermore, global transcriptional analysis of ahp2,3,5 leaves revealed down-regulation of many well-known stress- and/or ABA-responsive genes, suggesting that these three AHPs may control drought response in both ABA-dependent and ABA-independent manners. The discovery of mechanisms of activation and the targets of the downstream components of CK signaling involved in stress responses is an important and challenging goal for the study of plant stress regulatory network responses and plant growth. The knowledge gained from this study also has broad potential for biotechnological applications to increase abiotic stress tolerance in plants.


Effect of synthetic tumoral PTH-related peptide on cAMP production and Na-dependent Pi transport.
Malignant hypercalcemia can be associated with a biochemical syndrome very similar to that encountered in primary hyperparathyroidism. The putative tumoral factor responsible for this syndrome has been isolated very recently from conditioned medium of a cultured lung squamous cell carcinoma (BEN), cDNA clones characterized, and an amino-terminal fragment synthesized. We investigated and compared the effect of this synthetic amino-terminal fragment of parathyroid hormone-related peptide [PTHrP-(1-34)], to purified PTHrP-(1-141) isolated from the same lung squamous cell carcinoma, and to bovine parathyroid hormone [bPTH-(1-34)] on adenosine 3',5'-cyclic monophosphate (cAMP) production and sodium-dependent phosphate transport (NaPiT) in opossum kidney (OK) epithelial cells. PTHrP-(1-34) and bPTH-(1-34) were equipotent in eliciting a 30-fold increase of cAMP production. NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a concentration-dependent manner by either synthetic peptide. Half-maximal inhibition was observed with approximately 0.03-0.1 nmol/l of either bPTH-(1-34) or PTHrP-(1-34). At 10 nmol/l, either peptide produced an inhibition of 55 +/- 4 and 53 +/- 6%, respectively. This effect was specific for Pi, since the Na-dependent transport of glucose or alanine was not altered by either peptide. In OK cells dose-dependent stimulation of cAMP production and inhibition of NaPiT were also observed with purified native PTHrP-(1-141). In LLC-PK1 cells, which are devoid of PTH receptors, none of the peptides affected NaPiT. These results demonstrate a direct and specific effect of tumoral PTHrP on cAMP production and NaPiT in cultured renal epithelial cells in a way similar to bPTH.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative analysis of open, laparoscopic and robotic distal pancreatic resection: The United Kingdom's first single-centre experience.
Laparoscopic distal pancreatectomy (LDP) has potential advantages over its open equivalent open distal pancreatectomy (ODP) for pancreatic disease in the neck, body and tail. Within the United Kingdom (UK), there has been no previous experience describing the role of robotic distal pancreatectomy (RDP). This study evaluated differences between ODP, LDP and RDP. Patients undergoing distal pancreatectomy performed in the Department of Hepatobiliary and Pancreatic Surgery at the Freeman Hospital between September 2007 and December 2018 were included from a prospectively maintained database. The primary outcome measure was length of hospital stay, and the secondary outcome measures were complication rates graded according to the Clavien-Dindo classification. Of the 125 patients, the median age was 61 years and 46% were male. Patients undergoing RDP (n = 40) had higher American Society of Anesthesiologists grading III compared to ODP (n = 38) and LDP (n = 47) (57% vs. 37% vs. 38%, P = 0.02). RDP had a slightly lower but not significant conversion rate (10% vs. 13%, P = 0.084), less blood loss (median: 0 vs. 250 ml, P < 0.001) and a higher rate of splenic preservation (30% vs. 2%, P < 0.001) and shorter operative time, once docking time excluded (284 vs. 300 min, P < 0.001) compared to LDP. RDP had a higher R0 resection rate than ODP and LDP (79% vs. 47% vs. 71%, P = 0.078) for neoplasms. RDP was associated with significantly shorter hospital stay than LDP and ODP (8 vs. 9 vs. 10 days, P = 0.001). While there was no significant different in overall complications across the groups, RDP was associated with lower rates of Grade C pancreatic fistula than ODP and LDP (2% vs. 5% vs. 6%, P = 0.194). Minimally invasive pancreatic resection offers potential advantages over ODP, with a trend showing RDP to be marginally superior when compared to conventional LDP, but it is accepted that that this is likely to be at greater expense compared to the other current techniques.


