Prevalence of body dysmorphic disorder in a German psychiatric inpatient sample.
Body dysmorphic disorder (BDD) is a distressing or impairing preoccupation with an imagined or slight defect in appearance. Only a few studies have examined BDD prevalence in psychiatric settings. Prevalence rates vary widely and most studies have been conducted in outpatient samples. In the current study, we examined 155 adult psychiatric inpatients. Diagnostic criteria of BDD were assessed with the BDD module of the Structured Clinical Interview for DSM-IV. The prevalence of lifetime BDD was 2.6% (95% CI=0.1-5.1%). Currently 1.9% of the patients suffered from BDD (95% CI=0.0-4.0%). None of these patients were diagnosed with BDD on admission or during hospitalization. The BDD rates found in this study are considerably lower than lifetime and current prevalence rates reported by two other studies conducted in adult psychiatric inpatient settings (Grant et al., 2001; Conroy et al., 2008). The differences may be explained by divergent sample compositions and variation in diagnostic measures. The findings of the current study underline the need for further studies examining BDD prevalence in psychiatric settings and suggest using a combination of screening questionnaire and follow-up interview to diagnose BDD.


Posttraumatic stress disorder: the missed diagnosis.
Posttraumatic stress disorder (PTSD) is frequently underdiagnosed in maltreated samples. Protective services information is critical for obtaining complete trauma histories and determining whether to survey PTSD symptoms in maltreated children. In the current study, without protective services information to supplement parent and child report, diagnosing PTSD was missed in a significant proportion of the cases. Collaboration between mental health professionals and protective service workers is critical in determining psychiatric diagnoses and treatment needs of children involved with the child welfare system.


Surgical practice in rural communities: challenges and opportunities.
I have attempted to point out some problems that face the surgeon in a rural practice as well as some of the advantages of living in a rural community. Surgical residents may find that a career choice in rural surgery merits their attention and consideration because the apparent obstacles can be readily overcome, and practice in a rural area can be intellectually and professionally challenging and rewarding.


The Role of Emotion Regulation for General Self-Efficacy in Adolescents Assessed Through Both Neurophysiological and Self-Reported Measures.
Self-efficacy, the belief in one's ability and capacity to organize and execute actions required to achieve desired results, is associated with adolescent academic achievement and reduced risk for psychopathology. Adolescent emotion regulation represents an important component in the relationship between self-efficacy and developmental outcomes, but the underlying neurophysiological mechanisms are poorly understood. It is unclear how emotion regulation strategies, which change with experience, and emotion regulation capacity, which is largely determined by genetics, contribute to the development of self-efficacy. The present study aims to explore the relationship between emotion regulation and self-efficacy in adolescents. We hypothesize that neurophysiological emotion regulation capacity moderates the relationship between emotion regulation strategies and self-efficacy. The present study applied a cross-sectional design. A sample of high-school students (N = 45, nfemale = 31, age = 17-18) provided answers on the General Self-Efficacy Questionnaire and the Emotion Regulation Questionnaire. Vagal tone was used as an indicator for emotion regulation capacity. In the initial correlational analysis, reappraisal, but not expressive suppression nor vagal tone was associated with self-efficacy. Vagal tone was not associated with any self-report measures of emotion regulation or self-efficacy. Contrary to our hypothesis, vagal tone did not moderate the relationship between emotion regulation and self-efficacy. This is the first study assessing the relationship between neurophysiological indicators of emotion regulation and self-efficacy. Our results do not indicate that vagal tone moderates the relationship between emotion regulation strategies and general self-efficacy. Future studies should also assess the possible influence of metacognition and interoception on relationships.


Pterostilbene Reduces Acetaminophen-Induced Liver Injury by Activating the Nrf2 Antioxidative Defense System via the AMPK/Akt/GSK3β Pathway.
Pterostilbene (Pts), a natural dimethylated analog of resveratrol from blueberries, exerts antioxidative and anti-apoptotic effects in various diseases. This study aims to investigate the protective effects and mechanism of Pts against acetaminophen (APAP)-induced hepatotoxicity in vivo. C57BL/6 mice were treated with APAP or APAP+Pts. HepG2 cells were used to further explore the underlying mechanisms in vitro. The effects of Pts on hepatotoxicity were measured by commercial kits, Hematoxylin and Eosin (H&E) straining, TUNEL assay, Western blot analysis, and Flow cytometry assay. In vivo, Pts treatment effectively protected against APAP-induced severe liver injury by decreasing the lethality rate, the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, liver histological injury, liver malondialdehyde (MDA) formation and myeloperoxidase (MPO) levels and by increasing liver glutathione (GSH) and superoxide dismutase (SOD) levels. Moreover, in Pts-treated mice, the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway was activated; however, APAP-induced c-Jun NH2-terminal kinase (JNK) activation, mitochondrial Bcl-2 Associated X Protein (Bax) translocation, apoptosis-inducing factor (AIF) levels and cytochrome c release were attenuated. In vitro, Pts was found to reverse hydrogen peroxide (H2O2) -induced cytotoxicity, reactive oxygen species (ROS) production and apoptosis that depended on Nrf2 activation. Moreover, Pts induced a dose-dependent increase in the phosphorylation of AMP-activated protein kinase (AMPK), serine/threonine kinase (Akt), and glycogen synthase kinase 3β (GSK3β) in HepG2 cells. Moreover, Pts protect against APAP or H2O2-induced toxicity were effectively attenuated or abolished in HepG2 Nrf2-/- cells and Nrf2-/- mice. Our data suggest that Pts protects against APAP-induced toxicity by activating Nrf2 via the AMPK/Akt/GSK3β pathway.


The effect of local IL-4 delivery or CCL2 blockade on implant fixation and bone structural properties in a mouse model of wear particle induced osteolysis.
Modulation of macrophage polarization and prevention of CCL2-induced macrophage chemotaxis are emerging strategies to reduce wear particle induced osteolysis and aseptic total joint replacement loosening. In this study, the effect of continuous IL-4 delivery or bioactive implant coating that constitutively releases a protein inhibitor of CCL2 signaling (7ND) on particle induced osteolysis were studied in the murine continuous femoral intramedullary particle infusion model. Polyethylene particles with or without IL-4 were infused into mouse distal femurs implanted with hollow titanium rods using subcutaneous infusion pumps. In another experimental group, particles were infused into the femur through a 7ND coated rod. After 4 weeks, fixation of the implant was assessed using a pullout test. The volume of trabecular bone and the geometry of the local cortical bone were assessed by µCT and the corresponding structural properties of the cortical bone determined by torsional testing. Continuous IL-4 delivery led to increased trabecular bone volume as well as enhanced local bone geometry and structural properties, while 7ND implant coating did not have effect on these parameters. The results suggest that local IL-4 treatment is a promising strategy to mitigate wear particle induced osteolysis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2255-2262, 2016.


Redox potential and C-H bond cleaving properties of a nonheme Fe(IV)=O complex in aqueous solution.
High-valent iron-oxo intermediates have been identified as the key oxidants in the catalytic cycles of many nonheme enzymes. Among the large number of synthetic Fe(IV)=O complexes characterized to date, [Fe(IV)(O)(N4Py)](2+) (1) exhibits the unique combination of thermodynamic stability, allowing its structural characterization by X-ray crystallography, and oxidative reactivity sufficient to cleave C-H bonds as strong as those in cyclohexane (D(C-H) = 99.3 kcal mol(-1)). However, its redox properties are not yet well understood. In this work, the effect of protons on the redox properties of 1 has been investigated electrochemically in nonaqueous and aqueous solutions. While the cyclic voltammetry of 1 in CH(3)CN is complicated by coupling of several chemical and redox processes, the Fe(IV/III) couple is reversible in aqueous solution with E(1/2) = +0.41 V versus SCE at pH 4 and involves the transfer of one electron and one proton to give the Fe(III)-OH species. This is in fact the first example of reversible electrochemistry to be observed for this family of nonheme oxoiron (IV) complexes. C-H bond oxidations by 1 have been studied in H(2)O and found to have reaction rates that depend on the C-H bond strength but not on the solvent. Furthermore, our electrochemical results have allowed a D(O-H) value of 78(2) kcal mol(-1) to be calculated for the Fe(III)-OH unit derived from 1. Interestingly, although this D(O-H) value is 6-11 kcal mol(-1) lower than those corresponding to oxidants such as [Fe(IV)(O)(TMP)] (TMP = tetramesitylporphinate), [Ru(IV)(O)(bpy)(2)(py)](2+) (bpy = bipyridine, py = pyridine), and the tert-butylperoxyl radical, the oxidation of dihydroanthracene by 1 occurs at a rate comparable to rates for these other oxidants. This comparison suggests that the nonheme N4Py ligand environment confers a kinetic advantage over the others that enhances the C-H bond cleavage ability of 1.


Health care consumer report cards: what do patients and families really want to know? What should they want to know?
Much attention has recently been focused on the health care industry's ability to demonstrate the quality of the services they provide. Health care provider organizations have begun to face growing demands for performance information from all sides, both within the industry (accrediting and regulating bodies) as well as from consumers. At present, the health care industry defines quality in three basic dimensions: (1) clinical quality, (2) service quality, and (3) customer satisfaction. Information is available to the public regarding performance due to partnerships of accrediting bodies and health care purchasers. This article explores what patients and families really want to know about their providers and health care facilities.


Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome: A study from China.
Functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) represent a spectrum of constipation disorders. However, the majority of previous clinical investigations have focused on Western populations, with limited data originating from China. To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population. Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled. FC and IBS-C diagnoses were established using ROME IV criteria, and patients underwent high-resolution anorectal manometry (ARM) and a colonic transmit test using the Sitz marker study. Constipation-related symptoms were obtained through questionnaires. Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21. The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared. No significant differences in sex, age or abdominal discomfort symptoms were observed between IBS-C and FC patients (all P > 0.05). The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC (36.63% vs 15.91%, P < 0.05), while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group (50% vs 26.73%, P < 0.05). Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM. IBS-C patients were found to have a higher prevalence of depression than FC patients (66.30% vs 42.42%, P < 0.05). The scores for feelings of guilt, suicide, psychomotor agitation, diurnal variation, obsessive/compulsive disorder, hopelessness, self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients (P < 0.05). For IBS-C (χ2 = 5.438, P < 0.05) but not FC, patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time. For IBS-C patients but not FC patients, the threshold of first constant sensation, desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety (r = 0.414, r = 0.404, and r = 0.418, respectively, P < 0.05). The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression (69.6% vs 41.9%, χ2 = 4.054, P < 0.05). Our findings highlight both overlapping and distinctive patterns of colon transit, dyssynergic patterns, anorectal sensation, psychological distress, and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population, providing valuable insights into the pathophysiological underpinnings of these disorders.


Terazosin therapy for patients with female lower urinary tract symptoms: a randomized, double-blind, placebo controlled trial.
We determined the clinical efficacy and safety of terazosin in the treatment of patients with female lower urinary tract symptoms. A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine. Using a primary end point, 32 of 40 (80%) evaluable terazosin subjects responded in contrast to 22 of 40 (55%) evaluable placebo subjects (p <0.02). The secondary end point revealed a successful outcome in 85% of terazosin subjects vs 55% in placebo (p <0.01). Of the 7 International Prostate Symptom Score individual item scores, only item scores of frequency and straining showed statistically significant reductions with terazosin (p <0.01). All King's Health Questionnaire quality of life domains except domain of severity measures showed statistically significant improvement with terazosin (p <0.05). There were no differences between treatment groups in all objective assessment parameters. Of all evaluable subjects 23 of 40 (58%) on placebo experienced adverse events vs 16 of 40 (40%) on terazosin (p >0.05). Terazosin proved to be more effective and safe than placebo in patients with female lower urinary tract symptoms.


Nutritional and anthropometric analysis of edentulous patients wearing implant overdentures or conventional dentures.
As masticatory efficiency diminishes drastically in edentulous patients, several researchers have studied over the past two decades how dietary intake varies when different types of oral rehabilitation are provided. Since the use of implants to support prostheses in edentulous mandibles has been shown to significantly improve masticatory performance, the question remains as to whether this improvement will influence the nutritional status. The purose of this study was to evaluate the nutritional status of edentulous patients who randomly received either a mandibular conventional denture (CD) or an implant-supported overdenture (IP) 1 year previously. Weight, height, body composition and handgrip strength measurements were collected for analysis. Blood tests were performed to measure plasma parameters of diet intake. Participants responded to a Food Frequency Questionnaire and a Masticatory Function Questionnaire. Fifty-three people participated (58% men, 42% women; mean age = 53). Body composition indicators as well as plasma parameters were generally within normal range, and no statistically significant difference (p>0.05) was found between the groups. Patients in the CD group had significantly lower ratings for items regarding difficulty in chewing (p<0.05), but no significant difference was found for dietary intake (p>0.05). Although the CD wearers reported having more difficulty in chewing hard foods, both groups appeared to have a similar nutritional status.


Four great Asian trade collapses.
This paper introduces a new dataset of commodity-specific, bilateral import data for four large Asian economies in the interwar period: China, the Dutch East Indies, India and Japan. It uses these data to describe the interwar trade collapses in the economies concerned. These resembled the post-2008 Great Trade Collapse in some respects but not in others: they occurred along the intensive margin, imports of cars were particularly badly affected, and imports of durable goods fell by more than those of non-durables, except in China and India which were rapidly industrialising. On the other hand the import declines were geographically imbalanced, while prices were more important than quantities in driving the overall collapse.


Specific signaling molecule expressions in the interradicular septum in different age groups.
Orthodontic teeth movement is accompanied by the remodeling of alveolar bone, including the interradicular septum. Bone contains three cell types, osteoblasts, osteocytes, and osteoclasts that are in direct contact with all of the cellular elements in the bone marrow. Marrow is the source of both bone-building osteoblasts and bone destroying osteoclasts, and the turnover of bone occurs throughout life. Bone signalling molecules have important functions during osteogenesis, and they are active in the bone remodelling process. Patients involved in orthodontic treatment belong to different age groups: therefore age must be considered as a contributing factor compromising the osteogenetic potential of bone. The aim of the current study was to investigate the specific expression of signalling molecules in the interradicular septum in different age groups. The study group included 17 patients to whom the extraction of teeth was recommended as part of further orthodontic treatment. Patients (9 males and 8 females) - were divided into 3 groups 1st group - 12-14 years old); 2nd group - 15-22 years old; 3rd group - 23 years old or older. Expression of BMP 2/4, TGF-α, IL-1, IL-8, OPG, MMP-1, MMP-2, MMP-8, MMP-9, MMP-13, NGFR, NKpB 105, osteocalcin, and osteopontin in interradicular septum tissues was examined. TUNEL staining was also completed. The distribution of these factors was evaluated semi quantitalively. In the interradicular septum bone structure, the expression levels of osteocalcin, osteoprotegerin, matrix metalloproteinases 8 and 9, and nuclear factor kappa B were determined in all samples. TUNEL staining was also done. Age related decreases in the mean values of signalling factors and the number of apoptotic cells were statistically significant. Specific to interradicular septum osteoblasts and osteoclasts factors include osteoprotegerin, osteocalcin, matrix metalloproteinase 8, matrix metallproteniase 9, and nuclear factors kappa B. The mean expression levels of these proteins and the mean TUNEL staining statistically significantly decreased with age. This is preliminary study and more patients are necessary for more precise statistical analysis in the future.


WITHDRAWN: Home-based support for disadvantaged adult mothers.
Babies born to socio-economically disadvantaged mothers are at higher risk of a range of problems in infancy. Home visiting programs are thought to improve outcomes, both for mothers and children, largely through advice and support. To assess the effectiveness of home visiting programmes for women who have recently given birth and who are socially or economically disadvantaged. We searched the following electronic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2006); MEDLINE (1966 to March 2006); EMBASE (1980 to 2006 week 12); CINAHL (1982 to March week 4 2006); PsycINFO (1872 to March week 4 2006); ASSIA (1987 to March 2006); LILACS (1982 to March 2006); and Sociological Abstracts(1963 to March 2006). We searched grey literature using ZETOC (1993 to March 2006); Dissertation Abstracts International (late 1960s to 2006); and SIGLE (1980 to March 2006). We also undertook communication with published authors about ongoing or unpublished research. Included studies were randomised controlled trials investigating the efficacy of home visiting directed at disadvantaged adult mothers. Two reviewers (EC and JP or CB) independently assessed titles and abstracts identified in the search for eligibility. Data were extracted and entered into RevMan (EC, JP and CB), synthesised and presented in both written and graphical form (forest plots). Outcomes included in this review were established at the protocol stage by an international steering group. The review does not report on all outcomes reported in included studies. We included 11 studies with 4751 participants in this review. Data show no statistically significant differences for those receiving home visiting, either for maternal outcomes (maternal depression, anxiety, the stress associated with parenting, parenting skills, child abuse risk or potential or breastfeeding) or child outcomes (preventive health care visits, psychosocial health, language development, behaviour problems or accidental injuries. Evidence about uptake of immunisations is mixed, and the data on child maltreatment difficult to interpret. This review suggests that for disadvantaged adult women and their children, there is currently no evidence to support the adoption of home visiting as a means of improving maternal psychosocial health, parenting or outcomes for children. For reasons discussed in the review, this does not amount to a conclusion that home visiting programmes are ineffective, but indicates a need to think carefully about the problems that home visiting might influence, and improvements in the conduct of outcome studies in this area.


A systematic review and meta-analysis of written self-administered psychosocial interventions among adults with a physical illness.
The cost of implementing professionally-led psychosocial interventions has limited their integration into routine care. To enhance the translation of effective psychosocial interventions in routine care, a self-administered format is sometimes used. The meta-analysis examined the efficacy of written self-administered, psychosocial interventions to improve outcomes among individuals with a physical illness. Studies comparing a written self-administered intervention to a control group were identified through electronic databases searching. Pooled effect sizes were calculated across follow-up time points using random-effects models. Studies were also categorised according to three levels of guidance (self-administered, minimal contact, or guided) to examine the effect of this variable on outcomes. Forty manuscripts were retained for the descriptive review and 28 for the meta-analysis. Findings were significant for anxiety, depression, distress, and self-efficacy. Results were not significant for quality of life and related domains as well as coping. Purely self-administered interventions were efficacious for depression, distress, and self-efficacy; only guided interventions had an impact on anxiety. Findings showed that written self-administered interventions show promise across a number of outcomes. Self-administered interventions are a potentially efficacious and cost-effective approach to address some of the most common needs of patients with a physical illness.


