Probiotics for treatment of chronic constipation in children.
Functional constipation is defined as chronic constipation with no identifiable underlying cause. It is a significant cause of morbidity in children, accounting for up to 25% of visits to paediatric gastroenterologists. Probiotic preparations may sufficiently alter the gut microbiome and promote normal gut physiology in a way that helps relieve functional constipation. Several studies have sought to address this hypothesis, as well as the role of probiotics in other functional gut disorders. Therefore, it is important to have a focused review to assess the evidence to date. To evaluate the efficacy and safety of probiotics for the management of chronic constipation without a physical explanation in children. On 28 June 2021, we searched CENTRAL, MEDLINE, Embase, CINAHL, AMED, WHO ICTR, and ClinicalTrials.gov, with no language, date, publication status, or document type limitations. We included randomised controlled trials (RCTs) that assessed probiotic preparations (including synbiotics) compared to placebo, no treatment or any other interventional preparation in people aged between 0 and 18 years old with a diagnosis of functional constipation according to consensus criteria (such as Rome IV). We used standard methodological procedures expected by Cochrane. We included 14 studies (1127 randomised participants): 12 studies assessed probiotics in the treatment of functional constipation, whilst two studies investigated synbiotic preparations. Three studies compared probiotics to placebo in relation to the frequency of defecation at study end, but we did not pool them as there was very significant unexplained heterogeneity. Four studies compared probiotics to placebo in relation to treatment success. There may be no difference in global improvement/treatment success (RR 1.29, 95% CI 0.73 to 2.26; 313 participants; low-certainty evidence). Five studies compared probiotics to placebo in relation to withdrawals due to adverse events, with the pooled effect suggesting there may be no difference (RR 0.64, 95% CI 0.21 to 1.95; 357 participants; low-certainty evidence). The pooled estimate from three studies that compared probiotics plus an osmotic laxative to osmotic laxative alone found there may be no difference in frequency of defecation (MD -0.01, 95% CI -0.57 to 0.56; 268 participants; low-certainty evidence). Two studies compared probiotics plus an osmotic laxative to osmotic laxative alone in relation to global improvement/treatment success, and found there may be no difference between the treatments (RR 0.95, 95% CI 0.79 to 1.15; 139 participants; low-certainty evidence). Three studies compared probiotics plus osmotic laxative to osmotic laxative alone in relation to withdrawals due to adverse events, but it is unclear if there is a difference between them (RR 2.86, 95% CI 0.12 to 68.35; 268 participants; very low-certainty evidence). Two studies compared probiotics versus magnesium oxide. It is unclear if there is a difference in frequency of defecation (MD 0.28, 95% CI -0.58 to 1.14; 36 participants), treatment success (RR 1.08, 95% CI 0.74 to 1.57; 36 participants) or withdrawals due to adverse events (RR 0.50, 95% CI 0.05 to 5.04; 77 participants). The certainty of the evidence is very low for these outcomes. One study assessed the role of a synbiotic preparation in comparison to placebo. There may be higher treatment success in favour of synbiotics compared to placebo (RR 2.32, 95% CI 1.54 to 3.47; 155 participants; low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study assessed a synbiotic plus paraffin compared to paraffin alone. It is uncertain if there is a difference in frequency of defecation (MD 0.74, 95% CI -0.96, 2.44; 66 participants; very low-certainty evidence), or treatment success (RR 0.91, 95% CI 0.71 to 1.17; 66 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study compared a synbiotic preparation to paraffin. It is uncertain if there is a difference in frequency of defecation (MD -1.53, 95% CI -3.00, -0.06; 60 participants; very low-certainty evidence) or in treatment success (RR 0.86, 95% CI 0.65, 1.13; 60 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. All secondary outcomes were either not reported or reported in a way that did not allow for analysis. There is insufficient evidence to conclude whether probiotics are efficacious in successfully treating chronic constipation without a physical explanation in children or changing the frequency of defecation, or whether there is a difference in withdrawals due to adverse events when compared with placebo. There is limited evidence from one study to suggest a synbiotic preparation may be more likely than placebo to lead to treatment success, with no difference in withdrawals due to adverse events. There is insufficient evidence to draw efficacy or safety conclusions about the use of probiotics in combination with or in comparison to any of the other interventions reported. The majority of the studies that presented data on serious adverse events reported that no events occurred. Two studies did not report this outcome. Future studies are needed to confirm efficacy, but the research community requires guidance on the best context for probiotics in such studies, considering where they should be best considered in a potential treatment hierarchy and should align with core outcome sets to support future interpretation of findings.


[Effect of environmental factors on fish community structure in the Huntai River Basin at multiple scales].
In June 2012, fishes was investigated at 65 sampling sites in the Huntai River basin in Northeast of China. Forty species were collected, belonging to 9 orders, 14 families,33 genera. Cobitidae and Cyprinidae were the dominant fishes in the community structure in the Huntai River basin, accounting for 13. 21% and 65. 83% of the fish community, respectively. There were two types of spatial distribution of fish community, one was distributed in the head water and tributaries in the upstream, and the other was in the plain rivers. Nemachilus nudus, Cobitis granoei and Phoxinus lagowskii dominated the local community in the upper reaches of the Dahuofang Reservoir and shenwo River, while Carassius ayratus and Hemiculter leucisculdus dominated the local community in the plain rivers. CCA (canonical correspondence analysis) was used to distinguish the primary environmental variables that affected the fish community structure. The results indicated fish community was mainly affected by environment factors at watershed and reach scales. Proportions of woodland and urban land, and altitude were three important environmental factors affecting the fish community at the watershed scale. Dissolved oxygen, total nitrogen, pH and habitat inhomogeneity significantly affected the fish community at the reach scale, whereas substrate didn't show significant influence at the microhabitat scale. Environmental factors at watershed scale explained 7. 66% of the variation of fish community structure, environmental factors at reach scale explained 10. 57% of the variation of fish community structure. Environmental factors at reach scale influenced the fish community more significantly.


Early Response Time in Sexual Activity and Mood Following Testosterone Gel Replacement in Hypogonadal Males from the Testim(R) START Study.
Sexual activity, sexual desire, and mood decrease in men with low testosterone levels. The Testim(R) Study of Testosterone Androgen Response Time (START) explored the time to response in sexual activity, desire, and mood following testosterone replacement therapy with Testim for 30 days in 638 hypogonadal men. Response in sexual activity, desire, and mood all improved relative to baseline within the first week of Testim therapy. Patients reached a maximal response by the end of 2 weeks of therapy and maintained the response through 4 weeks of therapy. Frequency of intercourse showed a significant increase after 2 weeks of Testim therapy. Both measures of positive mood and negative mood improved significantly, beginning with the first week of therapy and reaching and maintaining a maximal response at the second week.