Validity of the WHIPLASHED as a tool to identify bipolar disorder in women.
The aim of this study was to investigate the validity of the WHIPLASHED clinician-administered interview, a mnemonic of questions on clinical factors and illness course used to screen for bipolar disorder, as a self-report questionnaire. Participants (n = 82) were females recruited from an outpatient academic women's mental health clinic. Relevant symptom data were extracted from a self-report questionnaire designed to parallel the WHIPLASHED interview questions. A score of ≥5 on WHIPLASHED was defined as a positive screen for bipolar spectrum disorder by its developer. We examined the capacity of self-reported WHIPLASHED scores ≥5 to differentiate bipolar from unipolar depression in women. Diagnostic assessments were conducted with the Mini International Neuropsychiatric Interview. Women were diagnosed with unipolar (n = 54) and bipolar (n = 28) depression. The majority of subjects were white (67%), employed (68%) and married (57%) with a mean age of 36.8 years. The receiver operating characteristic curve demonstrated that WHIPLASHED had strong predictive ability (AUC = 0.877) in differentiating bipolar from unipolar depression. A cutoff score of ≥5 generated 96% sensitivity and 52% specificity, while raising the threshold to 6 generated 89% sensitivity and 76% specificity for a bipolar disorder diagnosis. Our sample was small and composed of female patients at a single treatment center. In this sample, WHIPLASHED was a valid screening tool to differentiate bipolar from unipolar depression. While existing instruments focus on primary symptoms of bipolar disorder, the WHIPLASHED is useful in exploring subtypes of bipolar disorder in which depression dominates the clinical course.


Pancreatic injuries in the United Arab Emirates.
To study the mechanism, management and outcome of patients who had sustained pancreatic trauma. Patients who were treated for pancreatic trauma in Al-Ain Hospital between October 2002 and August 2007 were retrospectively studied. All eleven patients were males having a median age of 30 years (range 24-52 years). Nine had blunt trauma while two had suffered penetrating injury. Three presented with shock. associated injuries were present in nine patients (head, chest, and extremities) while seven had other intra-abdominal injuries. Only one patient had isolated pancreatic injury. Early serum amylase was elevated in six patients. CT abdomen was diagnostic for pancreatic injury in seven patients. Two cases were missed by early CT scan (sensitivity of 78%) while the remaining two patients were taken immediately to the operating theater. All patients underwent laparotomy. Five patients were treated by drainage alone, four had distal pancreatectomy, abdominal packing was performed in one patient and in another gastrocystostomy was carried out. Pancreatic fistula occurred in three patients. Median hospital stay was 25 days (range 12-152 days). Two patients (18%) died. Blunt trauma is the main cause of pancreatic injury in our country. Early CT scan may miss pancreatic injury in almost a quarter of the patients. Thin sliced CT scan, with special views in a dedicated abdominal pancreatic study, is recommended. A high index of clinical suspicion, depending on the mechanism of injury, is important for diagnosis of pancreatic injury. Mortality is mainly attributable to other associated injuries so simple procedures should initially be adopted for pancreatic injury, especially in haemodynamically unstable patients.


Orthodontic movement through a repaired buccal alveolar fracture: a case report.
Orthodontic treatment in adults often involved the extraction of a lower central incisor. The extraction of these teeth can be problematic. Some factors that can influence successful treatment include: difficult access for actual tooth removal; the existing contour and bulk of the alveolar ridge; the buccal tooth position; and the inclination of the tooth in the alveolus. A patient who had a lower central incisor removed experienced a buccal alveolar fracture because of thin buccal plate. Upon healing there was a buccal defect that prevented the later tooth movement that would have closed the extraction site. The area was grafted with a demineralized freeze dried bone allograft to provide a matrix for osteoinduction. Gore-Tex was used as the physical barrier. After 6 months, the extraction side was closed by passing the lateral incisor through the graft site. The result was good tooth alignment and slight horizontal bone loss in the defect area.


[Multifocal cerebral venous thrombosis].
Cerebral venous thrombosis is a rare condition and represents a neurological emergency. It is a particular subtype of stroke, characterized by a huge diversity of neurological symptoms. Due to the diversity of its potential clinical presentations, medical imaging plays an important role in its early detection, even on non-dedicated examinations often performed in search of another acute neurological pathology. The aim of this case report is to illustrate the different radiological signs of cerebral venous thrombosis and to discuss the difficulties in diagnosing it by imaging at the acute stage.