The Streptomyces lividans family 12 endoglucanase: construction of the catalytic cre, expression, and X-ray structure at 1.75 A resolution.
Cellulases are the glycoside hydrolases responsible for the enzymatic breakdown of the structural plant polymer cellulose. Together with xylanases they counteract the lmitless accumulation of plant biomass in nature and are of considerable fundamental and biotechnological interest. Endoglucanase CelB from Streptomyces lividans performs hydrolysis of the beta-1,4-glycosidic bonds of cellulose, with net retention of anomeric configuration. The enzyme is a member of glycoside hydrolase family 12 [Henrissat, B., and Bairoch, A. (1996) Biochem. J. 316, 695-696], which had previously eluded detailed structural analysis. A truncated, but cataytically competent form of CelB, locking the flexible linker region and cellulose-binding domain, has been constructed and overexpressed in a S. lividans expression system. The three-dimensional X-ray structure of the resulting catalytic domain, CelB2, has been solved by conventional multiple isomorphous replacement methods and refined to an R factor of 0.187 at 1.75 A resolution. The overall fold of the enzyme shows a remarkable similarity to that of family 11 xylanases, as previously predicted by hydrophobic clustering analysis [Törrönen, A., Kubicek, C.P., and Henrissat, B. (1993) FEBS Lett. 321, 135-139]. The 23 kDa protein presents a jelly-roll topology, built up mainly by antiparallel beta-sheets arranged in a sandwich-like manner. A deep substrate-binding cleft runs across the surface, as has been observed in other endoglucanase structures, and is potentially able to accommodate up to five binding subsites. The likely catalytic nucleophile and Brønsted acid/base, residues Glu 120 and Glue 203, respectively, have their carboxylate groups separated by a distance of approximately 7.0 A and are located approximately 15 A from one end of the cleft, implying a -3 to +2 active site.


2P-FLIM unveils time-dependent metabolic shifts during osteogenic differentiation with a key role of lactate to fuel osteogenesis via glutaminolysis identified.
Human mesenchymal stem cells (hMSCs) utilize discrete biosynthetic pathways to self-renew and differentiate into specific cell lineages, with undifferentiated hMSCs harbouring reliance on glycolysis and hMSCs differentiating towards an osteogenic phenotype relying on oxidative phosphorylation as an energy source. In this study, the osteogenic differentiation of hMSCs was assessed and classified over 14 days using a non-invasive live-cell imaging modality-two-photon fluorescence lifetime imaging microscopy (2P-FLIM). This technique images and measures NADH fluorescence from which cellular metabolism is inferred. During osteogenesis, we observe a higher dependence on oxidative phosphorylation (OxPhos) for cellular energy, concomitant with an increased reliance on anabolic pathways. Guided by these non-invasive observations, we validated this metabolic profile using qPCR and extracellular metabolite analysis and observed a higher reliance on glutaminolysis in the earlier time points of osteogenic differentiation. Based on the results obtained, we sought to promote glutaminolysis further by using lactate, to improve the osteogenic potential of hMSCs. Higher levels of mineral deposition and osteogenic gene expression were achieved when treating hMSCs with lactate, in addition to an upregulation of lactate metabolism and transmembrane cellular lactate transporters. To further clarify the interplay between glutaminolysis and lactate metabolism in osteogenic differentiation, we blocked these pathways using BPTES and α-CHC respectively. A reduction in mineralization was found after treatment with BPTES and α-CHC, demonstrating the reliance of hMSC osteogenesis on glutaminolysis and lactate metabolism. In summary, we demonstrate that the osteogenic differentiation of hMSCs has a temporal metabolic profile and shift that is observed as early as day 3 of cell culture using 2P-FLIM. Furthermore, extracellular lactate is shown as an essential metabolite and metabolic fuel to ensure efficient osteogenic differentiation and as a signalling molecule to promote glutaminolysis. These findings have significant impact in the use of 2P-FLIM to discover potent approaches towards bone tissue engineering in vitro and in vivo by engaging directly with metabolite-driven osteogenesis.


Impact of Electronic Health Records on Long-Term Care Facilities: Systematic Review.
Long-term care (LTC) facilities are an important part of the health care industry, providing care to the fastest-growing group of the population. However, the adoption of electronic health records (EHRs) in LTC facilities lags behind other areas of the health care industry. One of the reasons for the lack of widespread adoption in the United States is that LTC facilities are not eligible for incentives under the Meaningful Use program. Implementation of an EHR system in an LTC facility can potentially enhance the quality of care, provided it is appropriately implemented, used, and maintained. Unfortunately, the lag in adoption of the EHR in LTC creates a paucity of literature on the benefits of EHR implementation in LTC facilities. The objective of this systematic review was to identify the potential benefits of implementing an EHR system in LTC facilities. The study also aims to identify the common conditions and EHR features that received favorable remarks from providers and the discrepancies that needed improvement to build up momentum across LTC settings in adopting this technology. The authors conducted a systematic search of PubMed, Cumulative Index of Nursing and Allied Health (CINAHL), and MEDLINE databases. Papers were analyzed by multiple referees to filter out studies not germane to our research objective. A final sample of 28 papers was selected to be included in the systematic review. Results of this systematic review conclude that EHRs show significant improvement in the management of documentation in LTC facilities and enhanced quality outcomes. Approximately 43% (12/28) of the papers reported a mixed impact of EHRs on the management of documentation, and 33% (9/28) of papers reported positive quality outcomes using EHRs. Surprisingly, very few papers demonstrated an impact on patient satisfaction, physician satisfaction, the length of stay, and productivity using EHRs. Overall, implementation of EHRs has been found to be effective in the few LTC facilities that have implemented them. Implementation of EHRs in LTC facilities caused improved management of clinical documentation that enabled better decision making.


Explaining better hearing in Norway: a comparison of two cohorts 20 years apart - the HUNT study.
The hearing function at a given age seems to have improved in more recent born cohorts in industrialized countries. But the reasons for the improvement have not yet been explained. We investigated the extent to which better hearing in Norway is attributed to modifiable risk factors by using representative demographic and audiometric data from two cohorts of the Trøndelag Health Study, HUNT2 (1996-1998) and HUNT4 (2017-2019). We estimated natural indirect effects using causal inference methods in order to assess whether cohort improvement in hearing thresholds (HTs) was mediated by occupational noise exposure, recurrent ear infections, smoking and education. The improvement in HTs from HUNT2 to HUNT4 was 2.8 and 3.0 dB at low respectively high frequencies. Together all risk factors mediated this improvement by 0.8 dB (95% CI 0.7-0.9) and 0.8 dB (95% CI 0.7-0.9) respectively, corresponding to mediated proportions of 27 and 28%. Substantial mediation was specifically found for occupational noise in men and recurrent ear infections in women (mediated proportions of 11 and 17% at high frequencies, respectively). Increased education, less occupational noise exposure, ear infections and smoking contributed considerably to better hearing in Norway the last two decades.


Dynamic Prognostic Score to Predict Survival in East Asian Elderly Populations with Dysphagia.
Dysphagia is a common disorder in older adults, leading to severe complications, including aspiration pneumonia, dehydration, malnutrition, weight loss, and even death. However, no prognostic model has been developed to predict the prognosis of older adults with dysphagia. Data from patients with dysphagia at a single center were retrospectively reviewed between 2014 and 2017. All data were obtained from the Dryad Digital Repository. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features. Multiple Cox proportional hazard analysis was used to develop a model based on the training set. The nomogram comprised age, sex, percutaneous endoscopic gastrostomy, chronic heart failure, total lymphocyte count, daily calorie intake, and severe pneumonia, which provided favorable calibration and discrimination in the training dataset, with AUCs for the 1-year, 2-year, and 3-year survival predictions of 0.833, 0.871, and 0.886, respectively. Furthermore, it showed acceptable discrimination in the validation cohort, with AUCs for the 1-year, 2-year, and 3-year survival predictions of 0.884, 0.834, and 0.782, respectively. Moreover, the decision curve analysis results revealed that the nomogram was clinically beneficial. A nomogram, combining seven demographic and clinical factors, provided an excellent preoperative prediction of survival probability in older individuals with dysphagia. This predictive model can be used as a reference to assist clinicians in making clinical decisions.


Erythromycin, carbomycin, and spiramycin inhibit protein synthesis by stimulating the dissociation of peptidyl-tRNA from ribosomes.
In mutant Escherichia coli with temperature-sensitive peptidyl-tRNA hydrolase (aminoacyl-tRNA hydrolase; EC 220.127.116.11), peptidyl-tRNA accumulates at the nonpermissive temperature (40 degrees C), and the cells die. These consequences of high temperature were enhanced if the cells were first treated with erythromycin, carbomycin, or spiramycin at doses sufficient to inhibit protein synthesis in wild-type cells but not sufficient to kill either mutant or wild-type cells at the permissive temperature (30 degrees C). Since peptidyl-tRNA hydrolase in he mutant cells is inactivated rapidly and irreversibly at 40 degrees C, the enhanced accumulation of peptidyl-tRNA and killing were the result of enhanced dissociation, stimulated by the antibiotics, of peptidyl-tRNA from ribosomes. The implications of these findings for inhibition of cell growth and protein synthesis are discussed. Certain alternative interpretations are shown to be inconsistent with the relevant data. Previous conflicting observations on the effects of macrolide antibiotics are explained in terms of our observations. We conclude that erythromycin, carbomycin, and spiramycin (and probably all macrolides) have as a primary mechanism of action the stimulation of dissociation of peptidyl-tRNA from ribosomes, probably during translocation.


