Itch: from the skin to the brain - peripheral and central neural sensitization in chronic itch.
Similar to chronic pain, chronic itch is frequently linked to neural sensitization, a phenomenon wherein the nervous system becomes hypersensitive to stimuli. This process of neural sensitization of chronic itch is orchestrated by various signaling pathways and mediators in both the peripheral and central nervous systems. At the level of the peripheral nervous system, inflammation and neuroimmune interactions induce plastic changes to peripheral nerve fibers, thereby amplifying the transmission of itch signaling. Neural sensitization in the central nervous system occurs at both the spinal cord and brain levels. At the level of the spinal cord, it involves hyperactivity of itch-activating spinal pathways, dysfunction of spinal inhibitory circuits, and attenuation of descending supraspinal inhibitory pathways. In the brain, neural sensitization manifests as structural and functional changes to itch-associated brain areas and networks. Currently, we have a diverse array of neuroimmune-modulating therapies targeting itch neural sensitization mechanisms to help with providing relief to patients with chronic itch. Itch research is a dynamic and continually evolving field, and as we grow in our understanding of chronic itch mechanisms, so will our therapeutic toolbox. Further studies exploring the peripheral and central neural sensitization mechanisms in the context of chronic itch are needed.


Recombinant human granulocyte macrophage colony stimulating factor in deep second-degree burn wound healing.
The aim of this study was to explore the effects of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) on deep second-degree burn wound healing. In this study, 95 patients with a total of 190 burn wounds were treated with either rhGM-CSF or placebo, separated into 2 groups by treatment type. Wound healing rate, wound healing time, histopathological condition, and scar scale were all compared between the 2 groups. The healing rates in the rhGM-CSF group were remarkably higher than those in the placebo group (P < .01). The wound healing time in the rhGM-CSF group (18.8 ± 7.6 days) was significantly shorter than that in the placebo group (25.5 ± 4.6 days, P < .01). On the 14th day and 28th day, the average optical density of vascular endothelial factor (VEGF) in the rhGM-CSF group was larger than that in the placebo group. Meanwhile, the average optical density of fibroblast growth factor (FGF) in the rhGM-CSF group was also larger than that in the placebo group. Furthermore, the Vancouver scar scale scores of pigmentation, pliability, height, and vascularity were notable lower in the rhGM-CSF group than those in the placebo group (P < .01). The results suggest that rhGM-CSF can significantly accelerate deep second-degree burn wound healing.


Helping families mobilize their personal resources.
With changes in delivery of and payment for health care, hospital stays may be shorter and children may be going home sooner and sicker. Therefore, more care may be required at home. Even with access to a variety of services and resources in the community, families of medically fragile or chronically ill children can be overwhelmed and stressed. Relief can be provided to some degree if families creatively mobilize their own personal resources. However, for a variety of reasons, families may find it difficult to do this. While nurses and other health care professionals are accustomed to helping families find professional services and resources in the community, they can also be invaluable before discharge by assisting families with their personal resources--from giving encouragement and motivation to outlining practical planning steps. Pediatric nurses can use guidelines and a checklist to assist families with mobilizing their resources to ease the transition from hospital to home for the whole family.


Salivary duct carcinoma in the mandible: report of a case with immunohistochemical studies.
Salivary duct carcinoma is rare. We describe a 56-year-old man who developed salivary duct carcinoma in the mandible 10 years after removal of the right second and third molars. The tumour originated in the retromolar gland or the ectopic minor salivary gland in the mandible. The panoramic radiograph showed a radiolucent, poorly circumscribed area about 40 x 30 mm in size and distal to the lower right first molar. This tooth, together with all neoplastic tissue, was removed, and histopathological examination showed it to be a salivary duct carcinoma in the mandible. On immunohistochemical staining, keratin antibodies stained the ductal structure, 1A4 antibody stained myoepithelial cells, but S-100 protein and vimentin were not seen. The patient was well and with no sign with recurrence 6 years postoperatively.


The relation between mitral annular calcification and mortality in patients undergoing diagnostic coronary angiography.
To determine whether the observed association between mitral annular calcification (MAC) and mortality is independent of the severity of coronary artery disease (CAD), we analyzed data from 134 male veterans (age 63 +/- 10 years) followed for 5 years who had undergone diagnostic coronary angiography and transthoracic echocardiography within 6 months of each other. Echocardiograms were retrospectively reviewed for the presence of MAC. The relation of MAC to all-cause mortality was analyzed using logistic regression, and odds ratios (OR) were calculated. MAC was present in 49 (37%) subjects. Over the 5-year follow-up period, 38 (28%) patients expired. Five-year survival was 80% for subjects without MAC and 56% for subjects with MAC (P = 0.003). MAC (OR = 3.16, 95% confidence interval [CI]= 1.43-6.96, P = 0.003), ejection fraction (OR = 0.76, 95% CI = 0.59-0.97, P = 0.02), and left main CAD (OR = 2.70, 95% CI = 1.11-6.57, P = 0.02) were significantly associated with mortality in univariate analysis. After adjusting for left ventricular ejection fraction, number of obstructed coronary arteries and the presence of left main coronary artery stenosis, MAC significantly predicted death (OR = 2.48, 95% CI = 1.09-5.68, P = 0.03). Similarly, after adjusting for predictors of MAC, including ejection fraction, age, diabetes, peripheral vascular disease, and heart failure, MAC remained a significant predictor of death (OR = 2.38, 95% CI = 1.02-5.58, P = 0.04). MAC also predicted death independent of smoking status, hypertension, serum creatinine, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels (OR = 3.98, 95% CI = 1.68-9.40, P = 0.001). MAC detected by two-dimensional echocardiography independently predicts mortality and may provide an easy-to-perform and inexpensive way to improve risk stratification.


Effect of skin to skin care to neonates on pulse rate, respiratory rate SPO2 and blood pressure in mothers.
Physiological benefits of skin to skin care (STS) to newborns are known but there is scarcity of data on changes in physiological parameters like pulse rate, respiratory rate, SPO2 and blood pressure in mothers during STS. We hypothesize that STS is beneficial to mothers with respect to these parameters. Objective of this study was to assess the changes of these parameters in mothers while providing STS for one hour. STS was provided by 52 mothers for a total of 127 times and parameters were recorded at starting of STS, at 15 min, at 30 min, at 60 min of STS and at 5 min rest after stopping STS. There were no significant changes in pulse rate and SPO2 but blood pressure and respiratory rate reduced significantly during STS as compared to rest after stopping STS. Thus STS is physiologically beneficial to mothers.


Cost-utility analysis of short- versus long-course palliative radiotherapy in patients with non-small-cell lung cancer.
Radiotherapy can effectively palliate the symptoms of poor-prognosis patients with non-small-cell lung cancer. However, controversy remains about whether short-course or more protracted radiotherapy schedules provide better value for the money. We conducted a societal cost-utility analysis of a Dutch multicenter randomized trial with 1-year follow-up that compared the efficacy of radiotherapy schedules consisting of 10 fractions of 3 Gy (10 x 3 Gy) versus two fractions of 8 Gy (2 x 8 Gy) in 297 patients with inoperable stage IIIA/B or stage IV non-small-cell lung cancer. this trial found that the 10 x 3-Gy group had better survival than the 2 x 8-Gy group. Lifetime quality-adjusted life-years (QALYs) were estimated using the EuroQol questionnaire. Lifetime societal costs were estimated using a model estimated based on data from cost questionnaires filled out by a subset of patients (n = 56). Differences were analyzed statistically using two-sided nonparametric bootstrapping. Compared with the 2 x 8-Gy group, the 10 x 3-Gy group accrued statistically significantly more QALYs (20.0 versus 13.2 weeks; difference = 6.8 weeks, 95% confidence interval [CI] = 0.1 to 13.5 weeks, P = .05), which was mainly due to the statistically significantly better survival (38.1 versus 27.4 weeks; difference = 10.7 weeks, 95% CI = 0.9 to 20.6 weeks, P = .03) without a statistically significant difference with respect to the average valuation of health (P = .27). Total radiotherapy and radiotherapy-related costs were estimated at 5236 dollars for the 10 x 3-Gy group and 2512 dollars for the 2 x 8-Gy group (difference = 2724 dollars, 95% CI = 2501 dollars to 2947 dollars, P<.001). The 39% increase in life expectancy in the 10 x 3-Gy group as compared with the 2 x 8-Gy group was associated with a 30% increase in survival-related nonradiotherapy costs (11,254 dollars versus 8651 dollars, difference 2602 dollars, 95% CI = -357 dollars to 5562 dollars, P = .09). The cost-utility ratio for the 10 x 3-Gy schedule versus the 2 x 8-Gy schedule was estimated at 40,900 dollars per QALY (95% CI = 19,400 dollars to 1,100,000 dollars per QALY). In these poor-prognosis non-small-cell lung cancer patients, the estimated cost-utility ratio for the palliative 10 x 3-Gy schedule was acceptable according to current economic standards. However, the additional costs for the protracted schedule were justified not by improved quality of life but by longer survival.


A Cardiac Early Warning System with Multi Channel SCG and ECG Monitoring for Mobile Health.
Use of information and communication technology such as smart phone, smart watch, smart glass and portable health monitoring devices for healthcare services has made Mobile Health (mHealth) an emerging research area. Coronary Heart Disease (CHD) is considered as a leading cause of death world wide and an increasing number of people die prematurely due to CHD. Under such circumstances, there is a growing demand for a reliable cardiac monitoring system to catch the intermittent abnormalities and detect critical cardiac behaviors which lead to sudden death. Use of mobile devices to collect Electrocardiography (ECG), Seismocardiography (SCG) data and efficient analysis of those data can monitor a patient's cardiac activities for early warning. This paper presents a novel cardiac data acquisition method and combined analysis of Electrocardiography (ECG) and multi channel Seismocardiography (SCG) data. An early warning system is implemented to monitor the cardiac activities of a person and accuracy assessment of the early warning system is conducted for the ECG data only. The assessment shows 88% accuracy and effectiveness of our proposed analysis, which implies the viability and applicability of the proposed early warning system.


