PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning.
Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n = 84), PTSD+DS (n = 49), and age-matched healthy controls (n = 51). As compared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, as compared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.


Implementation of Protocolized Care in ARDS Improves Outcomes.
Treatments for ARDS that improve patient outcomes include use of lung-protective ventilation, prone ventilation, and conservative fluid management. Implementation of ARDS protocols via educational programs might improve adherence and outcomes. The objective of this study was to investigate the effects of an ARDS protocol implementation on outcomes and adherence with ARDS guidelines. This was a single-center, interventional, comparative study before and after protocol implementation. Staff education for the ARDS protocol was implemented between June 2014 and May 2015. A retrospective cohort analysis was conducted during between January 2012 and May 2014 (pre-protocol) and between June 2015 and June 2017 (post-protocol). A total of 450 subjects with ARDS were included. After propensity score matching, 432 subjects were analyzed. Of those, 330 subjects were treated after protocol implementation. The median (interquartile range [IQR]) plateau pressure and tidal volume over the first 3 d decreased significantly after protocol implementation (30.5 [IQR 24.2-33] vs 25.5 [IQR 21.7-30], P = .01 and 7.65 vs 7.4 mL/kg predicted body weight, P = .032, respectively). The percentage of subjects with unsafe tidal volume (> 10 mL/kg predicted body weight) decreased (14.4% vs 5.8%, P = .02). The percentage of subjects with safe plateau pressure (≤ 30 cm H2O) increased (47.4% vs 76.5%, P < .001). PEEP deviation from the ARDSNet PEEP/[Formula: see text] table was significantly lower after the implementation. Mortality at 28 and 90 days improved after implementation (53.9% vs 41.8% and 61.8% vs 48.2%, respectively). Adjusted odds ratios for 28-d and 90-d mortality were 0.47 (95% CI 0.28-0.78) and 0.45 (95% CI 0.27-0.76), respectively. ARDS protocol implementation was associated with improved survival and rate of adherence.


A ten-year review of neonatal bloodstream infections in a tertiary private hospital in Kenya.
Neonatal mortality in developing countries is usually due to an infectious cause. The gold standard of investigation in developing countries is a positive blood culture. It is important to know the aetiology of neonatal bloodstream infections so that empiric treatment can be effective. We conducted a retrospective clinical audit over ten years between January 2000 until December 2009, looking at the aetiology of both early and late onset neonatal sepsis. We analysed data from 152 (23%) patient isolates out of 662 suspected cases of neonatal sepsis. Our study revealed that Gram-positive organisms were the predominant cause of both early and late onset sepsis; the common isolates were Staphylococcus epidermidis (34%) and Staphylococcus aureus (27%). There were no isolates of group B Streptococcus. Candida species was isolated only in patients with late onset sepsis (6.9%). Bacterial isolates were relatively sensitive to the commonly used first- and second-line empiric antibiotics. Gram-positive organisms remain the major cause of neonatal bloodstream infections in our setup. The findings of this study will guide clinicians in prescribing the right empiric therapy in cases of suspected neonatal sepsis before the definitive culture results are obtained.


Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma.
Currently, tumor-node-metastasis stage and histologic type are the established prognostic factors for malignant pleural mesothelioma, whereas no prognostic markers have been established for clinical practice. We investigated the prognostic value of CD10, a metalloproteinase that can promote cancer aggressiveness through enzymatic degradation and intracellular signaling crosstalk, in malignant pleural mesothelioma. CD10 immunostaining was performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148; biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative (no staining) or positive (any staining). Epithelioid tumors were classified as pleomorphic subtype when cytologic pleomorphism was ≥10 % of the tumor. Overall survival (OS) was analyzed by log-rank tests and Cox proportional hazard models. Tumoral CD10 expression was identified in 42 % of epithelioid non-pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was correlated with higher mitotic count (p = 0.002). Overall survival for patients with positive CD10 expression was significantly shorter than that for patients with negative CD10 expression in all patients (p = 0.001) and in patients with epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019). Tumoral CD10 expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma.


Community consultation in emergency research.
Recent federal regulations allow for emergency research without prospective consent provided that additional protections for the subjects are provided. One of these is community consultation. To determine how to feasibly consult the community and what to do with the findings. In connection with an ongoing study of l-arginine for brain injury at a public hospital's trauma center, we consulted three sets of community representatives using different methods. To sample the entire population of the county, we conducted a random-digit dialing survey (456 residents). To sample individuals served by the hospital, we interviewed a convenience sample of 566 patients and individuals in the waiting area. To sample particularly interested individuals, we conducted a series of public meetings (114 participants). In each case, the same instrument was used to ascertain their attitudes toward the study in general and toward its major features (randomization, waiver of consent, location, risks/benefits). To control for framing effects, items were randomly presented in a positive or negative fashion. All methods proved feasible, but telephone surveys were most efficient and guaranteed the desired demography. Even for a very low-risk study, only 79.75% of respondents would be willing to participate. The rate of approval for the major features was lower, with only 67.78% approving of the risk/benefit ratio, 53.7% approving of randomization, 57.66% approving of the consent waiver, and 44.45% approving of the location. The most significant factors affecting the rate of approval were the method of consultation and the framing of items (both p < .001), age, ethnicity, and previous research participation (all p < .01). Community consultation is feasible, but its results depend heavily on method of consultation, framing of questions, and choice of community. It may well demonstrate unexpectedly substantial opposition. There needs to be a better definition of the process and a better understanding of how to respond to its results.


A forest ecosystem guide for the Amos Lowlands Ecological Region, northwestern Quebec: A forest management approach.
In Quebec, forest stations are defined as forest units that are reasonably homogeneous in terms of forest composition and site characteristics - as expressed by surficial deposit and moisture regime - and within which similar operational constraints for silvicultural potential and productivity levels may be expected. In the course of developing a field guide to the forest stations of the Amos Lowlands Ecological Region in northwestern Quebec, classifications of 12 site types and 72 forest stations (38 forest cover types or 16 general cover types) were developed. The classifications were based on a hybrid approach involving cluster analysis of forest ecological units inventoried in subregional studies, classical classification and ordination analyses performed on a regional biophysical inventory database, and empirically associating forest cover types to site types. The guide, while similar to other published forest ecosystem classification guides, emphasizes forest dynamics by presenting forest stations common to a given site type according to their successional stage. Field keys and general interpretations of forest potential and operational constraints are included in the guide. A summary description of the guide and accompanying documents is provided. A first draft has been distributed recently for feedback from industrial and government foresters and researchers in the region. Analyses of inventory data is continuing and modifications will be incorporated into a second draft before publication in 1995.


How the Level of Reward Awareness Changes the Computational and Electrophysiological Signatures of Reinforcement Learning.
The extent to which subjective awareness influences reward processing, and thereby affects future decisions, is currently largely unknown. In the present report, we investigated this question in a reinforcement learning framework, combining perceptual masking, computational modeling, and electroencephalographic recordings (human male and female participants). Our results indicate that degrading the visibility of the reward decreased, without completely obliterating, the ability of participants to learn from outcomes, but concurrently increased their tendency to repeat previous choices. We dissociated electrophysiological signatures evoked by the reward-based learning processes from those elicited by the reward-independent repetition of previous choices and showed that these neural activities were significantly modulated by reward visibility. Overall, this report sheds new light on the neural computations underlying reward-based learning and decision-making and highlights that awareness is beneficial for the trial-by-trial adjustment of decision-making strategies.SIGNIFICANCE STATEMENT The notion of reward is strongly associated with subjective evaluation, related to conscious processes such as "pleasure," "liking," and "wanting." Here we show that degrading reward visibility in a reinforcement learning task decreases, without completely obliterating, the ability of participants to learn from outcomes, but concurrently increases subjects' tendency to repeat previous choices. Electrophysiological recordings, in combination with computational modeling, show that neural activities were significantly modulated by reward visibility. Overall, we dissociate different neural computations underlying reward-based learning and decision-making, which highlights a beneficial role of reward awareness in adjusting decision-making strategies.


Development of an acute cutaneous swine model for Loxosceles envenomation.
To develop an acute cutaneous swine model for Loxosceles envenomation which could be used to objectively compare various treatment modalities. Nine weanling, mixed-breed domestic piglets. Piglets were injected intradermal in the hindlimb with Loxosceles deserta venom in increasing doses and concentrations until consistently large lesions were obtained. A minimum of 3 injections/venom preparation were carried out, with no more than 2 injections/animal. Repeat injections in the same animal were separated by 8 d. All lesions were measured daily for erythema and necrosis for 7 consecutive days. Data are reported as individual and mean maximal values. The piglets receiving 0.1, 0.2 or 0.3 ml of 5 microliters venom/ml saline developed small inconsistent lesions, with the largest necrotic lesion 5 mm. Those injected with 0.3 ml of venom diluted 15 microliters/ml saline developed small necrotic lesions (mean 4 mm, maximal 10 mm). All piglets injected with 25 microliters of venom diluted to 0.3 ml developed large necrotic lesions (mean 33 mm) with substantial erythema (mean 177 mm). Intradermal injection of 0.1 ml of 25 microliters purified Loxosceles deserta venom diluted to 0.3 ml with sterile saline produced large necrotic lesions in piglets. This model may be used to study Loxosceles envenomation and treatment.