Efficiency of prompt quarantine measures on a susceptible-infected-removed model in networks.
This study focuses on investigating the manner in which a prompt quarantine measure suppresses epidemics in networks. A simple and ideal quarantine measure is considered in which an individual is detected with a probability immediately after it becomes infected and the detected one and its neighbors are promptly isolated. The efficiency of this quarantine in suppressing a susceptible-infected-removed (SIR) model is tested in random graphs and uncorrelated scale-free networks. Monte Carlo simulations are used to show that the prompt quarantine measure outperforms random and acquaintance preventive vaccination schemes in terms of reducing the number of infected individuals. The epidemic threshold for the SIR model is analytically derived under the quarantine measure, and the theoretical findings indicate that prompt executions of quarantines are highly effective in containing epidemics. Even if infected individuals are detected with a very low probability, the SIR model under a prompt quarantine measure has finite epidemic thresholds in fat-tailed scale-free networks in which an infected individual can always cause an outbreak of a finite relative size without any measure. The numerical simulations also demonstrate that the present quarantine measure is effective in suppressing epidemics in real networks.


Cavitation-Mediated Immunomodulation and Its Use with Checkpoint Inhibitors.
The promotion of anti-tumour immune responses can be an effective route to the complete remission of primary and metastatic tumours in a small proportion of patients. Hence, researchers are currently investigating various methods to further characterise and enhance such responses to achieve a beneficial impact across a wider range of patients. Due to its non-invasive, non-ionising, and targetable nature, the application of ultrasound-mediated cavitation has proven to be a popular method to enhance the delivery and activity of immune checkpoint inhibitors. However, to optimise this approach, it is important to understand the biological and physical mechanisms by which cavitation may promote anti-tumour immune responses. Here, the published literature relating to the role that cavitation may play in modulating anti-tumour immunity is therefore assessed.


Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.


Oxylipin Profiles in Plasma of Patients with Wilson's Disease.
Wilson's disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene ATP7B gene, but influences of epigenetics, environment, age, and sex-related factors on the WD phenotype complicate diagnosis and clinical manifestations. Oxylipins, derivatives of omega-3, and omega-6 polyunsaturated fatty acids (PUFAs) are signaling mediators that are deeply involved in innate immunity responses; the regulation of inflammatory responses, including acute and chronic inflammation; and other disturbances related to any system diseases. Therefore, oxylipin profile tests are attractive for the diagnosis of WD. With UPLC-MS/MS lipidomics analysis, we detected 43 oxylipins in the plasma profiles of 39 patients with various clinical manifestations of WD compared with 16 healthy controls (HCs). Analyzing the similarity matrix of oxylipin profiles allowed us to cluster patients into three groups. Analysis of the data by VolcanoPlot and partial least square discriminant analysis (PLS-DA) showed that eight oxylipins and lipids stand for the variance between WD and HCs: eicosapentaenoic acid EPA, oleoylethanolamide OEA, octadecadienoic acids 9-HODE, 9-KODE, 12-hydroxyheptadecatrenoic acid 12-HHT, prostaglandins PGD2, PGE2, and 14,15-dihydroxyeicosatrienoic acids 14,15-DHET. The compounds indicate the involvement of oxidative stress damage, inflammatory processes, and peroxisome proliferator-activated receptor (PPAR) signaling pathways in this disease. The data reveal novel possible therapeutic targets and intervention strategies for treating WD.


Declining role of frozen section in surgical planning for thyroid nodules.
Needle biopsy (Bx) is superior to clinical selection of thyroid nodules for surgery. Is it superior to frozen section (FS) for surgical planning? Comparison of accuracy of the two procedures was made for 359 patients who underwent both procedures. Bx diagnoses consistent with a low risk of cancer predict a benign lesion at surgery with 90% accuracy. FS on the same patients was also 90% reliable in identifying benign or malignant nodules. Bx diagnoses consistent with a high risk of cancer predict a malignant lesion at surgery with 91% accuracy. FS on the same patients identified only 70% of the cancers. However, false positive diagnoses of cancer were less by FS. Bx diagnoses on nodules with an intermediate risk of cancer (32% to 43%) were insufficiently sensitive for reliable surgical planning. FS on the same nodules was also unreliable. Only three of 359 FS diagnoses contributed decisively to surgical planning. Reliance on Bx could eliminate as many as 99% of FSs.


A kinesin-like calmodulin-binding protein in Chlamydomonas: evidence for a role in cell division and flagellar functions.
Kinesin-like calmodulin-binding protein, KCBP, is a novel member of the C-kinesin superfamily first discovered in flowering plants. This minus-end-directed kinesin exhibits Ca(2+)-calmodulin-sensitive motor activity in vitro and has been implicated in trichome morphogenesis and cell division. A homologue of KCBP is also found in the unicellular, biflagellate green alga Chlamydomonas reinhardtii (CrKCBP). Unlike plant cells, Chlamydomonas cells do not form trichomes and do not assemble a phragmoplast before cell division. To test whether CrKCBP is involved in additional microtubule-based processes not observed in plants, we generated antibodies against the putative calmodulin-binding domain and used these antibodies in biochemical and localization studies. In interphase cells CrKCBP primarily localizes near the base of the flagella, although surprisingly, a small fraction also localizes along the length of the flagella. CrKCBP is bound to isolated axonemes in an ATP-dependent fashion and is not a component of the dynein arms, radial spokes or central apparatus. During mitosis, CrKCBP appears concentrated at the centrosomes during prophase and metaphase. However, during telophase and cytokinesis CrKCBP co-localizes with the microtubules associated with the phycoplast. These studies implicate CrKCBP in flagellar functions as well as cell division.


[Prostate cancer detection using mass-spectrometric profiling of low-molecular weight blood proteome].
Currently, there are no reliable biomarkers of blood plasma for early detection of prostate cancer (PC), a one of the most common malignancies in men. This study developed, universalized and tested a new standardized methodology of detection of prostate cancer biomarkers--profiling of low-molecular weight proteome of blood plasma (1-17 kDa). This approach includes three main components: a preliminary sample preparation, time-of-flight mass spectrometry with an matrix-assisted laser desorption/ionization ALDI-TOF-MS), and the processing of data using bioinformatics software package. The potentials and prospects of the approach developed for identification of potential PC markers are demonstrated. 46 samples of blood plasma of PC patients and 26 controls were screened. This evaluation identified peptides/polypeptides that have the potential to be used for the detection of disease.


Puerperal influence of bovine uterine health status on the mRNA expression of pro-inflammatory factors.
After parturition, uterine bacterial infections lead to inflammatory processes such as subclinical/clinical endometritis with high prevalence in dairy cows. Endometrial epithelial cells participate in this immune response with the production of pro-inflammatory factors. The objective of the present study was to evaluate the endometrial mRNA expression pattern of pro-inflammatory factors during a selected postpartum (pp) period. Dairy cows with three different uterine health conditions on days 24-30 pp (healthy: n = 11, subclinical endometritis: n = 10, clinical endometritis: n = 10) were sampled using the cytobrush technique. Subsequently, each cow was sampled 3 more times in weekly intervals (days 31-37 pp; days 38-44 pp; days 45-51 pp). Samples were subjected to mRNA analysis performed by RT-qPCR. Additionally, an analysis of cultivable bacteria was performed at the early/late stage of the selected puerperal period. mRNA expression of 16 candidate genes was analyzed by using two different approaches. The first approach referred to the initial grouping on days 24-30 pp to reveal long-term effects of the uterine health on the subsequent puerperal period. The second approach considered the current uterine health status at each sampling to elucidate the impact of different points in time. Long-term effects seem to appear for chemokines, prostacyclin synthase and prostaglandin D2 synthase. If related to the current uterine health, the majority of candidate genes were significantly higher expressed in endometritic cows on days 45-51 pp in contrast to earlier stages of the puerperium. Microbiological analysis revealed the significantly higher prevalence of Trueperella pyogenes findings in cows with clinical endometritis on days 24-30 pp, but no correlations were found on days 45-51 pp. In conclusion, a strong immune response to subclinical/clinical endometritis in the late puerperium may be related to the negative impact of these conditions on reproductive performance in dairy cows.


Identification of avian flapping motion from non-volant winged dinosaurs based on modal effective mass analysis.
The origin of avian flight is one of the most controversial debates in Paleontology. This paper investigates the wing performance of Caudipteryx, the most basal non-volant dinosaur with pennaceous feathered forelimbs by using modal effective mass theory. From a mechanical standpoint, the forced vibrations excited by hindlimb locomotion stimulate the movement of wings, creating a flapping-like motion in response. This shows that the origin of the avian flight stroke should lie in a completely natural process of active locomotion on the ground. In this regard, flapping in the history of evolution of avian flight should have already occurred when the dinosaurs were equipped with pennaceous remiges and rectrices. The forced vibrations provided the initial training for flapping the feathered wings of theropods similar to Caudipteryx.


Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate.
The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture. Metabolic differences were then investigated in the basal state or after chronic palmitate treatment. At basal, myocytes from sedentary individuals exhibited higher CD36 and HSP70 protein expression as well as elevated phosphorylation of c-Jun NH2-terminal kinase (JNK) and insulin receptor substrate 1 (IRS1) serine(307) compared to myocytes from active individuals. Despite equal lipid accumulation following palmitate treatment, myocytes from sedentary individuals exhibited delayed acetyl coenzyme A carboxylase phosphorylation compared to the active group. Myocytes from sedentary individuals had significantly higher basal glucose uptake and palmitate promoted insulin resistance in sedentary myocytes. Importantly, myocytes from active individuals were partially protected from palmitate-induced insulin resistance. Palmitate treatment enhanced IRS1 serine307 phosphorylation in myocytes from sedentary individuals and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance, a dysregulated function could have profound effects on health. Therefore the effects of lifestyle on satellite cells needs to be delineated.


Management of nephropathy in patients with type 2 diabetes.
To review evidence-based management of nephropathy in patients with type 2 diabetes. A literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed. Well-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected. Data and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients. Hypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions. Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.


Discovering new in silico tools for antimicrobial peptide prediction.
Antimicrobial peptides (AMPs) are important effectors of the innate immune system and play a vital role in the prevention of infections. Due to the increased emergence of new antibiotic-resistant bacteria, new drugs are constantly under investigation. AMPs in particular are recognized as promising candidates because of their modularity and wide antimicrobial spectrum. However, the mechanisms of action of AMPs, as well as their structure-activity relationships, are not completely understood. AMPs display no conserved three-dimensional structure and poor sequence conservation, which hinders rational design. Several bioinformatics tools have been developed to generate new templates with appealing antimicrobial properties with the aim of finding highly active peptide compounds with low cytotoxicity. The current tools reviewed here allow for the prediction and design of new active peptides with reasonable accuracy. However, a reliable method to assess the antimicrobial activity of AMPs has not yet been developed. The standardization of procedures to experimentally evaluate the antimicrobial activity of AMPs, together with the constant growth of current well-established databases, may allow for the future development of new bioinformatics tools to accurately predict antimicrobial activity.


Reprogramming homing endonuclease specificity through computational design and directed evolution.
Homing endonucleases (HEs) can be used to induce targeted genome modification to reduce the fitness of pathogen vectors such as the malaria-transmitting Anopheles gambiae and to correct deleterious mutations in genetic diseases. We describe the creation of an extensive set of HE variants with novel DNA cleavage specificities using an integrated experimental and computational approach. Using computational modeling and an improved selection strategy, which optimizes specificity in addition to activity, we engineered an endonuclease to cleave in a gene associated with Anopheles sterility and another to cleave near a mutation that causes pyruvate kinase deficiency. In the course of this work we observed unanticipated context-dependence between bases which will need to be mechanistically understood for reprogramming of specificity to succeed more generally.


Endothelin-1 mRNA is widely expressed in porcine and human tissues.
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide isolated from porcine endothelial cells. We have previously demonstrated widespread binding sites for ET-1 in blood vessels, heart, kidney, adrenal, lung, and brain in a distribution that paralleled that of endothelial cells. To determine whether these cells are capable of synthesizing ET-1 in close proximity to its binding sites, amplification of cDNA using the polymerase chain reaction and in situ hybridization were used to study the distribution of ET-1 mRNA. We have found widespread transcription of ET-1 mRNA in human and porcine tissues. The identity of the transcripts was confirmed by prediction of restriction fragment lengths or sequencing. In situ hybridization in the kidney showed that the regional expression of these transcripts is localized, probably to small blood vessels, but the failure to visualize ET-1 mRNA in the capillaries may reflect absence of expression or insufficient sensitivity of the technique. These results should permit investigation of the role of ET-1 as a local factor in vascular pathophysiology.


The effect of alpha-amanitin on the Arabidopsis seed proteome highlights the distinct roles of stored and neosynthesized mRNAs during germination.
To investigate the role of stored and neosynthesized mRNAs in seed germination, we examined the effect of alpha-amanitin, a transcriptional inhibitor targeting RNA polymerase II, on the germination of nondormant Arabidopsis seeds. We used transparent testa mutants, of which seed coat is highly permeable, to better ascertain that the drug can reach the embryo during seed imbibition. Even with the most permeable mutant (tt2-1), germination (radicle protrusion) occurred in the absence of transcription, while subsequent seedling growth was blocked. In contrast, germination was abolished in the presence of the translational inhibitor cycloheximide. Taken together, the results highlight the role of stored proteins and mRNAs for germination in Arabidopsis and show that in this species the potential for germination is largely programmed during the seed maturation process. The alpha-amanitin-resistant germination exhibited characteristic features. First, this germination was strongly slowed down, indicating that de novo transcription normally allows the synthesis of factor(s) activating the germination rate. Second, the sensitivity of germination to gibberellic acid was reduced 15-fold, confirming the role of this phytohormone in germination. Third, de novo synthesis of enzymes involved in reserve mobilization and resumption of metabolic activity was repressed, thus accounting for the failure in seedling establishment. Fourth, germinating seeds can recapitulate at least part of the seed maturation program, being capable of using mRNAs stored during development. Thus, commitment to germination and plant growth requires transcription of genes allowing the imbibed seed to discriminate between mRNAs to be utilized in germination and those to be destroyed.


Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database.
Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2-3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1). To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post-bronchodilator FEV1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models. Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of -0.931% predicted per year (95% CI -1.144 to -0.718) in the untreated group and a decline of -1.016% predicted per year (95% CI -1.319 to -0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71). In our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.


Somatotype and stress hormone levels in young soccer players.
The relationship between somatotype and cortisol and adrenocorticotropic (ACTH) hormone concentrations at rest or after exercise in adolescent soccer players at different time points throughout a soccer season is not understood. Therefore, the aim of this study was to examine the relationship between somatotype and cortisol and ACTH concentrations at rest and after exercise in adolescent soccer players at different time points during a soccer season. During the first 4 months of the soccer season, 47 soccer players (between 15-17 years of age) were tested at three different time points including at baseline, after 6 weeks, and at the end of 4 months. Testing included anaerobic threshold (AnT, km/h) and maximal speed of running (Max, km/h) were measured with Conconi protocol on treadmill. Before and after a maximal exercise Test, plasma levels of cortisol (ug/dL) and ACTH (pg/ml) were assessed by chemiluminometry enzyme amplificated method. Heath-Carter anthropometric somatotype model was used to determine 13 elements of somatotype. Descriptive statistics and multiple regression were used for statistical analysis (P<0.05). Body composition and AnT were not significantly different between each time point of testing. The mesomorph-ectomorph (N.=21), balanced mesomorph (N.=8) and balanced ectomorph (N.=7) were the most frequent somatotypes. There were significant decrements of cortisol plasma levels (at rest 33.4%; after test 27.46%), with insignificant changes of ACTH plasma levels, after 6 weeks of preparation phase and after finishing of half season, at rest and after maximal treadmill test. There were significant correlation between ACTH levels at rest (R=0.44; P<0.01) and some somatotypes (mesomorph endomorph, central and balanced endomorph) and ACTH levels after maximal exercise test (R=0.36; P<0.05) and balanced ectomorph and endomorph mesomorph. There were significant correlation between cortisol levels after maximal exercise test at the beginning of training process (R=0.59; P<0.01) and some somatotypes (mesomorph ectomorph, mesomorph endomorph, balanced endomorph and endomorph mesomorph) and after the finishing of training process (R=0.62; P<0.01) and some somatotypes (central, balanced ectomorph and mesomorph ectomorph). The significant decreases of cortisol plasma levels during soccer training process could indicate a stagnation of training process, accordingly with insignificant changes of AnT. The significant correlations of some somatotypes with stress hormonal responses could only suggest that the somatotype characteristics of young soccer players could be of interest in process of selection and planning of soccer training process with an essential need for more studies.


Differences in the protein fluorecence of the two iron(III)-binding sites of ovotransferrin.
1. Changes in the tryptophan fluorescence and the visible absorption spectrum resulting from the combination of apo-ovotransferrin with Fe3+, F,E2+, Cu2+, Zn2+, Mn2+, and Cd2+were measured. 2. As expected for a radiationless transfer of electronic excitation energy, only the ions Fe3+, Fe2+and Cu2+, which gave complexes with large extinctions between 300 and 370nm, resulted in large decreases in trytophan fluorescence. 3. The decrease in protein fluorescence was non-linear with increasing occupancy of the Fe3+ -and Cu2+ - binding sites. The decrease in fluorescence on binding of Fe3+ was biphasic and showed that the two metal-binding sites were being occupied sequentially at pH7.4-8.4. The first site reacted with Fe3+ instantaneously, the second was occupied over a minute. 5. The nonidentity of the two sites was also demonstrated by the preparation of a stable hybrid containing both Cu2+ and Zn2+.h Cu2+ and Zn2+


The quarter that changed the world.
The California Department of Public Health (CDPH), California Tobacco Control Program (CTCP) is one of the longest-running comprehensive tobacco control programmes in the USA, resulting from a 1988 ballot initiative that added a 25-cent tax on each pack of cigarettes and a proportional tax increase on other tobacco products. This programme used a social norm change approach to reduce tobacco use. The operation, structure, evolution, programme dissemination and results are reviewed. The sustained programme implementation has reduced adult per capita cigarette consumption by over 60% and adult smoking prevalence by 35%, from 22.7% in 1988 to 13.8% in 2007. From 1988 to 2004, lung and bronchus cancer rates in California declined at nearly four times the rate of decline seen in the rest of the USA and the programme is associated with an $86 billion savings in healthcare costs. Youth smoking rates among 12-17 years olds are the second lowest in the nation. The social norm change approach is effective at reducing tobacco consumption, adult smoking and youth uptake. This approach resulted in declines in tobacco-related diseases and is associated with savings in healthcare expenditures. In considering CTCP's effectiveness, the takeaway message is that it should be viewed as a unified programme rather than a collection of independent interventions. The programme was designed and implemented as one where the parts complement and reinforce each other. Its effectiveness is dependent on its comprehensive strategy rather than any one part of the intervention.


