Clostridium difficile-associated diarrhea and colitis in adults. A prospective case-controlled epidemiologic study.
In a one-year period, 149 adult cases of Clostridium difficile-associated diarrhea and colitis were compared with 148 diarrhea-free controls. Eighty-seven percent were nosocomial and 75% were on surgical services. Endoscopy revealed pseudomembranes in 51% of the 109 cases in which stool cytotoxin was present, compared with 11% of the 40 cases that were culture-positive but cytotoxin-negative. Cases diagnosed only by stool culture showed essentially no differences from controls, 21% of whom had asymptomatic stool colonization. We estimate that only 20% of these cases had diarrhea due to C difficile. Compared with controls, cases diagnosed by the presence of cytotoxin or pseudomembranes were found to have been hospitalized longer at diarrhea onset, to have had more antecedent infections, and to have received clindamycin, multiple antimicrobials, and therapeutic antimicrobials more often than controls, but controls received prophylactic antimicrobials more frequently than cases. Cultures of the environment, patients, and personnel failed to detect a mechanism of acquisition.


The relationship of some negative events and psychological factors to periodontal disease in an adult Swedish population 50 to 80 years of age.
Clinical observations and epidemiological studies suggest that experiences of negative life events, especially those manifested as depression, may contribute to an increased susceptibility to periodontal disease. In the present study, the prevalence of some negative life events and psychological factors and their relation to periodontal disease were investigated. The sample consisted of individuals 50-80 years of age from an extensive cross-sectional epidemiological study performed in 1993 in the city of Jönköping, Sweden. 298 dentate individuals from the Jönköping study were randomly selected. Clinical and radiographic examinations included registration of the number of existing teeth, plaque index, gingival index, pocket depth, and alveolar bone loss. In addition, a questionnaire about socioeconomic status, life events, and psychological and stress-related factors was used. The results revealed that, in addition to the well-documented periodontal disease risk factors such as increased age, oral hygiene status, and smoking, the loss of a spouse (being a widow or widower) and the personality trait of exercising extreme external control were also associated with severe periodontal disease. The findings support recent studies suggesting that traumatic life events such as the loss of a spouse may increase the risk for periodontal disease. Above all, the present results indicate that an individual's ability to cope with stressful stimuli (coping behavior), as measured by the beliefs of locus of control of reinforcements may play a role in the progression of periodontal disease.


Cutaneous sensory neurons expressing the Mrgprd receptor sense extracellular ATP and are putative nociceptors.
Sensory neurons expressing the Mrgprd receptor are known to innervate the outermost living layer of the epidermis, the stratum granulosum. The sensory modality that these neurons signal and the stimulus that they respond to are not established, although immunocytochemical data suggest they could be nonpeptidergic nociceptors. Using patch clamp of dissociated mouse dorsal root ganglion (DRG) neurons, the present study demonstrates that Mrgprd+ neurons have several properties typical of nociceptors: long-duration action potentials, TTX-resistant Na(+) current, and Ca(2+) currents that are inhibited by mu opioids. Remarkably, Mrgprd+ neurons respond almost exclusively to extracellular ATP with currents similar to homomeric P2X3 receptors. They show little or no sensitivity to other putative nociceptive agonists, including capsaicin, cinnamaldehyde, menthol, pH 6.0, or glutamate. These properties, together with selective innervation of the stratum granulosum, indicate that Mrgprd+ neurons are nociceptors in the outer epidermis and may respond indirectly to external stimuli by detecting ATP release in the skin.


Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice.
GH deficiency is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown benefit. To gain a better understanding of the role of GH secretion in ALS pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1(G93A) mice throughout the course of ALS disease. Male wild-type and hSOD1(G93A) mice were studied at the presymptomatic, onset, and end stages of disease. To assess the pathological features of disease, we measured motor neuron number and neuromuscular innervation. We report that GH secretion profile varies at different stages of disease progression in hSOD1(G93A) mice; compared with age-matched controls, GH secretion is unchanged prior to the onset of disease symptoms, elevated at the onset of disease symptoms, and reduced at the end stage of disease. In hSOD1(G93A) mice at the onset of disease, GH secretion is positively correlated with the percentage of neuromuscular innervation but not with motor neuron number. Moreover, this occurs in parallel with an elevation in the expression of muscle IGF-I relative to controls. Our data imply that increased GH secretion at symptom onset may be an endogenous endocrine response to increase the local production of muscle IGF-I to stimulate reinnervation of muscle, but that in the latter stages of disease this response no longer occurs.


A comparison of bootstrap methods and an adjusted bootstrap approach for estimating the prediction error in microarray classification.
This paper first provides a critical review on some existing methods for estimating the prediction error in classifying microarray data where the number of genes greatly exceeds the number of specimens. Special attention is given to the bootstrap-related methods. When the sample size n is small, we find that all the reviewed methods suffer from either substantial bias or variability. We introduce a repeated leave-one-out bootstrap (RLOOB) method that predicts for each specimen in the sample using bootstrap learning sets of size ln. We then propose an adjusted bootstrap (ABS) method that fits a learning curve to the RLOOB estimates calculated with different bootstrap learning set sizes. The ABS method is robust across the situations we investigate and provides a slightly conservative estimate for the prediction error. Even with small samples, it does not suffer from large upward bias as the leave-one-out bootstrap and the 0.632+ bootstrap, and it does not suffer from large variability as the leave-one-out cross-validation in microarray applications.


Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model.
Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.


Gastric fundic gland polyps and colonic polyps - is there a link, really?
A retrospective analysis of endoscopic investigation was carried out. Gastric fundic gland polyps occur in patients with familial adenomatous polyposis. The aim of our study was to investigate if colonic polyps is present and related to gastric fundic gland polyps. A 6 years retrospective analysis was carried out. At baseline upper gastrointestinal endoscopy, gastric fundic gland polyps were diagnosed in patients suffered from intestinal bleeding. Subjects received a colonoscopy additionally. A total of 500 patients were enrolled into study: 250 fulfilled the diagnostic criteria for gastric fundic gland polyps and 250 age and sex matched served as controls. Colonic cancer was more frequently observed in 39 (15.5%) patients who met the criteria of gastric fundic gland polyps as compared to 23 (9.2 %) patients of the controls (p <0.05). Patients with gastric fundic gland polyps tended to have more often colonic polyps 122 vs. 111, but these differences were not statistically significant. The prevalence of colonic cancer was elevated in patients with gastric fundic gland polyp. Furthermore, this relationship did not differ significantly according to occurrence of colonic polyps. Even tough colonoscopy is prophylactic in preventing colonic cancer; the use of colonoscopy should be encouraged in patients with gastric fundic gland polyps.


What do Swedish occupational therapists feel about research? A survey of perceptions, attitudes, intentions, and engagement.
The aim of this study was to identify Swedish occupational therapists' perceptions and attitudes to research-related activities as well as the therapists' present engagement in future plans for research. A follow up design was used, and the study was undertaken between 1997 and 2003. A total of 425 and 442 Swedish occupational therapists responded to a postal questionnaire (response rate 74.4% and 70.4%). Questions regarding research-related activities were measured on a Likert-type scale, whereas questions referring to attitudes towards research used a semantic differential scale. There were small differences between the two surveys. The result showed that occupational therapists considered research-related activities to be an important part of their development of the professional role and status. Reading research literature to update knowledge was the most important research activity and the second most important activity was applying research findings to improve occupational therapy practice. High workload and lack of time were the most commonly mentioned barriers to participation in research- related activities. Occupational therapists read a large variety of journals, preferably in Swedish. The barriers to participation in research-related activities did not change from 1997 to 2003. The fact that occupational therapists reported reading research as rating highly gives hope for the future development of the occupational therapy profession and practice.


AN EVALUATION OF ANTIBIOTIC PRESCRIPTION PRACTICES: PERSPECTIVES OF VETERINARY TRAINEES AND PRACTICING VETERINARIANS.
Antibiotic resistance is a major worldwide problem that has an impact on the well-being of humans as well as animals. Antibiotic resistance is caused by the misuse and excessive use of antibiotics. The key to reducing this issue lies in educating veterinary medical learners on the proper and accountable utilization of antibiotics for the care of animals. Objective - using awareness-raising and instruction as the foundation, this research of Indian veterinary learners can help resolve the issue of antibiotic resistance throughout the care of animals. The questionnaire survey was taken between June and July 2022 and it was aimed at learners registered in veterinary medical studies at academic and research institutions in India. The study included 500 pupils overall. The purpose of the survey was to gather information about students' knowledge of antibiotics, including antibiotic resistance, as well as their feelings on the consequences of antibiotic resistance on the globe at large and their acquaintance with the one health ideology. According to this study's findings, 83.3 percent of respondents thought antibiotic resistance was a serious problem. 57.92 percent of respondents understood the issue's worldwide consequences and its one health ideology. The study emphasizes the significance of expanding the veterinary educational program to include thorough instruction on prudent antibiotic usage and the concepts of one health.


Oxytocin-induced water intoxication. A case report.
Oxytocin-induced water intoxication is an uncommon iatrogenic condition with serious potential morbidity and mortality, which is preventable with a rational approach to therapy. Its pathogenesis, management and prevention are discussed.