A question of origin: dioxin-like PCBs and their relevance in stock management of European eels.
The stock of European Eel (Anguilla anguilla L.) has reached an all-time low in 2011. Spawner quality of mature eels in terms of health status and fitness is considered one of the key elements for successful migration and reproduction. Dioxin-like Polychlorinated Biphenyls (dl-PCBs) are known persistent organic pollutants potentially affecting the reproductive capability and health status of eels throughout their entire lifetime. In this study, muscle tissue samples of 192 European eels of all continental life stages from 6 different water bodies and 13 sampling sites were analyzed for contamination with lipophilic dl-PCBs to investigate the potential relevance of the respective habitat in light of eel stock management. Results of this study reveal habitat-dependent and life history stage-related accumulation of targeted PCBs. Sum concentrations of targeted PCBs differed significantly between life stages and inter-habitat variability in dl-PCB levels and -profiles was observed. Among all investigated life stages, migrant silver eels were found to be the most suitable life history stage to represent their particular water system due to habitat dwell-time and their terminal contamination status. With reference to a possible negative impact of dl-PCBs on health and the reproductive capability of eels, it was hypothesized that those growing up in less polluted habitats have a better chance to produce healthy offspring than those growing up in highly polluted habitats. We suggest that the contamination status of water systems is fundamental for the life cycle of eels and needs to be considered in stock management and restocking programs.


A genome-wide expression profile of adrenocortical cells in knockout mice lacking steroidogenic acute regulatory protein.
Steroidogenic acute regulatory protein (StAR) facilitates cholesterol transfer into the inner mitochondrial membrane in the acute phase of steroidogenesis. Mice lacking StAR (Star(-/-)) share phenotypes with human individuals having congenital lipoid adrenal hyperplasia including compromised production of steroid hormones and florid accumulation of cholesterol esters in adrenal glands and gonads. To define a specific pattern of molecular changes with StAR deficiency, we performed transcriptome analysis of adrenal cells selectively isolated by fluorescent-activated cell sorting at embryonic d 17.5 or 18.5 in seven wild-type (Star(+/+)) or four Star(-/-) mice having the transgene targeting the enhanced green fluorescent protein to cell lineages that express StAR. A gene expression profile was obtained by whole-mouse genome microarray and confirmed by quantitative real-time PCR, identifying 1206 and 767 significantly up-regulated and down-regulated genes, respectively, in Star(-/-) mice compared with Star(+/+) mice (fold difference ≥ 2 and P value < 0.05 with false discovery rate < 0.2). In Star(-/-) mice, expression levels of genes involved in cholesterol efflux and the inflammatory response were significantly up-regulated, whereas those related to steroid hormone biosynthesis or cholesterol biosynthesis and influx were not significantly changed. Immunoreactive Iba1 or F4/80 (macrophage marker) in adrenal glands of Star(-/-) mice was detected not only in an increased number of resident macrophages but also in most adrenocortical cells. These findings expand our understanding of the pathophysiology of adrenal glands with the disruption of StAR and propose a reciprocal interaction between adrenocortical cells and resident macrophages inside adrenal glands of Star(-/-) mice.


Differences in physician compliance with guideline on lipid profile determination within 24 h after acute myocardial infarction.
To evaluate the American College of Cardiology/American Heart Association guidelines on blood lipid testing within 24 h of the onset of chest pain in patients with myocardial infarction. This is a cross-sectional observational study on 83 patients (77 male, 6 female) admitted into the Coronary Care Units of the Al-Amiri and Mubarak Al-Kabeer Hospitals, Kuwait with myocardial infarction. The lipid profiles were obtained within 24 h of the onset of chest pain. Twenty patients were on treatment with statins prior to admission. Diagnosis of myocardial infarction in all patients was based on standard criteria. Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (Tg) were measured and low-density lipoprotein (LDL) cholesterol was calculated. Twenty-three patients had normal cardiac markers on admission but later developed increased serum markers and ECG changes of acute myocardial infarction. Mean (95% confidence interval) TC, HDL, Tg and LDL were 5.1 (4.8-5.4); 0.93 (0.88-0.98); 1.85 (1.56-2.14), and 3.39 (3.13-3.65) mmol/l, respectively. 70% of the patients had normal or only mild elevations of LDL with low HDL and poor HDL:TC ratio (<20%). Thirty-eight patients had low HDL (<0.9 mmol/l) and only 22 (27%) patients met the National Cholesterol Education Program guideline of target LDL <2.6 mmol/l. Fifty-six patients were classified as having the metabolic syndrome according to the criteria of the WHO. The findings indicate that HDL appears to be the main lipid risk factor in patients presenting with AMI in Kuwait, therefore primary prevention strategies should focus on treatment modalities that increase HDL. We recommend that the lipid profile should be done within 24 h of admission and lipid-lowering therapy initiated as part of secondary prevention strategy.


Proposed design of a Josephson diode.
We propose a new type of Josephson junction formed by two superconductors close to the superconductor-Mott-insulator transition, one of which is doped with holes and the other is doped with electrons. A self-organized Mott-insulating depletion region is formed at the interface between two superconductors, giving rise to an asymmetric response of current to the external voltage. The collective excitations of the depletion region result in a novel phase dynamics that can be measured experimentally in the noise spectrum of the Josephson current.


Aggregation of cancer in first-degree relatives of patients with glioma.
Previous studies have been inconclusive in estimating the risk of different cancer sites among close relatives of glioma patients; however, malignant melanoma has consistently been described. We obtained family history information from 1,476 glioma patients under age 75 years who registered at M. D. Anderson Cancer Center between June 1992 and June 2006. The number of observed cancers (N=1,001) among 8,746 first-degree relatives (FDR) was compared with the number expected from age-, sex-, and calendar year-specific rates from the Surveillance, Epidemiology, and End Results Program using standardized incidence ratios (SIR). The overall SIR for any cancer was 1.21 (95% confidence interval, 1.14-1.29). Among FDRs under 45 years the overall SIR was 5.08, and for relatives >45 years the overall SIR was 0.95. The SIRs were significantly elevated for brain tumors (2.14), melanoma (2.02), and sarcoma (3.83). We observed an excess of pancreatic cancer, which was significantly higher only among mothers. We observed an overall 21% increase in cancer among the FDRs of glioma patients including excess cases of brain tumors and melanoma, which could point to similar genetic contributions to these two malignancies. A large international linkage study is under way to examine potential genomic regions important for familial glioma.


Leopard syndrome.
LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4-5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable.


Curd and whey proteins in the nutrition of low birthweight babies.
Some animals thrive more satisfactorily on a milk that contains whey and curd protein. For this reason human milk protein (which contains about 40% whey) may have some advantages over cows' milk protein (which contains about 15% whey) and so infants feeding formulae based on demineralised whey in which the protein has been modified to achieve a curd:whey ratio similar to that in human milk may also thrive more satisfactorily. As the exact situation in the human newborn is unclear, the effects of feeding a formula containing unmodified cows' milk protein (mainly curd) and one containing the same amount of modified cows' milk protein (curd and whey) were studied in 57 low birthweight babies during the first 3 months of life. During the early weeks of life the curd and whey group grew bigger, absorbed more nitrogen, and excreted proportionately less urea. These results suggest that a curd and whey formula has advantages in the protein nutrition of low birthweight babies, especially the preterm ones. We feel it would be unwise to reduce the protein content of a formula based on cows' milk below 15 g/1 unless it was modified to achieve a larger proportion of whey protein and hence, among other qualities, more cysteine. Although some of the qualities of human milk protein can be mimicked by the use of demineralised whey formulae, others cannot.


Dermatosis frequency evaluation in the ambulatorial attendance of dermatology.
The objective was to evaluate the prevalence of skin diseases in patients seen at the Dermatology outpatients' clinic of the Santa Casa de São Paulo during the period from June to October 2005, comparing the results with a similar survey conducted at the same center in 1977. During the period of study, the electronic medical charts of 3011 patients seen in a first visits were analyzed.


Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients.
Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.


Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria.
Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.


Scale-dependent effects of host patch traits on species composition in a stickleback parasite metacommunity.
A core goal of ecology is to understand the abiotic and biotic variables that regulate species distributions and community composition. A major obstacle is that the rules governing species distributions can change with spatial scale. Here, we illustrate this point using data from a spatially nested metacommunity of parasites infecting a metapopulation of threespine stickleback fish from 34 lakes on Vancouver Island, British Columbia. Like most parasite metacommunities, the composition of stickleback parasites differs among host individuals within each host population, and differs between host populations. The distribution of each parasite taxon depends, to varying degrees, on individual host traits (e.g., mass, diet) and on host-population characteristics (e.g., lake size, mean host mass, mean diet). However, in most cases in this data set, a given parasite was regulated by different factors at the host-individual and host-population scales, leading to scale-dependent patterns of parasite-species co-occurrence.