Compliance Issues Facing Practices.
Healthcare fraud enforcement has increased exponentially over the past few years. Practice groups have seen increased enforcement specifically from the federal government. It has never been more important to ensure everyone in your organization understands the various compliance issues and the risks they present. This article highlights the top compliance issues to help your practice groups understand the risks related to healthcare fraud. Once everyone in your organization understands these issues, you can work toward developing effective compliance programs to limit the risks.


Regulation of cholecystokinin secretion by peptones and peptidomimetic antibiotics in STC-1 cells.
Peptones are potent stimulants of cholecystokinin (CCK) release in rats, both in vivo and ex vivo in a model of isolated vascularly perfused duodeno-jejunum preparation and in vitro in the intestinal CCK-producing cell line STC-1. The underlying mechanisms were here investigated with this cell line. Protein hydrolysates from various origins (meat, casein, soybean, and ovalbumin; 0.5-1%, wt/vol) dose dependently increased CCK release. Cephalosporin antibiotics, which mimic tripeptides, also stimulated the release of CCK over the concentration range 1-20 mM. The study of concentration dependence of cephalosporin uptake indicated a passive diffusion process at either pH 7.4 or pH 6.0, thus arguing against the involvement of a peptide transporter in CCK secretion. After pertussis toxin treatment (200 ng/ml; 5 h), the peptone- and cephalexin-induced CCK secretion was significantly reduced, suggesting the involvement of pertussis toxin-sensitive heterotrimeric G protein(s) in the secretory activity of STC-1 cells. Consistent with this was the identification by Western blot of G(i2)alpha, G(i3)alpha, and G(o)alpha immunoreactivities in STC-1 cell extracts. Additionally, peptones and cephalexin increased the cellular content in inositol phosphates, whereas a mild increase in cAMP content was restricted to peptone-treated cells. Protein kinase A or C inhibition did not modify peptone- or antibiotic drug-evoked CCK release. The extracellular Ca2+ chelator EGTA (500 microM) and the intracellular Ca2+ chelator BAPTA-AM [1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester; 20 microM] abolished the peptone- and antibiotic drug-induced CCK release. Nifedipine and verapamil (10 microM) reduced by about 50% the CCK secretion evoked by these two secretagogues. In conclusion, peptones and some cephalosporins are potent stimulants of CCK release in the STC-1 cell line. The cellular mechanisms involve pertussis toxin-sensitive G protein(s) and are dependent on Ca2+ availability. We suggest that the STC-1 cell line is a useful model to study the molecular basis of peptone-induced CCK secretion.


Identification of novel transcription factors regulating secondary cell wall formation in Arabidopsis.
The presence of lignin in secondary cell walls (SCW) is a major factor preventing hydrolytic enzymes from gaining access to cellulose, thereby limiting the saccharification potential of plant biomass. To understand how lignification is regulated is a prerequisite for selecting plant biomass better adapted to bioethanol production. Because transcriptional regulation is a major mechanism controlling the expression of genes involved in lignin biosynthesis, our aim was to identify novel transcription factors (TFs) dictating lignin profiles in the model plant Arabidopsis. To this end, we have developed a post-genomic approach by combining four independent in-house SCW-related transcriptome datasets obtained from (1) the fiber cell wall-deficient wat1 Arabidopsis mutant, (2) Arabidopsis lines over-expressing either the master regulatory activator EgMYB2 or (3) the repressor EgMYB1 and finally (4) Arabidopsis orthologs of Eucalyptus xylem-expressed genes. This allowed us to identify 502 up- or down-regulated TFs. We preferentially selected those present in more than one dataset and further analyzed their in silico expression patterns as an additional selection criteria. This selection process led to 80 candidates. Notably, 16 of them were already proven to regulate SCW formation, thereby validating the overall strategy. Then, we phenotyped 43 corresponding mutant lines focusing on histological observations of xylem and interfascicular fibers. This phenotypic screen revealed six mutant lines exhibiting altered lignification patterns. Two of them [Bel-like HomeoBox6 (blh6) and a zinc finger TF] presented hypolignified SCW. Three others (myb52, myb-like TF, hb5) showed hyperlignified SCW whereas the last one (hb15) showed ectopic lignification. In addition, our meta-analyses highlighted a reservoir of new potential regulators adding to the gene network regulating SCW but also opening new avenues to ultimately improve SCW composition for biofuel production.


A mouse model for pain and neuroplastic changes associated with pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest human malignancies and is associated with excruciating pain, which is a serious complication and severely impacts the quality of life in patients. In human patients, poor survival prognosis is linked to remarkable remodeling of intrapancreatic nerves, which, in turn, is correlated to increased pain intensity. Understanding mechanisms underlying pain associated with PDAC has been hampered by the lack of animal models which replicate all germane aspects of the disease and importantly, enable analyses of pain associated with PDAC. In this study, we describe an immunocompetent orthotopic mouse model of PDAC involving intrapancreatic growth of K8484 mouse PDAC cells, which reliably exhibits a large number of key characteristics of human PDAC, including its unique histopathology and neuroplastic changes. We observed that tumor-bearing mice demonstrated significant abdominal mechanical hypersensitivity to von Frey stimuli as well as on-going pain in the conditioned place preference paradigm. Moreover, a myriad of other behavioral tests revealed that indicators of overall well-being were significantly reduced in tumor-bearing mice as compared to sham mice. Morphological and immunohistochemical analyses revealed structural remodeling in several different types of sensory and autonomic nerve fibers. Finally, perineural invasion of tumor cells, a cardinal manifestation in human PDAC, was also observed in our orthotopic mouse model. Thus, we describe a validated tumor model for quantitatively testing hypersensitivity and pain in PDAC, which lays a crucial basis for interrogating tumor-nerve interactions and the molecular and cellular mechanisms underlying pain in PDAC.


The Use of Frozen Section in the Early Diagnosis of Acute Invasive Fungal Sinusitis.
Objectives Acute invasive fungal sinusitis (AIFS) remains a significant cause of morbidity and mortality in the immunocompromised patient population. Early diagnosis is key to improving patient outcomes. Frozen section biopsies have been shown to decrease time to diagnosis when compared with permanent pathology. However, its accuracy has not been adequately described in the literature, specifically in regard to AIFS. The aim of this study is to evaluate the statistical diagnostic accuracy of frozen sections and to review the etiology, clinical presentation, and current diagnostic protocols in management of AIFS. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Retrospective review included 67 pathologic records in Co-Path, with search criteria including invasive fungal, clinical history, frozen section, and final diagnosis between the dates of 2006 and 2015. Results Sixty-seven cases were reviewed per the search criteria in Co-Path. Of these, 31 met further criteria of having had frozen section analysis. Variables such as sensitivity, specificity, positive predictive value, and negative predictive value were assessed. All 21 positive frozen sections correlated with positive permanent pathology, giving a positive predictive value of 100%. Frozen section biopsies were 87.5% sensitive and 100% specific. Conclusion Early diagnosis of AIFS has been shown to decrease morbidity and mortality. Frozen section biopsies remain key in obtaining an early diagnosis among patients with a high clinical suspicion for invasive fungal sinusitis. Frozen section biopsies positive for invasive fungal pathology were universally consistent with definitive diagnosis.


Teachers and artificial intelligence. The Logo connection.
This article describes a three-phase program for training special education teachers to teach Logo and artificial intelligence. Logo is derived from the LISP computer language and is relatively simple to learn and use, and it is argued that these factors make it an ideal tool for classroom experimentation in basic artificial intelligence concepts. The program trains teachers to develop simple demonstrations of artificial intelligence using Logo. The material that the teachers learn to teach is suitable as an advanced level topic for intermediate- through secondary-level students enrolled in computer competency or similar courses. The material emphasizes problem-solving and thinking skills using a nonverbal expressive medium (Logo), thus it is deemed especially appropriate for hearing-impaired children. It is also sufficiently challenging for academically talented children, whether hearing or deaf. Although the notion of teachers as programmers is controversial, Logo is relatively easy to learn, has direct implications for education, and has been found to be an excellent tool for empowerment-for both teachers and children.