Rapid isolation of Brachyspira hyodysenteriae and Brachyspira pilosicoli from pigs.
The aim of this study was to compare and evaluate the time required to isolate Brachyspira hyodysenteriae and Brachyspira pilosicoli from porcine faeces. This was done using previously described selective media (spectinomycin) S400, (colistin, vancomycin and spectinomycin) CVS and (spectinomycin, vancomycin, colistin, spiramycin and rifampin with swine faecal extract) BJ, compared with the method based on blood agar modified medium, with spectinomycin and rifampin (BAM-SR), including a pre-treatment step. Fourteen spirochaetal strains were obtained in pure cultures after 5 days (48 h in BAM-SR primary plate and three passages every 24 h in brain heart infusion (BHI) without antibiotics) pre-treating simulated samples in brain heart infusion broth with spectinomycin (400 microg/ml) and rifampin (15 microg/ml), before streaking on the selective BAM-SR medium. Spirochaetes from samples in S400, CVS and BJ, with and without pre-treatment, were obtained in pure cultures only after repeatedly transferring on plates of the same selective medium requiring 15-18 days according to the strain. BAM-SR used after the pre-treatment step showed a detection limit ranging from 3.5 x 10(2) to 6.7 x 10(7) cells/g faeces and was the only method able to support the growth of spirochaetes after 48 h.


Baculovirus as vaccine vectors.
Application of viral vectors derived from human viruses to mediate immune response in animals and humans has been greatly hampered by the problems associated with pre-existing immunity and associated toxicities. Among few non-human viral vectors, baculovirus has now evolved as a novel tool for vaccine vector development. With broad tissue tropism and expanded bio-safety profile suitably supplemented with intrinsic immunostimulatory properties, baculovirus has now attained a niche position in the arena of vaccine development. Recombinant envelope-modified baculovirus equipped with novel shuttle promoters for in vivo transduction has shown promising results in several animal models. Baculovirus mediated induction of systemic and mucosal immune responses through intranasal or oral administration has now open an entirely new way for the development of new generation vaccines. Gaining additional insight into the baculovirus biology and its interaction with non-native hosts will certainly promote this human-friendly virus as a potential vector for clinical applications.


Life success of males on nonoffender, adolescence-limited, persistent, and adult-onset antisocial pathways: follow-up from age 8 to 42.
A random sample of 196 males, drawn from the Jyväskylä Longitudinal Study of Personality and Social Development, was divided into four groups of offenders using information from government registers of convictions between ages 21 and 47, from local police registers searched at age 21, from a Self-Report Delinquency Scale administered at age 36, from a Life History Calendar for ages 15-42, and from personal interviews at ages 27, 36, and 42. The groups were: persistent offenders (offences before and after age 21; 29% of the men); adolescence-limited offenders (offences before age 21; 27%); adult-onset offenders (offences after age 21; 16%); and nonoffenders (28%). The profile of the persistent offenders included many characteristics of antisocial personality and problems of social and psychological functioning at all ages. In childhood and adolescence, the adolescence-limited offenders tended to display higher self-control than the other offenders indicated by less negative emotionality and higher constraint. In early middle age, they were well established in terms of work and marriage, but they differed from the nonoffenders in higher neuroticism, aggressiveness, and psychosomatic symptoms as did the other offender groups. The adult-onset offenders displayed an emotionally unstable personality, and in adulthood, they tended to be heavy users of alcohol. Parental SES did not differentiate the groups, but the parents of the persistent offenders tended to use alcohol heavily, and the social capital of the family tended to be low compared with the other groups.


Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19.
Little is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes. We conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020). 126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge. Persistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.


Use of contraceptives and unmet need for family planning among tribal women in India and selected hilly states.
The paper provides a comprehensive picture of knowledge and use of contraceptives among scheduled tribes of India and selected central hilly states where tribal population contributes more than 30% of the total tribal population of the country. An attempt is also made to know how far scheduled tribes differ from non-tribes in the states, namely Jharkhand, Madhya Pradesh, and Chhattisgarh, using information collected in the third round of District-level Household Survey (DLHS-RCH III: 2007-2008). Bivariate analysis was used for understanding the level of knowledge, use of and unmet need for contraception among different tribal and non-tribal groups. Binary logistic regression was used for understanding the factors associated with the use of contraception and unmet need for family planning among tribal women. Knowledge and use of temporary contraceptive methods are considerably lower among tribal women compared to their non-tribal counterparts in the three states under study. Low acceptance due to phobia of adverse health consequences, accessibility to and lack of sound knowledge of contraception are the leading reasons for not using contraceptives. The unmet need for family planning among them was quite high, especially in the state of Jharkhand. Multivariate analysis substantiated the role of women and husbands' education, age of women, and number of surviving boys in the use of any modem method of contraception. Educating women and their respective husbands about proper use and benefits of modem contraceptives is important to solve the problem of high unmet need for family planning among these tribal women. A simultaneous attention to the health systems strengthening component is crucial for ensuring sustained delivery of good-quality family planning services.


Activity of three muscles associated with the uncinate processes of the giant Canada goose Branta canadensis maximus.
The activity of three muscles associated with the uncinate processes, (i) external intercostal, (ii) appendicocostalis and (iii) external oblique, were examined using patch and sew-through electrodes during sitting, standing and moderate speed treadmill running in the giant Canada goose. The external intercostal muscles demonstrated no respiratory activity, being active only during running, suggesting they play some role in trunk stabilisation. The appendicocostalis and external oblique muscles are respiratory muscles, being active during inspiration and expiration, respectively. The activity of the appendicocostalis muscles increased during sitting, suggesting that the uncinate processes in birds play an important role in facilitating lateral flaring of the rib cage when sternal rocking is prevented. We suggest that the uncinate processes in birds facilitate movements of the ribs and sternum during breathing and therefore are integral to the breathing mechanics of birds.


Concussion Disrupts Normal Brain White Matter Microstructural Symmetry.
Injuries and illnesses can alter the normal bilateral symmetry of the brain, and determining the extent of this disruption may be useful in characterizing the pathology. One way of quantifying brain symmetry is in terms of bilateral correlation of diffusion tensor metrics between homologous white matter tracts. With this approach, we hypothesized that the brains of patients with a concussion are more asymmetrical than those of healthy individuals without a history of a concussion. We scanned the brains of 35 normal individuals and 15 emergency department patients with a recent concussion. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for regions of interest (ROI) defined by a standard white-matter atlas that included 21 bilateral ROIs. For each ROI pair, bilateral correlation coefficients were calculated and compared between the two subject groups. A symmetry index, defined as the ratio between the difference and the sum of bilateral measures, was also calculated for each ROI pair and compared between the groups. We found that in normal subjects, the extent of symmetry varied among regions and individuals, and at least subtle forms of structural lateralization were common across regions. In patients, higher asymmetry was found overall as well as in the corticospinal tract specifically. Results indicate that a concussion can manifest in brain asymmetry that deviates from a normal state. The clinical utility of characterizing post-concussion pathology as abnormal brain asymmetry merits further exploration.


Integrating omic approaches for abiotic stress tolerance in soybean.
Soybean production is greatly influenced by abiotic stresses imposed by environmental factors such as drought, water submergence, salt, and heavy metals. A thorough understanding of plant response to abiotic stress at the molecular level is a prerequisite for its effective management. The molecular mechanism of stress tolerance is complex and requires information at the omic level to understand it effectively. In this regard, enormous progress has been made in the omics field in the areas of genomics, transcriptomics, and proteomics. The emerging field of ionomics is also being employed for investigating abiotic stress tolerance in soybean. Omic approaches generate a huge amount of data, and adequate advancements in computational tools have been achieved for effective analysis. However, the integration of omic-scale information to address complex genetics and physiological questions is still a challenge. In this review, we have described advances in omic tools in the view of conventional and modern approaches being used to dissect abiotic stress tolerance in soybean. Emphasis was given to approaches such as quantitative trait loci (QTL) mapping, genome-wide association studies (GWAS), and genomic selection (GS). Comparative genomics and candidate gene approaches are also discussed considering identification of potential genomic loci, genes, and biochemical pathways involved in stress tolerance mechanism in soybean. This review also provides a comprehensive catalog of available online omic resources for soybean and its effective utilization. We have also addressed the significance of phenomics in the integrated approaches and recognized high-throughput multi-dimensional phenotyping as a major limiting factor for the improvement of abiotic stress tolerance in soybean.


N-terminal sequence of soybean beta-amylase.
The blocked N-terminus and N-terminal sequence of soybean beta-amylase were determined by analyzing the acidic peptides derived on peptic digestion of the enzyme. The acidic peptides were separated from the digest on a Dowex 50 X 2 column and purified by reversed phase-high performance liquid chromatography (RP-HPLC). The major acidic peptide, Pep-4, was a heptapeptide with a molecular weight of 766. Forty-eight hundredths mol acetyl group and 0.61 mol acetyl-Ala per mol of Pep-4 were detected on RP-HPLC analysis. The N-terminal 9 amino acid sequence of soybean beta-amylase was deduced to be acetyl-Ala-Thr-Ser-Asp-Ser-Asn-Met-(Gly-Leu) from the results of sequence analysis of Pep-4 and amino acid analysis of other acidic peptides.