[Study of active myocardial damage in children with suspected myocarditis using antimyosin monoclonal antibodies (AMMoAb-111In)].
The study with monoclonal antimyosin antibody-111In has proved to be useful in the detection of the myocardial damage present in different processes. There is active myocardial damage and specific antimyosin uptake in myocarditis, as both experimental and clinical trials have shown. In experimental models the evolution of myocardial damage has been studied, where a parallelism between the histological changes of the myocardial damage and the evolution on the antimyosin uptake has been found. In clinical myocarditis it is difficult to do an histological follow up of the inflammatory process, and therefore the evolution of myocardial damage present in myocarditis is unknown. The antimyosin antibody images allow a non-invasive study of this evolution. a) to study with monoclonal antimyosin antibody-111In, the myocardial damage present regarding the disease evolution in children with suspected clinical diagnosis of myocarditis; b) to evaluate the evolution of the active myocardial damage reflected on the changes on the monoclonal antimyosin antibody-111In uptake. A study with monoclonal antimyosin antibody-111In was carried out on 43 children, 16 males and 27 females with a median age of 39 months (SD 48 m; range: 2-167) with suspected diagnosis of acute myocarditis defined as the presence of congestive cardiac failure or severe ventricular arrhythmia with less than 12 months of evolution. The image evaluation was done visually and through the heart to lung ratio. Twenty of these patients were also followed up with antimyosin antibody scan for a period of 19 +/- 9 months, and 3.8 +/- 1.7 studies were performed on them in this time. The prevalence of positive myocardial uptake was 83.72%. There is a negative correlation (r = -0.352; p < 0.02) between the evolution time of the process and the heart to lung ratio: patients studied before two months, have a higher heart to lung ratio and greater prevalence of positive studies than those studied later (heart to lung ratio 2.09 vs 1.74; p = 0.013; 90% vs 69.2%). Of the patients followed up with antimyosin antibody scans, 6 showed a clinical relapse which increased their heart to lung ratio. The other 14 showed an progressive decrease of the heart to lung ratio reaching normality in 14 +/- 6 months. a) the uptake intensity of monoclonal antimyosin antibody-111In, as a reflection of the myocardial damage, depends on the disease evolution time, as in the first two months is when the major damage happens; b) the uptake intensity slowly decreases, tending to normality around the 14th month, although this evolution may be altered by the appearance of relapses.


Comparable Quality Performance of Acute Low-Back Pain Care in Telemedicine and Office-Based Cohorts.
Introduction: Back pain is among the most common presentations in primary care offices. National organizations have standardized the appropriate use of imaging for acute low-back pain (LBP). The objective of this study was to evaluate the use of imaging in LBP between telemedicine and in-person clinical encounters. Methods: This retrospective cohort compared secondary data from 20,624 telemedicine and office encounters in a large nonprofit health system from July 1, 2019, to June 30, 2021. The proportion of patients aged 18-50 years who did not receive imaging for acute LBP (X-ray, computed tomography, or magnetic resonance imaging) within 28 days of the provider encounter was measured according to Healthcare Effectiveness Data and Information Set specifications. Performance was compared across race, ethnicity, age, body mass index, overall risk score, and insurance type. Chi-squared tests determined significant differences between cohorts (p < 0.05). Results: Patients seen via telemedicine had significantly lower rates of imaging within 28 days of their physician encounter (office: 16.32%, telemedicine: 11.20%; difference: 5.12%; p < 0.01). This was consistent across racial, ethnic, and risk score subgroups. Discussion: For practices and health systems, telemedicine might be a higher value approach for initial evaluation of acute LBP in primary care. For policy makers, telemedicine can save on health care costs without negatively impacting quality performance measures. Conclusions: Telemedicine is unlikely to compromise quality of acute LBP care, supporting this virtual space as an alternative care venue. The most beneficial use of telemedicine might be triaging initial encounters of acute LBP in primary care. Stronger evidence could support its long-term potential for driving value through cost savings.


Identification of a family of endocytic proteins that define a new alpha-adaptin ear-binding motif.
Endocytosis by clathrin-coated vesicles (CCVs) is an important mechanism mediating protein internalization. Here, we show that two proteins identified through a proteomics analysis of CCVs are new components of the endocytic machinery. The proteins, named NECAP (adaptin-ear-binding coat-associated protein) 1 and 2, are paralogues that display no sequence similarity or common domains with any known protein. Both are enriched in CCV coats, and further analysis of the brain-enriched isoform, NECAP 1, shows its partial localization to clathrin-coated pits and direct binding to the globular ear domain of the alpha-adaptin subunit (alpha-ear) of the adaptor protein 2 (AP-2) complex. Intriguingly, this interaction is mediated by a new motif, WVQF, that uses a distinct alpha-ear interface relative to known alpha-ear-binding partners. Disruption of this interaction blocks clathrin-mediated endocytosis. Together, our studies identify a new family of endocytic proteins that define a unique AP-2-binding motif.


Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010.
Tumor necrosis factor (TNF)-α antagonists have been associated with the induction of de novo or worsening psoriasis. We sought to retrospectively examine the clinical characteristics and outcomes of patients with psoriasis associated with anti-TNF-α therapy. We performed a retrospective review of patients with new-onset or worsening psoriasis during TNF-α inhibitor therapy between 1998 and 2010. Of the 56 patients (mean age at psoriasis onset, 48.1 years), 41 (73%) were female. In all, 22 patients (39%) had Crohn's disease and 14 (25%) had rheumatoid arthritis. Thirty patients (54%) were treated with infliximab, 19 (34%) with adalimumab, and 7 (12%) with etanercept. New-onset or worsening psoriasis occurred after a mean treatment duration of 17.1 months. Plaque psoriasis (n = 27), palmoplantar pustulosis (n = 25), scalp psoriasis (n = 12), generalized pustular psoriasis (n = 7), erythrodermic psoriasis (n = 2), and inverse psoriasis (n = 2) were the cutaneous presentations. Among the 39 patients for whom full treatment response data were available, 33 (85%) had a complete or partial response; combined response rates (complete and partial) were slightly higher among those who discontinued anti-TNF-α therapy (16 of 17 patients [94%]) than among those who continued anti-TNF-α therapy (17 of 22 patients [77%]). Retrospective nature, possible referral bias, and lack of complete follow-up for some patients are limitations. Although some patients sufficiently controlled their psoriasis while continuing anti-TNF-α therapy, those who discontinued therapy achieved higher rates of complete response. Further studies should explore the efficacy and safety of switching to an alternative anti-TNF-α agent.


Negatively charged RNase-susceptible molecules on the surface of ascites tumor cells.
RNase-susceptible ionogenic groups on the cell surface membranes of two leukemic and two nonleukemic strains of ascites tumor cells were studied by cell electrophoresis, DEAE-Sephadex A-25 column and paper chromatography, and indirect membrane immunofluorescence. RNase treatment of the nonleukemic ascites tumor cells (Ehrlich ascites tumor and Sarcoma 180) produced a significant reduction in their electrophoretic mobilities. When the cells were labeled with [3H]uridine then incubated with RNase, there was a marked increased in the radioactive nucleotides present in the incubation medium as compared to the results of the experiment with RNase-untreated controls. Indirect membrane immunofluorescence studies of nonleukemic ascites tumor cells suggest that the sites that react with anti-RNA antibody are distributed diffusely on their surfaces. RNase treatment of these cells markedly reduced their ability to react with the antibody. It thus appears that RNAs are present on the surface membrane of nonleukemic ascites tumor cells and that RNase digests these RNAs, removing negatively charged nucleotides from their electrophoretic surfaces. This results in a reduction in mobility. In contrast, leukemic ascites cells (L1210 and C1498) incubated with RNase showed no significant change in mobility or in the amount of nucleotides released into the incubation medium. Moreover, no fluorescence was found on the surface of cells examined by indirect membrane immunofluorescence. This suggests that leukemic ascites cells are devoid of RNAs on their surface.


Continuous ingestion of different chlordecone (Kepone) concentrations and changes in quail reproduction.
To determine the effects of continuous ingestion of different chlordecone concentrations on quail reproduction and mortality, 5-wk-old female japanese quail were fed a diet containing 10, 40, 80, and 160 ppm chlordecone for exactly 250 d. Continuous ingestion of 10-80 ppm chlordecone did not induce excessive mortality or significantly alter reproductive functions. Similar ingestion of 160 ppm chlordecone increased quail mortality, produced a log in egg production, and affected the normal sequence of egg laying. Increased mortality occurred in quail that either did not initiate egg laying or ceased egg laying completely. Reproductive tracts of dead quail were noticeably reduced and the ovaries atrophied. Quail that continued to ingest the highest chlordecone dose produced significantly more defective eggs, which were eigher cracked, soft-shelled, or shell-less.


Association Between Telomere Length, Chronic Kidney Disease, and Renal Traits: A Systematic Review.
Telomere length (TL) is an important biological variable that can influence a variety of disease-related complex traits as well as host-environment interactions such as drug and nutritional responses. Chronic kidney disease (CKD) is a common global health challenge especially with the currently aging world population. We conducted a PubMed database search according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines for systematic reviews. Studies in adults (18 years and above) in which TL was determined and correlated with CKD, renal traits, and function were included, while animal model studies were excluded. Nine studies comprising 7829 participants, published between 2005 and 2016, met the inclusion criteria. These included eight observational studies (six being prospective), and one clinical trial. Participants in two studies were diabetic patients with varying stages of CKD, and nondialysis chronic glomerulonephritis CKD patients in two other studies. TL measurements used polymerase chain reaction in five studies, terminal restriction fragmentation in three studies, and quantitative fluorescence in situ hybridization in one study. Short TL was independently associated with increased risk of prevalent microalbuminuria in diabetic men with CKD (p = 0.007). Among CKD patients with heterogeneous etiologies, however, there was an unadjusted lower risk (p < 0.001). Short TL was significantly associated with CKD progression among smokers (p = 0.001) and diabetic patients (p = 0.03). On the other hand, long TL was paradoxically associated with longer diagnosed duration of moderate CKD. We postulate that shortening TL might be associated with CKD prevalence/occurrence or declining kidney function, but this association is likely offset by the cellular telomere reparative process in those surviving longer with CKD. This systematic review underscores the need for future omics and human genetics research to delineate the contribution of TL to CKD, renal dysfunction, and related health outcomes. Telomeres and telomerase activity hold great promise for CKD risk stratification and personalized medicine.