2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one inhibit DHHC-mediated palmitoylation in vitro.
Pharmacologic approaches to studying palmitoylation are limited by the lack of specific inhibitors. Recently, screens have revealed five chemical classes of small molecules that inhibit cellular processes associated with palmitoylation (Ducker, C. E., L. K. Griffel, R. A. Smith, S. N. Keller, Y. Zhuang, Z. Xia, J. D. Diller, and C. D. Smith. 2006. Discovery and characterization of inhibitors of human palmitoyl acyltransferases. Mol. Cancer Ther. 5: 1647-1659). Compounds that selectively inhibited palmitoylation of N-myristoylated vs. farnesylated peptides were identified in assays of palmitoyltransferase activity using cell membranes. Palmitoylation is catalyzed by a family of enzymes that share a conserved DHHC (Asp-His-His-Cys) cysteine-rich domain. In this study, we evaluated the ability of these inhibitors to reduce DHHC-mediated palmitoylation using purified enzymes and protein substrates. Human DHHC2 and yeast Pfa3 were assayed with their respective N-myristoylated substrates, Lck and Vac8. Human DHHC9/GCP16 and yeast Erf2/Erf4 were tested using farnesylated Ras proteins. Surprisingly, all four enzymes showed a similar profile of inhibition. Only one of the novel compounds, 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one [Compound V (CV)], and 2-bromopalmitate (2BP) inhibited the palmitoyltransferase activity of all DHHC proteins tested. Hence, the reported potency and selectivity of these compounds were not recapitulated with purified enzymes and their cognate lipidated substrates. Further characterization revealed both compounds blocked DHHC enzyme autoacylation and displayed slow, time-dependent inhibition but differed with respect to reversibility. Inhibition of palmitoyltransferase activity by CV was reversible, whereas 2BP inhibition was irreversible.


Dietary Amino Acid Source Elicits Sex-Specific Metabolic Response to Diet-Induced NAFLD in Mice.
Non-alcoholic fatty liver disease (NAFLD) is a sexually dimorphic disease influenced by dietary factors. Here, the metabolic and hepatic effects of dietary amino acid (AA) source is assessed in Western diet (WD)-induced NAFLD in male and female mice. The AA source is either casein or a free AA mixture mimicking the composition of casein. As expected, males fed a casein-based WD display glucose intolerance, fasting hyperglycemia, and insulin-resistance and develop NAFLD associated with changes in hepatic gene expression and microbiota dysbiosis. In contrast, males fed the AA-based WD show no steatosis, a similar gene expression profile as males fed a control diet, and a distinct microbiota composition compared to males fed a casein-based WD. Females are protected against WD-induced liver damage, hepatic gene expression, and gut microbiota changes regardless of the AA source. Free dietary AA intake prevents the unhealthy metabolic outcomes of a WD preferentially in male mice.


Measuring Respiratory Pressures with Mercury Manometer in Low Economic Health Care Settings- An Analytical Study.
Health care economics restricts many health centers from using hi-tech diagnostics equipment. Mercury manometers are used for calibration of pressure transducers. If standardized it would be a cost effective, simple alternative to transducers in low economic settings. To analyse the feasibility of mercury manometer usage in respiratory pressure measurement. The experimental study was conducted with 30 healthy volunteers of age group 17-19 yrs. They were recruited by using simple random sampling method. The volunteers were made familiarized to lab environment, instrument and techniques of maximum inspiratory (Pimax) and expiratory pressures (Pemax). Then parameters were recorded using mercury manometer connected to different syringes as mouth piece (2.5 ml, 10 ml, and 20 ml) and with sphygmomanometer. Statistical analysis was done by using IBM SPSS statistics version 21. The Pimax was 111.07 ± 6.53 with a 2.5 ml syringe as mouth piece. With 20 ml syringe it was 61.47 ± 9.98. PEmax with 2.5 ml syringe was 70.33 ± 8.19 with a confidence limit of 2.93 and with sphygmomanometer was 99.33 ± 8.16 with a confidence limit of 2.92. There was a change in recorded pressure and the correlation analysis result showed a significant difference from both above and below 10 ml mouth piece range. Mercury manometers could be used for recording respiratory pressures in low economic facilities once standardized. Size of syringe to be used as mouth piece needs further more works although this study finds 10 ml syringe as suitable.


Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma.
Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets. We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort. Unsupervised clustering identified two "TME subtypes", in each of the cohorts: the "immune-enriched" and the "immune-low". Within AXIPAP trial cohort, the "immune-enriched" cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the "immune-enriched" group (adjusted p<0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations. For the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This "immune-enriched" group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies. NCT02489695.


Hyalinizing pancreatic adenocarcinoma in six dogs.
Exocrine pancreatic carcinoma is a particularly malignant neoplasm of the dog. Clinical and pathologic findings of an unusual variant of exocrine pancreatic neoplasia termed hyalinizing pancreatic adenocarcinoma were evaluated in 6 dogs. On microscopic examination, neoplasms were composed of tubules and acini of epithelial cells, with bright eosinophilic granular apical cytoplasm. Tubular lumina and tumor stroma contained abundant hyaline material that resembled amyloid. The hyaline material was not congophilic, and tumor cells and hyaline material were immunohistochemically negative for amyloid A, immunoglobulin light chains (kappa and lambda), amylin (islet amyloid polypeptide), laminin, and alpha(1)-antitrypsin. Two patients survived longer than 15 months after diagnosis; one of these dogs was untreated and had grossly evident metastasis at the time of diagnosis. The deaths of the other 4 dogs occurred as a result of poor recovery after partial pancreatectomy or in association with other concurrent life-threatening conditions. Two dogs were diagnosed with panniculitis, a condition rarely associated with pancreatic disease. Further evaluation is needed to determine the composition and biologic significance of intratumor hyaline material. Studies that associate exocrine pancreatic carcinoma grade and histologic subtype with prognostic outcomes in the dog are warranted such that appropriate therapy can be elected.


Outcomes of the Learn, Share & Live breast cancer education program for older urban women.
This study assessed whether the Learn, Share & Live breast cancer education program resulted in favorable, replicable, and sustainable outcomes. The program was implemented at index (year 1) and replication (year 2) sites. Baseline interviews (year 1; n = 240) and 2 follow-up telephone interviews (years 2 and 3; n = 337 and 323) were used to assess postintervention changes. From baseline to year 2, mammography adherence and stage of adoption improved at the index site relative to the replication site. Knowledge scores and percentages of respondents reporting that a friend had spoken with them about mammography improved significantly. Improvements were sustained through year 3 (2 years postintervention). In year 3, replication participants showed improvements in regard to knowledge and perceived mammography benefits, and there was a trend toward increased adherence. Site differences in postintervention adherence may have stemmed from respective choices of follow-up activities. The study outcomes affirm the impact of Learn, Share & Live, indicating a replicated and sustained program effect. Future studies should continue longer follow-up and explore the importance of providing mammography opportunities along with education.


Differential behavioural and hormonal responses of voles and spiny mice to owl calls.
Rodents usually respond to the presence of owls by reducing overall activity, in particular foraging. In this study, a playback of recorded tawny owl, Strix aluco, calls was sufficient to induce a marked effect in the social (Gunther's) vole, Microtus socialis. Some of the voles exposed to owl calls reduced their activity ('freeze' pattern) unlike control voles exposed to a human voice. Other voles, however, dashed around the cage ('flee' pattern). Owl calls also increased corticosterone levels in the voles, showing that the calls induced stress. We suggest that the behavioural dichotomy to freeze or flee in voles is a result of differences in individual normal behaviour and/or in stimulus interpretation. In the common spiny mouse, Acomys cahirinus, no behavioural changes were detected after exposure to owl calls, despite increased cortisol levels which are indicative of stress. Differences in the habitats of voles and spiny mice may explain the apparent lack of behavioural response in the latter. They are rock-dwelling rodents preferentially foraging between boulders and in rock crevices, where they are relatively protected from aerial predation, whereas voles forage in relatively open spaces. Copyright 1999 The Association for the Study of Animal Behaviour.


[Sample size and costs estimate in epidemiological survey of dental caries].
This study aimed to analyze how the prevalence and the distribution of dental caries influence the sample size in epidemiological surveys, and how much are the costs. Secondary data of oral health surveys in 12-year-old schoolchildren from Bauru in 1976, 1984, 1990, 1994, and 2001, and from Piracicaba in 2001 and 2005 were studied. Sample sizes were estimated taking into account the mean DMFT and standard deviation of each survey, establishing sampling errors of 1%, 2%, 5%, and 10%. Costs were estimated considering permanent material, consumption material and human resources. The sample size in both towns needed to be increased, ranging from 119 in 1976 to 1,118 in 2001 in Bauru, and from 954 in 2001 to 1,252 in 2005 in Piracicaba, when a sampling error of 10% was considered. The cost of dental caries surveys was verified considering different sampling errors. This cost depends on how acceptable is the margin of difference between the true mean and the one found in the survey. In conclusion, the reduction in the prevalence of dental caries has determined the need for increase in sample size and in costs for conducting the surveys.