Evaluation of cytopathological findings in thyroid nodules with macrocalcification: macrocalcification is not innocent as it seems.
Microcalcification is strongly correlated with papillary thyroid cancer. It is not clear whether macrocalcification is associated with malignancy. In this study, we aimed to assess the result of fine needle aspiration biopsies (FNAB) of thyroid nodules with macrocalcifications. We retrospectively evaluated 269 patients (907 nodules). Macrocalcifications were classified as eggshell and parenchymal macrocalcification. FNAB results were divided into four groups: benign, malignant, suspicious for malignancy, and non-diagnostic. There were 79.9% female and 20.1% male and mean age was 56.9 years. Macrocalcification was detected in 46.3% nodules and 53.7% nodules had no macrocalcification. Parenchymal and eggshell macrocalcification were observed in 40.5% and 5.8% nodules, respectively. Cytologically, malignant and suspicious for malignancy rates were higher in nodules with macrocalcification compared to nodules without macrocalcification (p = 0.004 and p = 0.003, respectively). Benign and non-diagnostic cytology results were similar in two groups (p > 0.05). Nodules with eggshell calcification had higher rate of suspicious for malignancy and nodules with parenchymal macrocalcification had higher rates of malignant and suspicious for malignancy compared to those without macrocalcification (p = 0.01, p = 0.003 and p = 0.007, respectively). Our findings suggest that macrocalcifications are not always benign and are not associated with increased nondiagnostic FNAB results. Macrocalcification, particularly the parenchymal type should be taken into consideration.


Carcinoid Tumors of the Orbit and Ocular Adnexa.
Well-differentiated neuroendocrine or carcinoid tumors are found most commonly in the gastrointestinal tract. When metastatic to the orbit, they tend to have a propensity for the extraocular muscles. The purpose of this study was to better understand the diversity in presentation of orbital carcinoid disease and to determine predictors for survival. In this observational cross-sectional cohort study, data from 8 tertiary orbital practices were compiled. Demographic, clinical, pathologic, American Joint Committee on Cancer stage and grade, imaging, and management data were extracted for all the patients. Descriptive statistics were calculated. Subgroups were compared utilizing analysis of variance analyses and Kaplan-Meier curves. Time to progression and disease-specific and overall mortality were calculated. Comparisons were performed for the following a priori pairs: unknown versus known primary tumor, single versus multiple extraocular muscle involvement, unilateral versus bilateral orbital disease, extraocular muscle versus other orbital involvement, and excisional versus incisional surgery. A total of 28 patients with carcinoid tumors of the orbit were identified. Of these, 57.1% of patients were female, the mean age at diagnosis of the primary tumor was 58.8 years and the mean age at diagnosis of orbital disease was 62.6 years. At primary presentation, all patients were American Joint Committee on Cancer stage III or IV and 21.4% demonstrated carcinoid syndrome. Muscle involvement was noted in 78.6% of patients, and of these, 72% were noted to have single muscle disease. Eight patients had no primary tumor identified; 3 of these 8 demonstrated disseminated disease at the time of diagnosis. The overall 5-year survival rate was 81.8% from diagnosis of primary tumor and 50% from diagnosis of orbital disease. Subgroup analysis revealed that patients with unilateral orbital disease when compared with bilateral orbital disease had a longer progression-free survival and time to death from all causes (p = 0.025). Patients with disease localized to the orbit at presentation had longer time to death than those with disseminated disease. Treatment with surgery, radiation, or octreotide did not appear to affect survival. Patients managed with systemic chemotherapy had a shorter time of survival than the rest of the group. All other subgroup comparisons were not found to be statistically significant. Neuroendocrine tumors of the orbit represent a wide spectrum of disease, with some cases being part of disseminated disease, while others being localized presentations. This heterogeneity may be responsible for the slightly higher overall survival in these patients than others with metastatic carcinoid tumors in other locations.


Detection of mutagenic activity in cigarette smoke condensates.
The Salmonella typhimurium microsomal test system for mutagenic activity was successfully used to detect the presence of mutagenic compounds in the smoke condensates of several types of cigarettes. The condensates were shown to contain compounds which could cause frameshift mutations when activated by microsomal enzymes. An analysis of fractions of smoke condensate revealed that the detected mutagenic activity was distributed in several of the fractions. Most of the activity of the whole condensate was in basic fractions and in a weakly acidic fraction. Condensates from cigarettes treated with magnesium nitrate differed from other condensates in two respects. They contained frameshift mutagens which did not require microsomal activation and mutagens which could cause base-pair substitution mutations. Although the detection system usually employs rat liver microsomal preparations, a rat lung microsomal preparation was also found to be capable of converting smoke condensates and known chemical carcinogens into mutagenic forms.


Western sandpipers have altered migration tactics as peregrine falcon populations have recovered.
The presence of top predators can affect prey behaviour, morphology and life history, and thereby can produce indirect population consequences greater and further reaching than direct depredation would have alone. Raptor species in the Americas are recovering since restrictions on the use of dichlorodiphenyltrichloroethane (DDT) and the implementation of conservation measures, in effect constituting a hemisphere-wide predator-reintroduction experiment, and profound effects on populations of their prey are to be expected. Here, we document changes in the behaviour of western sandpipers (Calidris mauri) at migratory stopover sites over two decades. Since 1985, migratory body mass and stopover durations of western sandpipers have fallen steadily at some stopovers in the Strait of Georgia, British Columbia. Comparisons between years, sites and seasons strongly implicate increasing danger from the recovery of peregrine falcons (Falco peregrinus) as a causal factor. A decade-long ongoing steep decline in sandpiper numbers censused on our study site is explained entirely by the shortening stopover duration, rather than fewer individuals using the site. Such behavioural changes are probably general among migratory shorebird species, and may be contributing to the widespread census declines reported in North America.


The role of growth factors and cytokines during implantation: endocrine and paracrine interactions.
Implantation, a critical step for establishing pregnancy, requires molecular and cellular events resulting in uterine growth and differentiation, blastocyst adhesion, invasion, and placental formation. Successful implantation requires a receptive endometrium, a normal and functional embryo at the blastocyst stage, and a synchronized dialogue between maternal and embryonic tissues. In addition to the well-characterized role of sex steroids, the complexity of embryo implantation and placentation is exemplified by the number of cytokines and growth factors with demonstrated roles in these processes. Disturbances in the normal expression and action of these cytokines result in an absolute or partial failure of implantation and abnormal placental formation in mice and human. Members of the gp130 cytokine family, interleukin-11 (IL-11) and leukemia inhibitory factor, the transforming growth factor beta superfamily, the colony-stimulating factors, and the IL-1 and IL-15 systems are crucial molecules for a successful implantation. Chemokines are also important, both in recruiting specific cohorts of leukocytes to the implantation site and in trophoblast trafficking and differentiation. This review provides discussion of the embryonic and uterine factors that are involved in the process of implantation in autocrine, paracrine, and/or juxtacrine manners at the hormonal, cellular, and molecular levels.


Fluid resuscitation in acutely injured patients.
Injuries are the third leading cause of death in the United States, exceeded only by heart disease and cancer. The success of resuscitation after an acute injury is dependent on providing adequate oxygenation, restoring intravascular fluid volume, and maintaining optimum cardiac output and cellular perfusion. Fluid resuscitation is essential to the successful management of hemorrhagic shock; it involves obtaining venous access, administration of the appropriate type and amount of fluid and blood products, and ongoing monitoring of the patient. There are special considerations in fluid resuscitation for the pediatric and burn patient. Care of the trauma patient is a dynamic process and requires ongoing evaluation of clinical parameters. Fluid resuscitation is a central component in the overall management of the trauma patient.


Network analysis of kick-in possession chains in elite Australian football.
The study aim was to investigate ball movement patterns using network analysis techniques, to compare between successful and unsuccessful outcomes and teams in the Australian Football League (AFL). This analysis focused on possession chains starting from a kick-in (n = 1,720), drawn from all games played in the 2015 AFL Premiership season (18 teams, 206 games). Player interactions were quantified using four network metrics: cluster coefficient, degree centrality, network density, and entropy. Three-way ANOVA with Tukey post hoc and ω2 effect sizes were calculated to assess whether differences existed between kick-in outcomes, ladder brackets, and match outcomes for each network metric. No significant differences were observed between ladder brackets or match outcomes for any network metric. More successful kick-in chains were characterised by lower density (ω2 = 0.26, large effect; F(9, 1678) = 66.6, p < 0.00) and higher entropy (ω2 = 0.17, large effect; F(9, 1678) = 39.6, p < 0.00). This suggests that chains resulting in successful kick-in outcomes exhibited lower interconnectedness, with a high number of players involved, and lower predictability in ball movement patterns. These findings have practical value for coaches and performance analysts and support further applications of network analysis in Australian football.