Extent of gene duplication in the genomes of Drosophila, nematode, and yeast.
We conducted a detailed analysis of duplicate genes in three complete genomes: yeast, Drosophila, and Caenorhabditis elegans. For two proteins belonging to the same family we used the criteria: (1) their similarity is > or =I (I = 30% if L > or = 150 a.a. and I = 0.01n + 4.8L(-0.32(1 + exp(-L/1000))) if L < 150 a.a., where n = 6 and L is the length of the alignable region), and (2) the length of the alignable region between the two sequences is > or = 80% of the longer protein. We found it very important to delete isoforms (caused by alternative splicing), same genes with different names, and proteins derived from repetitive elements. We estimated that there were 530, 674, and 1,219 protein families in yeast, Drosophila, and C. elegans, respectively, so, as expected, yeast has the smallest number of duplicate genes. However, for the duplicate pairs with the number of substitutions per synonymous site (K(S)) < 0.01, Drosophila has only seven pairs, whereas yeast has 58 pairs and nematode has 153 pairs. After considering the possible effects of codon usage bias and gene conversion, these numbers became 6, 55, and 147, respectively. Thus, Drosophila appears to have much fewer young duplicate genes than do yeast and nematode. The larger numbers of duplicate pairs with K(S) < 0.01 in yeast and C. elegans were probably largely caused by block duplications. At any rate, it is clear that the genome of Drosophila melanogaster has undergone few gene duplications in the recent past and has much fewer gene families than C. elegans.


[The "major" proteins of the human myocardium in ontogeny].
Two-dimensional electrophoresis according to O'Farrell was used for studying changes in the content of major proteins of human myocardium at various stages of pre- and postnatal development. On the basis of the protein pattern specific of certain stages of myocardium differentiation the degree of development of the human cardiac muscle can be determined. The most pronounced changes in myocardium protein spectra are characteristic of the first half of pregnancy.


Drug distribution in human hair by infrared microscopy.
Localization of drug metabolites within human hair is important in determining the pharmacokinetics of drug incorporation in hair. This information is critical to validate drug testing data from hair. Microspectroscopic probing of small areas within longitudinally microtomed hair sections provides a profile of the deposition of drug along a growth line and thus indicates localization as a function of time. Probing across individual hairs may reveal the hydrophobic/hydrophilic characteristics of the substance. Hydrophobic drugs tend to bind to the central core or medulla of the hair while hydrophilic drugs tend to be spread throughout the cortex of the hair and appear, generally, in lower concentrations per dose. Profiles of distribution with high spatial resolutions of the regions of the hair are necessary for these determinations. This information is available to a certain extent in normal infrared microscopy and enhanced in synchrotron powered infrared microscopy.


Low-field magnetic resonance imaging of the canine middle and inner ear.
A series of low-field magnetic resonance images of the normal canine middle and inner ear are presented to serve as a reference. A completely balanced steady-state gradient echo pulse sequence with a slice thickness of 0.9 mm can be used to acquire images of the relevant structures within and neighboring the inner ear. These were the cochlear duct, semicircular ducts, vestibule, facial and vestibulocochlear nerves, as well as the temporal sinus. Within the middle ear, no applied sequence was able to allow identification of the auditory ossicles or the tympanic membrane.


Pathogenesis and immunity in murine salmonellosis.
Salmonella is traditionally described as a facultative intracellular parasite, and host macrophages are regarded as the primary effector cells in both native and acquired immunity in mouse typhoid. This concept has not been unanimously accepted in the literature. Based on cell culture experiments and electron microscopic examinations of infected tissues, we observed that virulent Salmonella typhimurium is killed within polymorphs and macrophages of guinea pigs and mice. In a systemic disease, the organism propagates primarily in the extracellular locations of sinusoids and tissue lesions and within hepatocytes. Hence, it is more likely to be an extracellular pathogen and its virulence is directly related to its antiphagocytic property. The conspicuous absence of macrophages in the primary lesions of murine salmonellosis disputes the likelihood of their significant role in native resistance to the disease. Acquired cellular immunity is expressed as an enhanced antibacterial activity of macrophages facilitated by cytophilic antibodies rather than as an altered antibacterial action of immune macrophages. It is proposed that acquired immunity in murine salmonellosis is a synergistic manifestation of the innate capacity of polymorphs and macrophages to destroy ingested salmonellae, the activated antibacterial functions of macrophages mediated by cytophilic antibodies, the opsonic and agglutinating actions of antiserum, and the accelerated inflammation associated with delayed hypersensitivity to bacterial antigens. Unlike live attenuated vaccines, nonviable vaccines offer a significant, though not a solid, protection against subsequent challenges.


Lacticin 481: in vitro reconstitution of lantibiotic synthetase activity.
The lantibiotic lacticin 481 is synthesized on ribosomes as a prepeptide (LctA) and posttranslationally modified to its mature form. These modifications include dehydration of serines and threonines, followed by intramolecular addition of cysteines to the unsaturated amino acids, which generates cyclic thioethers. This process breaks eight chemical bonds and forms six newbonds and is catalyzed by one enzyme, LctM. We have characterized the in vitro activity of LctM, which completely processed a series of LctA mutants, displaying a permissive substrate specificity that holds promise for antibiotic engineering.


Predicting fruit and vegetable consumption in long-haul heavy goods vehicle drivers: Application of a multi-theory, dual-phase model and the contribution of past behaviour.
Fruit and vegetable intake is insufficient in industrialized nations and long-haul heavy goods vehicle (HGV) drivers are considered a particularly at-risk group. The aim of the current study was to test the effectiveness of a multi-theory, dual-phase model to predict fruit and vegetable consumption in Australian long-haul HGV drivers. A secondary aim was to examine the effect of past fruit and vegetable consumption on model paths. A prospective design with two waves of data collection spaced one week apart was adopted. Long-haul HGV drivers (N = 212) completed an initial survey containing theory-based measures of motivation (autonomous motivation, intention), social cognition (attitudes, subjective norms, perceived behavioural control), and volition (action planning, coping planning) for fruit and vegetable consumption. One week later, participants (n = 84) completed a self-report measure of fruit and vegetable intake over the previous week. A structural equation model revealed that autonomous motivation predicted intentions, mediated through attitudes and perceived behavioural control. It further revealed that perceived behavioural control, action planning, and intentions predicted fruit and vegetable intake, whereby the intention-behaviour relationship was moderated by coping planning. Inclusion of past behaviour attenuated the effects of these variables. The model identified the relative contribution of motivation, social cognition, and volitional components in predicting fruit and vegetable intake of HGV drivers. Consistent with previous research, inclusion of past fruit and vegetable consumption led to an attenuation of model effects, particularly the intention-behaviour relationship. Further investigation is needed to determine which elements of past behaviour exert most influence on future action.


Prevention and control of enterohaemorrhagic Escherichia coli (EHEC) infections: memorandum from a WHO meeting. WHO Consultation on Prevention and Control of Enterohaemorrhagic Escherichia coli (EHEC) Infections.
Escherichia coli is a commonly occurring inhabitant of the intestine of humans and other animals, but there are several pathogenic types of E. coli which cause a variety of human diseases. One of these pathogenic types, E. coli O157:H7, belongs to the group of enterohaemorrhagic E. coli (EHEC) which produce potent toxins and cause a particularly severe form of disease, haemorrhagic colitis (HC). About 10% of patients with HC can go on to develop haemolytic uraemic syndrome (HUS), a life-threatening complication of E. coli O157:H7 infection that is characterized by acute renal failure, haemolytic anaemia, and thrombocytopenia. These sequelae are particularly serious in young children and older people. On average, 2-7% of patients with HUS die, but in some outbreaks among the elderly the mortality rate has been as high as 50%. This Memorandum reviews the growing importance of E. coli O157:H7 as a foodborne pathogen and reports on the issues of surveillance, outbreak investigation, and control strategies with respect to EHEC infections that were discussed at the WHO Consultation on Prevention and Control of EHEC Infections, held in Geneva on 28 April to 1 May 1997. Recommended measures for prevention and control include the following: use of potable water in food production; presentation of clean animals at slaughter; improved hygiene throughout the slaughter process; appropriate use of food processing measures; thorough cooking of foods; and the education of food handlers, abattoir workers, and farm workers on the principles and application of food hygiene.


A syndemic of COVID-19 and methanol poisoning in Iran: Time for Iran to consider alcohol use as a public health challenge?
Methanol poisoning has been a significant public health challenge for several decades in Iran. Even though alcohol use is highly criminalized, people consume illicit alcohol, which tends to be predominantly homemade and often contains methanol. Consequently, thousands of individual poisonings and hundreds of deaths annually are attributable to methanol poisoning. From February 19, 2020 through April 27, 2020, the 2019 coronavirus disease (COVID-19) epidemic rapidly expanded in Iran, and has been associated with 90,481 confirmed cases and 5710 confirmed deaths. Secondary to misinformation about the potential for alcohol to neutralize SARS-CoV-2, there has also been a significant escalation in methanol-related morbidity and mortality, with over 5000 people poisoned and over 500 confirmed deaths for the same period from February through April 2020. In some provinces, the case-fatality rate of methanol poisoning was higher than that from COVID-19. The high morbidity and mortality associated with methanol poisoning preceding and exacerbated by COVID-19 highlight the potential population level health impacts of the implementation of evidence-based education and harm reduction strategies focused on alcohol use across Iran.


Cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid gastric administration during the pregestational and gestational periods does not influence the follicular endowment of the progeny.
Fetal programming suggests that maternal stimulation and nutrition during the period of fetal development can program the progeny. Conjugated linoleic acid (CLA), an isomer of linoleic acid, has been characterized in several aspects, but few studies have been performed on its involvement in reproduction and fetal programming. The aim of this study was to evaluate the F1, F2 and F3 progeny of female mice supplemented with CLA during the pregestational and gestational periods with respect to biometric and reproductive parameters, as well as ovarian morphophysiology. The F1 progeny of mothers supplemented with CLA exhibited stable weight gain, while the F2 progeny showed no effects (P=0.0187 and P=0.0245, respectively). A reduction in Lee's Index was observed in both generations at the second post-weaning evaluation week in the animals treated with CLA (P=0.0100 and P=0.0078, respectively). The F2 generation showed an increase in the anogenital index in both sexes of the animals treated with CLA (P= 0.0114 and P<0.0001, female and male respectively). CLA administration to mothers did not affect any of the following in their progeny: ovarian follicle mobilization (P>0.05), follicle number (P>0.05) and the integrated density of the lipid content of oocytes included in antral follicles (P>0.05). This study evaluated the use of CLA in mothers and found that it did not affect the progeny regarding murine reproductive performance, suggesting that this supplement can be used safely.


Reactions of electron-deficient alkynes and allenes under phosphine catalysis.
The development of some new synthetic reactions derived from nucleophilic addition of phosphines to electron-deficient carbon-carbon triple bonds is described. These reactions show that the phosphine plays the role of a nucleophile as well as an excellent leaving group. The central problem is to generate a 1,3-dipole from alkynoates or allenoates (2,3-butadienoates) by interaction with various phosphines. This study illuminates the unusual phenomena and shows how this understanding allows control of the reaction.


Regulation of the display ratio of enzymes on the Saccharomyces cerevisiae cell surface by the immunoglobulin G and cellulosomal enzyme binding domains.
We constructed a novel cell surface display system to control the ratio of target proteins on the Saccharomyces cerevisiae cell surface, using two pairs of protein-protein interactions. One protein pair is the Z domain of protein A derived from Staphylococcus aureus and the Fc domain of human immunoglobulin G. The other is the cohesin (Coh) and dockerin (Dock) from the cellulosome of Clostridium cellulovorans. In this proposed displaying system, the scaffolding proteins (fusion proteins of Z and Coh) were displayed on the cell surface by fusing with the 3' half of alpha-agglutinin, and the target proteins fused with Fc or Dock were secreted. As a target protein, a recombinant Trichoderma reesei endoglucanase II (EGII) was secreted into the medium and immediately displayed on the yeast cell surface via the Z and Fc domains. Display of EGII on the cell surface was confirmed by hydrolysis of beta-glucan as a substrate, and EGII activity was detected in the cell pellet fraction. Finally, two enzymes, EGII and Aspergillus aculeatus beta-glucosidase 1, were codisplayed on the cell surface via Z-Fc and Dock-Coh interactions, respectively. As a result, the yeast displaying two enzymes hydrolyzed beta-glucan to glucose very well. These results strongly indicated that the proposed strategy, the simultaneous display of two enzymes on the yeast cell surface, was accomplished by quantitatively controlling the display system using affinity binding.


Mediastinal goiters. The need for an aggressive approach.
We reviewed the cases of 52 patients with substernal goiters to examine clinical presentation, workup, technique of removal, malignancy, and outcome. Half of the patients were asymptomatic; half had at least one compressive symptom. Chest film was the most used; computed tomography or magnetic resonance imaging was by far the most useful study. Thyroid scans often failed to show the intrathoracic goiter. Fine-needle aspiration was not helpful because of the gland's inaccessibility. Seventeen percent (nine) of the thyroids showed malignancy, 21% (11) including incidental papillary carcinomas. These were not identified by duration of goiter, symptoms, or fine-needle aspiration. Except for lymphomas, prognosis was good after resection. Removal was almost always accomplished via cervical incision, with low morbidity and no deaths. The threat of compression, the substantial chance of malignancy, and the safety of resection mean that the presence of substernal goiter is an indication for surgery.


Discordant immunophenotypic profiles of adhesion molecules and cytokines in acute myeloid leukemia involving bone marrow and skin.
We investigated the role of adhesion molecules in skin involvement by acute myeloid leukemia (AML) using immunohistochemical analysis. Ten paired cases of skin and bone marrow biopsy specimens from patients with myeloid leukemia cutis (MLC) and 15 bone marrow biopsy specimens from patients without MLC were studied with antibodies directed against CD29, CD34, CD54, CD62-L, CD183, and cutaneous lymphocyte antigen (CLA). CLA was expressed in all cases of leukemia whereas CD54 was negative within blasts. CD62-L was expressed in 4 of 10 specimens of marrow infiltrates with MLC and 6 of 10 specimens of matching skin infiltrates; in marrows without MLC, only 2 of 15 were positive. CD29 was expressed in 1 of 10 marrow infiltrate specimens with MLC and 4 of 10 matching skin infiltrate specimens; in marrows without MLC, only 1 of 15 were positive. CD183 was expressed in 1 of 10 marrow infiltrate specimens with MLC and 4 of 10 matching skin infiltrate specimens; in marrows without MLC, CD183 was negative. The gain of CD62-L, CD29, and CD183 expression in bone marrow and skin infiltrates in leukemia cutis, relative to bone marrow infiltrates of cases without MLC, suggests a role for these markers in AML homing to skin.


[Proteins of bacterial membranes. NADH-dehydrogenase from the cells of Acholeplasma laidlawii].
Using ion-exchange chromatography on DEAE-cellulose and gel filtration, a purified NADH-dehydrogenase was prepared from cell membranes of A. laidlawii. The enzyme specific activity exceeds the activity of the membrane preparation 45-fold. The enzyme is thermolabile and sensitive to lecithine. Electrophoresis of the enzyme preparation in the presence of Na-DS resulted in two proteins with Mr of 65 000 and 72 000. Specific staining of the gels with triphenyltetrasolium chloride in the presence of Triton X-100 revealed two protein bands, while in the presence of Triton X-100 and urea only one protein band was produced.


ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics.
The eukaryotic single-stranded DNA (ssDNA)-binding protein Replication Protein A (RPA) plays a crucial role in various DNA metabolic pathways, including DNA replication and repair, by dynamically associating with ssDNA. While the binding of a single RPA molecule to ssDNA has been thoroughly studied, the accessibility of ssDNA is largely governed by the bimolecular behavior of RPA, the biophysical nature of which remains unclear. In this study, we develop a three-step low-complexity ssDNA Curtains method, which, when combined with biochemical assays and a Markov chain model in non-equilibrium physics, allow us to decipher the dynamics of multiple RPA binding to long ssDNA. Interestingly, our results suggest that Rad52, the mediator protein, can modulate the ssDNA accessibility of Rad51, which is nucleated on RPA coated ssDNA through dynamic ssDNA exposure between neighboring RPA molecules. We find that this process is controlled by the shifting between the protection mode and action mode of RPA ssDNA binding, where tighter RPA spacing and lower ssDNA accessibility are favored under RPA protection mode, which can be facilitated by the Rfa2 WH domain and inhibited by Rad52 RPA interaction.


Glutamate, aspartate and co-localization with calbindin in the medial thalamus. An immunohistochemical study in the rat.
Topographical and quantitative features of medial thalamic neurons in which aspartate (ASP) or glutamate (GLU) might act as neurotransmitters were investigated in the rat. The calcium-binding protein calbindin D-28k (CB) was exploited as a marker of neuronal subsets, thus allowing us to study also the relationships between the CB-containing neurons and those immunoreactive to excitatory amino acids. Double immunocytochemistry of ASP and CB or GLU and CB was performed in 40-microm-thick sections. The three markers were distributed in the thalamic midline, mediodorsal, anterior intralaminar and ventromedial nuclei, with regional variations. ASP-immunoreactive neurons appeared more numerous than the GLU-immunoreactive ones throughout these structures; ASP-CB or GLU-CB double-immunostained neurons were evident. ASP-, GLU- and CB-immunoreactive cells were then quantitatively evaluated in 5-microm-thick consecutive sections. Interindividual variations and different anti-ASP and anti-GLU antibodies did not result in significant differences. ASP and GLU were not co-localized. Single ASP- or GLU-immunoreactive neurons accounted for 60% of the total number of immunostained cells, and single ASP-immunopositive cells represented more than half of these neurons. Among the CB-immunoreactive cells (40% of the total), half were double immunostained; the proportion of double CB-ASP-immunopositive neurons was sevenfold higher than that of the CB-GLU-immunoreactive ones. These results indicate that ASP may act as excitatory neurotransmitter in a relatively high proportion of medial thalamic neurons, in which ASP frequently coexists with CB. Approximately 50% of the CB-immunoreactive cells did not contain either ASP or GLU, suggesting that some medial thalamic neurons may utilize a different neurotransmitter.


Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase.
The intestinal hormone guanylin and bacterial heat-stable enterotoxins (STs) are members of a peptide family that activates intestinal membrane guanylate cyclase. Two different peptides that activate the human intestinal T84 cell guanylate cyclase have been purified from urine and intestinal mucosa of opossums (Didelphis virginiana). The highly acidic peptide, QEDCELCINVACTGC, was named uroguanylin because it was isolated from urine and shares 53% identity with guanylin. A second peptide, SHTCEICAFAACAGC, was purified from urine and intestinal mucosa. This alanine-rich peptide was 47% identical to uroguanylin and 73% identical to human guanylin, suggesting that it may be an opossum homologue of guanylin. Synthetic uroguanylin-(2-15) (i.e., EDCELCINVACTGC) was 10-fold more potent than synthetic rat guanylin, but both peptides were less potent than Escherichia coli ST in the T84 cell cGMP bioassay. Uroguanylin-(2-15) and guanylin inhibited 125I-ST binding to T84 cell receptors in competitive radioligand binding assays. Transepithelial Cl- secretion was stimulated by 1 microM uroguanylin, indicated by an increase in the short circuit current of T84 cells. Thus, uroguanylin is another paracrine hormone in the emerging peptide family that activates intestinal membrane guanylate cyclase. The second peptide may be the opossum form of guanylin, or perhaps, it is still another member of this peptide family. The presence of uroguanylin and guanylin in urine and receptors in proximal tubules suggests that these peptides may also originate from renal tissue and may regulate kidney function.


Examination of the three-dimensional geometry of cetacean flukes using computed tomography scans: hydrodynamic implications.
The flukes of cetaceans function in the hydrodynamic generation of forces for thrust, stability, and maneuverability. The three-dimensional geometry of flukes is associated with production of lift and drag. Data on fluke geometry were collected from 19 cetacean specimens representing eight odontocete genera (Delphinus, Globicephala, Grampus, Kogia, Lagenorhynchus, Phocoena, Stenella, Tursiops). Flukes were imaged as 1 mm thickness cross-sections using X-ray computer-assisted tomography. Fluke shapes were characterized quantitatively by dimensions of the chord, maximum thickness, and position of maximum thickness from the leading edge. Sections were symmetrical about the chordline and had a rounded leading edge and highly tapered trailing edge. The thickness ratio (maximum thickness/chord) among species increased from insertion on the tailstock to a maximum at 20% of span and then decreasing steadily to the tip. Thickness ratio ranged from 0.139 to 0.232. These low values indicate reduced drag while moving at high speed. The position of maximum thickness from the leading edge remained constant over the fluke span at an average for all species of 0.285 chord. The displacement of the maximum thickness reduces the tendency of the flow to separate from the fluke surface, potentially affecting stall patterns. Similarly, the relatively large leading edge radius allows greater lift generation and delays stall. Computational analysis of fluke profiles at 50% of span showed that flukes were generally comparable or better for lift generation than engineered foils. Tursiops had the highest lift coefficients, which were superior to engineered foils by 12-19%. Variation in the structure of cetacean flukes reflects different hydrodynamic characteristics that could influence swimming performance.


Early Improvement of Psychiatric Symptoms with Long-Acting Injectable Antipsychotic Predicts Subsequent Social Functional Remission in Patients with Schizophrenia.
The aim of this study was to clarify whether early symptomatic improvement in response to a long-acting injectable antipsychotic (LAI) contributes to subsequent social functional remission in patients with schizophrenia using the previous clinical trial data (EudraCT registration number: 2011-004889-15). Associations between other factors and social functional remission were also explored. We analyzed 428 patients with schizophrenia in which the personal and social performance scale (PSP) and the involvement evaluation questionnaire (IEQ) at the time of the base line were recorded. Social functional remission was defined as participants who scored PSP >70 at the end of 65 weeks. Logistic regression analyses were done to examine associations between social functional remission and clinical and demographic characteristics including early symptomatic response evaluated by Positive and Negative Syndrome Scale (PANSS) at week one. One hundred out of 428 patients showed social functional remission at the end of the observation period. Shorter duration of illness, higher baseline score of supervision evaluated by IEQ and higher baseline PSP were significantly associated with the social functional remission. Improvement of positive subscale of PANSS at one week was significantly associated with later social functional remission when baseline PSP scores were excluded from predictive variables. Shorter duration of illness, residual type of schizophrenia, higher baseline score of supervision and higher baseline social functioning were predictors of subsequent social functional remission. Although its effect seems to be limited, early symptomatic improvement could be also was a predictor of social functional remission.


Multiple roles of a conserved GAF domain tyrosine residue in cyanobacterial and plant phytochromes.
The phytochrome family of red/far-red photoreceptors has been optimized to support photochemical isomerization of a bound bilin chromophore, a process that triggers a conformational change and modulates biochemical output from the surrounding protein scaffold. Recent studies have established that the efficiency of this photochemical process is profoundly altered by mutation of a conserved tyrosine residue (Tyr176) within the bilin-binding GAF domain of the cyanobacterial phytochrome Cph1 [Fischer, A. J., and Lagarias, J. C. (2004) Harnessing phytochrome's glowing potential, Proc. Natl. Acad. Sci. U.S.A. 101, 17334-17339]. Here, we show that the equivalent mutation in plant phytochromes behaves similarly, indicating that the function of this tyrosine in the primary photochemical mechanism is conserved. Saturation mutagenesis of Tyr176 in Cph1 establishes that no other residue can support comparably efficient photoisomerization. The spectroscopic consequences of Tyr176 mutations also reveal that Tyr176 regulates the conversion of the porphyrin-like conformation of the bilin precursor to a more extended conformation. The porphyrin-binding ability of the Tyr176Arg mutant protein indicates that Tyr176 also regulates the ligand-binding specificity of apophytochrome. On the basis of the hydrogen-bonding ability of Tyr176 substitutions that support the nonphotochemical C15-Z,syn to C15-Z,anti interconversion, we propose that Tyr176 orients the carboxyl side chain of a conserved acidic residue to stabilize protonation of the bilin chromophore. A homology model of the GAF domain of Cph1 predicts a C5-Z,syn, C10-Z,syn, C15-Z,anti configuration for the chromophore and implicates Glu189 as the proposed acidic residue stabilizing the extended conformation, an interpretation consistent with site-directed mutagenesis of this conserved acidic residue.


Trends and Predictors of National Institutes of Health Funding to Plastic Surgery Residency Programs.
Recent studies have demonstrated low levels of National Institutes of Health funding for surgical research. The authors compared the funding in plastic surgery with the funding for other surgical specialties. A query of National Institutes of Health grants awarded to departments of surgical specialties was performed using the National Institutes of Health RePORTER database (2008 to 2016). Trends in funding were compared by specialty and adjusted for the number of active physicians in each specialty. Plastic surgery residency program characteristics were correlated with funding procurement. Eight hundred eighty-nine faculty at 94 plastic surgery residency programs were queried. Forty-eight investigators (5.4 percent) at 23 programs (24.4 percent) had National Institutes of Health funding. From 2008 to 2016, a total of $84,142,138 was awarded through 81 grants. Funding supported translational (44.6 percent), clinical (26.4 percent), basic science (27.2 percent), and educational (1.7 percent) research. In 2016, plastic surgery received the least amount of National Institutes of Health funding per active physician ($1,530) relative to orthopedic surgery ($3124), obstetrics and gynecology ($3885), urology ($5943), otolaryngology ($9999), general surgery ($11,649), ophthalmology ($11,933), and neurologic surgery ($20,874). Plastic surgery residency program characteristics associated with National Institutes of Health funding were high ranking and had more than 10 clinical faculty (p < 0.05). Plastic surgery receives the least National Institutes of Health funding among the surgical specialties. Departments and divisions of plastic surgery should support investigators applying for research grants to increase future National Institutes of Health funding.


[A pongid (primates: pongidae) from the Pannonian (late Miocene) of lower austria].
Description of an (?) M-1 of a small pongid (Dryopithecus brancoi Schlosser) from the Late Miocene (Pannonian = Vallesian) of Mariathal in Lower Austria. The accompanying fauna is a typical Hipparion fauna with Hipparion primigenium, Gomphotherium (Tetralophodon) longirostre, Dinotherium giganteum, Aceratherium bavaricum, Anchitherium aurelianense, Chalicotherium goldfussi, Microstonyx (Korynochoerus) palaeochoerus, Dorcatherium naui, Amphiprox anocerus and Miotragocerus pannoniae. It is the first documentation of Dryopithecus brancoi in Austria and one of the youngest occurrences of a pongid in Middle Europe. The existence of this species in a biotop which is comparable with the recent mixed mesophytic forests in southeastern Asia is discussed. It is a vegetation of the warm-temperate zone, but between 48 degrees and 50 degrees of northern latitude.


Generalized linear mixed models for mapping multiple quantitative trait loci.
Many biological traits are discretely distributed in phenotype but continuously distributed in genetics because they are controlled by multiple genes and environmental variants. Due to the quantitative nature of the genetic background, these multiple genes are called quantitative trait loci (QTL). When the QTL effects are treated as random, they can be estimated in a single generalized linear mixed model (GLMM), even if the number of QTL may be larger than the sample size. The GLMM in its original form cannot be applied to QTL mapping for discrete traits if there are missing genotypes. We examined two alternative missing genotype-handling methods: the expectation method and the overdispersion method. Simulation studies show that the two methods are efficient for multiple QTL mapping (MQM) under the GLMM framework. The overdispersion method showed slight advantages over the expectation method in terms of smaller mean-squared errors of the estimated QTL effects. The two methods of GLMM were applied to MQM for the female fertility trait of wheat. Multiple QTL were detected to control the variation of the number of seeded spikelets.