Anti-NMDA Encephalitis in the Acute Setting.
Encephalitis associated with antibodies targeted against the N-methyl-D-aspartate (NMDA) receptor is increasingly recognised as a major cause of an acute presentation of organic psychosis. Misdiagnosis and subsequent inappropriate referral to psychiatric services is common and avoidable. This review focuses on addressing this issue in the acute setting. The authors present a review of existing literature relating to the pathophysiology and presentation of anti-NMDA receptor encephalitis, prior to proposing a management pathway avoiding delays to treatment incurred through misdiagnosis or inappropriate referral. Acute care physicians should have a low threshold for suspecting anti-NMDA receptor encephalitis in any patient presenting with acute psychosis in the context of non-specific coryzal and constitutional symptoms in whom infective causes have been excluded. The presence of pleocytosis and reduced protein in routine CSF analysis should further raise suspicion, and samples should be sent for immunohistochemical testing. Availability and efficiency of this testing is currently suboptimal.


[On compulsive hand-washing--psychopathology of "touching"].
Compulsive hand-washing has been well known to the psychiatrists, since Legrand du Saulle described this disorder by the name of "délire du toucher" (1866), which refers to mysophobia or contact-phobia. But its clinical significance seems to have been not fully examined, except from the psychoanalytical point of view, that has observed the repression of sexuality in its pathology. This report presents four cases of compulsive hand-washing, and explores why they exclusively wash their hands. In order to elucidate the reason for their hand-washing and its significance, this report aims to study the relation of following three elements; "Sexuality", "hand" and "touching". As the idioms using "hand" often represent the various modes of sexual life in Japanese language as well as in English, so the "touching by hand" is reasonably considered to evoke the sexual impulsions, which the hand-washers fear and wish to avoid. On the other hand, "touching" is, necessarily in nature, to be touched by the touched object. For example, one who touches the lover's hand is inevitably to be touched by hers. That is; one is forced to be an object of one's object, which becomes to be a subject. In this sense, the act of "touching" means to lose one's "being subject" and to melt oneself into the situation where the structural distinction of subject and object can disappear. So one's act of "touching" or vivid contact with the other can cause anxiety by means of losing one's ego, which may be also a critical point to introduce to create something new. A compulsive hand-washer fears and avoids this critical moment that can make him lose his "being subject", so he "washes his hands of (cuts off relation with)" the situation that can undermine his ego. This avoidance of having contact can be compared to "the lose of vivid contact with the reality (la perte du contact avec la réalité (Minkowski)" observed in schizophrenia. In their ways of life, many hand-washers are not less autistic than the schizophrenics.om


Genetics of resistance to mastitis in dairy cattle.
Genetic variability of mastitis resistance is well established in dairy cattle. Many studies focused on polygenic variation of the trait, by estimating heritabilities and genetic correlation among phenotypic traits related to mastitis such as somatic cell counts and clinical cases. The role of Major Histocompatibility Complex in the susceptibility or resistance to intrammamary infection is also well documented. Finally, development from molecular genome mapping led to accumulating information of quantitative trait loci (QTL) related to mastitis resistance and better understanding of the genetic determinism of the trait. From economic and genetic analyses, and according to welfare and food safety considerations and to breeders and consumer's concern, there is more and more evidence that mastitis should be included in breeding objective of dairy cattle breeds. Many countries have implemented selection for mastitis resistance based on linear decrease of somatic cell counts. Given biological questioning, potential unfavourable consequences for very low cell counts cows are regularly investigated. Improvement of selection accuracy for mastitis resistance is ongoing and includes: advances in modelling, optimal combination of mastitis related traits and associated predictors, such as udder morphology, definition of global breeding objective including production and functional traits, and inclusion of molecular information that is now available from QTL experiments.


Parenting stress, self-efficacy and COVID-19 health risks as predictors of general stress among nurses.
The purpose of the study was to examine the influence of parenting stress, self-efficacy and COVID-19 health risks on general stress among nurses in the Midwest, United States, during the pandemic. As frontline workers amidst the coronavirus disease 2019 (COVID-19) pandemic, nurses have been subject to stressors at home and at work. This quantitative, cross-sectional study included 896 nurses with at least one child below 18 years of age. Using purposive sampling, participants answered an online survey composed of demographic questions, perception of COVID-19 health risks, measures of self-efficacy, general stress and parenting stress. Bivariate correlation and multiple regression were conducted. Data were collected from July 13 to August 13, 2020. The four predictors, along with eight demographic covariates, accounted for 40% of the variance in general stress. Parenting stress and COVID-19 health risks were positively related to general stress, while self-efficacy was negatively associated with general stress. Results highlight the negative influence of parenting stress on nurses' general stress and the importance of self-efficacy in reducing stress. Findings suggest that support services for nurses should focus not only on work-related stressors but also consider parenting stressors, work-home imbalances and self-efficacy.


Demystifying and addressing internalized racism and oppression among Asian Americans.
Asian Americans (AAs) are a diverse group who come from many different cultures, backgrounds, immigration histories, geographic regions, and experiences. Unfortunately, AAs are commonly stereotyped as a model minority, used as an intermediary minority, and consequently have been marginalized and left out of dialogues of racism and discrimination. Internalized racism (IR), defined as the internalization of bias and oppression toward one's group, is an especially insidious form of divisive racism that remains largely misunderstood and unaddressed in AAs. In addition to devaluing oneself, IR creates division in communities and reinforces systems of oppression. This paper reviews the extant literature on IR among AAs and discusses the importance of addressing this deleterious issue and its consequences on individual, family, and community mental health. Moreover, I discuss and elucidate how stereotypes about AAs (e.g., model minority, perpetual foreigner, gendered stereotypes, and conceptions of beauty) directly promote and reinforce different types of internalized oppression (e.g., intraracial hierarchies, intraethnic othering, gendered emasculation, and hypersexualization, colorism and Western standards of beauty). Clinical and community recommendations are provided through a multilevel preventive intervention framework. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Chemotaxis-driven stationary and oscillatory patterns in a diffusive HIV-1 model with CTL immune response and general sensitivity.
In this paper, a reaction-diffusion-chemotaxis HIV-1 model with a cytotoxic T lymphocyte (CTL) immune response and general sensitivity is investigated. We first prove the global classical solvability and L∞-boundedness for the considered model in a bounded domain with arbitrary spatial dimensions, which extends the previous existing results. Then, we apply the global existence result to the case with a linear proliferation immune response and an incidence rate. We study the spatiotemporal dynamics about the three types of spatially homogeneous steady states: infection-free steady state S0, CTL-inactivated infection steady state S1, and CTL-activated infection steady state S∗. Our analyses indicate that S0 is globally asymptotically stable if the basic reproduction number R0 is less than 1; if R0 is between 1 and a threshold, then S1 is globally asymptotically stable. However, if R0 is larger than the threshold, then the chemoattraction and chemorepulsion can destabilize S∗, and thus, a spatiotemporal pattern forms as the chemotactic sensitivity crosses certain critical values. We obtain two kinds of important patterns, which are induced by chemotaxis: stationary Turing pattern and irregular oscillatory pattern. We also find that different chemotactic response functions can affect system's dynamics. Based on some empirical parameter values, numerical simulations are given to illustrate the effectiveness of the theoretical predications.