Inhibition of Pathological Phenotype of Hypertrophic Scar Fibroblasts Via Coculture with Adipose-Derived Stem Cells.
Hypertrophic scar (HS) is a dermal fibroproliferative disease characterized by fibroblast over-proliferation, overproduction, and deposition of the extracellular matrix. Growing evidence demonstrated that adipose-derived stem cells (ASCs) secrete a plethora of trophic and antifibrotic factors, which suppress inflammation and ameliorate fibrosis of different tissues. However, few studies investigate their effect on repressing HS activity. This study evaluated the suppressing effect of ASCs on HS fibroblast bioactivity and the possible mechanism via a coculture model. HS-derived fibroblasts (HSFs) and ASCs were isolated from individual patients. HSFs or HSFs treated with transforming growth factor-β1 (TGF-β1) were cocultured with ASCs and the change of HSF cellular behaviors, such as cell proliferation, migration, contractility, and gene/protein expression of scar-related molecules, were evaluated by cell counting assay, cell cycle analysis, scratch wound assay, fibroblast-populated collagen lattice (FPCL) contractility assay, real-time quantitative polymerase chain reaction, ELISA, and western blotting assay. After 5 days of ASC coculture treatment, the expression levels of collagen I (Col 1), collagen III (Col 3), fibronectin (FN), TGF-β1, interleukin-6 (IL-6), interleukin-8 (IL-8), connective tissue growth factor (CTGF), and alpha-smooth muscle actin (α-SMA) in HSFs decreased significantly while the expression levels of decorin (DCN) and MMP-1/TIMP-1 (matrix metalloproteinase/tissue inhibitor of MMP) ratio increased significantly. Besides, after 5 days of exogenous TGF-β1 stimulation, the expression levels of Col 1, FN, TGF-β1, IL-6, CTGF, and α-SMA in HSFs increased significantly. Impressively, all these increased gene expression levels were reversed by 5 days of ASCs coculture treatment. Additionally, the proliferation, migration, and contractility of HSFs were all significantly reduced by ASC coculture treatment. Furthermore, the protein levels of TGF-β1 and intracellular signal pathway-related molecules, such as p-smad2, p-smad3, p-Stat3, and p-ERK, were downregulated significantly in HSFs after 5 days of ASCs coculture treatment. This study demonstrated that coculture of HSFs with ASCs not only inhibited proliferation, migration, and contractility of HSFs but also decreased the expression levels of HSF-related or TGF-β1-induced molecules. Additionally, the antifibrotic effect on HSFs was likely mediated by the inhibition of multiple intracellular signaling. The results of this study suggest the therapeutic potential of ASCs for HS treatment, which is worth of further investigation.


Associations Between Self-Reported and Biological Measures of Nicotine Consumption Among Young Adult Nondaily Cigarette Smokers.
Intermittent, dual use of cigarettes and e-cigarettes is a common pattern among youth and young adults. However, little is known about the validity of self-report measures of nicotine consumption in these populations. The goal of the present study was to examine associations between self-reported frequency of cigarette and e-cigarette use and nicotine levels in hair samples at two assessments 1 year apart. Participants (n = 90; 65% female) were 19- to 25-year-old intermittent cigarette smokers recruited from the community for a longitudinal study of tobacco use. They submitted hair samples via mail, 1 and 2 years after enrollment in the parent study. Findings indicated that days of use of both cigarettes and e-cigarettes in the past 30 days independently predicted hair nicotine in the full sample, and when examining only timepoints at which any cigarette use was reported. Timepoints when any e-cigarette use was reported, hair nicotine was positively associated with e-cigarette but not cigarette frequency. Data suggest that self-report measures are valid methods of assessing intermittent use of both cigarettes and e-cigarettes. Findings also suggest that dual users may tend to consume more nicotine and thus be at greater risk for dependence than single product users. These results are among the first to indicate that hair analysis can be used to detect intermittent nicotine exposure via both cigarettes and e-cigarettes. (Am J Addict 2020;29:471-475).


Phenotype Report on Patients with Congenital Factor V Deficiency in Southern Iran: Recent Ten Years' Experience.
This study aimed to investigate clinical symptoms in patients with congenital factor V (FV) deficiency and the relationship between phenotype and factor activity level. Thirteen patients with congenital FV deficiency were investigated and the factor activity level and first clinical presentations were studied for each patient. The most common first signs and symptoms were post-surgery, post-partum, post-circumcision, and post-traumatic bleeding (30.76%), followed by easy bruising in 23.10% of the patients. The median age at the onset of clinical signs was 18 (range: 1-53) years. Patients were categorized into two groups of major and minor bleeding based on their first clinical bleeding symptoms. There was not a significant difference between the two groups with regard to factor activity level, age at diagnosis, prothrombin time, partial thromboplastin time, and international normalized ratio (p>0.05). There is a discrepancy between plasma FV activity level and the severity of clinical presentations.


Violent behaviors associated with cocaine use: possible pharmacological mechanisms.
Violent behaviors are increasingly noted in clinical practice to be associated with cocaine use; however, few studies actually characterize these behaviors. Cocaine addicts who made self-inquiries for themselves to obtain information about the effects, diagnosis, and treatment of cocaine dependence were interviewed. The study examined in a structured telephone interview their violent behaviors associated with cocaine use. The types of violent behavior reported by these cocaine addicts ranged from minor psychological aggressions to major physical acts that included murder and rape. The pharmacological mechanisms underlying the induction of cocaine-associated violence may involve known neurotransmitter systems affected by cocaine. A possible explanation may be that cocaine acts in those areas of the brain, particularly the limbic system, that subserve aggressive and violent behaviors.


An equine herpesvirus-1 gene 71 deletant is attenuated and elicits a protective immune response in mice.
The pathogenesis of pulmonary infection and the immune response following intranasal inoculation of mice with two equine herpesvirus type 1 (EHV-1) deletion mutants have been assessed. The mutants, ED71 and ED75, have deletions in genes 71 (EUS4) and 75 (10K), respectively. Deletions were replaced by the Escherichia coli lacZ gene driven by the simian virus 40 (SV40) early promoter. It has previously been shown that the protein products of genes 71 and 75 are dispensable in vitro but that removal of gene 71 results in a defect in virus maturation and capsid envelopment which impairs the ability of mutant virus to spread via release and readsorption. This study demonstrated that the 192-kDa gene 71 product is required for full expression of virulence in mice, whereas the putative 10-kDa product of gene 75 has minimal effect. Both mutants exhibited the same tissue and cytotropism as wild-type EHV-1 and induced both humoral and cell-mediated immune responses indistinguishable from those induced by the parental strain. Irrespective of the reduced pathogenicity of the gene 71 mutant, infected mice were protected against a challenge with wild-type EHV-1. These findings highlight the potential of ED71 as a vaccine candidate.


Speech sound disorder at 4 years: prevalence, comorbidities, and predictors in a community cohort of children.
The epidemiology of preschool speech sound disorder is poorly understood. Our aims were to determine: the prevalence of idiopathic speech sound disorder; the comorbidity of speech sound disorder with language and pre-literacy difficulties; and the factors contributing to speech outcome at 4 years. One thousand four hundred and ninety-four participants from an Australian longitudinal cohort completed speech, language, and pre-literacy assessments at 4 years. Prevalence of speech sound disorder (SSD) was defined by standard score performance of ≤79 on a speech assessment. Logistic regression examined predictors of SSD within four domains: child and family; parent-reported speech; cognitive-linguistic; and parent-reported motor skills. At 4 years the prevalence of speech disorder in an Australian cohort was 3.4%. Comorbidity with SSD was 40.8% for language disorder and 20.8% for poor pre-literacy skills. Sex, maternal vocabulary, socio-economic status, and family history of speech and language difficulties predicted SSD, as did 2-year speech, language, and motor skills. Together these variables provided good discrimination of SSD (area under the curve=0.78). This is the first epidemiological study to demonstrate prevalence of SSD at 4 years of age that was consistent with previous clinical studies. Early detection of SSD at 4 years should focus on family variables and speech, language, and motor skills measured at 2 years.


Effective coverage measurement in maternal, newborn, child, and adolescent health and nutrition: progress, future prospects, and implications for quality health systems.
Intervention coverage-the proportion of the population with a health-care need who receive care-does not account for intervention quality and potentially overestimates health benefits of services provided to populations. Effective coverage introduces the dimension of quality of care to the measurement of intervention coverage. Many definitions and methodological approaches to measuring effective coverage have been developed, resulting in confusion over definition, calculation, interpretation, and monitoring of these measures. To develop a consensus on the definition and measurement of effective coverage for maternal, newborn, child, and adolescent health and nutrition (MNCAHN), WHO and UNICEF convened a group of experts, the Effective Coverage Think Tank Group, to make recommendations for standardising the definition of effective coverage, measurement approaches for effective coverage, indicators of effective coverage in MNCAHN, and to develop future effective coverage research priorities. Via a series of consultations, the group recommended that effective coverage be defined as the proportion of a population in need of a service that resulted in a positive health outcome from the service. The proposed effective coverage measures and care cascade steps can be applied to further develop effective coverage measures across a broad range of MNCAHN services. Furthermore, advances in measurement of effective coverage could improve monitoring efforts towards the achievement of universal health coverage.