Ross operation after failure of aortic valve repair.
Repair failure remains one of the most important complications of aortic valve reconstruction. Young patients might benefit from a Ross procedure in such a scenario, provided it can be performed safely and with adequate durability. The aim of this study was to assess the safety and clinical outcomes of a Ross operation following a failed repair. Between 1996 and 2019, 80 patients (male, 76%; mean age, 31±13 years) underwent a Ross procedure after a median of 6.6 (1.7-15.9) years following an initial aortic valve repair. The previous valve repair was performed for unicuspid (53%), bicuspid (39%), tricuspid (7%), and quadricuspid morphology (1%). Median follow-up after the Ross operation was 2.8 (0.964-13.25) years, mean 5±5 years (92% complete). Median cardiopulmonary bypass and cross-clamp times were 144 [106-154] minutes and 98 [79-113] minutes, respectively. Thirty-two patients (40%) required a concomitant procedure, most commonly, an ascending aortic replacement (n=23). There were no peri-operative deaths, myocardial infarctions, or neurological complications. There was one late death from a non-cardiac cause. At 10 years, overall survival was 99%±1%, similar to that of an age- and gender-matched population. Nine patients required re-intervention after their Ross procedure (five on the autograft and four on the pulmonary conduit). The autograft re-interventions were valve-sparing procedures in all patients. The cumulative incidence of re-intervention on the autograft at 8 years was 5.1%±3.1%. The stepwise strategy of an initial valve repair followed by Ross operation represents a safe and valid option for failed aortic valve repair. It is associated with low peri-operative morbidity. Mid-term survival is excellent, similar to that of a matched general population. The probability of re-intervention after the Ross procedure appears similar to that of a primary Ross operation, deeming it a warranted consideration in cases of failed aortic valve repair.


Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore.
Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.


The use of methylmethacrylate for vertebral-body replacement and anterior stabilization of pathological fracture-dislocations of the spine due to metastatic malignant disease.
Metastatic malignant lesions involving the spine occasionally cause severe enough vertebral-body collapse to result in either spinal instability or neural compression, or both. Conventional decompressive laminectomy in such cases rarely results in neural improvement. It may, however, cause local instability of the spine, leading to a progressive kyphotic deformity and an increasing neural deficit. Anterior decompression allows excision of the focus of tumor and direct neural decompression. However, anterior stabilization by bone grafts usually does not succeed, as postoperative irradiation in dosages sufficient for tumor control may interfere with incorporation of the graft. Over a four and one-half-year period, fourteen patients with spinal instability secondary to metastatic pathological fractures of one or more vertebrae received anterior stabilization by replacement of the affected vertebral bodies with methylmethacrylate polymerized in situ. No postoperative external support was required, and the acrylic fixation achieved by this method was not affected adversely by subsequent irradiation averaging 4375 rads. There was only one soft-tissue infection, which did not involve the anterior stabilization. Twelve patients had major neural impairment preoperatively and required spinal cord or nerve-root decompression anteriorly prior to fixation. Nine had complete neural recovery postoperatively, two others were improved significantly, and one remained unchanged. None deteriorated neurologically. Five patients had undergone decompressive laminectomy before the anterior stabilization was attempted. None had improved neurologically, and all had increased spinal instability. There was one failure of fixation. The remaining thirteen patients had excellent relief of pain and restoration of spinal stability which did not deteriorate during the follow-up period, ranging from thirteen to forty-five months postoperatively.


Clinical- and Cost-Effectiveness of a Mandibular Advancement Device Versus Continuous Positive Airway Pressure in Moderate Obstructive Sleep Apnea.
Limited evidence exists on the cost-effectiveness of mandibular advancement device (MAD) compared to continuous positive airway pressure (CPAP) therapy in moderate obstructive sleep apnea (OSA). Therefore, this study compares the clinical and cost-effectiveness of MAD therapy with CPAP therapy in moderate OSA. In a multicentre randomized controlled trial, patients with an apnea-hypopnea index (AHI) of 15 to 30 events/h were randomized to either MAD or CPAP. Incremental cost-effectiveness and cost-utility ratios (ICER/ICUR, in terms of AHI reduction and quality-adjusted life-years [QALYs, based on the EuroQol Five-Dimension Quality of Life questionnaire]) were calculated after 12 months, all from a societal perspective. In the 85 randomized patients (n = 42 CPAP, n = 43 MAD), AHI reduction was significantly greater with CPAP (median reduction AHI 18.3 [14.8-22.6] events/h) than with MAD therapy (median reduction AHI 13.5 [8.5-18.4] events/h) after 12 months. Societal costs after 12 months were higher for MAD than for CPAP (mean difference €2.156). MAD was less cost-effective than CPAP after 12 months (ICER -€305 [-€3.003 to €1.572] per AHI point improvement). However, in terms of QALY, MAD performed better than CPAP after 12 months (€33.701 [-€191.106 to €562.271] per QALY gained). CPAP was more clinically effective (in terms of AHI reduction) and cost-effective than MAD. However, costs per QALY was better with MAD as compared to CPAP. Therefore, CPAP is the first-choice treatment option in moderate OSA and MAD may be a good alternative. Registry: ClinicalTrials.gov; Identifier: NCT01588275.


Comparative Effectiveness Study of Chloramphenicol and Ceftriaxone in the Treatment of Typhoid Fever in Children Admitted to Putri Hijau Kesdam I/Bb Hospital Medan.
Typhoid fever is a disease caused by Salmonella typhi bacteria, especially attacking the digestive tract. Chloramphenicol is the main drug of choice for the treatment of typhoid fever. But along with the advancement of the medical field, other medicines were developed. Ceftriaxone is an effective drug for the treatment of typhoid fever in the short term. But the price of ceftriaxone is more expensive. The aim of this study was comparative effectiveness study of Chloramphenicol and Ceftriaxone in the treatment of typhoid fever in children admitted to Putri Hijau Kesdam I/BB Hospital Medan. This study was conducted cross-sectionally about the treatment of typhoid fever in children who were hospitalized at TK II PutriHijau Hospital Kesdam I/BB Medan. the patient used cloramfenikol antibiotics in 13 patients and used ceftriaxone in 17 patients. Patient age ranges from 0-19 years. Antibiotic analysis is the best effectiveness using the ACER method. He results of the patient characteristics show that the children of patients who suffer from typhoid fever, the highest age is 12-16 years (50%), by gender male 60% and female 40%. Patients hospitalized using chloramfenicol averaged 6.53 days (7 days) while ceftriaxon averaged 4.17 days. The average number of direct medical costs in pediatric patients suffering from typhoid fever using cloramfenikol was 3,212,776/patient while ceftriaxon 1,967,045/patient. Cost effectiveness analysis using ACER method obtained results for cloramenicenicol at 492.002/day and ceftriaxon 471,713/day. Ceftriaxone has a better treatment effectiveness compared to chloramphenicol in typhoid fever patients in children.


Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation.
The dopamine (DA) D2 receptor (D2R) is an important target for the treatment of neuropsychiatric disorders such as schizophrenia and Parkinson's disease. However, the development of improved therapeutic strategies has been hampered by our incomplete understanding of this receptor's downstream signaling processes in vivo and how these relate to the desired and undesired effects of drugs. D2R is a G protein-coupled receptor (GPCR) that activates G protein-dependent as well as non-canonical arrestin-dependent signaling pathways. Whether these effector pathways act alone or in concert to facilitate specific D2R-dependent behaviors is unclear. Here, we report on the development of a D2R mutant that recruits arrestin but is devoid of G protein activity. When expressed virally in "indirect pathway" medium spiny neurons (iMSNs) in the ventral striatum of D2R knockout mice, this mutant restored basal locomotor activity and cocaine-induced locomotor activity in a manner indistinguishable from wild-type D2R, indicating that arrestin recruitment can drive locomotion in the absence of D2R-mediated G protein signaling. In contrast, incentive motivation was enhanced only by wild-type D2R, signifying a dissociation in the mechanisms that underlie distinct D2R-dependent behaviors, and opening the door to more targeted therapeutics.


Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates.
Burkholderia thailandensis is a non-pathogenic environmental saprophyte closely related to Burkholderia pseudomallei, the causative agent of the often fatal animal and human disease melioidosis. To study B. thailandensis genomic variation, we profiled 50 isolates using a pan-genome microarray comprising genomic elements from 28 Burkholderia strains and species. Of 39 genomic regions variably present across the B. thailandensis strains, 13 regions corresponded to known genomic islands, while 26 regions were novel. Variant B. thailandensis isolates exhibited isolated acquisition of a capsular polysaccharide biosynthesis gene cluster (B. pseudomallei-like capsular polysaccharide) closely resembling a similar cluster in B. pseudomallei that is essential for virulence in mammals; presence of this cluster was confirmed by whole genome sequencing of a representative variant strain (B. thailandensis E555). Both whole-genome microarray and multi-locus sequence typing analysis revealed that the variant strains formed part of a phylogenetic subgroup distinct from the ancestral B. thailandensis population and were associated with atypical isolation sources when compared to the majority of previously described B. thailandensis strains. In functional assays, B. thailandensis E555 exhibited several B. pseudomallei-like phenotypes, including colony wrinkling, resistance to human complement binding, and intracellular macrophage survival. However, in murine infection assays, B. thailandensis E555 did not exhibit enhanced virulence relative to other B. thailandensis strains, suggesting that additional factors are required to successfully colonize and infect mammals. The discovery of such novel variant strains demonstrates how unbiased genomic surveys of non-pathogenic isolates can reveal insights into the development and emergence of new pathogenic species.