HPV mRNA is more specific than HPV DNA in triage of women with minor cervical lesions.
In Norway, repeat cytology and HPV testing comprise delayed triage of women with minor cytological lesions. The objective of this study was to evaluate HPV DNA and HPV mRNA testing in triage of women with an ASC-US/LSIL diagnosis. We used repeat cytology, HPV DNA testing (Cobas 4800) and HPV mRNA testing (PreTect HPV-Proofer) to follow up 311 women aged 25-69 years with ASC-US/LSIL index cytology. Of 311 women scheduled for secondary screening, 30 women (9.6%) had ASC-H/HSIL cytology at triage and 281 women (90.4%) had ASC-US/LSIL or normal cytology. The HPV DNA test was positive in 92 (32.7%) of 281 instances, and 37 (13.2%) were mRNA positive. Of the 132 women with repeated ASC-US/LSIL, we received biopsies from 97.0% (65/67) of the DNA-positive and 92.9% (26/28) of the mRNA-positive cases. The positive predictive values for CIN2+ were 21.5% (14/65) for DNA positive and 34.6% (9/26) for mRNA positive (ns). The odds ratio for being referred to colposcopy in DNA-positive cases were 2.8 times (95% CI: 1.8-4.6) higher that of mRNA-positive cases. Compared to the mRNA test, the DNA test detected four more cases of CIN2 and one case of CIN3. The higher positivity rate of the DNA test in triage leads to higher referral rate for colposcopy and biopsy, and subsequent additional follow-up of negative biopsies. By following mRNA-negative women who had ASC-US/LSIL at triage with cytology, the additional cases of CIN2+ gained in DNA screening can be discovered. Our study indicates that in triage of repeated ASC-US/LSIL, HPV mRNA testing is more specific and is more relevant in clinical use than an HPV DNA test.


Sidestream capnographic monitoring reduces the incidence of arterial oxygen desaturation during propofol ambulatory anesthesia for surgical abortion.
This study investigated whether early intervention based on additional use of sidestream capnography could reduce the incidence of oxygen desaturation and hypoxic events in patients receiving propofol anesthesia during surgical abortion. We recruited 704 ASAI-III female patients, 18-52 years old and scheduled for planned painless surgical abortion, and randomized them into a control group (n=359) receiving standard monitoring and an experimental group (n=341) receiving standard monitoring and additional capnography. Exclusion criteria were preexisting cardiovascular disease, preexisting hypotension, bradycardia or arrhythmia, and drug allergy. Anesthesia was induced in all patients with propofol using target-controlled infusion at a target propofol plasma concentration of 4 μg/ml. All patients received flurbiprofen axetil 50 mg and 0.5 μg/kg fentanyl 5 min before anesthesia. Bispectral index was used and maintained between 45 and 60. Main outcome measures were apnea or abnormal ventilation status, rate of oxygen desaturation, occurrence of hypoxia and severe hypoxia, and perioperative side effects. The experimental group had significantly higher rate of apnea or abnormal ventilation, significantly lower rate of oxygen desaturation, and significant lower occurrence of hypoxia and severe hypoxia compared to the control group. We found no statistically significant differences between the 2 groups in the rates of increased oxygen supplementation, assisted ventilation, bradycardia, hypotension, dosage of atropine, dosage of ephedrine or phenylephrine, and the amount of propofol consumed. Sidestream capnographic monitoring improves early detection of alterations in ventilation parameters and reduces the incidence of oxygen desaturation and hypoxemia resulting from propofol anesthesia during surgical abortion.


Evidence for methionine-sulfoxide-reductase gene transfer from Alphaproteobacteria to the transcriptionally active (macro)nucleus of the ciliate, Euplotes raikovi.
Deleterious phenomena of protein oxidation affect every aerobic organism and methionine residues are their elective targets. The reduction of methionine sulfoxides back to methionines is catalyzed by methionine-sulfoxide reductases (Msrs), enzymes which are particularly active in microorganisms because of their unique nature of individual cells directly exposed to environmental oxidation. From the transcriptionally active somatic genome of a common free-living marine protist ciliate, Euplotes raikovi, we cloned multiple gene isoforms encoding Msr of type A (MsrA) committed to repair methionine-S-sulfoxides. One of these isoforms, in addition to including a MsrA-specific nucleotide sequence, included also a sequence specific for a Msr of type B (MsrB) committed to repair methionine-R-sulfoxides. Analyzed for its structural relationships with MsrA and MsrB coding sequences of other organisms, the coding region of this gene (named msrAB) showed much more significant relationships with Msr gene coding sequences of Rhodobacterales and Rhizobiales (Alphaproteobacteria), than of other eukaryotic organisms. Based on the fact that the msrAB gene is delimited by Euplotes-specific regulatory 5' and 3' regions and telomeric C4A4/G4T4 repeats, it was concluded that E. raikovi inherited the coding region of this gene through a phenomenon of horizontal gene transfer from species of Alphaproteobacteria with which it coexists in nature and on which it likely feeds.


Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.
Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes.


Current advances and trends in the treatment of depression.
The pathophysiology of major affective illness is poorly understood. However, several lines of preclinical and clinical evidence indicate that an enhancement of 5-HT-mediated neurotransmission might underlie the therapeutic effect of most antidepressant treatments. This net effect would, however, be obtained via different mechanisms. A better understanding of the neurobiological basis for the delayed onset of action of antidepressant treatments has led to the elaboration of strategies that could accelerate the antidepressant response. These strategies are discussed in this article by Pierre Blier and Claude de Montigny.


Rapid cold hardening in young hoppers of the migratory locust Locusta migratoria L. (Orthoptera: Acridiidae).
This paper describes a rapid cold hardening process for first instar hoppers of the migratory locust Locusta migratoria L. First instar hoppers of this species are often subjected to subzero temperatures or frosts in early April or May after their emergence from the soil. The mean supercooling point of hoppers is -13.0 +/- 1.4 degrees C; the fact that none could survive this temperature suggests they are freezing intolerant. When young hoppers were transferred directly from 30 degrees C to -7 degrees C for 2 h, there was only 35.8% survival. However, exposure to 0 degrees C for 2 h prior to transfer to -7 degrees C increased the apparent survival to 75%. A similar rapid cold hardening response can also be induced by gradual cooling at rates of between 0.05 and 0.1 degreess C min(-1). Rapid cold hardening also elevates the Ltime50 of first instar hoppers at -7 degrees C by approximately 3 fold, and reduces the lethal temperature from -10 degrees C to -12 degrees C. However, the protection from cold shock gained through rapid cold hardening was transient and easily lost within 2 h of hoppers being returned to 30 degrees C. The rapid cold hardening response is possibly advantageous to first instar hoppers that are often exposed to large temperature fluctuations in spring or early summer.


Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review.
DNA samples collected as part of a large population-based case-control study were genotyped to examine the associations of five prothrombotic gene polymorphisms with pre-eclampsia (PE) and gestational hypertension (GH). The polymorphisms studied were: G1691A in Factor V (Factor V Leiden; FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, plasminogen activator inhibitor-1 4G/5G and the platelet collagen receptor alpha2beta1 C807T. A group of 404 women who developed PE were retrospectively compared with 303 women with GH and 164 control women. The frequency of genotypes did not differ significantly between cases of PE or GH and controls for any of the five polymorphisms studied. We conclude that these prothrombotic genotypes are not associated with the development of PE or GH in our population. The systematic review supports our conclusion, for all but cases of severe disease. which appear to be associated with FVL and, to a lesser extent, MTHFR C677T. There is little value in antenatal screening for prothrombotic polymorphisms to predict the development of pre-eclampsia or gestational hypertension.


miR-455-5p downregulation promotes inflammation pathways in the relapse phase of relapsing-remitting multiple sclerosis disease.
MicroRNA-455-5p (miR-455-5p) seems to have an anti-inflammatory role in the immune system since its expression is induced by IL-10 cytokine. Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the central nervous system that is caused by an autoimmune inflammatory attack against the myelin insulation of neurons. The expression level of miR-455-5p and its role in MS pathogenesis has yet to be elucidated. We found that miR-455-5p expression was highly correlated with disease severity in MS patients. miR-455-5p expression inversely correlates with its inflammatory-predicted targets (MyD88 and REL) in relapse- and remitting-phase patients. Luciferase assays confirm that MyD88 and REL are direct targets of miR-455-5p. This study represents the first report of the miR-455-5p acts as an anti-inflammatory role in MS, at least partially through targeting MyD88 and REL. This study may provide important information for the use of miR-455-5p as a novel strategy to improve the severity of disease and control inflammation and attack in MS patients.


Pan vs. Selective Computed Tomography Scans in Management of Multiple Trauma Patients; a Brief Report.
Using pan or selective computed tomography (CT) scan in management of multiple trauma patient is a matter of debate. Therefore, the present study was designed aiming to compare the findings of pan and selective CT scans in management of multiple trauma patients. This is a prospective cross-sectional study, on patients presented to the emergency department (ED) of Shohadaye Haftome Tir Hospital, Tehran, Iran, following blunt multiple trauma over a 1-year period, from March 2014 to March 2015. Findings regarding presence or absence of injury in head, face, neck, chest, abdomen and hip were compared between patients that underwent pan and selective CT using SPSS 21. 443 patients with the mean age of 34.54 ± 17.88 years were evaluated (78% male). 248 (56%) patients underwent selective CT scan and 195 (44%) underwent pan CT scan. The 2 groups were similar regarding vital signs and mean age. Mean hospital length of stay was 21.05 ± 24.64 days for selective CT scan group and 18.18 ± 22.75 days for the other one (p = 0.209). A significant difference was only seen regarding findings of chest injury between the 2 groups (p < 0.001). In other cases a proper overlap was seen between findings of the 2 groups. Based on the results of the present study, it seems that doing selective CT scan yields results similar to pan CT in detection of head and face, neck and abdomen and hip injuries in multiple trauma patients. However, using pan CT in these patients led to 16% increase in detection and diagnosis of traumatic intra-thoracic injuries.


Antibiotic and anti-inflammatory therapies for cystic fibrosis.
Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed.


[High dose intravenous immunoglobulins in therapeutic arsenal in autoimmune and systemic diseases].
Immune globulin are extracted from plasma pooled from 1000 or more donors. Each lot should contain at least 90% of intact IgG. Intravenous immune globulin are recommended unequivocally for some diseases: acute autoimmune thrombocytopenic purpura of childhood, autoimmune erythroblastopenia, haemophilia with anti-VIII antibodies, Kawasaki's syndrome, and perhaps, Guillain-Barré syndrome. Nevertheless, this therapy has been reported to be beneficial for more than 35 diseases thought to be produced by immunopathology. Large amounts of immune globulin, such as 400 to 2000 mg/kg are proposed over a period of two to five days. The safety of this treatment, which may be introduced without any special structure, is a very interesting quality of the intravenous immune globulin therapy. However, comparative efficacy against reference therapy, surveillance for long-term positive and adverse effects and cost-effectiveness should be carried out.


Functional isocyanide metal complexes as building blocks for supramolecular materials: hydrogen-bonded liquid crystals.
Gold, palladium and platinum complexes with an unusual isocyanide ligand containing a carboxylic acid function, [AuCl(CNC(6)H(4)COOH)], cis-[MI(2)(CNC(6)H(4)COOH)(2)] and trans-[MI(2)(CNC(6)H(4)COOH)(2)] (M = Pd, Pt) have been isolated. The carboxylic acid group of the coordinated isocyanide acts as a hydrogen donor for hydrogen-bonding and three series of stable hydrogen-bonded liquid crystalline metal complexes have been prepared with decyloxystilbazole. Although all the metal acid derivatives used are not mesomorphic, and decyloxystilbazole only shows an ordered Smectic E phase, four out of the five hydrogen-bonded decyloxystilbazole complexes studied display enantiotropic smectic A or nematic mesophases. The single crystal X-ray diffraction structure of trans-[PdI(2)(CNC(6)H(4)COOH)(2)].C(4)H(8)O(2) has been determined and confirms the formation of a supramolecular array in the solid state supported by hydrogen-bonding.


Multilevel Obstructive Sleep Apnea Surgery.
Continuous positive airway pressure (CPAP) is the primary treatment of obstructive sleep apnea/hypopnea syndrome (OSA). Most sleep physicians are in agreement that a certain number of OSA patients cannot or will not use CPAP. Although other conservative therapies, such as oral appliance, sleep hygiene, and sleep positioning, may help some of these patients, there are many who fail all conservative treatments. As sleep surgeons, we have the responsibility to screen patients for both symptoms and signs of OSA. As experts of upper airway diseases, we often view an airway clearly and help the patient understand the importance of assessment and treatment for OSA. Surgery for OSA is not a substitute for CPAP but is a salvage treatment for those who failed CPAP and other conservative therapies and therefore have no other options. Most early studies and reviews focused on the efficacy of uvulopalatopharyngoplasty, a single-level procedure for the treatment of OSA. Since OSA is usually caused by multilevel obstructions, the true focus on efficacy should be on multilevel surgical intervention. The purpose here is to provide an updated overview of multilevel surgery for OSA patients.