Are sputum autoantibodies more clinically relevant in idiopathic pulmonary fibrosis than serum autoantibodies?
The adaptive immune system plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) has been reported previously. However, the association between airway and circulating autoantibodies (AAbs) levels is unclear. The aim of this study is to investigate the link between the AAb levels in airway and circulation in stable patients with IPF. From June 2016 to March 2017, 21 stable IPF patients and 22 healthy volunteers were recruited. We established Luminex interacting AAbs with bead-antigen complex to detect the immunoglobulin G antibodies levels of ten autoantigens which were matched serum (Se) and sputum (Sp) samples collected from recruited subjects, including Smith (Sm), Anti-ribosomal P antibody (P0), Sjögren syndrome type A antigen (SSA), La/Sjögren syndrome type B antigen (SSB), DNA topoisomerase (Scl-70), histidyl-tRNA synthetase (Jo-1), U1 small nuclear ribonucleoprotein (U1-SnRNP), thyroid peroxidase, Proteinase 3, and Myeloperoxidase. Spearman's rank correlation matrix was applied to explore the associations of Ab profiles between Se and Sp. For IPF patients, Spearman's correlation matrix showed multiple intercorrelations among Sp-AAbs and Sp-AAbs (P < 0.05), while only the levels of AAb against Sm and anti-La in Se were correlated with those Sp-AAb counterparts (P < 0.05). For healthy individuals, only anti-La in Se was associated with those Sp-AAb counterparts (P < 0.05). For IPF patients, there was a positive correlation between carbon monoxide diffusing capacity (DLCO)% predicted and Sp-anti-P0 level (r = 0.464, P = 0.034). Forced vital capacity% predicted was positively correlated with Sp-anti-Scl-70 level (r = 0.466, P = 0.033). Comparing to Se-AAbs, Sp-AAbs are more associated with clinical parameters in the patients with IPF. In order to better understand the role of autoimmunity in the pathogenesis of IPF, detection of Sp-AAbs for local autoimmune responses may be a good choice.


Catheter ablation versus medical rate control for persistent atrial fibrillation in patients with heart failure: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.
The effectiveness of restoring the sinus rhythm by catheter ablation relative to that of medical rate control for persistent atrial fibrillation (AF) patients with heart failure (HF) remains to be defined. We systematically searched Embase, Pubmed, the Cochrane Library, and ClinicalTrials.gov for articles that compared the outcomes of interest between catheter ablation and medical rate control therapy in persistent AF patients with HF and left ventricular systolic dysfunction (LVSD). The primary endpoint was the change in the left ventricular ejection fraction (LVEF) following catheter ablation or medical rate control therapy relative to baseline. Other endpoints included changes in cardiac function and exercise capacity, including the New York Heart Association (NYHA) class, the brain natriuretic peptide (BNP) level, the peak oxygen consumption (peak VO2), the 6-minute walk test (6MWT) results, and quality of life (QOL). Three randomized controlled trials (RCTs) with 143 patients were included. At the overall term follow-up, catheter ablation significantly improved the LVEF (mean difference [MD]: 6.22%; 95% confidence interval [CI]: 0.7-11.74, P = 0.03) and peak VO2 (MD: 2.81 mL/kg/min; 95% CI: 0.78-4.85, P = 0.007) and reduced the NYHA class (MD: 0.9; 95% CI: 0.59-1.21, P < 0.001) and the Minnesota Living with Heart Failure Questionnaires (MLHFQ) scores (MD: -11.05; 95% CI: -19.45 - -2.66, P = 0.01) compared with the medical rate control for persistent AF patients with HF. Alterations in parameters, such as the BNP level, 6MWT, and Short Form-36 (SF-36) questionnaire scores also revealed trends that favored catheter ablation therapy, although these differences were not significant. Catheter ablation resulted in improved LVEF, cardiac function, exercise capacity, and QOL for persistent AF patients with HF compared with the medical rate control strategy.


Gliclazide attenuates the intracellular Ca2+ changes induced in vitro by ischemia in the retinal slices of rats with streptozotocin-induced diabetes.
To investigate the dynamics of the intracellular Ca2+ concentration ([Ca2+]i) during retinal ischemia in rats with streptozotocin (STZ)-induced diabetes and the effect of gliclazide, a sulfonylurea with a potent free-radical scavenging activity on ischemia-induced [Ca2+]i dynamics. Rats with STZ (65 mg/kg) induced diabetes were divided into three groups: the untreated diabetic group, the gliclazide-treated group, and the glibenclamide-treated group. An ischemic condition was imposed in vitro on the retinal slices by perfusion with an oxygen/glucose deprived solution. The [Ca2+]i was measured in individual layers of the rat retinal slices loaded with the Ca2+ indicator fluo-3. As compared to that in the normal rat retina, both the amplitude and the kinetics of the [Ca2+]i increase were suppressed in the intermediate layers of the retinal slices from the diabetic rats under the ischemic condition. These changes were attenuated by the administration of gliclazide but not by that of glibenclamide. Hyperglycemia influences ischemia-induced [Ca2+]i dynamics predominantly in the intermediate layers of the retina, and gliclazide, as compared to glibenclamide without a free radical scavenging activity, potently attenuates the ischemia-induced changes in the calcium dynamics.


PHYLOGENETIC ESTIMATION OF PLASMID EXCHANGE IN BACTERIA.
The existence of differential horizontal gene transfer may be assessed by comparing the phylogenetic trees derived from two different genes. We use this concept to estimate quantitatively the amount of plasmid exchange that has occurred in a bacterial population. By means of computer simulations we studied the effect of gene transfer on the topological distortion between two phylogenetic trees: one obtained from an euchromosomal gene and another from a plasmid-borne sequence, which may be subjected to horizontal transfer. The basic assumptions of our simulations were (a) that plasmid exchange had occurred recently (after the last population split); and (b) that either the amount of chromosomal horizontal exchange was negligible or that it was only a fraction of the amount of plasmid exchange in which case we will be estimating relative amounts of plasmid transfer. We found that the topological difference between two such trees is a function of the number of plasmid exchange events that have occurred. It can be explained by a logistic model that relates the average distortion index between two trees (dT ) to the number of transfer events (x). The behavior remains the same under different conditions that were tested (symmetry of the topology, number of taxa in the tree, effect of reconstruction errors, mutation after plasmid transfer). We have also tried our method on empirical data from the literature and estimated the amount of gene transfer that may have occurred among Sym plasmids in agricultural field populations of Rhizobium leguminosarum biovar phaseoli. We found that between 15.77 to 29.98% of all genetic types in these populations have been either the source or the target of a plasmid transfer event. When the comparisons were made among trees derived exclusively from plasmid probes this value dropped to 2.00%. Phylogenetic trees derived from symbiotic and nonsymbiotic sequences were also used to infer the number of gene transfer events among 11 isolates from R. galegae. The estimated number of transfer events of symbiotic sequences was 10.515 (although we do not know out of how many genetic types). We concluded that intraspecific transfer of symbiotic sequences is widespread in these two species of the genus Rhizobium.


Predicting marital separation: do parent-child relationships matter?
This study used a family systems perspective in modeling predictors of marital separation within married-parent families with adolescents. Specifically, we examined whether mother-adolescent closeness and negativity, father-adolescent closeness and negativity, and couple relationship quality (mothers' and fathers' positive marital behaviors) prospectively predicted the likelihood of marital separation, operationalized as the father moving out of the household. Data were derived from the first 4 waves of the National Longitudinal Survey of Youth, 1997 (n = 1649), assessing both biological and stepfather families. Results from complementary log-log analyses revealed that marital separations were related to complex family relationships. Specifically, greater mother-adolescent closeness predicted a higher likelihood of marital separation, whereas greater father-child closeness predicted a lower likelihood. In addition, mothers' more positive marital behaviors toward fathers predicted a lower likelihood of marital separation. Patterns were largely similar between biological and stepfather families, with the exception that mothers' positive marital behaviors toward fathers were more influential within biological father families.


Spatio-temporal X-wave.
We introduce an illumination configuration which is a spatiotemporal analog of a non-diffracting X-wave. By interfering multiple ultrashort converging plane waves, we generate a tight central spot at which a transform limited ultrashort pulse is formed. Outside this tight focus a spatiotemporal speckle field with longer duration and reduced peak power is created. We investigate this spatiotemporal X-wave configuration analytically, numerically, and experimentally demonstrate the effect using two photon excitation fluorescence.


[Current questions in the radiotherapy of lymphoproliferative tumors].
Radiation therapy traditionally plays a major role in the treatment of lymphoproliferative diseases. Diagnostics and treatment of these tumors improved tremendously in the recent decades. Molecular diagnostics is able to discriminate its subtypes more precisely than ever and opens the possibility of the introduction of targeted medicines. Imaging, especially functional imaging now has an established role in forming treatment strategy. Radiation therapy showed substantial technical development too. As a consequence of these, the role, dose and technique of radiotherapy changes instantly. In this short review we discuss situations which clinicians, both hemato-oncologists and radiation oncologist may face day by day. These are: the changing role of radiation therapy in early Hodgkin's disease, including dose and filed size reduction and PET-driven radiation therapy; the use of radiation in advanced Hodgkin's disease; the role of radiation therapy of diffuse large B-cell lymphoma in the light of the use of rituximab; and finally the use of modern radiation therapy techniques like intensity-modulated radiation therapy or particle therapy.


[Dental rehabilitation in a young patient with glycogen storage disease type 1B].
A young woman, known to have glycogen storage disease type 1B (GSD1B) presents with severe periodontitis. GDS1B causes decreased hepatic and renal glucose production and in many cases neutropenia and neutrophil dysfunction leading to recurrent infections. It was decided to treat the patient by extraction of the most affected teeth and retention of the remaining teeth through periodontal treatment, both with antibiotic prophylaxis. After a follow-up period of 1.5 years, during which there was no visible improvement, it was decided to do a full dental extraction and fabricate complete dentures. Due to subsequent bone resorption in both jaws, the dentures were not functional. After consulting the internist and the oral and maxillofacial surgeon, the decision was then made to place dental implants in both the upper and lower jaw for implant-supported prosthetics. After successful treatment and an osseointegration period, the prosthetics were placed. 1 year after placement, there is a stable implantological situation, without pockets or apparent bone loss. The start of SGLT2 medication may have played a significant role in this.