Glucocorticoid adrenal steroids and glucocorticoid-inducible kinase isoforms in the regulation of GluR6 expression.
Generation of memory is enhanced during stress, an effect attributed to stimulation of neuronal learning by adrenal glucocorticoids. The glucocorticoid-dependent genes include the serum- and glucocorticoid-inducible kinase SGK1. SGK1 is activated through the phosphatidylinositol 3 kinase (PI3-kinase) pathway by growth factors such as insulin-like growth factor-1 (IGF1) or tumour growth factor beta (TGF-beta). Previously, a fourfold higher expression of SGK1 has been observed in fast-learning rats as compared with slow-learning rats. The mechanisms linking glucocorticoids or SGK1 with neuronal function have, however, remained elusive. We show here that treatment of mice with the glucocorticoid dexamethasone (238 microg day-1 for 8-20 days) enhances hippocampal expression of GluR6. Immunohistochemistry reveals significantly enhanced GluR6 protein abundance at neurones but not at astrocytes in mice. Immunohistochemistry and patch clamp on hippocampal neurones in primary culture reveal upregulation of GluR6 protein abundance and kainate-induced currents following treatment with dexamethasone (1 microm) and TGF-beta (1 microm). In Xenopus oocytes expressing rat GluR6, coexpression of SGK1 strongly increases glutamate-induced current at least partially by increasing the abundance of GluR6 protein in the plasma membrane. The related kinases SGK2 and SGK3 similarly stimulate GluR6, but are less effective than SGK1. The observations point to a novel mechanism regulating GluR6 which contributes to the regulation of neuronal function by glucocorticoids.


Modeling suggests that microliter volumes of contaminated blood caused an outbreak of hepatitis C during computerized tomography.
Acute hepatitis C (AHC) is not frequently identified because patients are usually asymptomatic, although may be recognized after iatrogenic exposures such as needle stick injuries, medical injection, and acupuncture. We describe an outbreak of AHC among 12 patients who received IV saline flush from a single multi-dose vial after intravenous contrast administration for a computerized tomography (CT) scan. The last patient to receive IV contrast with saline flush from a multi-dose vial at the clinic on the previous day was known to have chronic HCV genotype 1b (termed potential source, PS). Here we sought to confirm (via genetic analysis) the source of infection and to predict the minimal contaminating level of IV saline flush needed to transmit infectious virus to all patients. In order to confirm the source of infection, we sequenced the HCV E1E2 region in 7 CT patients, in PS, and in 2 control samples from unrelated patients also infected with HCV genotype 1b. A transmission probabilistic model was developed to predict the contamination volume of blood that would have been sufficient to transmit infectious virus to all patients. Viral sequencing showed close clustering of the cases with the PS. The transmission probabilistic model predicted that contamination of the multi-dose saline vial with 0.6-8.7 microliters of blood would have been sufficient to transmit infectious virus to all patients. Analysis of this unique cohort provides a new understanding of HCV transmission with respect to contaminating volumes and viral titers.


Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies.
The classic cardiac manifestation of neonatal lupus is congenital heart block, attributed to antibody-mediated inflammation and subsequent fibrosis of the atrioventricular (AV) node. In considering the pathologic process of injury it may be that tissue damage results in a range of conduction abnormalities. Identification of less-advanced degrees of block or of fibrosis around the AV node without any conduction abnormality on EKG would support this pathologic model, and serve as a potential marker for treatment if the conduction defect could be shown to progress. To ascertain the spectrum of arrhythmias associated with maternal anti-SSA/Ro-SSB/La antibodies, records of all children enrolled in the Research Registry for Neonatal Lupus were reviewed. Of 187 children with congenital heart block whose mothers have anti-SSA/Ro-SSB/La antibodies, nine had a prolonged PR interval on EKG at birth, four of whom progressed to more advanced AV block. A child whose younger sibling had third degree block was diagnosed with first degree block at age 10 years at the time of surgery for a broken wrist. Two children diagnosed in utero with second degree block were treated with dexamethasone and reverted to normal sinus rhythm by birth, but ultimately progressed to third degree block. Four children had second degree block at birth: of these, two progressed to third degree block. Sinus bradycardia (< 100 bpm) was present in three (3.8%) of 78 fetuses for whom atrial rates were recorded by echocardiogram. Of 40 neonates for whom EKGs were available, the mean atrial rate was 137+/-20 bpm (range 75-200). These data have important research and clinical implications. In contrast to the AV node, permanent sinoatrial nodal involvement is not clinically apparent. Perhaps many fetuses sustain mild inflammation, but resolution is variable, as suggested by the presence of incomplete AV block. Since subsequent progression of less-advanced degrees of block can occur, an EKG should be performed on all infants born to mothers with anti-SSA/Ro-SSB/La antibodies.


Effect of luminal ions on the transepithelial electrical potential difference of human rectum.
Skin electrodes are the most convenient reference electrodes for clinical measurements of electrical potential differences (pd) across the epithelium of the alimentary tract but the presence of an electrical charge on normal skin introduces an error. In the present study, by comparison with results obtained using subcutaneous and intravenous electrodes, it was shown that an intradermal injection of saline abolished the skin potential differences. This simple method, therefore, allows skin electrodes to be used to measure the true transepithelial potential differences of gut mucosa. The method was applied to investigate the effect on the rectal potential difference of altering the composition of the luminal solutions. Changes in the cations (sodium, potassium, magnesium) showed that sodium was the most important cationic determinant of the potential difference, especially when sodium absorption was stimulated by giving mineralocorticoids. Changes in the anions (chloride, iodide, bromide, nitrate, bicarbonate, sulphate, phosphate, citrate, and acetate) indicated that the molecular size of the anion rather than its chemical nature was the significant factor and suggested that the ions had to cross a barrier relatively impermeable to anions of radius greater than 3.5 to 4 A degrees . Changes in osmolality and glucose concentration were without effect.


Mouse model of gastric infection with cytotoxin-expressing strain of Helicobacter pylori in studying of pathogenesis of chronic gastric ulcer.
Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm2 ) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori-infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori-infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)-Iß and IL-12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin-somatostatin link.


Absence of Luttinger's theorem due to zeros in the single-particle Green function.
We show exactly with an SU(N) interacting model that even if the ambiguity associated with the placement of the chemical potential, μ, for a T=0 gapped system is removed by using the unique value μ(T→0), Luttinger's sum rule is violated even if the ground-state degeneracy is lifted by an infinitesimal hopping. The failure stems from the nonexistence of the Luttinger-Ward functional for a system in which the self-energy diverges. Since it is the existence of the Luttinger-Ward functional that is the basis for Luttinger's theorem which relates the charge density to sign changes of the single-particle Green function, no such theorem exists. Experimental data on the cuprates are presented which show a systematic deviation from the Luttinger count, implying a breakdown of the electron quasiparticle picture in strongly correlated electron matter.


Evolution of CRISPR-enabled biosensors for amplification-free nucleic acid detection.
CRISPR biosensors enable rapid and accurate detection of nucleic acids without resorting to target amplification. Specifically, these systems facilitate the simultaneous detection of multiple nucleic acid targets with single-base specificity. This is an invaluable asset that can ultimately facilitate accurate diagnoses of biologically complex diseases.


Clinical Characteristics and Predictors of Mortality in Critically Ill Influenza Adult Patients.
Severe influenza is associated with high morbidity and mortality. The aim of this study was to investigate the factors affecting the clinical outcomes of critically ill influenza patients. In this retrospective study, we enrolled critically ill adult patients with influenza at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated the demographic, clinical, and laboratory findings and examined whether any of these measurements correlated with mortality. We then created an event-based algorithm as a simple predictive tool using two variables with statistically significant associations with mortality. Between 2015 and 2018, 102 critically ill influenza patients (median age, 62 years) were assessed; among them, 41 (40.1%) patients died. Of the 94 patients who received oseltamivir therapy, 68 (72.3%) began taking oseltamivir 48 hours after the onset of illness. Of the 102 patients, the major influenza-associated complications were respiratory failure (97%), pneumonia (94.1%), acute kidney injury (65.7%), adult respiratory distress syndrome (ARDS) (51%), gastrointestinal bleeding (35.3%), and bacteremia (16.7%). In the multivariate regression model, high lactate levels, ARDS, acute kidney injury, and gastrointestinal bleeding were independent predictors of mortality in critically ill influenza patients. The optimal lactate level cutoff for predicting mortality was 3.7 mmol/L with an area under curve of 0.728. We constructed an event-associated algorithm that included lactate and ARDS. Fifteen (75%) of 20 patients with lactate levels 3.7 mmol/L and ARDS died, compared with only 1 (7.7%) of 13 patients with normal lactate levels and without ARDS. We identified clinical and laboratory predictors of mortality that could aid in the care of critically ill influenza patients. Identification of these prognostic markers could be improved to prioritize key examinations that might be useful in determining patient outcomes.