Isolation of non-tuberculous mycobacteria in children investigated for pulmonary tuberculosis.
To evaluate the frequency and clinical significance of non-tuberculous mycobacteria (NTM) isolates among children investigated for pulmonary tuberculosis in a rural South African community. Children were investigated for pulmonary tuberculosis as part of a tuberculosis vaccine surveillance program (2001-2005). The clinical features of children in whom NTM were isolated, from induced sputum or gastric lavage, were compared to those with culture-proven M. tuberculosis. Mycobacterial culture demonstrated 114 NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6% (95% CI 5-7). The comparative yield of positive NTM cultures from gastric lavage was 40% (95% CI 31-50), compared to 67% (95% CI 58-76) from induced sputum. 95% of children with NTM isolates were symptomatic. Two children were HIV-infected. By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11% (95% CI 9-12). Compared to those with culture-proven M. tuberculosis, children with NTM isolates were less likely to demonstrate acid-fast bacilli on direct smear microscopy (OR 0.19; 95% 0.0-0.76). Children with NTM were older (p<0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001), including fever (p = 0.003) and loss of weight or failure to gain weight (p = 0.04), but less likely to demonstrate a strongly positive tuberculin skin test (p<0.0001) or radiological features consistent with pulmonary tuberculosis (p = 0.04). NTM were isolated in 6% of all children investigated for pulmonary tuberculosis and in more than one third of those with a positive mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that lack capacity for mycobacterial species identification. The association of NTM isolates with constitutional symptoms suggestive of host recognition requires further investigation.


External rotation immobilization for primary shoulder dislocation: a randomized controlled trial.
The traditional treatment for primary anterior shoulder dislocations has been immobilization in a sling with the arm in a position of adduction and internal rotation. However, recent basic science and clinical data have suggested recurrent instability may be reduced with immobilization in external rotation after primary shoulder dislocation. We performed a randomized controlled trial to compare the (1) frequency of recurrent instability and (2) disease-specific quality-of-life scores after treatment of first-time shoulder dislocation using either immobilization in external rotation or immobilization in internal rotation in a group of young patients. Sixty patients younger than 35 years of age with primary, traumatic, anterior shoulder dislocations were randomized (concealed, computer-generated) to immobilization with either an internal rotation sling (n = 29) or an external rotation brace (n = 31) at a mean of 4 days after closed reduction (range, 1-7 days). Patients with large bony lesions or polytrauma were excluded. The two groups were similar at baseline. Both groups were immobilized for 4 weeks with identical therapy protocols thereafter. Blinded assessments were completed by independent observers for a minimum of 12 months (mean, 25 months; range, 12-43 months). Recurrent instability was defined as a second documented anterior dislocation or multiple episodes of shoulder subluxation severe enough for the patient to request surgical stabilization. Validated disease-specific quality-of-life data (Western Ontario Shoulder Instability index [WOSI], American Shoulder and Elbow Surgeons evaluation [ASES]) were also collected. Ten patients (17%, five from each group) were lost to followup. Reported compliance with immobilization in both groups was excellent (80%). With the numbers available, there was no difference in the rate of recurrent instability between groups: 10 of 27 patients (37%) with the external rotation brace versus 10 of 25 patients (40%) with the sling redislocated or developed symptomatic recurrent instability (p = 0.41). WOSI scores were not different between groups (p = 0.74) and, although the difference in ASES scores approached statistical significance (p = 0.05), the magnitude of this difference was small and of uncertain clinical importance. Despite previous published findings, our results show immobilization in external rotation did not confer a significant benefit versus sling immobilization in the prevention of recurrent instability after primary anterior shoulder dislocation. Further studies with larger numbers may elucidate whether functional outcomes, compliance, or comfort with immobilization can be improved with this device. Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.


Polymorphisms in nucleotide excision repair genes and endometrial cancer risk.
Exposure to estrogens increases the risk of endometrial cancer. Certain estrogen metabolites can form bulky DNA adducts, which are removed via nucleotide excision repair (NER), and the ability to carry out this repair might be related to endometrial cancer risk. We examined 64 tag and functional single-nucleotide polymorphisms (SNPs) in the NER genes ERCC1, ERCC2 (XPD), ERCC3 (XPB), ERCC4 (XPF), ERCC5 (XPG), LIG1, XPA, and XPC in a population-based case-control study in Washington state, with 783 endometrial cancer cases and 795 controls. The presence of ERCC5 rs4150386 C, LIG1 rs3730865 C, XPA rs2808667 T, or XPC rs3731127 T alleles was associated with risk of endometrial cancer, with respective age-, county-, and reference year-adjusted per-allele ORs and 95% CIs of 0.68 (0.53-0.87, P = 0.002), 1.46 (1.02-2.10, P = 0.04), 0.71 (0.52-0.97, P = 0.03), and 1.57 (1.13-2.17, P = 0.007), respectively. Certain ERCC5, LIG1, XPA, and XPC genotypes might influence endometrial cancer risk. Because of multiple redundancies in DNA repair pathways (and therefore a low prior probability) and the large number of associations examined, false-positive findings are likely. Further characterization of the relation between variation in NER genes and endometrial cancer risk is warranted.


Hypertension study in anaesthetized rabbits: protocol proposal for AT1 antagonists screening.
The aim of this study was to establish an optimized fast and safe protocol for the pharmacological screening of AT(1) antagonists. The pharmaceutical prototype AT(1) antagonist losartan, its active metabolite EXP3174 and the synthetic compound MMK1 were analysed in order to validate the protocol. Ang II was continuously infused while the animals received the drugs in two procedures. In the post-treatment procedure drugs were administered either in a single bolus dose or in a sequential manner. When losartan was administered in a single bolus dose, efficacy was evident until the 7th min (p=0.012) whilst EXP3174 infusion extended the efficiency up to the end of the study (p=0.006). In addition, the sequential injections of losartan prolonged the inhibitory time interval until the end of the study (p=0.045). In the pre-treatment procedure, results suggested a dose-dependent inhibitory effect for both antagonists. The pressor response to Ang II was unchanged after MMK1 administration either in the post- or in the pre-treatment mode. The proposed protocol appears to be safe, simple and fast for the pharmacological screening of AT(1) antagonists and enables the evaluation of new antagonists using lower doses than any other reported in the literature.


Enhancement of interleukin-2 production in human lymphocytes by two new quinolone derivatives.
The effect of two quinolone derivatives, ciprofloxacin and ofloxacin, on the production of interleukin-2 (IL-2) was studied in human peripheral blood lymphocytes (PBL) and in a T-cell leukemia cell line (Jurkat) following phytohemagglutinin (PHA) stimulation. Both antimicrobial agents markedly increased IL-2 production in PHA-stimulated PBL cultures. No such effect was observed without PHA stimulation. The effect of the two quinolones on IL-2 production was both time and concentration dependent, reaching a 3-5 fold increase at a drug concentration of 50-100 micrograms/ml, following 24 h incubation. IL-2 synthesized in response to ciprofloxacin or ofloxacin stimulation, exhibited identical chromatographic properties and molecular weight to IL-2 synthesized at standard IL-2 inducing conditions. Only ciprofloxacin enhanced IL-2 production in PHA or in PHA and phorbol myristic acetate (PMA)-stimulated Jurkat cells. The stimulatory effect observed in Jurkat cells at optimal dose concentration (10-50 micrograms/ml), was at most 50% above control levels. In contrast to the effect of ciprofloxacin as a costimulator of IL-2 production in PHA-stimulated PBL, the drug excerted a prominent inhibitory effect on the incorporation of radioactive thymidine and amino acids into these cells. Ciprofloxacin, but not ofloxacin, enhanced interferon (IFN) production in PHA-induced PBL, whereas immunoglobulin M [IgM] production in a SKW6 cell line was enhanced only by ofloxacin.