Spinal sepsis due to Streptococcus milleri: two cases and review.
We have recently cared for two patients with spinal sepsis secondary to infection with Streptococcus milleri. One patient had a spinal epidural abscess and the other had meningitis as well as a spinal subdural empyema. A review of the English-language literature revealed only two previously reported cases of spinal epidural abscess due to S. milleri and no cases of spinal subdural empyema due to S. milleri. We report two cases of spinal sepsis due to S. milleri and discuss pertinent literature.


The relationship between tooth eruption and ingestion of 15 food items among children aged 18-20 months.
Objectives If children in formative stages ingest foods that are too hard or too soft, they can experience delays in oral cavity functions. Therefore, it is important for young children to receive foods of appropriate hardness in relation to their chewing ability. We investigated the relationship between the ingestion of 15 different food items and tooth eruption among children aged 18-20 months.Methods Caregivers from Japanese municipalities who took their children for an 18-month health check-up were given an anonymous questionnaire. Questionnaires were only given to caregivers who provided direct consent and were returned by mail upon completion. The questions inquired about the ingestion of 15 different food items in an attempt to elucidate a correlation between the degree of food hardness that children can chew, tooth eruption, and development of oral functions. A chi-squared test and Fisher's exact test were used to evaluate the relationship between the ingestion of the 15 food items and tooth eruption. The Hokkaido University Human Research Ethics Committee approved this study.Results Of the 501 caregivers who received the questionnaire, there were 210 responses (40.9%) and 202 (40.3%) of those were used in the analysis. Thirty children (14.9%) had non-eruption of the premolars. Children without absolute eruption of the premolars ate pork and/or beef steak more frequently than those who had their first four premolars.Conclusion Our results suggest that at least 10% of children at the standard tooth eruption age experience delays in oral cavity maturation. This percentage indicates some children consume hard foods inappropriate for premolar development. We propose that caregivers prepare fresh greens and meat of suitable hardness according to the chewing ability of developing children.


Use of an objective clinical scale in the assessment and management of alcohol withdrawal in a large general hospital.
A modified version of the Clinical Institute Withdrawal Assessment Scale (CIWA) was used in the management of alcohol withdrawal in a general hospital. Patients who developed seizures or confusion were noted to score higher on the scale, even before these complications, than patients who remained uncomplicated (21.7 +/- 1.2 compared to 15.6 +/- 0.55). When the score was used as a guide for treatment, it was found that patients scoring greater than 15 were at significantly increased risk of severe alcohol withdrawal if they remained untreated (RR, 3.72; 95% confidence interval, 2.85-4.85). The higher the score the greater this relative risk. Some patients however, still suffered complicated withdrawals although their scores were low or they were apparently adequately treated. It is concluded that the use of an objective clinical scale of alcohol withdrawal is valuable in a general hospital to identify those patients in early withdrawal who need sedation to avoid complication. There will however, be a small group of patients whose clinical course will be difficult to predict and further work is needed to determine the reasons for this.


Identifying resource needs for sepsis care and guideline implementation in the Democratic Republic of the Congo: a cluster survey of 66 hospitals in four eastern provinces.
The ongoing conflict in the Eastern Republic of the Congo (DRC) has claimed up to 5.4 million lives by 2008. Whereas few deaths were directly due to violence, most victims died from medical conditions such as infectious diseases. This survey investigates the availability of resources required to provide adequate sepsis care in Eastern DRC. The study was conducted as a self-reported, questionnaire-based survey in four Eastern provinces of the DRC. Questionnaires were sent to a cluster of 80 urban-based hospitals in the North Kivu, South Kivu, Maniema and Orientale provinces. The questionnaire contained 74 questions on the availability of resources required to adequately treat sepsis patients as suggested by the latest Surviving Sepsis Campaign (SSC) guidelines. Sixty-six questionnaires were returned (82.5%) and analyzed. Crystalloid solutions and intravenous fluid giving sets were the only resources constantly available in all hospitals. None of the respondents reported to have constant access to piperacillin, carbapenems, fresh frozen plasma, platelets, dobutamine, activated protein C, echocardiography or equipment to measure lactate levels, invasive blood pressure, central venous pressure, cardiac output, pulmonary artery pressure or endtidal carbon dioxide. No respondent stated that a mechanical ventilator, syringe pump, fluid infuser, peritoneal dialysis or haemodialysis/hemofiltration machine was constantly available at his/her hospital. Resources required for consistent implementation of the SSC guidelines were not available in any hospital. care and implement the SSC guidelines in a cluster of hospitals in the Eastern DRC.


Tetrahydrobiopterin in intestinal lumen: its absorption and secretion in the small intestine and the elimination in the large intestine.
In treating hereditary deficiency of tetrahydrobiopterin (BH(4)), supplementation with BH(4) might be the ultimate choice of therapy. Oral administration of BH(4) has been believed to be inefficient owing to poor absorption of BH(4) in the intestine. In this study, we found a considerable amount of BH(4) as well as its oxidized pterins in the ingredients of intestinal lumen of mice when they were served food that did not contain significant amounts of biopterin. Ligation of the biliary duct led to significant decrease in luminal biopterin. Supplementation of BH(4) either by intraperitoneal administration of sepiapterin or of 6RBH(4) ((6R)-L-erythro-5,6,7,8-tetrahydrobiopterin) increased the BH(4) content in the intestinal lumen with a slight delay after the rise of blood BH(4). In these mice, biopterin appeared in the large intestine, caecum and colon, 2 h after the administration. The appearance of BH(4) in the large intestine was accompanied by a large amount of pterin (2-amino-4-hydroxypteridine). The amounts of biopterin + pterin that appeared in the large intestine after intraperitoneal administration of BH(4) were not greater than those found after oral administration at the same dose. When the mice were treated with a large dose of antibiotics prior to the BH(4) administration, the amount of biopterin increased in the caecum but the amount of pterin decreased greatly. These results suggested that a large proportion of BH(4) administered moved to the large intestine, where most biopterin was decomposed presumably by enteric bacteria. Nonetheless, most of the orally administered biopterin was taken up by the small intestine and the amount of biopterin reaching the large intestine was almost the same as that which appeared after direct injection of 6RBH(4) into the peritoneal cavity.


Monolayer Silane-Coated, Water-Soluble Quantum Dots.
A one-step method to produce ≈12 nm hydrodynamic diameter water-soluble CdSe/ZnS quantum dots (QDs), as well as CdS/ZnS, ZnSe/ZnMnS/ZnS, AgInS2 /ZnS, and CuInS2 /ZnS QDs, by ligand exchange with a near-monolayer of organosilane caps is reported. The method cross-links the surface-bound silane ligands such that the samples are stable on the order of months under ambient conditions. Furthermore, the samples may retain a high quantum yield (60%) over this time. Several methods to functionalize aqueous QD dispersions with proteins and fluorescent dyes have been developed with reaction yields as high as 97%.


Bimodal odor processing with a trigeminal component at sub- and suprathreshold levels.
Odors are typically bimodal in nature, interacting with the olfactory and trigeminal systems. The trigeminal component may be noticed (e.g. menthol) or perceptually ignored, leading to different neural substrates being recruited during odor encoding. Therefore, the current study was designed to explore the perceptual and central-nervous activations in response to pleasant bimodal odors using functional magnetic resonance imaging (fMRI). In this study, healthy subjects were exposed to odorants alone (unimodal) or with a "cooling" trigeminal component (bimodal) at sub- and suprathreshold concentrations with a portable olfactometer in a 3T fMRI scanner. Within the scanner, subjects reported all odorants as pleasant and intensity increasing with trigeminal concentration. Many of the regions of interest [orbital frontal cortex (OFC), insula, thalamus, cerebellum, postcentral gyrus and cingulate cortex] were activated during bimodal odor conditions when contrasted with unimodal, and interestingly, most of these activations were seen prior to trigeminal perception (e.g. at a sub-threshold level). This includes large bilateral activations within the OFC, insula, cerebellum and parts of the cingulate cortex. Additionally, activation of the thalamus was seen early in the stages of bimodal odor encoding suggesting its role of mediating attention toward the presence of two stimuli. Lastly, intensity encoding during bimodal processing shows overlap of previously demonstrated simple trigeminal encoding areas (medial cingulate cortex) and the more complex olfactory encoding areas (bilateral insula, superior temporal gyrus, OFC, and cerebellum), but not the amygdala.


Neuromelanin, aging, and neuronal vulnerability in Parkinson's disease.
Neuromelanin, a dark brown intracellular pigment, has long been associated with Parkinson's disease (PD). In PD, neuromelanin-containing neurons preferentially degenerate, tell-tale neuropathological inclusions form in close association with this pigment, and neuroinflammation is restricted to neuromelanin-containing areas. In humans, neuromelanin accumulates with age, which in turn is the main risk factor for PD. The potential contribution of neuromelanin to PD pathogenesis remains unknown because, in contrast to humans, common laboratory animals lack neuromelanin. The recent introduction of a rodent model exhibiting an age-dependent production of human-like neuromelanin has allowed, for the first time, for the consequences of progressive neuromelanin accumulation-up to levels reached in elderly human brains-to be assessed in vivo. In these animals, intracellular neuromelanin accumulation above a specific threshold compromises neuronal function and triggers a PD-like pathology. As neuromelanin levels reach this threshold in PD patients and presymptomatic PD patients, the modulation of neuromelanin accumulation could provide a therapeutic benefit for PD patients and delay brain aging. © 2019 The Author. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Management of soft tissue wounds of the face.
Since time, immemorial soft-tissue injuries to the face have been documented in literature and even depicted in sculptures, reflecting the image of society. In a polytrauma the face may be involved or there may be isolated injury to the face. The face consists of several organs and aesthetic units. The final outcome depends on initial wound care and primary repair. So one should know the "do's and don'ts". Disfigurement following trauma, becomes a social stigma and has the gross detrimental effect on the personality and future of the victim. Therefore, such cases are most appropriately managed by Plastic Surgeons who have a thorough knowledge of applied anatomy, an aesthetic sense and meticulous atraumatic tissue handling expertise, coupled with surgical skill to repair all the composite structures simultaneously.