Hepatitis B in Senegal: A Successful Infant Vaccination Program but Urgent Need to Scale Up Screening and Treatment (ANRS 12356 AmBASS survey).
Senegal introduced the infant hepatitis B virus (HBV) vaccination in 2004 and recently committed to eliminating hepatitis B by 2030. Updated epidemiological data are needed to provide information on the progress being made and to develop new interventions. We estimated the prevalence of hepatitis B surface antigen (HBsAg) in children and adults living in rural Senegal and assessed hepatitis B treatment eligibility. A cross-sectional population-based serosurvey of HBsAg was conducted in 2018-2019 in a large sample (n = 3,118) of residents living in the Niakhar area (Fatick region, Senegal). Individuals positive for HBsAg subsequently underwent clinical and biological assessments. Data were weighted for age and sex and calibrated to be representative of the area's population. Among the 3,118 participants, 206 were HBsAg positive (prevalence, 6.9%; 95% confidence interval [CI], 5.6-8.1). Prevalence varied markedly according to age group in individuals aged 0-4, 5-14, 15-34, and ≥35 years as follows: 0.0% (95% CI, 0.00-0.01); 1.5% (95% CI, 0.0-2.3); 12.4% (95% CI, 9.1-15.6); and 8.8% (95% CI, 6.1-11.5), respectively. Of those subsequently assessed, 50.9% (95% CI, 41.8-60.0) had active HBV infection; 4 (2.9%; 95% CI, 0.9-9.4) were eligible for hepatitis B treatment. Conclusion: In this first population-based serosurvey targeting children and adults in rural Senegal, HBsAg prevalence was very low in the former, meeting the World Health Organization's (WHO) < 1% HBsAg 2020 target; however, it was high in young adults (15-34 years old) born before the HBV vaccine was introduced in 2004. To reach national and WHO hepatitis elimination goals, general population testing (particularly for adolescents and young adults), care, and treatment scale-up need to be implemented.


CFA with binary variables in small samples: a comparison of two methods.
Asymptotically optimal correlation structure methods with binary data can break down in small samples. A new correlation structure methodology based on a recently developed odds-ratio (OR) approximation to the tetrachoric correlation coefficient is proposed as an alternative to the LPB approach proposed by Lee et al. (1995). Unweighted least squares (ULS) estimation with robust standard errors and generalized least squares (GLS) estimation methods were compared. Confidence intervals and tests for individual model parameters exhibited the best performance using the OR approach with ULS estimation. The goodness-of-fit chi-square test exhibited the best Type I error control using the LPB approach with ULS estimation.


Using spatial analysis to demonstrate the heterogeneity of the cardiovascular drug-prescribing pattern in Taiwan.
Geographic Information Systems (GIS) combined with spatial analytical methods could be helpful in examining patterns of drug use. Little attention has been paid to geographic variation of cardiovascular prescription use in Taiwan. The main objective was to use local spatial association statistics to test whether or not the cardiovascular medication-prescribing pattern is homogenous across 352 townships in Taiwan. The statistical methods used were the global measures of Moran's I and Local Indicators of Spatial Association (LISA). While Moran's I provides information on the overall spatial distribution of the data, LISA provides information on types of spatial association at the local level. LISA statistics can also be used to identify influential locations in spatial association analysis. The major classes of prescription cardiovascular drugs were taken from Taiwan's National Health Insurance Research Database (NHIRD), which has a coverage rate of over 97%. The dosage of each prescription was converted into defined daily doses to measure the consumption of each class of drugs. Data were analyzed with ArcGIS and GeoDa at the township level. The LISA statistics showed an unusual use of cardiovascular medications in the southern townships with high local variation. Patterns of drug use also showed more low-low spatial clusters (cold spots) than high-high spatial clusters (hot spots), and those low-low associations were clustered in the rural areas. The cardiovascular drug prescribing patterns were heterogeneous across Taiwan. In particular, a clear pattern of north-south disparity exists. Such spatial clustering helps prioritize the target areas that require better education concerning drug use.


Identification and Targeting of Mutant Peptide Neoantigens in Cancer Immunotherapy.
In recent decades, adoptive cell transfer and checkpoint blockade therapies have revolutionized immunotherapeutic approaches to cancer treatment. Advances in whole exome/genome sequencing and bioinformatic detection of tumour-specific genetic variations and the amino acid sequence alterations they induce have revealed that T cell mediated anti-tumour immunity is substantially directed at mutated peptide sequences, and the identification and therapeutic targeting of patient-specific mutated peptide antigens now represents an exciting and rapidly progressing frontier of personalized medicine in the treatment of cancer. This review outlines the historical identification and validation of mutated peptide neoantigens as a target of the immune system, and the technical development of bioinformatic and experimental strategies for detecting, confirming and prioritizing both patient-specific or "private" and frequently occurring, shared "public" neoantigenic targets. Further, we examine the range of therapeutic modalities that have demonstrated preclinical and clinical anti-tumour efficacy through specifically targeting neoantigens, including adoptive T cell transfer, checkpoint blockade and neoantigen vaccination.