Concordance of metabolic enzyme genotypes assayed from paraffin-embedded, formalin-fixed breast tumors and normal lymphatic tissue.
Translational epidemiology studies often use archived tumor specimens to evaluate genetic hypotheses involving cancer outcomes. When the exposure of interest is a germline polymorphism, a key concern is whether the genotype assayed from tumor-derived DNA is representative of the germline. We evaluated the concordance between breast tumor-derived and normal lymph node-derived genotypes for three polymorphic tamoxifen-metabolizing enzymes. We assayed paired DNA samples extracted from archived tumor and normal lymph node tissues from 106 breast cancer patients. We used TaqMan assays to determine the genotypes of three enzyme variants hypothesized to modify tamoxifen effectiveness, ie, CYP2D6*4, UGT2B15*2, and UGT1A8*2. We assessed genotype agreement between the two DNA sources by calculating the percent agreement and the weighted kappa statistic. We successfully obtained genotypes for CYP2D6*4, UGT2B15*2, and UGT1A8*2 in 99%, 100%, and 84% of the paired samples, respectively. Genotype concordance was perfect for the CYP2D6*4 and UGT1A8*2 variants (weighted kappa for both = 1.00; 95% confidence interval [CI] 1.00, 1.00). For UGT2B15*2, one pair out of 106 gave a discordant result that persisted over several assay repeats. We observed strong agreement between DNA from breast tumors and normal lymphatic tissue in the genotyping of polymorphisms in three tamoxifen-metabolizing enzymes. Genotyping DNA extracted from tumor tissue avoids the time-consuming practice of microdissecting adjacent normal tissue when other normal tissue sources are not available. Therefore, the demonstrated reliability of tumor-derived DNA allows resources to be spent instead on increasing sample size or the number of polymorphisms examined.


Two Cases of Adverse Reactions of Hyaluronic Acid-based Filler Injections.
Hyaluronic acid (HA) is one of the natural components of the human body with high biocompatibility, biodegradability, and nonimmunogenicity, which makes it the ideal biomedical filling agent currently available. However, for many medical practitioners, HA filler injections remain a relatively new item to carry out. Learning while practicing, it is inevitable to encounter some difficulties and adverse reactions in its application. Here we report two cases of adverse reactions to HA-based filler injections, including anaphylactic reaction on the face and vascular thrombosis after augmentation rhinoplasty with HA filler. In this report, we highlight the management and prevention of the adverse reactions, especially in case 2, because vascular thrombosis is one of the severe complications and injectors should know how to avoid it and how to deal with it, thereby increasing the safety of HA-based procedures.


[A man with consolidation of the right lung].
A 68-year-old man, who had been exposed to asbestos in the past, presented with pleural effusion and right lower lobe consolidation due to rounded atelectasis.


Fructosamine levels in CAPD: its value as glycemic index.
We have studied fructosamine (measured by colorimetric methods) and glycosylated hemoglobin (HbA1c) using a high pressure liquid chromatography (HPLC) in 20 uremic patients managed conservatively (8 diabetics and 12 non-diabetics) and 20 patients treated with continuous ambulatory peritoneal dialysis (CAPD) including 12 diabetics and 8 non-diabetics. Twenty healthy subjects were used as control group. We have correlated the mean blood glucose (MBG) of the preceding days to fructosamine and HbA1c measurements. No differences were detected in mean fructosamine and HbA1c levels in non-diabetics patients in the CAPD or conservatively treated groups compared to controls. In diabetic patients undergoing conservative treatment or CAPD, mean fructosamine and HbA1c values were elevated when compared with control group. Both glycemic indicators were increased in most of the diabetic patients, was higher values in those patients with higher MBG. There was a good correlation in CAPD diabetic patients between fructosamine and HbA1c with MBG of the 21 previous days (r = 0.84, p less than 0.01 and r = 0.74, p less than 0.01 respectively). There was also correlation between fructosamine and HbA1c in CAPD diabetic patients (r = 0.78, p less than 0.01). We conclude that fructosamine does not seem to be influenced by uremia or by CAPD. Fructosamine and also glycosylated hemoglobin, when c-fraction is measured and HPLC method is used, can be utilized as glycemic indexes in CAPD diabetic patients.


In vivo and in vitro availability of commercial vitamin C tablets.
In vitro release of vitamin C from commercial tablets of three different manufacturers was measured by the Levy beaker, a modified USP basket and Magnetic Basket techniques and this was correlated with urinary excretion of the drug from normal, healthy, human males of 23 to 25 years of age weighing 50-72 Kg. Results showed that there was dissolution variability between the different brands of vitamin C tablets as well as between the in vitro dissolution methods used. There was also an inverse correlation between the time of in vitro release and the percent vitamin C excreted at the end of 2 hours. However, at the end of 24 hours the most rapidly dissolving tablets in vitro indicated only 66 percent excretion of the vitamin C as compared with nearly 83 percent for the slow dissolving types. It is concluded that to determine the total drug from a particular formulation, only disintegration and/or dissolution is not a good measure for an unstable and relatively rapid dissolving substance such as vitamin C. It is further suggested that perhaps if unstable rapid-dissolving substances were made more slowly released by formulation, a greater quantity of the drug would be physiologically avaiable.


Resolution of cultural and biological inheritance by path analysis.
Analysis of family resemblance is developed in terms of three genetic parameters, six parameters for cultural inheritance, and one parameter for an index estimating family environment. With efficient use of nuclear families the model is fully determinate. Other biological and social relationship provide additional degrees of freedom for testing goodness of fit. Performance of the model is satisfactory on simulated data with extreme gene-environment interaction. Applied to a large body of published data on I.Q., neither genetic assortative mating nor gene-environment covariance is significant by a likelihood ratio test, but heritability is less and cultural inheritance is greater for adults than children. Whereas family resemblance of children is largely genetic, for adults it is largely due to their childhood environments, presumably acting on occupational aspirations. Further resolution is more likely to come from nuclear families than from the rare relationships that were favored by classical human genetics.


Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome.
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut-brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.