Detection and treatment of refractory status epilepticus in the intensive care unit.
Status epilepticus (SE) is not rare in critically ill intensive care unit (ICU) patients, but its diagnosis is often delayed or missed, in part because it is mistaken for other causes of altered mental status. Even once diagnosed, SE in the ICU can be refractory to treatment. We sought to determine the causes, clinical features, and difficulties in diagnosis of SE in the ICU, and the effects of antiepileptic drugs (AEDs) on its course. We reviewed the course of ICU patients with both clinical and EEG evidence of SE, attempting to determine which patients are at risk for unsuspected SE, what was the typical delay in diagnosis, and whether AED treatment made a difference in their clinical courses. By clinical and EEG evidence, 91 ICU patients with SE were identified, all with abnormal mental status: 74 were comatose. Vascular disease (in 24) and anoxia (22) were the most common causes; most had multiple medical problems. Although 76 patients had clinically evident seizures earlier (and 56, clinical SE) only 20 were thought to be in SE at the time of the diagnostic EEG. There was a median delay of 48 hours from clinical deterioration until diagnosis in patients with earlier clinical seizures and 72 hours without seizures. Among the 68 nonanoxic patients treated with AEDs, 38 (56%) seemed to improve in alertness, including 25 who were comatose. Although patients who were stuporous or confused (vs. comatose) improved more often on AEDs, they were less often realized to be in SE before the EEG. Patients with earlier seizures were also more likely to improve, but no more likely to be diagnosed before the EEG. Patients who responded to AEDs were more likely to survive. ICU patients with altered mental status and EEG evidence of SE often have severe medical and surgical illnesses, refractory SE, and a high mortality. The delay to diagnosis is substantial, but a significant subset of patients improves on AEDs once SE is discovered. This diagnosis should be sought more often in ICU patients with abnormal mental status, especially after clinical seizures or SE without full recovery.


Construction of protein distance matrix based on amino acid indices and Discrete Fourier Transform.
Protein distance matrix is widely used in various protein sequence analyses, and mainly obtained by using pairwise sequence alignment scores or protein sequence homology, which fail to take into consideration of individual physical characteristics of protein sequences and amino acids, or a combination of these features. In this paper, a new method is therefore proposed for constructing protein distance matrix based on natural amino acid indices in combination with Discrete Fourier Transform (DFT). For the proposed method, protein distance matrices can be generated using any given set of amino acid indices, each one of which represents a unique biological feature of protein sequences. In this study, the results are based on the combination of 25 widely accepted amino acid indices, which produced the best results, according to the biological relationships between proteins. As a case study 26 Cluster of Differentiation 4 (CD4) protein sequences were used in order to construct a distance matrix based on the proposed method. The results show that the pairwise relationship between CD4 protein sequences remain the same in comparison with their pairwise percent identity. For another group of protein sequences the pairwise relationship between CD4 protein sequences dramatically changed with the proposed method in comparison to the pairwise percent identity. The proposed distance matrix has been shown to have a positive impact on these case studies and therefore is expected to be useful in several fields such as multiple protein sequence alignment and phylogenetic analysis, where an accurate distance matrix based on natural generalized protein properties plays an important role.


Low-Temperature-Processed Brookite-Based TiO2 Heterophase Junction Enhances Performance of Planar Perovskite Solar Cells.
In the design of electron-transport layers (ETLs) to enhance the efficiency of planar perovskite solar cells (PSCs), facile electron extraction and transport are important features. Here, we consider the effects of different titanium oxide (TiO2) polymorphs, anatase and brookite. We design and fabricate high-phase-purity, single-crystalline, highly conductive, and low-temperature (<180 °C)-processed brookite-based TiO2 heterophase junctions on fluorine-doped tin oxide (FTO) as the substrate. We test and compare single-phase anatase (A) and brookite (B) and heterophase anatase-brookite (AB) and brookite-anatase (BA) as ETLs in PSCs. The power-conversion efficiencies (PCEs) of PSCs with low-temperature-processed single-layer FTO-B as the ETL were as high as 14.92%, which is the highest reported efficiency of FTO-B-based single-layer PSC. This implies that FTO-B serves as an active phase and can be a potential candidate as an n-type ETL scaffold in planar PSCs. Moreover, the surface of highly crystalline brookite TiO2 exhibits a tendency toward interparticle necking, leading to the formation of compact scaffolds. Furthermore, PSCs with heterophase junction FTO-AB ETLs exhibited PCEs as high as 16.82%, which is superior to those of PSCs with single-phase anatase (FTO-A) and brookite (FTO-B) as the ETLs (13.86% and 14.92%, respectively). In addition, the PSCs with FTO-AB exhibited improved efficiency and decreased hysteresis compared with those with FTO-BA (13.45%) due to the suitable band alignment with the perovskite layer, which resulted in superior photogenerated charge-carrier extraction and reduced charge accumulation at the interface between the heterophase junction and perovskite. Thus, the present work presents an effective strategy by which to develop heterophase junction ETLs and manipulate the interfacial energy band to further improve the performance of planar PSCs and enable the clean and eco-friendly fabrication of low-cost mass production.


Sex determination of dried blood stains using the polymerase chain reaction (PCR) with homologous X-Y primers of the zinc finger protein gene.
The ability to "sex" unknown dried bloodstains is frequently of evidentiary value in forensic casework. Chelex-extracted DNA from 115 specimens (105 dried blood standards and 10 casework samples) was amplified for specific ZFX and ZFY regions of the X and Y chromosomes and subsequent restriction enzyme digestion. The polymerase chain reaction (PCR) yielded a 209 base pair (bp) product containing a polymorphic position with a Y chromosome portion including an additional Hae III restriction site while the X chromosome portion contains only one. The digested PCR product was separated by polyacrylamide gel electrophoresis (PAGE) and detected by silver staining. Female samples exhibit bands of 172 bp and 37 bp only while male samples (XY) exhibit 2 additional bands appearing as an 88/84 bp doublet. Initially the 105 known bloodstains were typed according to the procedure discussed here and correct gender determination was achieved for all samples therefore establishing the reliability of this method. The 10 casework samples yielded the expected results as well. This assay demonstrates potential in both presumptive and confirmatory capacities.


Mycobacterium paratuberculosis cultured from milk and supramammary lymph nodes of infected asymptomatic cows.
Milk and supramammary lymph node samples were obtained from asymptomatic cows infected with Mycobacterium paratuberculosis at the time of slaughter. Of 81 supramammary lymph node samples, 22 (27%) were culture positive for M. paratuberculosis. Of 77 milk samples, 9 (11.6%) were culture positive. The prevalence of supramammary lymph node or milk infection was highest with heavy fecal shedding of M. paratuberculosis and lowest with light shedding. The serologic status of the cow was not useful for predicting the risk of supramammary lymph node or milk infection. Shedding of M. paratuberculosis occurs in the milk of asymptomatic infected cows but, apparently, less frequently than previously reported for symptomatic cows.


Nanoscale structure of the BMP antagonist chordin supports cooperative BMP binding.
Bone morphogenetic proteins (BMPs) orchestrate key cellular events, such as proliferation and differentiation, in development and homeostasis. Extracellular antagonists, such as chordin, are essential regulators of BMP signaling. Chordin binds to BMPs blocking interaction with receptors, and cleavage by tolloid proteinases is thought to relieve this inhibition. A model has been previously proposed where chordin adopts a horseshoe-like arrangement enabling BMP binding cooperatively by terminal domains (1). Here, we present the nanoscale structure of human chordin using electron microscopy, small angle X-ray scattering, and solution-based biophysical techniques, which together show that chordin indeed has a compact horseshoe-shaped structure. Chordin variants were used to map domain locations within the chordin molecule. The terminal BMP-binding domains protrude as prongs from the main body of the chordin structure, where they are well positioned to interact with the growth factor. The spacing provided by the chordin domains supports the principle of a cooperative BMP-binding arrangement that the original model implied in which growth factors bind to both an N- and C-terminal von Willebrand factor C domain of chordin. Using binding and bioactivity assays, we compared full-length chordin with two truncated chordin variants, such as those produced by partial tolloid cleavage. Cleavage of either terminal domain has little effect on the affinity of chordin for BMP-4 and BMP-7 but C-terminal cleavage increases the efficacy of chordin as a BMP-4 inhibitor. Together these data suggest that partial tolloid cleavage is insufficient to ablate BMP inhibition and the C-terminal chordin domains play an important role in BMP regulation.


Molecular analysis of the SGLT2 gene in patients with renal glucosuria.
The role of SGLT2 (the gene for a renal sodium-dependent glucose transporter) in renal glucosuria was evaluated. Therefore, its genomic sequence and its intron-exon organization were determined, and 23 families with index cases were analyzed for mutations. In 21 families, 21 different SGLT2 mutations were detected. Most of them were private; only a splice mutation was found in 5 families of different ethnic backgrounds, and a 12-bp deletion was found in two German families. Fourteen individuals (including the original patient with 'renal glucosuria type 0') were homozygous or compound heterozygous for an SGLT2 mutation resulting in glucosuria in the range of 14.6 to 202 g/1.73 m(2)/d (81 - 1120 mmol/1.73 m(2)/d). Some, but not all, of their heterozygous family members had an increased glucose excretion of up to 4.4 g/1.73 m(2)/d (24 mmol/1.73 m(2)/d). Likewise, in index cases with glucosuria below 10 g/1.73 m(2)/d (55 mmol/1.73 m(2)/d) an SGLT2 mutation, if present, was always detected in the heterozygous state. We conclude that SGLT2 plays an important role in renal tubular glucose reabsorption. Inheritance of renal glucosuria shows characteristics of a codominant trait with variable penetrance.