Assessment of oral self-care in patients with periodontitis: a pilot study in a dental school clinic in Japan.
Oral hygiene education is central to every stage of periodontal treatment. Successful management of periodontal disease depends on the patient's capacity for oral self-care. In the present study, the oral self-care and perceptions of patients attending a dental school clinic in Japan were assessed using a short questionnaire referring to existing oral health models. A cross-sectional study design was used. The study population consisted of sixty-five patients (age range 23-77) with chronic periodontitis. The pre-tested 19-item questionnaire comprised 3 domains; 1) oral hygiene, 2) dietary habits and 3) perception of oral condition. The questionnaire was used as a part of the comprehensive assessment. Analyses of the assessment data revealed no major problems with the respondents' perceived oral hygiene habits, although their actual plaque control levels were not entirely adequate. Most of the respondents acknowledged the importance of prevention of dental caries and periodontal diseases, but less than one third of them were regular users of the dental care system. Twenty-five percent of the respondents were considered to be reluctant to change their daily routines, and 29% had doubts about the impact of their own actions on oral health. Analyzing the relationships between patient responses and oral hygiene status, factors like 'frequency of tooth brushing', 'approximal cleaning', 'dental check-up' and 'compliance with self-care advice' showed statistically significant associations (P < 0.05) with the plaque scores. The clinical utilization of the present questionnaire facilitates the inclusion of multiple aspects of patient information, before initiation of periodontal treatment. The significant associations that were found between some of the self-care behaviors and oral hygiene levels document the important role of patient-centered oral health assessment in periodontal care.


Positioning cytokinesis.
Cytokinesis is the terminal step of the cell cycle during which a mother cell divides into daughter cells. Often, the machinery of cytokinesis is positioned in such a way that daughter cells are born roughly equal in size. However, in many specialized cell types or under certain environmental conditions, the cell division machinery is placed at nonmedial positions to produce daughter cells of different sizes and in many cases of different fates. Here we review the different mechanisms that position the division machinery in prokaryotic and eukaryotic cell types. We also describe cytokinesis-positioning mechanisms that are not adequately explained by studies in model organisms and model cell types.


Pattern of Morphological Variability in Unrepaired Unilateral Clefts With and Without Cleft Palate May Suggest Intrinsic Growth Deficiency.
In individuals with cleft lip and palate (CLP) an iatrogenic effect of operations on subsequent maxillary growth is well-known. Much less is known about the association between occurrence of CLP and intrinsic growth deficiency of the maxillofacial complex. The aim of this study was to compare morphological variability in subjects with unilateral cleft lip and alveolus/palate and unaffected controls using geometric morphometric methods. The research hypothesis was that if subjects with unrepaired unilateral CLP have intrinsic growth deficiency, the pattern of their craniofacial growth variation may differ from that in unaffected individuals. Lateral cephalograms were available of three groups of the same ethnic background (Proto-Malayid): (a) non-syndromic unrepaired unilateral complete cleft lip, alveolus, and palate (UCLP), N = 66, mean age 24.5 years (b) non-syndromic unrepaired unilateral complete cleft lip and alveolus (UCLA), N = 177, mean age 23.7 years, and (c) NORM (N = 50), mean age 21.2 years without a cleft. Using geometric morphometrics shape variability in groups and shape differences between groups was analyzed. Principal component analysis (PCA) was used to examine shape variability, while differences between groups and sexes were evaluated with canonical variate analysis. Sexual dimorphism was evaluated with discriminant function analysis (DA). Results showed that in comparison to NORM subjects, shape variability in UCLA and UCLP is more pronounced in the antero-posterior than in vertical direction. Pairwise comparisons of the mean shape configurations (NORM vs. UCLA, NORM vs. UCLP, and UCLA vs. UCLP) revealed significant differences between cleft and non-cleft subjects. The first canonical variate (CV1, 68.2% of variance) demonstrated that differences were associated with maxillary shape and/or position and incisor inclination, while in females, the CV1 (69.2% of variance) showed a combination of differences of "maxillary shape and/or position and incisor inclination" and inclination of the cranial base. Shape variability demonstrated considerable differences in subjects with UCLA, UCLP, and NORM. Moreover, in subjects with a cleft, within-sample variability was more pronounced in the antero-posterior direction, while in non-cleft subjects, within-sample variability was more pronounced in the vertical direction. These findings may suggest that subjects with unilateral clefts have intrinsic growth impairment affecting subsequent facial development.


[Diagnosis and treatment of dementia].
Dementia is one of the most common conditions in the elderly. In Norway the total prevalence is about 60,000. The paper is based on the author's clinical experience and a review of the literature. No biological marker exists for Alzheimer's disease and other dementias. The diagnostic work-up thus consists of a comprehensive clinical neuropsychological, physical and psychiatric examination. Imaging of the brain could be useful in the differential diagnostic work-up. In mild cases and cases of suspected dementia, the work-up is carried out in specialist health care. Moderate and severe cases are assessed on primary care. There is currently no cure for dementia disorders, although acetylcholinesterase inhibitors may prove effective for Alzheimer's disease and Lewy body dementia. Behavioural and psychiatric symptoms can be pharmacologically treated. A careful diagnostic work-up must be carried out to diagnose dementia. Symptomatic treatment is available and should be initiated.


Facility-Level Factors Associated With CNA Turnover and Retention: Lessons for the Long-Term Services Industry.
Certified nursing assistant (CNA) turnover and retention are critical aspects of facilities' ability to provide cost-effective, high-quality person-centered care. Previous studies and industry practice often treat turnover and retention as similar concepts, assuming that low turnover and high retention are synonymous. The study addressed the question of whether turnover and retention rates differ and if so, what those differences mean for nursing home practice, policy, and research. This study examines facility-level factors associated with CNA retention and turnover rates using 2015 data from the Ohio Biennial Survey of Long-Term Care Facilities, Ohio Medicaid Cost Reports, Certification and Survey Provider Enhanced Report, and the Area Health Resource File. Using bivariate tests and regression analysis, we compare rates and the factors associated with retention and turnover. The mean facility annual retention rate was 64% and the mean annual turnover rate was 55%. As expected, there was a statistically significant and negative correlation between the rates (r = -0.26). However, some facilities had both high retention and high turnover and some had low rates for both measures. Not all the variables that are associated with turnover are also associated with retention. CNA retention is not simply the absence of CNA turnover. Given the differences, nursing homes may need to use strategies and policies designed to target a particular stability measure.


Fractal dimension brain morphometry: a novel approach to quantify white matter in traumatic brain injury.
Traumatic brain injury (TBI) is the main cause of disability in people younger than 35 in the United States. The mechanisms of TBI are complex resulting in both focal and diffuse brain damage. Fractal dimension (FD) is a measure that can characterize morphometric complexity and variability of brain structure especially white matter (WM) structure and may provide novel insights into the injuries evident following TBI. FD-based brain morphometry may provide information on WM structural changes after TBI that is more sensitive to subtle structural changes post injury compared to conventional MRI measurements. Anatomical and diffusion tensor imaging (DTI) data were obtained using a 3 T MRI scanner in subjects with moderate to severe TBI and in healthy controls (HC). Whole brain WM volume, grey matter volume, cortical thickness, cortical area, FD and DTI metrics were evaluated globally and for the left and right hemispheres separately. A neuropsychological test battery sensitive to cognitive impairment associated with traumatic brain injury was performed. TBI group showed lower structural complexity (FD) bilaterally (p < 0.05). No significant difference in either grey matter volume, cortical thickness or cortical area was observed in any of the brain regions between TBI and healthy controls. No significant differences in whole brain WM volume or DTI metrics between TBI and HC groups were observed. Behavioral data analysis revealed that WM FD accounted for a significant amount of variance in executive functioning and processing speed beyond demographic and DTI variables. FD therefore, may serve as a sensitive marker of injury and may play a role in outcome prediction in TBI.


Use of a DVD to provide dietary and lifestyle information to pregnant women who are overweight or obese: a nested randomised trial.
We conducted a nested randomised trial to evaluate the effect of an educational DVD, providing information about healthy food choices and exercise during pregnancy, on diet and physical activity, among pregnant women who were overweight or obese. We conducted a nested randomised trial within the context of the LIMIT randomised trial. Women were eligible with a singleton pregnancy between 10 and 20 weeks gestation, and body mass index at the time of their first antenatal appointment of ≥25 kg/m(2). All women who were randomised to the Lifestyle Advice Group of the LIMIT trial received a series of consultations with both research dieticians and research assistants, in addition to standard written dietary and exercise materials (Standard Materials Group). Women randomised to the DVD Group received the same consultations and written materials, and additionally received an educational DVD (DVD Group). The primary study outcome was the Healthy Eating Index. Other study outcomes included physical activity, and gestational weight gain. Women completed a qualitative evaluation of all the materials provided. 1,108 women in the LIMIT Lifestyle Advice Group participated in the nested trial, with 543 women randomised to the DVD Group, and 565 women to the Standard Materials Group. Women who received the DVD compared with those who did not, had a higher mean Healthy Eating Index at 36 weeks gestation (73.6 vs 72.3; adjusted mean difference 1.2; 95% CI 0.2 to 2.3; p = 0.02), but not at 28 weeks gestation (73.2 vs 73.5; adjusted mean difference -0.1; 95% CI -1.1 to 0.9; p = 0.82). There were no statistically significant differences in physical activity or total gestational weight gain. While most women evaluated the materials positively, frequency of utilisation was poor. Ongoing attention to the delivery of information is required, particularly with the increased use and availability of digital and multi-media interactive technologies. Australian and New Zealand Clinical Trials Registry ACTRN12607000161426.