Development of TRPM8 Antagonists to Treat Chronic Pain and Migraine.
A review. Development of pharmaceutical antagonists of transient receptor potential melastatin 8 (TRPM8) have been pursued for the treatment of chronic pain and migraine. This review focuses on the current state of this progress.


Enhancement of chemotaxis in Spirochaeta aurantia grown under conditions of nutrient limitation.
Spirochaeta aurantia M1 cells were grown in a chemostat under conditions of energy and carbon source limitation. The chemotactic responses of the chemostat-grown cells were compared with those of S. aurantia cells grown in batch culture in the presence of excess energy and carbon source. Chemotactic responses were measured by determining the number of cells that entered a capillary tube containing a solution of attractant. S. aurantia cells grown in the chemostat under energy and carbon source limitation exhibited enhanced chemotactic responses and detected lower concentrations of attractant, as compared with cells grown in batch culture. The chemotactic response toward an attractant was specifically enhanced when that attractant was the growth-limiting energy and carbon source. The medium used contained either D-glucose or D-xylose as the sole energy and carbon source. Cells had the greatest chemotactic response toward glucose when grown at a dilution rate (D) of 0.045 h-1 under glucose limitation and toward xylose when grown at D = 0.06 h-1 under xylose limitation. When cells were grown under glucose limitation (D = 0.045 h-1), they sensed concentrations of attractant (glucose) ca. 1,000 times lower than those sensed by batch-grown cells. A similar enhancement of sensing ability (toward xylose) was observed in cells grown under xylose limitation. The results indicated that S. aurantia cells are able to regulate their chemosensory system in response to nutrient limitation. Maximum enhancement of chemotaxis occurs in cells growing at very low concentrations of energy and carbon source. Most likely, this property provides the spirochetes with competitive advantages when the availability of nutrients becomes severely limited in their habitats.


Leptin normalizes photic synchronization in male ob/ob mice, via indirect effects on the suprachiasmatic nucleus.
Mounting evidence indicates a strong link between metabolic diseases and circadian dysfunctions. The metabolic hormone leptin, substantially increased in dietary obesity, displays chronobiotic properties. Here we investigated whether leptin is involved in the alteration of timing associated with obesity, via direct or indirect effects on the suprachiasmatic nucleus (SCN), the site of the master clock. Photic synchronization was studied in obese ob/ob mice (deficient in leptin), either injected or not with high doses of recombinant murine leptin (5 mg/kg). This was performed first at a behavioral level, by shifting the light-dark cycle and inducing phase shifts by 30-minute light pulses and then at molecular levels (c-FOS and P-ERK1/2). Moreover, to characterize the targets mediating the chronomodulatory effects of leptin, we studied the induction of phosphorylated signal transducer and activator of transcription 3 (P-STAT3) in the SCN and in different structures projecting to the SCN, including the medial hypothalamus. Ob/ob mice showed altered photic synchronization, including augmented light-induced phase delays. Acute leptin treatment normalized the photic responses of the SCN at both the behavioral and molecular levels (decrease of light-induced c-FOS). Leptin-induced P-STAT3 was modulated by light in the arcuate nucleus and both the ventromedial and dorsomedial hypothalamic nuclei, whereas its expression was independent of the presence of leptin in the SCN. These results suggest an indirect action of leptin on the SCN, possibly mediated by the medial hypothalamus. Taken together, these results highlight a central role of leptin in the relationship between metabolic disturbances and circadian disruptions.


Acute gouty arthritis during pyrazinamide treatment: a case report.
Abstract Gout is a disease caused by an inflammatory response to an aggregation of monosodium urate crystals that develop secondary to hyperuricemia. Throughout its natural history it has four stages: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout, and chronic tophaceous gout. In this article, we report the case of a patient who had asymptomatic hyperuricemia secondary to pyrazinamide, which was prescribed for pulmonary tuberculosis, and had developed an acute gouty arthritis immediately after the "Feast of Sacrifice" due to a dietary excess of purine.


Efficient Multicomponent Active Template Synthesis of Catenanes.
We describe a simple and high yielding active template synthesis of [2]catenanes. In addition to mechanical bond formation using a single premacrocycle bearing an azide and alkyne moiety, our method is also suitable for the co-macrocyclization of readily available bis-alkyne and bis-azide comonomers and even short alkyne/azide components which oligomerize prior to mechanical bond formation.


Effects of inorganics on the degradation of micropollutants with vacuum UV (VUV) advanced oxidation.
This research focused on the effects of inorganic water constituents on the efficiency of vacuum UV (VUV) for the degradation of micropollutants in surface water supplies. Atrazine was used as a model miropollutant, and bicarbonate, sulphate, and nitrate were used as the most common inorganic constituents in the water matrix. First, the absorbance of radiation at 254 and 185 nm was measured in the presence of different ions. At 254 nm, only nitrate showed a measurable absorption coefficient of [Formula: see text] = 3.51 M[Formula: see text] cm[Formula: see text], and all other ions showed a molar absorption coefficient below the detection limit. However, at 185 nm, all the ions showed high absorption coefficients, with nitrate giving the highest absorption coefficient of [Formula: see text] = 5568 M[Formula: see text] cm[Formula: see text]. Second, the hydroxyl radical (HO[Formula: see text]) scavenging effects of the same inorganic ions were evaluated; nitrate and bicarbonate showed a negative effect during the UV/H2O2 and VUV advanced oxidation processes. Sulfate was photolyzed with 185 nm UV to form HO[Formula: see text], and for this reason, it assisted the degradation of the target micropollutant, as demonstrated by increases in the degradation rate constant. An additional component of this work involved developing a method for measuring the quantum yield of atrazine at 185 nm. This made it possible to distinguish the contribution of OH radical attach from that of direct photolysis towards the degradation of atrazine.


Spontaneous Celiac Artery Dissection with Splenic Infarction: A Report of Two Cases.
Spontaneous isolated celiac artery dissection (SICAD) is a rare condition that is characterized by sudden onset abdominal pain, typically occurring in middle-aged men. Although its clinical course is mostly benign, it may progress to true lumen occlusion. No established therapeutic guidelines are available for SICAD associated with splenic infarction. This report describes two patients who presented with sudden onset abdominal pain and were diagnosed with SICAD with splenic infarction based on computed tomography (CT) findings. Patients were treated with bowel rest and anticoagulants. After a week of medical therapy, the abdominal pain resolved. Follow-up CT revealed no progression of the dissection flap. The patients received oral anticoagulants for 3 months and did not experience any symptom recurrence. Medical therapy with anticoagulants may be considered for patients with SICAD and splenic infarction. Associated splenic infarction itself is not an indication for endovascular or surgical intervention for SICAD.


Towards a smart object network for clinical services.
Radio Frequency Identification (RFID) technology has become prevalent in logistics to support and optimize processes and numerous projects investigate its opportunities and challenges in the clinical context. However, most approaches are focused on one specific application using only a few possibilities of the technology. We describe the development of a smart object network to serve as a generic platform for various clinical services. Based on two disparate scenarios - tracking medical devices and transfusion safety - the architecture, implementation issues and prospects of such a platform are discussed.


Role of eye muscle antibody measurement in diagnosis of thyroid-associated ophthalmopathy: a laboratory update.
To review the current role of measurement of serum eye muscle antibodies in thyroid-associated ophthalmopathy (TAO). We conducted laboratory studies to determine the prevalences of serum autoantibodies reactive with eye muscle antigens in patients with active and inactive TAO, Graves' hyperthyroidism, and Hashimoto's thyroiditis as well as in normal subjects. The two antigens most often recognized in immunoblotting with crude human or porcine eye muscle membranes by serum autoantibodies in patients with TAO are eye muscle membrane proteins of 55 and 64 kd. One 64-kd eye muscle protein has recently been cloned by screening a human eye muscle expression library with two different antibody probes and identified from a computer gene bank search as the calcium-binding protein calsequestrin. A fragment of a 220-kd eye muscle protein, called G2s, has also been cloned by screening the eye muscle library with affinity-purified antibodies reactive with a 55-kd eye muscle membrane protein. The prevalences of autoantibodies reactive with these two antigens in our study groups were as follows. Antibodies against calsequestrin were detected in 38% of patients with TAO for <1 year, in 17% of those with TAO for >3 years, in 17% of patients with Graves' hyperthyroidism without ophthalmopathy, in 12% of patients with Hashimoto's thyroiditis without ophthalmopathy, and in 21% of normal subjects. Antibodies reactive with the 64-kd protein were demonstrated in 62% of patients with recent-onset active TAO, in 33% with eye disease for >3 years, in 39% of patients with Graves' hyperthyroidism without ophthalmopathy, in 25% of patients with Hashimoto's thyroiditis, and in 16% of normal control subjects. Antibodies reactive with G2s fusion protein were detected in 67% of patients with recent-onset active TAO, in 46% of patients with Graves' hyperthyroidism, and in 20% of normal subjects. Antibodies reactive with the parent protein, of which G2s is a fragment, may be markers of early eye muscle swelling and inflammation, whereas those reactive with the 64-kd protein and, less often, calsequestrin are associated with established eye disease. Measurement of serum eye muscle antibodies is recommended as an aid to the early diagnosis of ophthalmopathy in predisposed patients and first-degree relatives of patients with TAO as well as to monitor active or progressive eye disease.