[Immunopharmacological method for the diagnosis of multiple sclerosis].
Using the data on increased level of opioids in the internal media of patients with multiple sclerosis it was found that blood lymphocytes from MS patients had elevated adhesive activity to opiates, including morphine, in the reaction of specific rosette formation. Immunopharmacologic method for MS diagnosis is proposed based on detection of considerably increased level of the rosette forming cells, specific to morphine (morphine test). This test is a reliable additional marker for all clinical forms of the disease and provides differential diagnosis of both MS and some other diseases with similar clinical symptomatology at any age, any duration and a character of a course of the disease.


Trading Land: A Review of Approaches to Accounting for Upstream Land Requirements of Traded Products.
Land use is recognized as a pervasive driver of environmental impacts, including climate change and biodiversity loss. Global trade leads to "telecoupling" between the land use of production and the consumption of biomass-based goods and services. Telecoupling is captured by accounts of the upstream land requirements associated with traded products, also commonly referred to as land footprints. These accounts face challenges in two main areas: (1) the allocation of land to products traded and consumed and (2) the metrics to account for differences in land quality and land-use intensity. For two main families of accounting approaches (biophysical, factor-based and environmentally extended input-output analysis), this review discusses conceptual differences and compares results for land footprints. Biophysical approaches are able to capture a large number of products and different land uses, but suffer from a truncation problem. Economic approaches solve the truncation problem, but are hampered by the limited disaggregation of sectors and products. In light of the conceptual differences, the overall similarity of results generated by both types of approaches is remarkable. Diametrically opposed results for some of the world's largest producers and consumers of biomass-based products, however, make interpretation difficult. This review aims to provide clarity on some of the underlying conceptual issues of accounting for land footprints.


Current Use of Hearts From Hepatitis C Viremic Donors.
Strategies to improve donor heart utilization are required in the setting of limited donor availability. One innovative strategy is to consider the use of hepatitis C viremic (HCV) nucleic acid amplification test positive donors in hepatitis C-negative recipients, given the availability of highly effective direct acting antiviral agents. We utilized United Network for Organ Sharing data to evaluate the geographic distribution, clinical characteristics, and post-transplant outcomes of HCV+ donor hearts. The United Network for Organ Sharing registry was queried for all HCV+ recovered donors and those considered for heart donation classified by sex, age group, United Network for Organ Sharing region, and cause of death from January 1, 2014, to December 31, 2017. Propensity score matching (3:1) was applied to the recipients based on the index for mortality prediction after cardiac transplantation score and donor risk index. A total of 1306 HCV+ donors were recovered from 2014 to 2017 of whom 1078 (82.5%) were 18 to 49 and predominantly from the Appalachia region (United Network for Organ Sharing regions 2, 3, and 11). A total of 64 (5%) HCV+ donor hearts were transplanted in this interval. The match-adjusted risk difference in survival was estimated to be 0.87% ( P=0.83) at 12 months. To meet the demands of heart transplantation, we must consider additional strategies to expand the donor pool. From 2014 to 2017, despite availability of highly effective direct acting antiviral therapy, only 5% of HCV+ donor hearts were accepted for transplantation. National efforts may be required to capitalize on this resource while we continue to carefully monitor the safety of this novel approach.


Evaluation of five immunodiagnostic techniques in echinococcosis patients.
Double diffusion (DD), indirect haemagglutination (IHA), immunoelectrophoresis (IEP), latex agglutination (LA), and complement fixation (CF) tests were evaluated for sensitivity and specificity in the diagnosis of 141 surgically-proven Turkana echinococcosis patients and 10 controls. The overall sensitivities for the tests were: IHA, 86.7%; LA, 53.3%; CF, 63.3%; DD, 55.0%; IEP, 55.0%. LA and CF tests produced a high number of false positive results; IHA gave a false positive result in 10% of cases; no false positives were obtained with IEP and DD. A combination of the latter three tests would therefore offer the best chance of detecting specific anti-Echinococcus antibodies, with an average sensitivity of 62.7%. The possible reasons for the relatively high incidence of false negative values are discussed.


Scandinavian clinical practice guidelines on general anaesthesia for emergency situations.
Emergency patients need special considerations and the number and severity of complications from general anaesthesia can be higher than during scheduled procedures. Guidelines are therefore needed. The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine appointed a working group to develop guidelines based on literature searches to assess evidence, and a consensus meeting was held. Consensus opinion was used in the many topics where high-grade evidence was unavailable. The recommendations include the following: anaesthesia for emergency patients should be given by, or under very close supervision by, experienced anaesthesiologists. Problems with the airway and the circulation must be anticipated. The risk of aspiration must be judged for each patient. Pre-operative gastric emptying is rarely indicated. For pre-oxygenation, either tidal volume breathing for 3 min or eight deep breaths over 60 s and oxygen flow 10 l/min should be used. Pre-oxygenation in the obese patients should be performed in the head-up position. The use of cricoid pressure is not considered mandatory, but can be used on individual judgement. The hypnotic drug has a minor influence on intubation conditions, and should be chosen on other grounds. Ketamine should be considered in haemodynamically compromised patients. Opioids may be used to reduce the stress response following intubation. For optimal intubation conditions, succinylcholine 1-1.5 mg/kg is preferred. Outside the operation room, rapid sequence intubation is also considered the safest method. For all patients, precautions to avoid aspiration and other complications must also be considered at the end of anaesthesia.


The confined [Bmim][BF4] ionic liquid flow through graphene oxide nanochannels: a molecular dynamics study.
Ionic liquid (IL) flow in graphene oxide (GO) nanochannels plays a key role in the performance of IL- and GO-based fluidics devices and other chemical separator techniques. Here, we investigate the flow behavior of ILs in GO nanochannels via molecular dynamics simulations. The quantitative relation between slip velocity and shear stress has been identified, showing that the interfacial friction coefficient can be enhanced by almost sixty times, while the slip length is reduced by about three orders of magnitude, with the fraction of hydroxylation in graphene ranging from 0% to 15%. The great change in interfacial properties can be attributed to the structural changes of IL layers near GO, which is proved by the detailed analysis of density distribution, charge distribution and radial distribution function. Besides, the viscosity will increase as a fraction of hydroxylation because of the partial breaking of coulombic ordering of confined ILs. Meanwhile, the hydroxyls have more significant effects on IL flow than water flow in GO nanochannels due to the stronger interaction networks in IL/GO interfaces. In summary, hydroxylation can be a convincing method to regulate the IL flow in nanochannels. The quantitative properties of confined ILs in GO nanochannels and their relation to the fraction of hydroxylation could deepen the understanding of ILs and benefit the applications of ILs and GO in the fields of chemical engineering and various other nanofluidic devices.


2-Pentanone production from hexanoic acid by Penicillium roqueforti from blue cheese: is this the pathway used in humans?
Production of 2-pentanone, a methylketone, is increased in fasting ketotic humans. Its origin is unknown. We hypothesised that it is formed via β -oxidation of hexanoic acid by the peroxisomal pathway proposed for methylketone-producing fungi and yeasts. We used Penicillium roqueforti cultured on fat (margarine) to investigate 2-pentanone production. Headspace gas of incubates of the mould with a range of substrates was analysed using solid-phase microextraction with gas chromatography-mass spectrometry. Consistent with the proposed pathway, 2-pentanone was formed from hexanoic acid, hexanoyl-CoA, hexanoylcarnitine, and ethyl-3-oxohexanoic acid but not from ethylhexanoic, 2-ethylhexanoic, octanoic, or myristic acids, octanoylcarnitine, or pentane. However, the products from deuterated (D) hexanoic-D11 acid and hexanoic-2, 2-D2 acid were 9D- and 2D-2-pentanone, respectively, and not 8D- and 1D-2-pentanone as predicted. When incubated under (18)O2/(14)N2, there was only a very small enrichment of [(16)O2]- with [(18)O2]-containing 2-pentanone. These are new observations. They could be explained if hydrogen ions removed from hexanoyl-CoA by acyl-CoA oxidase at the commencement of β -oxidation were cycled through hydrogen peroxide and reentered the pathway through hydration of hexenoyl-CoA. This would protect other proteins from oxidative damage. Formation of 2-pentanone through a β -oxidation cycle similar to Penicillium roqueforti would be consistent with observations in humans.


[Normative study of the Boston naming test in 7-year-old Japanese children].
The Boston Naming Test (BNT) has been used to assess the language development of children in many epidemiology studies, and its usefulness is confirmed. The BNT consists of 60 black and white line drawings of objects and animals. There are no normative data available for this test for Japanese children. The purpose of this study was to collect normative information in Japan and to examine the correlation between the score of the BNT and Intelligence Quotient (IQ) of the Wechsler Intelligence Scale for Children third edition (WISC-III). The BNT was translated into Japanese and administered in children registered to the birth cohort of the Tohoku Study of Child Development at the age of 84 months. The participants for analysis in this study were 449 children (237 boys, 212 girls). There were four items with percentage scores below 1%; Igloo, Knocker, Muzzle, and Yoke. Many Japanese children could answer 'abacus' and 'compass', which are difficult for US children. Although the score of the BNT correlated with IQ of the WISC-III (p<0.001), as compared with the previous studies, the correlation coefficient was low. The BNT is quick and easy to use and valuable for researchers in evaluating language ability in children. Since the BNT was developed in the United States, the cultural values of that country are reflected in the BNT score. This implies that the BNT should be modified to fit Japanese population.