[Morphology of organs of the immune system in perinatally dying babies with autosomal trisomies].
Morphology of the immune system organs was studied in 13 babies with autosomal trisomies (Down's, Edwards', and Patau's syndromes) dying in the perinatal period and having no morphological signs of infectious diseases. The control group included 5 babies without congenital malformations and 12 babies with unclassified multiple malformations. Hypoplasia of the lymphoid tissue was demonstrated in autosomal trisomies (the relative weight of the thymus decreased 2-fold; the spleen, lymph nodes and the intestinal tract deficient in lymphocytes). In Down's disease hypoplasia was most marked; besides, a 3-fold increase in the average area of Hassall's bodies as compared with that in Patau's and Edwards' syndromes and in the controls was observed. Babies with congenital malformations of non-chromosomal origin had no significant differences in the condition of the immune system organs as compared with babies without malformations which indicates the influence of chromosomal pathology on the formation of the immune system in the intrauterine period.


Place cells, grid cells, attractors, and remapping.
Place and grid cells are thought to use a mixture of external sensory information and internal attractor dynamics to organize their activity. Attractor dynamics may explain both why neurons react coherently following sufficiently large changes to the environment (discrete attractors) and how firing patterns move smoothly from one representation to the next as an animal moves through space (continuous attractors). However, some features of place cell behavior, such as the sometimes independent responsiveness of place cells to environmental change (called "remapping"), seem hard to reconcile with attractor dynamics. This paper suggests that the explanation may be found in an anatomical separation of the two attractor systems coupled with a dynamic contextual modulation of the connection matrix between the two systems, with new learning being back-propagated into the matrix. Such a scheme could explain how place cells sometimes behave coherently and sometimes independently.


Geographic variation of native people along the Pacific Coast.
Data gathered by Boas in the 1890s from 1749 adult males and 1056 adult females were subjected to anthropometric analyses to investigate possible effects of climatic adaptation. The subjects were native people from California, Oregon, Washington, the panhandle of Alaska, and British Columbia. They were categorized by their tribe's latitude and longitude (the center point of tribal distribution) and by habitat (characterized as coastal, western lowlands, and interior). Multiple R regressions were used to determine complex relationships between age, habitat, latitude, rainfall, mean January temperature, mean July temperature, and blood quantum, all of which affected some anthropometric variables to statistically significant degrees in both the male and the female samples. Body size and proportional differences support other studies of Bergmann's and Allen's rules, and variation in the nasal index supports prior studies of selection of longer, narrower noses in cold and dry climates and broader noses in warmer, moister ones. Recent disruption in the central portion of the study area was detectable in reduced size of subjects in these regions. Other complicating factors, such as ethnicity and the possibility of prior migrations and intermarriage between populations, are discussed.


Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis.
The diagnostic value of interferon-γ release assays (IGRAs) for active tuberculosis in low- and middle-income countries is unclear. We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models. Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)-uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%-92%) for T-SPOT and 60% (95% CI, 34%-82%) for QFT-GIT. HSROC/bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%-79%]; QFT-GIT, 52% [95% CI, 41%-62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%-63%]; QFT-GIT, 50% [95% CI, 35%-65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active tuberculosis diagnosis. In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active tuberculosis diagnosis in adults, especially in the context of HIV coinfection.


Alzheimer's disease and vascular deficiency: lessons from imaging studies and down syndrome.
Down syndrome (DS) individuals are at high risk for developing Alzheimer's disease (AD) and consequently provide a unique opportunity to examine the factors leading to the onset of AD. This paper focuses on the neglected vascular parallels between AD and DS that can readily be examined in DS. Several recent AD studies provide evidence that internal jugular vein (IJV) reflux may result in white matter lesions and a 30% decrease in cerebrospinal fluid (CSF) clearance of amyloid-β. At the same time, studies analyzing the synthesis of amyloid-β in DS showed greater than expected amounts of Aβ than would be predicted by the increase in gene dosage, perhaps due to slower clearance. These studies are discussed along with the possibility that the venous and CSF dysfunction found in AD patients may be present early in life in persons with DS, leaving them particularly vulnerable to early onset AD. Studying IJV function in DS provides an opportunity to understand the role of vascular function in the initiation of AD.


Charge-induced unilamellar vesicle formation and phase separation in solutions of Di-n-decylmethylamine oxide.
A double-tail amine oxide surfactant, di-n-decylmethylamine oxide (2C10MAO), was prepared, and the effects of protonation on aggregate structure were examined by small-angle neutron scattering (SANS), cryo-transmission electron microscopy (cryo-TEM), turbidity, electric conductivity, and solubilization of an oil-soluble dye at various degrees of neutralization, X, defined as the mole ratio of HCl/2C10MAO. The surfactant makes an L(2) phase in the nonprotonated state (X = 0) in water. The L(2) phase is in equilibrium with an aqueous L(1) phase. On protonation, unilamellar vesicles (ULVs) are formed over a wide range of compositions (0.05 < X< 0.4-0.5 at C = 10 mM) as observed by cryo-TEM. At X = 0.2, the ULV is stable over a wide concentration range (3 mM < or = C < 0.1 M), but an L(alpha) phase replaces the vesicle phase at C > 0.1 M. SANS results show that the mean radius of the ULV is about 25 nm and the bilayer thickness is about 2 nm, consistent with the extended configuration of the alkyl chains of the surfactant. An important contribution to the enhanced stability of the bilayer structures over the L(2) phase is suggested to be the translational entropy of the counterions. The enhanced stability of the bilayers diminishes as the counterion concentration increases either by an increase of X or by the addition of a salt. When the counterion concentration exceeds a critical value, the ULV solutions transform into the L(2) phase (or L(2)/L(1) two-phase system at low surfactant concentrations). The critical composition X is about 0.4-0.5 in water, but it is below 0.4 in D(2)O. The critical NaCl concentration is below 5 mM at X = 0.2. The stability of ULVs against multilamellar vesicles is ascribed partly to undulation forces and partly to the adjustable nature of the spontaneous curvature of amine oxide monolayers. The characteristics of the ULV of the surfactant remain the same within a temperature range 25-50 degrees C at X = 0.2. An iridescent lamellar phase and possibly an L(3) phase were observed in a very narrow X range (0 < X < 0.02) prior to the vesicle phase.


Evaluation of a transport medium for campylobacter (Vibrio) fetus.
A quantitative assessment was performed on a serum enrichment medium for Campylobacter (Vibrio) fetus, to test its effectiveness as a transport medium. Abundant yields of C fetus were obtained with an inoculum size of 10(4), even after keeping the medium in air at 22 to 23 C for 4 days prior to incubation at 37 C under microaerophilic conditions. The organism could be isolated from the medium kept in air at 22 to 23 C for at least 2 days, with an inoculum as small as 100 organisms. It was concluded that this formulation comprises a convenient and effective transport medium for field use. Transit time should not exceed 3 days and, ideally, should be restricted to less than or equal to 2 days. At least duplicate vials of transport medium should be inoculated with each sample.


An abscisic acid-independent oxylipin pathway controls stomatal closure and immune defense in Arabidopsis.
Plant stomata function in innate immunity against bacterial invasion and abscisic acid (ABA) has been suggested to regulate this process. Using genetic, biochemical, and pharmacological approaches, we demonstrate that (i) the Arabidopsis thaliana nine-specific-lipoxygenase encoding gene, LOX1, which is expressed in guard cells, is required to trigger stomatal closure in response to both bacteria and the pathogen-associated molecular pattern flagellin peptide flg22; (ii) LOX1 participates in stomatal defense; (iii) polyunsaturated fatty acids, the LOX substrates, trigger stomatal closure; (iv) the LOX products, fatty acid hydroperoxides, or reactive electrophile oxylipins induce stomatal closure; and (v) the flg22-mediated stomatal closure is conveyed by both LOX1 and the mitogen-activated protein kinases MPK3 and MPK6 and involves salicylic acid whereas the ABA-induced process depends on the protein kinases OST1, MPK9, or MPK12. Finally, we show that the oxylipin and the ABA pathways converge at the level of the anion channel SLAC1 to regulate stomatal closure. Collectively, our results demonstrate that early biotic signaling in guard cells is an ABA-independent process revealing a novel function of LOX1-dependent stomatal pathway in plant immunity.