[Carriage of A Allele of Polymorphic Marker G(-238)A of TNF-alfa Gene Is Associated With Unfavorable Prognosis in Patients With Chronic Systolic Heart Failure].
to elucidate association between polymorphic markers of interleukin- 6 (Il-6) and tumor necrosis factor (TNF) genes and unfavorable outcomes in patients with chronic heart failure (CHF). We determined levels of TNF and Il-6 and genotypes of polymorphic markers G(-238)A of TNF gene (rs361525) and G(-174)C of IL-6 gene (rs1800795) in 151 patients (mean age 64.5 years) hospitalized because of decompensation of systolic CHF (left ventricular ejection fraction less or equal 40%) after stabilization of their state. Unfavorable outcomes were registered during follow-up for 2 years. Mean levels of NT-proBNP, Il-6, and TNF were 2481.1+/-199.86 fmol/ml, 21.8+/-7.46 rg/ml, and 10.07+/-0.65 rg/ml, respectively. 138 (94.4%), 13 (8.6%) and 0 patients were carriers of genotypes GG, AG, and AA of polymorphic marker G(-238)A of TNF gene, respectively; 54 (35.8%), 69 (45.7%), and 28 (18.5%) patients carried genotypes GG, GC, and of polymorphic marker G(-174)C gene IL-6, respectively. There was no association between Il-6, TNF levels and carriage of either of genotypes as well as unfavorable clinical course of CHF. Mean survival time before repetitive episode of CHF decompensation (including lethal one) was significantly shorter among carriers of A allele compared with carriers of G allele of polymorphic marker G(-238)A of TNF gene (243+/-97.7 and 947+/-78 days, respectively, =0.018). Mean time before all cause death was also shorter in carriers of A compared with carriers of G allele (289+/-122.9 and 1039+/-73.3 days, respectively, p=0.03). The studied polymorphism of IL-6 gene had no prognostic value. We obtained data on association between carriage of A allele of polymorphic marker G(-238)A of TNF gene and unfavorable prognosis in patients with CHF and inpraired left ventricular systolic function.


Functional and morphological alterations induced by Helicobacter pylori infection in gastric nerve supply.
Helicobacterpylori (HP) infection is the most common cause of many gastric diseases. One of its pathogenic mechanisms involves the production of a wide spectrum of alterations in different components of the gastric enteric nervous system. Changes in neural circuitry encompass structural abnormalities, sensitive and motor function impairment, altered content and release of neurotransmitters, and seem to be related rather to the inflammatory response of gastric wall than to the bacterial colonization. Although gathered data provide new insights into the complex mechanisms underlying the interactions between HP and enteric nervous system, there still are some controversial aspects. Interestingly, it has been suggested that impaired neural activity might have a potential role in gastric carcinogenesis, but this hypothesis requires further investigation. Future studies shall, therefore, elucidate the neuromodulatory influences of Helicobacter pylori infection on the enteric nervous system. A better comprehension on neural changes during HP-induced inflammation could help in identifying new therapeutic options.


Kawasaki disease. Some recent studies on pathogenetic mechanisms.
Kawasaki disease is diagnosed with increasing frequency in countries outside Japan. It has attracted widespread interest because of the possibility of coronary aneurysms and sudden death in the patients. While advances in treatment have been achieved, and in particular, the value of intravenous gamma-globulin therapy, the etiology of the disease is still uncertain. This paper is a brief review of some recent studies which have shed light on the pathogenesis of the disease. Studies from animal models and information from immunological abnormalities, platelet immune complex interactions and coagulation abnormalities point to the importance of immunoregulatory mechanisms in pathogenesis. Evidence so far do not support a major role for genetic factors.


Elf-1 binds to GGAA elements on the FcRgamma promoter and represses its expression.
The Fc receptor (FcR) gamma-chain has been shown to be up-regulated in T cells when the TCR zeta-chain is decreased. We demonstrate that Elf-1, but not other Ets family transcription factors, bind to a cluster of GGAA sites located within the 200 bp upstream from the transcription initiation site of the FcRgamma promoter. Forced expression of Elf-1 results in the suppression of FcRgamma expression, whereas silencing its expression with small interfering RNA Elf-1 results in increased FcRgamma expression. Elf-1 represents the first transcription factor identified to be involved in the transcriptional regulation of FcRgamma, and cells that fail to express Elf-1, as is the case with human systemic lupus erythematosus T cells, will express FcRgamma-chain.


Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.
Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI < or = 25 kg/m2). Various indices of insulin sensitivity and beta cell function derived from the oral glucose tolerance test (OGTT) results were used. We found the rate of RH to be 50% in lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P < 0.05 and P > 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.


Miscellaneous conditions of the appendix.
A variety of miscellaneous conditions affect the appendix, both as incidental findings and as causes of clinical signs and symptoms that often mimic appendicitis. Congenital abnormalities of the appendix are rare; the two most commonly reported are congenital absence and appendiceal duplication. Diverticular disease may be an incidental finding, but when inflamed, can be clinically confused with appendicitis. Endometriosis of the appendix, which usually occurs in the setting of generalized gastrointestinal endometriosis, often presents as acute appendicitis, but may present as intussusception, lower intestinal bleeding, and, particularly during pregnancy, perforation. Peritoneal endosalpingiosis often involves the appendiceal serosa and occasionally the wall but has no clinical manifestations in contrast to endometriosis. Vasculitis may be either isolated to the appendix or part of a systemic vasculitis, most often polyarteritis nodosa. Neural proliferations of the appendix include lesions associated with von Recklinghausen's disease, as well as mucosal and axial neuromas that are theorized to progress to fibrous obliteration of the appendix. Mesenchymal tumors of the appendix are most often of smooth muscle type, usually leiomyoma but rarely leiomyosarcoma; nonmyogenic neoplasms such as gastrointestinal stromal tumor, granular cell tumor, Kaposi's sarcoma, and miscellaneous other curiosities occur rarely. Lymphoma affects the appendix exceptionally; in children, Burkitt lymphoma is most common whereas in adults, large cell lymphomas and low grade B-cell lymphomas predominate. Secondary involvement of the appendix by leukemia has been reported. Secondary involvement of the appendix by carcinomas of the female genital tract, particularly ovary, and diverse other sites are in aggregate common but only rarely a clinical or pathological difficulty. Occasionally, however, appendiceal neoplasia that is secondary from another site may dominate the clinical picture and lead to potential pathologic misdiagnosis as primary appendiceal disease.


Effect of doxorubicin and verapamil on circulatory system in rabbits.
The cardiovascular effect of a single intravenous dose of doxorubicin (DXR) given to the rabbits pretreated intravenously for 3 weeks with DXR, verapamil (Vp) or both drugs was investigated. It was found that cardiac index and stroke index were higher in the rabbits pretreated with DXR plus Vp than with DXR alone. Mean arterial blood pressure was lower in each group of animals. However, total peripheral resistance was reduced significantly in both groups of rabbits pretreated with Vp. DXR produced a significant decrease of the heart rate and dangerous arrhythmias in rabbits pretreated with both drugs. Histologically degenerative changes in nuclei but less in myofibrils were observed in this group of animals.


A Pilot Intervention to Promote Positive Parenting in Refugees from Syria in Lebanon and Jordan.
Early childhood development (ECD) is a crucial milestone that shapes a child's health, wellbeing, education, and personality. Several factors come into play, and each requires the nurturing care of caregivers. Although the importance of ECD is well understood, the implementation of ECD programs is scarce, especially in poor and vulnerable communities. To improve parents' wellbeing, parenting stress levels, parenting behavior, and discipline strategies after the implementation of a newly designed parenting intervention. Parents from Syria (125 mothers and fathers) in three refugee camps in Lebanon and Jordan. This was a pilot cohort study in which parents' wellbeing, parenting stress levels, parenting behavior, and discipline strategies were evaluated before and after participating in training in the form of interactive and educational sessions to ameliorate their relations and interactions with their children. By the end of this study, parents' mental health and wellbeing improved (p < 0.001, Cohen's d: 0.61) and their parenting index score was reduced (p < 0.001, Cohen's d: 1.24). Some of their dysfunctional interactions with their children as well as the perceived difficulties and conduct problems in their children aged 3 to 6 years were also reduced significantly. The intervention used in this study succeeded in improving some aspects of parenting practices and disciplines and in improving the parents' wellbeing; however, more research is needed to assess its long-term effects on parents and their children. Moreover, some adjustments need to be made in the intervention to be more adapted to the context of refugees and underprivileged communities.