Convulsive seizures induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjection into the mesencephalic reticular formation in rats.
Effects of microinjections of a single 2 or 10 nmol dose of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the unilateral mesencephalic reticular formation (MRF) on behavior and on the electroencephalogram were examined in rats (n=30) over a 15-min period (Exp. 1); subsequent effects of sound stimulation with key jingling applied at 15, 30, and 45 min after the injection were observed (Exp. 2). The microinjections of a 2 nmol dose of AMPA (n=15) induced hyperactivity (15 of 15 rats) and running/circling (10 of 15 rats) in Exp. 1, and hyperactivity (5 of 15 rats) in Exp. 2. Moreover, the microinjections of a 10 nmol dose of AMPA (n=15) induced hyperactivity (15 of 15 rats), running/circling (13 of 15 rats), generalized tonic-clonic seizures (GTCS) (4 of 15 rats), and amygdala kindling-like seizures (AMKS) (8 of 15 rats) in Exp. 1; electroencephalographic seizure discharges were predominantly observed in the MRF during hyperactivity, running/circling and GTCS, while those predominantly observed in the amygdala were during AMKS. In Exp. 2, hyperactivity (15 of 15 rats), running/circling (14 of 15 rats) and GTCS (6 of 15 rats) were elicited by sound stimulation, although AMKS were not. The control group of rats (n=15) which received a single dose of saline microinjection into the unilateral MRF showed no behavioral or electroencephalographic changes in both Exp. 1 and 2. These findings suggest that potentiation of excitatory amino acid neurotransmission induced by AMPA injection into the MRF plays an important role not only in the development of hyperactivity, running/circling, GTCS and AMKS, but also in the development of audiogenic seizures.


Peritoneal Dialysis Is an Independent Factor Associated to Lower Intima Media Thickness in Dialysis Patients Free From Previous Cardiovascular Disease.
Carotid intima media thickness (cIMT) displays prognostic value as a marker of cardiovascular risk in dialysis patients. However, few data are available regarding the impact of dialysis modality on cIMT. The aim of this study is to determine whether the modality of dialysis influences cIMT values. We compared 237 peritoneal dialysis (PD) and 451 hemodialysis (HD) patients without previous cardiovascular disease included in NEFRONA, a prospective, observational and multicenter study. This cross sectional study included the determination of cIMT in 6 carotid territories by arterial ultrasound. cIMT was determined in territories without atheroma plaque and averaged. A second analysis was performed using all territories, giving a truncated cIMT value of 1,5 mm to territories presenting with atheroma plaque. Age and plaque presence at baseline were the clinical variables more closely associated to cIMT in dialysis patients. The evaluation of the impact of the modality of dialysis on cIMT showed that PD patients had lower cIMT than HD patients, both in territories with no plaques and when using truncated cIMT values. No differences were found between right and left sides, neither in cIMT or truncated cIMT values. Lineal multivariate analysis adjusted by several clinical variables showed a statistically significant association of PD with a lower cIMT (slope -0.036; SD 0.010). These results were also confirmed when truncated cIMT values were used. We conclude that the modality of dialysis has an impact on cITM. HD patients have greater global cIMT than PD patients, and PD is and independent factor associated with a lower cIMT.


Measuring tumor hypoxia with ¹⁸F-FETNIM PET in esophageal squamous cell carcinoma: a pilot clinical study.
The purpose of this study was to evaluate hypoxia in esophageal squamous cell carcinoma (SCC) with (18)F-fluoroerythronitroimidazole positron emission tomography/computed tomography ((18)F-FETNIM PET/CT). We determined an imaging threshold for hypoxia, quantified the spatiotemporal variability of hypoxia in untreated tumor, and evaluated the ability of (18)F-FETNIM PET to predict clinical response following concurrent chemoradiotherapy (CCRT). Twenty-eight consecutive patients with inoperable SCC of the esophagus were consecutively accrued between April 2007 and June 2010. The first 10 patients received two pretreatment (18)F-FETNIM PET/CT scans on separate days. The remaining 18 patients only underwent (18)F-FETNIM PET/CT once before CCRT. The ratio of the maximum standardized uptake value (SUV(max) ) of 336 normal tissue regions (i.e. heart, lung, brain, or muscle) to the mean standardized uptake value (SUV(mean)) of the respective patient's spleen was calculated, and the imaging threshold for hypoxia defined as the level of uptake demonstrated by less than 5% of tissue regions. Among the patients with two pretreatment scans, each pair of scans was compared with respect to location and intensity of uptake to assess for baseline spatiotemporal variability. Logistic regression analysis was used to determine whether pretreatment imaging characteristics are predictive of clinical response. The mean and median ratios of the SUV(max) of tissue : SUV(mean) of spleen were nearly identical, and 95% of the ratios fell below 1.3. The mean Dice similarity coefficient for the hypoxic volumes on pretreatment PET scans acquired in the same patient on different days was 0.12 (range, 0.05-0.21). Individuals' tumor SUV(max) and SUV(mean) did not vary significantly, but on average, the geometric centers of hypoxic regions shifted 15 mm (range, 8-20 mm) from the first pretreatment scan to the second. SUV(max) was the imaging characteristic most predictive of treatment response (P= 0.041), with high SUVmax associated with poor clinical response. (18)F-FETNIM PET/CT can depict hypoxia in esophageal SCC. Prior to CCRT, tumor hypoxia demonstrates spatial variability on different days, although overall (18)F-FETNIM uptake remains similar. Baseline SUV(max) may be predictive of treatment response.


Related Enteric Viruses Have Different Requirements for Host Microbiota in Mice.
Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota.IMPORTANCE Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.


Role of antrum in regulation of pancreaticobiliary secretion in humans.
Little is known about the role of the gastric phase in the postprandial pancreaticobiliary response. We evaluated the effect of antral distension on pancreatic, biliary, and gastric secretions and on the release of cholecystokinin (CCK), gastrin, and pancreatic polypeptide in five healthy volunteers. Studies were performed using a duodenal tube with an inflatable balloon in the antrum and a separate gastric tube. Outputs were compared with responses to a maximal CCK stimulus (caerulein), and the role of cholinergic mechanisms was investigated using atropine. Graded antral distension by 50-, 200-, and 350-ml balloon volumes and constant antral distension by 350 ml elicited a marked stimulation of pancreaticobiliary secretions. Mean lipase outputs amounted to 52-60%, and mean bilirubin outputs reached 14-22% of maximal. Atropine completely abolished pancreaticobiliary responses to antral distension. Antral distension did not affect bicarbonate and gastric secretions. Plasma pancreatic polypeptide levels increased markedly during antral distension, and this effect was completely suppressed by atropine. There were no changes in circulating gastrin and CCK. These data demonstrate that antral distension with already small volumes of 50 ml elicits a hitherto unknown potent stimulatory effect, indicating a major role of the antrum in the postprandial pancreaticobiliary response in humans, which is mediated by cholinergic mechanisms.


Role of the supracellular actomyosin cable during epithelial wound healing.
The closure of wounds in epithelia is center to many physiological processes in both development and repair of multicellular organisms. Depending on the biochemical and mechanical environment as well as cell type, this collective cellular movement often involves coordinated cell crawling and the purse-string contraction of a supracellular actomyosin ring around the wound. However, it remains uncertain how these two mechanisms cooperatively contribute to the wound healing, and especially the role of the ring is not clear. To decipher this complex process, we develop a particle-based model that includes purse-string contraction, cell crawling and other properties incorporated with monolayers of Madin-Darby canine kidney (MDCK) cells. Our model captures the traction force patterns under several different conditions in experiments. In addition to traction force pointing away from the wound on the leading edge, we observed patterns of traction force pointing towards the wound. We show this inward pointing force pattern is induced by the purse-string contraction. Our model also explains the effects of the purse-string ring and which parameters affect the relative efficiency of these two mechanisms.


Procainamide-induced systemic lupus erythematosus. Renal involvement with deposition of immune complexes.
A 54-year-old man sustained an acute anterior myocardial infarction and was subsequently treated with procainamide hydrochloride for 5 1/2 months, resulting in development of a drug-induced systemic lupus erythematosus (SLE) syndrome with renal involvement. In over 60 reported cases of procainamide-induced SLE, clinical renal evaluation has led to the concept that renal involvement is a rarity in this disease. Direct immunofluorescence examination of necropsy kidney tissue revealed mesangial deposition of immunoproteins and C3 in a granular pattern characteristically seen in idiopathic SLE. Ultrastructural studies confirm mesangial deposition of immune complexes. The immunological and ultrastructural pattern of immune complex deposition in glomeruli suggests similar pathological mechanisms for glomerular injury in procainamide as seen in idiopathic SLE.