A "minimal" sodium channel construct consisting of ligated S5-P-S6 segments forms a toxin-activatable ionophore.
The large size (six membrane-spanning repeats in each of four domains) and asymmetric architecture of the voltage-dependent Na+ channel has hindered determination of its structure. With the goal of determining the minimum structure of the Na+ channel permeation pathway, we created two stable cell lines expressing the voltage-dependent rat skeletal muscle Na+ channel (micro1) with a polyhistidine tag on the C terminus (muHis) and pore-only micro1 (muPore) channels with S1-S4 in all domains removed. Both constructs were recognized by a Na+ channel-specific antibody on a Western blot. muHis channels exhibited the same functional properties as wild-type micro1. In contrast, muPore channels did not conduct Na+ currents nor did they bind [3H]saxitoxin. Veratridine caused 40 and 54% cell death in muHis- and muPore-expressing cells, respectively. However, veratridine-induced cell death could only be blocked by tetrodotoxin in cells expressing muHis, but not muPore. Furthermore, using a fluorescent Na+ indicator, we measured changes in intracellular Na+ induced by veratridine and a brevotoxin analogue, pumiliotoxin. When calibrated to the maximum signal after addition of gramicidin, the maximal percent increases in fluorescence (deltaF) were 35 and 31% in cells expressing muHis and muPore, respectively. Moreover, in the presence of 1 microm tetrodotoxin, deltaF decreased significantly to 10% in muHis- but not in muPore-expressing cells (43%). In conclusion, S5-P-S6 segments of micro1 channels form a toxin-activable ionophore but do not reconstitute the Na+ channel permeation pathway with full fidelity.


MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.
Patients with colorectal cancers (CRC) and high microsatellite instability (MSI) have a better outcome than their chromosome-unstable counterpart. Given the heterogeneity of microsatellite-unstable CRCs, we wanted to see whether any MSI-associated molecular features are specifically associated with prognosis. One hundred and nine MSI-high CRCs were typed for primary mismatch repair (MMR) defect and for secondary loss of MMR proteins. Frameshifts at seven target genes, mutations in the RAS pathway, and methylation at MLH1/CDKN2A promoters were also searched. The interplay of molecular findings with clinicopathologic features and patient survival was analyzed. Of 84 MLH1-deficient CRCs, 31 (36.9%) had MSH3 and 11 (13.1%) had MSH6 loss (P < 0.001), biallelic frameshift mutations at mononucleotide repeats accounting for most (78%) MSH3 losses. As compared with MSH3-retaining cancers, MLH1-deficient tumors with MSH3 loss showed a higher number of mutated target genes (3.94 ± 1.56 vs. 2.79 ± 1.75; P = 0.001), absence of nodal involvement at pathology [N0; OR, 0.11; 95% confidence interval (CI), 0.04-0.43, P < 0.001], and better disease-free survival (P = 0.06). No prognostic value was observed for KRAS status and for MLH1/CDKN2A promoter methylation. The association between MSH3 loss and N0 was confirmed in an independent cohort of 71 MLH1-deficient CRCs (OR, 0.23; 95% CI, 0.06-0.83, P = 0.02). MLH1-deficient CRCs not expressing MSH3 have a more severe MSI, a lower rate of nodal involvement, and a better postsurgical outcome.


The two-dimensional Monte Carlo: a new methodologic paradigm for dose reconstruction for epidemiological studies.
Retrospective dose estimation, particularly dose reconstruction that supports epidemiological investigations of health risk, relies on various strategies that include models of physical processes and exposure conditions with detail ranging from simple to complex. Quantification of dose uncertainty is an essential component of assessments for health risk studies since, as is well understood, it is impossible to retrospectively determine the true dose for each person. To address uncertainty in dose estimation, numerical simulation tools have become commonplace and there is now an increased understanding about the needs and what is required for models used to estimate cohort doses (in the absence of direct measurement) to evaluate dose response. It now appears that for dose-response algorithms to derive the best, unbiased estimate of health risk, we need to understand the type, magnitude and interrelationships of the uncertainties of model assumptions, parameters and input data used in the associated dose estimation models. Heretofore, uncertainty analysis of dose estimates did not always properly distinguish between categories of errors, e.g., uncertainty that is specific to each subject (i.e., unshared error), and uncertainty of doses from a lack of understanding and knowledge about parameter values that are shared to varying degrees by numbers of subsets of the cohort. While mathematical propagation of errors by Monte Carlo simulation methods has been used for years to estimate the uncertainty of an individual subject's dose, it was almost always conducted without consideration of dependencies between subjects. In retrospect, these types of simple analyses are not suitable for studies with complex dose models, particularly when important input data are missing or otherwise not available. The dose estimation strategy presented here is a simulation method that corrects the previous deficiencies of analytical or simple Monte Carlo error propagation methods and is termed, due to its capability to maintain separation between shared and unshared errors, the two-dimensional Monte Carlo (2DMC) procedure. Simply put, the 2DMC method simulates alternative, possibly true, sets (or vectors) of doses for an entire cohort rather than a single set that emerges when each individual's dose is estimated independently from other subjects. Moreover, estimated doses within each simulated vector maintain proper inter-relationships such that the estimated doses for members of a cohort subgroup that share common lifestyle attributes and sources of uncertainty are properly correlated. The 2DMC procedure simulates inter-individual variability of possibly true doses within each dose vector and captures the influence of uncertainty in the values of dosimetric parameters across multiple realizations of possibly true vectors of cohort doses. The primary characteristic of the 2DMC approach, as well as its strength, are defined by the proper separation between uncertainties shared by members of the entire cohort or members of defined cohort subsets, and uncertainties that are individual-specific and therefore unshared.


Serum vitamin D, physical activity, and metabolic risk factors in Korean children.
The purpose of this study was to investigate the relationship of serum vitamin D levels with lifestyle factors, including body fatness and physical activity (PA) parameters, and the clustering of metabolic risk factors in the Korean pediatric population. Serum 25-hydroxyvitamin D levels, accelerometer-based PA, and body fatness and metabolic syndrome parameters were assessed in a sample of children of Korean descent (N = 310). Correlation and multivariate linear regression were used to explore the relationships among serum vitamin D levels, lifestyle factors, and the clustering of metabolic risk factors in the study sample. Serum vitamin D levels were negatively associated with body fatness parameters, including body mass index, percent body fat, and waist circumference, but positively associated with accelerometer-based PA including low, moderate, and vigorous levels. In addition, serum vitamin D levels were inversely related to total cholesterol, triglycerides, fasting glucose, and insulin. A stepwise linear regression model showed that both low serum vitamin D levels and decreased vigorous PA were independent predictors for individual variation in the clustering of metabolic risk factors in this study sample. The results of this study suggest that an increase in vigorous PA and vitamin D intake should be two major targets of public health inventions against the clustering of metabolic risk factors in the Korean pediatric population.


Temporal clusters of bovine Salmonella cases at a veterinary medical teaching hospital, 1996-2007.
The objectives of this study were to identify and characterize temporal clusters of bovine Salmonella cases at a veterinary medical teaching hospital and to determine which clusters were likely to have involved nosocomial transmission. Data on fecal Salmonella shedding status, serotype, and antimicrobial resistance were collected retrospectively for all cattle admitted to the Cornell University Equine and Farm Animal Hospital between January 1, 1996, and June 1, 2007. Pulsed-field gel electrophoresis (PFGE) was performed on all available isolates. Cluster analysis was used to identify temporal clusters of cases. A total of 5398 cattle were admitted during the study period; the prevalence of fecal Salmonella shedding among clinical suspects was 6.5%, whereas that among nonsuspects tested through routine surveillance was 2.5%. Eight temporal clusters (including 57 cattle) were investigated as possible outbreaks involving nosocomial transmission, ranging in size from 4 to 10 cases. All but one cluster were centered over the month of August or September. A total of 15 Salmonella serotypes were represented, with the most common being Typhimurium (33%), Newport (23%), and Agona (12%). Among the isolates available for PFGE analysis, there were 19 PFGE types represented. The majority of temporal clusters during the study period were not nosocomial in origin. However, two of the clusters were outbreaks directly resulting from nosocomial Salmonella transmission, based on case histories, serotype data, antimicrobial resistance patterns, and PFGE analysis. The clear seasonal pattern exhibited by these clusters underscores the need for heightened Salmonella vigilance during the late summer and early fall. The combination of statistical methods, routine bacteriologic data, and PFGE analysis is an effective means of conducting surveillance and outbreak investigations in a hospital setting.


Retinoic acid receptor expression vector inhibits differentiation of F9 embryonal carcinoma cells.
Expression vectors have been constructed for a region of the human retinoic acid receptor-alpha (hRAR-alpha) and transferred into F9 embryonal carcinoma (EC) cells. When the vectors are overexpressed in F9 cells, clones can be selected for resistance to retinoic acid-induced differentiation. This effect is obtained even when the hRAR-alpha region is expressed as a beta-galactosidase fusion protein. Using the beta-galactosidase component of the fusion protein as a marker, overexpression of the fusion protein has been correlated with the retinoic acid-resistance effect. The clones resistant to retinoic acid no longer exhibit the normal retinoic acid induction of endo B cytokeratin, laminin B-1, and tissue plasminogen activator mRNAs observed with normal F9 cells. Retinoic acid induction of type IV alpha-1 collagen and Hox-1.3 RNAs is observed with these clones. When transfected with a thyroid receptor DNA-binding sequence (TRE)/thymidine kinase promoter/luciferase construct, the retinoic acid-resistant clones do not yield the same retinoic acid-induced level of luciferase obtained with F9 cells. It is hypothesized that the RAR vectors are interfering with endogenous RAR(s) in a dominant-negative manner to inhibit retinoic acid-induced differentiation of F9 EC cells.