Heart rate responses during small-sided games and short intermittent running training in elite soccer players: a comparative study.
The purpose of this study was to compare heart rate (HR) responses within and between physical controlled (short-duration intermittent running) and physical integrated (sided games) training methods in elite soccer players. Ten adult male elite soccer players (age, 26 +/- 2.9 years; body mass, 78.3 +/- 4.4 kg; maximum HR [HRmax], 195.4 +/- 4.9 b x min(-1) and velocity at maximal aerobic speed (MAS), 17.1 +/- 0.8 km x h(-1)) performed different short-duration intermittent runs, e.g., 30-30 (30 seconds of exercise interspersed with 30 seconds of recovery) with active recovery, and 30-30, 15-15, 10-10, and 5-20 seconds with passive recovery, and different sided games (1 versus 1, 2 versus 2, 4 versus 4, 8 versus 8 with and without a goalkeeper, and 10 versus 10). In both training methods, HR was measured and expressed as a mean percentage of HR reserve (%HRres). The %HRres in the 30-30-second intermittent run at 100% MAS with active recovery (at 9 km.h with corresponding distance) was significantly higher than that with passive recovery (85.7% versus 77.2% HRres, respectively, p < 0.001) but also higher than the 1 versus 1 (p < 0.01), 4 versus 4 (p <or= 0.05), 8 versus 8 (p < 0.001), and 10 versus 10 (p < 0.01) small-sided games. The %HRres was 2-fold less homogeneous during the different small-sided games than during the short-duration intermittent running (intersubjects coefficient of variation [CV] = 11.8% versus 5.9%, respectively). During the 8 versus 8 sided game, the presence of goalkeepers induced an approximately 11% increase in %HRres and reduced homogeneity when compared to games without goalkeepers (intersubject CV = 15.6% versus 8.8%). In conclusion, these findings showed that some small-sided games allow the HR to increase to the same level as that in short-duration intermittent running. The sided game method can be used to bring more variety during training, mixing physical, technical, and tactical training approaching the intensity of short-duration intermittent running but with higher intersubject variability.


[Hallermann-Streiff syndrome: should spontaneous resorption of the lens opacity be awaited?].
As the lens may become absorbed spontaneously extraction of the congenital cataract in the Hallermann-Streiff syndrome is controversial. A male newborn with Hallermann-Streiff syndrome was referred to the eye clinic because of a bilateral mature cataract. The risks of an operation seemed too serious because the eyes were extremely microphthalmic (a-p diameter approx. 10.5 mm). Instead, it was decided to await spontaneous lens absorption which then occurred slowly and completely between the beginning of the 2nd and the end of the 3rd year of life without considerable inflammatory responses. In the meantime, the child has a good orientation and is able to paint and to discriminate colours without optic correction. The critical investigation of the literature reveals that the frequency of spontaneous lens absorption in the Hallermann-Streiff syndrome is probably (widely) underestimated. It can be estimated with up to 50% (or even more) if patients which were operated on are excluded and if untreated patients are followed up till the end of the 5th year of life. Functional results seem to be quite similar for treated and untreated eyes. Therefore we would recommend to await the spontaneous lens absorption in the Hallermann-Steiff syndrome especially when the cataract is combined with considerable microphthalmia.


Genome-wide analysis of homozygosity regions in european simmental bulls.
The study of Runs of Homozygosity (ROH) is a useful approach for the characterization of the genome of livestock populations. Due to their high relationship with autozygosity, ROH allow to make inference about population genetic history, to estimate the level of inbreeding, to assess within breed heterogeneity and to detect the footprints of selection on livestock genomes. Aim of this study was to investigate the distribution of runs of homozygosity in bulls belonging to five European Simmental populations and to assess the relationship between three production traits (milk yield, fat and protein contents) and autozygosity. ROH count, distribution and ROH-based coefficient of inbreeding (FROH ) were calculated for 3,845 Simmental bulls of five different European countries: Austria (AT), Switzerland (CH), Czech Republic (CZ), Germany (DE) and Italy (IT). Average values of ROH number per animal, and total genome length covered by ROH were 77.8 ± 20.7 and 205 ± 74.4 Mb, respectively. Bulls from AT, DE and IT exhibited similar ROH characteristics. Swiss animals showed the highest (12.6%), while CZ the lowest (4.6%) FROH coefficient. The relationship between ROH occurrence and milk production traits was investigated through a genome-wide ROH-traits association analysis (GWRA). A total of 34 regions previously associated with milk traits (yield and/or composition) were identified by GWRA. Results of the present research highlight a mixed genetic background in the 5 European Simmental populations, with the possible presence of three subgroups. Moreover, a strong relationship between autozygosity and production traits has been detected.


Involvement of the same TNFR1 residue in mendelian and multifactorial inflammatory disorders.
TNFRSF1A is involved in an autosomal dominant autoinflammatory disorder called TNFR-associated periodic syndrome (TRAPS). Most TNFRSF1A mutations are missense changes and, apart from those affecting conserved cysteines, their deleterious effect remains often questionable. This is especially true for the frequent R92Q mutation, which might not be responsible for TRAPS per se but represents a susceptibility factor to multifactorial inflammatory disorders. This study investigates TRAPS pathophysiology in a family exceptional by its size (13 members) and compares the consequences of several mutations affecting arginine 92. TNFRSF1A screening was performed by PCR-sequencing. Comparison of the 3-dimensional structure and electrostatic properties of wild-type and mutated TNFR1 proteins was performed by in silico homology modeling. TNFR1 expression was assessed by FACS analysis, western blotting and ELISA in lysates and supernatants of HEK293T cells transiently expressing wild-type and mutated TNFR1. A TNFRSF1A heterozygous missense mutation, R92W (c.361C>T), was shown to perfectly segregate with typical TRAPS manifestations within the family investigated (p<5.10(-4)). It was associated with very high disease penetrance (0.9). Prediction of its impact on the protein structure revealed local conformational changes and alterations of the receptor electrostatic properties. R92W also impairs the TNFR1 expression at the cell surface and the levels of soluble receptor. Similar results were obtained with R92P, another mutation previously identified in a very small familial form with incomplete penetrance and variable expressivity. In contrast, TNFR1-R92Q behaves like the wild-type receptor. These data demonstrate the pathogenicity of a mutation affecting arginine 92, a residue whose involvement in inflammatory disorders is deeply debated. Combined with previous reports on arginine 92 mutations, this study discloses an unusual situation in which different amino acid substitutions at the same position in the protein are associated with a clinical spectrum bridging Mendelian to multifactorial conditions.


Trans-mastoid anchorage as a novelty in glenoid fossa reconstruction for hemifacial microsomia with agenesis of zygomatic arch and external acoustic meatus - Technical note with a case illustration.
Total joint reconstruction (TJR) has become the most preferred method of reconstruction in recent years for hemifacial microsomia (HFM). This requires meticulous planning for the glenoid fossa and ramus prosthesis along with the arch in certain indications. TJR in a type V HFM is extremely challenging due to agenesis/hypolasia of the zygoma and arch which compromises anchorage of the glenoid prosthesis. Conventional options used for such indications incorporate extended designs for the fossa. However, the two designs used commonly are associated with limitations; (i) the temporal extension is overtly large and cannot be anchored in patients with thin temporal bone and (ii) the glenoid fossa incorporated into the arch prosthesis, where the fossa is not positioned on stable bone and occlusal loading is non-physiological; transmitted onto the arch prosthesis rather than the skull base. The authors propose the use of the mastoid process as an alternative for anchorage of fossa prosthesis. This technique offers stable anchorage while facilitating ideal positioning on the skull base for optimal masticatory load transmission. The case illustration depicts reconstruction of the TMJ, zygoma and the zygomatic arch in a 31-year-old man with type V HFM, with a three-year follow-up, with good clinical outcomes sans complications.


An intraoperative test device for aortic valve repair.
Aortic valve repair is currently in transition from surgical improvisation to a reproducible operation and an option for many patients with aortic regurgitation. Our research efforts at improving reproducibility include development of methods for intraoperatively testing and visualizing the valve in its diastolic state. We developed a device that can be intraoperatively secured in the transected aorta allowing the aortic root to be pressurized and the closed valve to be inspected endoscopically. Our device includes a chamber that can be pressurized with crystalloid solution and ports for introduction of an endoscope and measuring gauges. We show use of the device in explanted porcine hearts to visualize the aortic valve and to measure leaflet coaptation height in normal valves and in valves that have undergone valve repair procedures. The procedure of introducing and securing the device in the aorta, pressurizing the valve, and endoscopically visualizing the closed valve is done in less than 1 minute. The device easily and reversibly attaches to the aortic root and allows direct inspection of the aortic valve under conditions that mimic diastole. It enables the surgeon to intraoperatively study the valve immediately before repair to determine mechanisms of incompetence and immediately after the repair to assess competence. We also show its use in measuring valve leaflet coaptation height in the diastolic state. This device enables more relevant prerepair valve assessment and also enables a test of postrepair valve competence under physiological pressures.


[Effects of myeloid specific deficiency of FBXW7 on lung metastasis of murine melanoma].
Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein of Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. After 14 d, the mice were sacrificed, and the lungs were removed and weighed. B16F10 tumor colonies in the lungs were counted. The myeloid cells were analyzed by flow cytometry. Results: Myeloid-specific deficiency of FBXW7 mice were generated successfully, as FBXW7 expressions in peritoneal macrophages and bone marrow-derived macrophages (BMDMs) of Lysm+FBXW7f/f mice were knockdown. Flow cytometry results showed the deletion of FBXW7 in myeloid lineages did not affect the development of myeloid immune cell subsets. Metastasis was reduced in Lysm+FBXW7 f/f mice compared with control mice. The number of tumor colonies was 165±42, 122±12 respectively. The proportion of metastasis-associated macrophages (MAM) in the lungs of Lysm+FBXW7 f/f mice was reduced [(23.15±7.59)% vs (13.13±2.26)%], while the proportion of resident macrophages was increased [(5.426±0.42)% vs (10.42±1.90)%]. The proportion of myeloid-derived suppressor cells in the lung showed no difference between Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. Conclusion: Myeloid-specific deficiency of FBXW7 can inhibit lung metastasis of B16F10 melanoma in mice, and the mechanism may be associated with regulation of MAM in the metastatic tumor lesions.