Transcriptomes of three species of Tipuloidea (Diptera, Tipulomorpha) and implications for phylogeny of Tipulomorpha.
Tipulomorpha has long been a problematic taxon in terms of familial composition, phylogenetic relationships among families and position relative to other 'lower' Diptera. Whole-transcriptome shotgun sequencing provides a powerful basis for phylogenetic studies. We performed de novo transcriptome sequencing to produce the first transcriptome datasets representing the families Pediciidae, Limoniidae and Cylindrotomidae using high-throughput sequencing technologies. We assembled cDNA libraries for Pedicia vetusta (Alexander) (Pediciidae), Rhipidia sejuga Zhang, Li and Yang (Limoniidae) and Liogma simplicicornis Alexander (Cylindrotomidae). Using the Illumina RNA-Seq method, we obtained 28,252, 44,152 and 44,281 unigenes, from the three respective species. Based on sequence similarity searches, 12,475 (44.16%), 20,334 (46.05%) and 17,478 (39.47%) genes were identified. Analysis of genes highly conserved at the amino acid sequence level revealed there were 1,709 single-copy orthologs genes across the analyzed species. Phylogenetic trees constructed using maximum likelihood (ML) based on the 1,709 single-copy orthologs genes indicated that the relationship between the four major infraorders of lower Diptera was: Culicomorpha + (Tipulomorpha + (Psychodomorpha + (Bibionomorpha + Brachycera))). Trichoceridae belongs within Tipulomorpha as the sister-group of Tipuloidea. Highly supported relationships within the Tipuloidea are Pediciidae + (Limoniidae + (Cylindrotomidae + Tipulidae)). Four-cluster likelihood mapping was used to study potential incongruent signals supporting other topologies, however, results were congruent with the ML tree.


Microbiological and Clinical Aspects of Raoultella spp.
The genus Raoultella was established in 2001. Species of Raoultella and Klebsiella share many ecological, biochemical, clinical, and microbiological features. Given the shortcomings of available technology for species identification in the clinical microbiology laboratory, are practically indistinguishable. Since the late 2000s there has been an increase in case reports of human Raoultella infections. Therefore, several authors are postulating that Raoultella spp. are rare and/or emerging pathogens. Conclusions:Raoultella spp. are very similar to Klebsiella spp. The epidemiology and the clinical relevance of the human Raoultella spp. infections is uncertain and further studies are required. The previous difficulties in the identification of Raoultella spp. and the introduction of more precise identification techniques may explain the recent increase in the number of case reports. Raoultella spp. might be rather underdiagnosed than rare or emerging pathogens.


Social position of adolescents with chronic digestive disorders.
To investigate the consequences of having a chronic digestive disorder on the social position of adolescents. Five diagnostic groups, including inflammatory bowel disease (IBD), chronic liver diseases, congenital digestive disorders, coeliac disease and food allergy (total n = 758, ages 12-25 years), were each compared with a population-based control group in a multicentre study using a cross-sectional design. Social position was assessed by a mailed questionnaire measuring 24 aspects, categorized as education, leisure activities, friendship, labour participation, financial situation, partnership and sexuality. Eight aspects of social position were found to be affected negatively by one or more chronic digestive diseases: absence from school due to illness, going out, having a paid job, needing re-education in order to get a job, getting benefits as main income source, encountering bottlenecks in establishing financial commitments, having self-confidence in making a pass at someone, and restrictions in making love. Adolescents with chronic liver disease and IBD were found to experience more restrictions in social position. Adolescents with food allergy and congenital digestive disorders appear to experience some restrictions, but to a lesser degree, and adolescents with coeliac disease do not appear to have any problems regarding social position compared with controls. The social position of adolescents is affected negatively by having a chronic digestive disease, in particular chronic liver disease and IBD. Negative consequences occur in education, leisure activities, labour participation, financial situation, partnership and sexuality.


Age-Appropriate Functions and Dysfunctions of the Neonatal Neutrophil.
Neonatal and adult neutrophils are distinctly different from one another due to well-defined and documented deficiencies in neonatal cells, including impaired functions, reduced concentrations of microbicidal proteins and enzymes necessary for pathogen destruction, and variances in cell surface receptors. Neutrophil maturation is clearly demonstrated throughout pregnancy from the earliest hematopoietic precursors in the yolk sac to the well-developed myeloid progenitor cells in the bone marrow around the seventh month of gestation. Notable deficiencies of neonatal neutrophils are generally correlated with gestational age and clinical condition, so that the least functional neutrophils are found in the youngest, sickest neonates. Interruption of normal gestation secondary to preterm birth exposes these shortcomings and places the neonate at an exceptionally high rate of infection and sepsis-related mortality. Because the fetus develops in a sterile environment, neonatal adaptive immune responses are deficient from lack of antigen exposure in utero. Newborns must therefore rely on innate immunity to protect against early infection. Neutrophils are a vital component of innate immunity since they are the first cells to respond to and defend against bacterial, viral, and fungal infections. However, notable phenotypic and functional disparities exist between neonatal and adult cells. Below is review of neutrophil ontogeny, as well as a discussion regarding known differences between preterm and term neonatal and adult neutrophils with respect to cell membrane receptors and functions. Our analysis will also explain how these variations decrease with postnatal age.


[A multi-institutional questionnaire survey on surgical treatment for a small renal mass: factors related with decision-making in indications for partial nephrectomy].
This study aimed to investigate factors taken into account when considering the indication of partial nephrectomy (PN). In October 2011, a questionnaire prepared with reference to the American Urological Association small renal mass survey and RENAL nephrometry score, and focusing on the factors taken into account when considering the use of PN, such as differences among candidates for open PN or laparoscopic PN was sent to 40 institutions. We received replies from 32 of the 40 institutions (average 611 beds) to which the questionnaire was sent. The total number of surgeries performed for renal tumors at the 32 institutions was 844 in 2009 and 889 in 2010. The number of PNs performed was 174 in 2009 (open : 61, laparoscopic : 113), and 241 in 2010 (open : 103, laparoscopic : 138), which represents a 38.3% increase. All respondents reported that renal function prior to PN was considered to be important, followed by tumor size, tumor number, and hereditariness. There were significantly more indications for open PN than for laparoscopic PN, and they were based on tumor size, degree of protrusion, and distance from the renal sinus. In addition, a clear tendency toward avoiding laparoscopic PN for cystic renal cancer was found. In addition, the institutions with a larger number of PNs tended to indicate more complicated cases including larger tumor size or entirely endophytic cases. This study has a limitation in that it was intended for a relatively large hospital, but these results can be useful information for institutions that are considering the introduction of open or laparoscopic PN.


[Construction and identification of nanobody phage display library targeting Middle East respiratory syndrome coronavirus].
Objective To construct a phage display library of specific nano-antibodies against the Middle East respiratory syndrome coronavirus (MERS-CoV) and apply it to the screening of neutralizing nano-antibodies. Methods MERS-CoV receptor-binding domain (RBD) recombinant protein was used to immunize alpaca. After the last immunization, peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood and total RNA was extracted. The VHH gene was amplified by PCR and used to construct recombinant phages. TG1 Escherichia coli was transformed by these recombinant phages. A phage display library of specific nano-antibodies against the MERS-CoV were obtained and used to screen and characterize the nano-antibodies. Results The volume of this library of nano-antibodies was 1.31×108 and its abundance rate was 5.65×1010/mL. The ratio of VHH insertion in the constructed library reached 96%. There was a rich diversity of nano-antibodies in this library. Nano-antibodies with neutralizing activity were identified and expressed from this library. Conclusion We successfully constructed a library of phages which could be effectively applied to the screening of nano-antibodies against MERS-CoV virus.


Translational efficiency of bovine pyruvate carboxylase 5' untranslated region messenger ribonucleic acid variants.
The bovine pyruvate carboxylase (PC) gene is expressed as 6 alternatively spliced variants that share a common open reading frame but that differ within their 5' untranslated regions (UTR). The PC 5' UTR variants (A through F) contain 6 combinations of 5 exons and are 68, 253, 363, 89, 226, 178 bp in length, respectively. The objective of this experiment was to determine whether or not the bovine PC mRNA variants exhibit different translational efficiencies. Each bovine PC 5' UTR variant was linked to the firefly luciferase coding region, and the resulting constructs were transcribed and translated in a rabbit reticulocyte lysate assay. All constructs resulted in synthesis of luciferase protein. The abundance of luciferase protein synthesized from the UTR of bovine PC 5' D was greater (P < 0.05) than synthesis from either PC 5' UTR C or E, and the abilities of UTR D, A, B, and F to drive protein translation were similar. The disproportionate contribution to protein synthesis of the PC 5' D UTR compared with UTR variant C or E indicates a complexity of control for PC enzyme synthesis in the bovine that is dependent on the profile of PC variants. These observations are consistent with differences in PC variant expression that have been observed in vivo and indicate that when PC mRNA is elevated, the pattern of variants directs an increase in PC activity through augmented PC enzyme synthesis.


Role of microRNAs in herpesvirus latency and persistence.
The identification of virally encoded microRNAs (miRNAs) has had a major impact on the field of herpes virology. Given their ability to target cellular and viral transcripts, and the lack of immune response to small RNAs, miRNAs represent an ideal mechanism of gene regulation during viral latency and persistence. In this review, we discuss the role of miRNAs in virus latency and persistence, specifically focusing on herpesviruses. We cover the current knowledge on miRNAs in establishing and maintaining virus latency and promoting survival of infected cells through targeting of both viral and cellular transcripts, highlighting key publications in the field. We also discuss potential areas of future research and how novel technologies may aid in determining how miRNAs shape virus latency in the context of herpesvirus infections.


Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.
Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan. The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA) strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE) strains, but not to TEN sequences. A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.


Carbodiimide and Isocyanate Hydroboration by a Cyclic Carbodiphosphorane Catalyst.
We report hydroboration of carbodiimide and isocyanate substrates catalyzed by a cyclic carbodiphosphorane catalyst. The cyclic carbodiphosphorane outperformed the other Lewis basic carbon species tested, including other zerovalent carbon compounds, phosphorus ylides, an N-heterocyclic carbene, and an N-heterocyclic olefin. Hydroborations of seven carbodiimides and nine isocyanates were performed at room temperature to form N-boryl formamidine and N-boryl formamide products. Intermolecular competition experiments demonstrated the selective hydroboration of alkyl isocyanates over carbodiimide and ketone substrates. DFT calculations support a proposed mechanism involving activation of pinacolborane by the carbodiphosphorane catalyst, followed by hydride transfer and B-N bond formation.


CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration.
Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochemistry analysis of clinical tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. In vitro loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth in vivo. In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients' prognosis and therapeutic target for developing more effective drug for GC treatment.


Non-Gaussian signatures from the postinflationary early universe.
We consider contributions to non-Gaussianity of the cosmic microwave background (CMB) from remnants of phase transitions in the very early Universe. Such signatures can optimistically be used to discover evidence of new particle physics through cosmological observations. More conservatively they may provide an obstacle to extracting information about the non-Gaussian nature of primordial density fluctuations from any detection in the CMB. We study this explicitly by computing the bispectrum from global textures, which occur in a wide class of particle physics models.


Determination of thyroxine, triiodothyronine, and cortisol changes during simultaneous adrenal and thyroid function tests in healthy dogs.
Changes in thyroxine (T4), triiodothyronine (T3), and cortisol during a combined adrenal (dexamethasone suppression/adrenocorticotrophic hormone response test) and thyroid function tests (thyroid-stimulating hormone [TSH] response test) were determined in 20 healthy hospitalized pet dogs. The effect of dexamethasone on T4 and T3 changes was evaluated during a simultaneous TSH response/dexamethasone suppression adrenocorticotrophic hormone response test. Greater ranges in basal cortisol concentrations and slower changes after dexamethasone was administered were observed in healthy pet dogs kenneled in a hospital setting than those reported for conditioned laboratory dogs. Pet dogs were observed to demonstrate cortisol suppression more reliably at 4 hours than at 2 hours after dexamethasone was administered. Dexamethasone had no effect on the response to TSH as assessed by T4 and T3 assays, thus supporting the validity of combining adrenal and thyroid response tests in a 5-hour period.


Quantifying the spatio-temporal drivers of planned vegetation restoration on ecosystem services at a regional scale.
Vegetation restoration often has a significant effect on the supply of an ecosystem service (ES). Assessment of this effect is crucial for informed decision-making in sustainable ecosystem management. In this respect, this study analyses three regulating, two provisioning, and a single cultural ES over a 30-year period (1985 to 2015, with 15 years pre-restoration and 15 years post-restoration) in the Loess Plateau, China, using data from a combination of modelling and statistical yearbooks. On applying a suite of standard statistical tools, results indicate: (1) regional scale restoration promotes the increase of vegetation cover as the coverage increased faster between 2000 and 2015 than between 1985 and 2000; (2) vegetation restoration changes the temporal trend of regulating ESs, and enhances the supply of provisioning and cultural ESs; (3) the 40 municipalities of the Loess Plateau can be divided into four ES categories where areas with poor ES delivery account for about 30% of the Loess Plateau; (4) vegetation restoration changes the interaction among ESs, resulting in synergistic relationships between provisioning and regulating ESs; (5) precipitation has a significant impact on regulating ESs, while population density is critical for provisioning and cultural ESs. This study demonstrates that ESs, their interactions and their groupings can change across both time and space following the implementation of a vegetation restoration programme, which makes understanding ES dynamics complicated. Recommendations are provided for improved and coherent ecosystem management.


BMP-7 loaded microspheres as a new delivery system for the cultivation of human chondrocytes in a collagen type-I gel.
In recent years, interest in chondrocyte cultures for transplantation has gained increasing attention. We investigated the use of PGLA microspheres as a new delivery system for BMP-7 and the effects on human chondrocytes cultivated in a 3D collagen gel culture. In an in vitro study, human chondrocytes obtained from osteoarthritic knee joints were released, transferred into a collagen type-I gel, and cultivated up to 14 days. In the treatment group PGLA microspheres loaded with human recombinant BMP-7 protein were added to the matrix. After the cultivation period, histological and immunohistochemical investigations were performed. In addition, the aggrecan core protein and type-II collagen mRNA concentrations were measured by real-time PCR. Histological staining for proteoglycan and collagen type-II protein and quantification via digital image processing revealed a significantly higher content in the samples cultivated with BMP-7 loaded microspheres in comparison to the control samples. Moreover, the collagen gel scaffold was partially remodeled by the chondrocytes and replaced by newly synthesized extracellular matrix. Cellular proliferation as well as apoptosis were low. In conclusion, we consider the PGLA microsphere system to be a functional device for the delivery of growth factors during the cultivation of articular chondrocytes leading to an increased content of type-II collagen and proteoglycan in the extracellular matrix.


Temporal analysis and stimulus fluctuation in listeners with normal and impaired hearing.
The first experiment investigated the effects of mild to moderate sensorineural hearing impairment on temporal analysis for noise stimuli of varying bandwidth. Tasks of temporal gap detection, amplitude modulation (AM) detection, and AM discrimination were examined. Relatively high levels of stimulation were used in order to reduce the possibility that the results of the listeners with hearing impairment would be influenced strongly by audibility. A general summary of results was that there was relatively great interlistener variation among the listeners with hearing impairment, with most listeners showing normal performance and some showing degraded performance, regardless of the bandwidth of the stimulus carrying the temporal information. A second experiment investigated the hypothesis that listeners with sensorineural hearing impairment might have poor gap detection due to loudness recruitment. Here, gap markers were presented at levels where loudness growth was steeper for the listeners with hearing impairment than for the listeners with normal hearing. Although gap detection was sometimes poorer in listeners with hearing impairment than in listeners with normal hearing, there was no clear relation between gap detection performance and loudness recruitment in listeners with mild to moderate sensorineural hearing impairment.


Alkene anti-Dihydroxylation with Malonoyl Peroxides.
Malonoyl peroxide 1, prepared in a single step from the commercially available diacid, is an effective reagent for the anti-dihydroxylation of alkenes. Reaction of 1 with an alkene in the presence of acetic acid at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (35-92%) with up to 13:1 anti-selectivity. A mechanism consistent with experimental findings is proposed that accounts for the selectivity observed.


Factors Associated With Impeding the Reintegration of Incest Survivors: A Qualitative Study in Selected Safe Homes in Nepal.
Incest is a globally prevalent phenomenon and is defined as sexual relations between closely related family members. Despite being a criminal offense irrespective to the gender and age incest is a prevalent issue in Nepal. Incest survivors are sheltered in safe homes for specific periods and reintegrated into their families following their healing. This research aims to explore the challenges and issues involved in the reintegration of incest survivors and investigate how the interconnected perceptions of families and individuals relate to the incest survivors' successful reintegration. This qualitative study was conducted in three districts of Nepal. Fourteen incest survivors, five service providers from safe homes, and 22 community members were purposefully and theoretically selected. Semi-structured interviews were carried out to collect the study data, which were subsequently coded and analyzed using a grounded theory approach. The results indicate the importance of the reintegration of incest survivors, as staying in a safe home may not offer a long-term solution for these individuals. However, reintegration is challenging without acceptance and support from the survivors' families and communities, the survivors' readiness to reintegrate, and agreement from the survivors' safe homes. Factors found to influence the unsuccessful reintegration of survivors included family fragmentation, socio-economic status, family resistance, the survivor-perpetrator relationship, survivors' interests, fears, and the possibility of repeated incidents, harmful social norms and cultural practices, community intervention, and negative perceptions. This study found that factors associated with impeding the reintegration of incest survivors are found in survivors, their families, and their communities. Creating harmonious family systems, providing education on gender equality, empowering women to fight against all sorts of abuse, and governmental assurances on the implementation of legal aid, human rights, ratified conventions on child rights and women's rights may help prevention of incest, and address the reintegration challenges of incest victims.


Body composition in Central Asia populations: Fat patterning variation in the Kazakhs of the Tien Shan mountains and the Uighurs of Semericia.
Eleven anthropometric variables related to fat patterning were analyzed in two populations of Central Asia, the Kazakhs of the Tien Shan mountains (2100 m) and the Uighurs of the Semericia plains. Subjects were healthy unrelated males, 122 Kazakhs and 79 Uighurs, 19-65 years. Comparisons were done with a preliminary analysis of variance and then by covariance analysis, taking into account the influence of age. The Uighurs, independently of age, show higher values than Kazakhs for all of the characteristics related to fat patterning, but principal components analysis suggests a similar somatic structure in the two samples. The presence of lower adiposity in the Kazakhs than in the Uighurs could be related to stress, probably associated with nutrition and lifestyle in a mountain environment. Am. J. Hum. Biol. 10:241-247, 1998. © 1998 Wiley-Liss, Inc.


[Predictive factors of the first digestive hemorrhage and death in cirrhotic patients with esophageal varices].
Predictive factors for the first digestive tract hemorrhage and for death in cirrhotic patients have been partially studied in prophylactic shunt trials and never prospectively according to multivariate analysis method. We prospectively followed 106 cirrhotic patients (88 p. 100 with alcohol abuse) with large esophageal varices without past history of bleeding during a mean period of 13.3 +/- 6.1 months. Of 23 clinical and biochemical variables recorded at entry as well as alcohol withdrawal evaluated during the course of the study, we looked for those which had independent prognostic value for the risks of bleeding and death according to a multiple regression analysis (Cox's model). At the end of the study, 30 patients had bled and 40 were dead. The cumulative one-year percentages of patients were 72 p. 100 free of bleeding and 65 p. 100 surviving (95 p. 100 confidence limits: 62 and 81, 54 and 73, respectively). The bleeding risk was positively correlated with variceal size, plasma creatinine and negatively correlated with age and mean arterial pressure. The bleeding risk varied according to variceal size: medium: 23 p. 100, large: 44 p. 100 (p less than 0.05). An increase in Child-Pugh score, plasma creatinine and mean corpuscular volume as well as hepatomegaly were independent predictive factors for death. The death rate was (according to Child-Pugh grade): A: 14 p. 100, B: 33 p. 100, C: 50 p. 100 (p less than 0.01). We conclude that bleeding risk is maximum in young patients with large varices and the death rate is dependent on severity of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)