High-Precision Wearable Displacement Sensing System for Clinical Diagnosis of Anterior Cruciate Ligament Tears.
An anterior cruciate ligament (ACL) tear is a common musculoskeletal injury with a high incidence. Traditional diagnosis employs magnetic response imaging (MRI), physical testing, or other clinical examination, which relies on complex and expensive medical instruments, or individual doctoral experience. Herein, we propose a wearable displacement sensing system based on a grating-structured triboelectric stretch sensor to diagnose the ACL injuries. The stretch sensor exhibits a high resolution (0.2 mm) and outstanding robustness (over 1,000,000 continuous operation cycles). This system is employed in clinical trial to diagnose ACL injuries. It measures the displacement difference between the affected leg and the healthy leg during Lachman test. And when such a difference is greater than 3 mm, the ACL is considered to be at risk for injury or tear. Compared with the gold standard of arthroscopy, the consistency rate of this wearable diagnostic system reached about 85.7%, which is higher than that of the Kneelax3 arthrometer (78.6%) with a large volume. This shows that the wearable system possesses the feasibility to supplement and improve existing arthrometers for facile diagnosing ACL injuries. It may take a promising step for wearable healthcare.


Depressive-like behaviour induced by an intracerebroventricular injection of streptozotocin in mice: the protective effect of fluoxetine, antitumour necrosis factor-α and thalidomide therapies.
Information on the effect of an intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) on noncognitive behaviour in rodents such as depression states is scarce. Thus, the aim of this study was to examine the depressive-like effect of STZ injected by the i.c.v. route in mice and the potential protective effect of fluoxetine, antitumour necrosis factor-α (anti-TNF-α) and thalidomide. Our results indicated that a single injection of STZ (0.1 mg/site) promoted depressive-like behaviour in the tail suspension and sucrose preference tests without altering either locomotor activity or plasma glucose levels. We also showed that STZ increased TNF-α levels in the hippocampus of mice. Fluoxetine (32 mg/kg, intraperitoneally. 30 min before STZ injection), and the anti-TNF-α antibody (0.1 pg/site, i.c.v.) and thalidomide (3 mg/kg, subcutaneously), coadministered with STZ, prevented these effects. This is the first study to report depressive-like effects of STZ using the i.c.v. route in mice. We concluded that fluoxetine, anti-TNF-α antibody and thalidomide were effective in preventing depressive-like behaviour and the increase in TNF-α levels in the hippocampus of mice induced by an i.c.v. injection of STZ, reinforcing the involvement of TNF-α in the pathophysiology of depression. This model and the mechanisms studied may contribute towards the development of new antidepressant drugs and enhance the options for studying depression.


Indocyanine Green Lymphographic Evidence of Surgical Efficacy Following Microsurgical and Supermicrosurgical Lymphedema Reconstructions.
Background Microsurgical vascularized lymph node transfer (VLNT) and supermicrosurgical lymphaticovenular anastomosis (LVA) are increasingly performed to treat lymphedema. The surgical outcome is commonly assessed by volume-based measurement (VBM), a method that is not consistently reliable. We describe indocyanine green (ICG) lymphography as an alternative postoperative tracking modality after lymphatic reconstruction with VLNT and LVA. Methods VLNT and LVA were performed in patients with therapy-refractory lymphedema. Patients were evaluated qualitatively by clinical assessment, quantitatively with VBM, and lymphographically using ICG lymphography. The evaluation was performed preoperatively, and at 3, 6, and 12-month postoperatively. Results Overall, 21 patients underwent lymphatic reconstruction with either VLNT or LVA. All reported prompt and durable relief of symptoms during the study period. All experienced disease regression based on the Campisi criteria. Out of the 21 patients, 20 (95%) demonstrated lymphographic down staging of disease severity. Out of the 21 patients, 3 (14%) developed a paradoxical increase in limb volume based on VBM despite clinical improvement. Conclusions ICG lymphography correlated highly with patient self-assessment and clinical examination, and is an effective postoperative tracking modality after lymphatic reconstruction.


Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study.
COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection. Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared. Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05). In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001). Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died. The other four patients received anticoagulant treatment with enoxaparin and 2 of them died. As of 24 March 2020, six patients with CVD died (54.5%). Acute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.


Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms.
The metabolic disorders caused by diabetes can lead to various complications, including dysfunction of the male reproductive system. In patients with diabetes, long-term hyperglycemia results in diabetic vascular neuropathy, oxidative stress injury, abnormal zinc metabolism, and insulin resistance syndrome. In addition, insulin deficiency and resistance in diabetes can damage the hypothalamus, pituitary gland, gonads, and perigonads. This can reduce the secretion of sex hormones including gonadotropin-releasing hormone, follicle stimulating hormone, luteinizing hormone, and testosterone, and can lead to testicular atrophy, stromal cell atrophy, seminiferous tubule damage, spermatogenic cell damage, and other structural injuries of the male reproductive organs. These actions can affect male fertility and reproductive health. Herein, we review studies that report a causative role of diabetes in male reproductive function. We also discuss the evidence-based mechanisms involved in the processes of diabetes-related male sexual and reproductive dysfunction as well as the progress in treatment.


Bayesian variable selection based on clinical relevance weights in small sample studies-Application to colon cancer.
Using clinical data to model the medical decisions behind sequential treatment actions raises methodological challenges. Physicians often have access to many covariates that may be used when making sequential treatment decisions for individual patients. Statistical variable selection methods may help finding which of these variables are used for this decision in everyday practice. When the sample size is not large, Bayesian variable selection methods can address this setting and allow for expert information to be incorporated into prior distributions. Motivated by clinical practice data involving repeated dose adaptation for Irinotecan in colorectal metastatic cancer, we propose a modification of the stochastic search variable selection (SSVS) method, which we call weight-based SSVS (WBS). We use clinical relevance weights elicited from physician experts to construct prior distributions, with the goal to identify the most influential toxicities and other covariates used for dose adjustment. We evaluate and compare the WBS model performance to the Lasso and SSVS through an extensive simulation study. The simulations show that WBS has better performance and lower rates of false positives and false negatives than the other methods but depends strongly on the covariate weights.


[Oncogenetic factors of some herpesvirus infection agents].
Currently, debate continues about the etiological role of pathogens, in particular viruses, in the development of bladder tumors, their impact on the rate of recurrence and invasive and metastatic forms. The literature has reported some evidence for oncomodulating effect of cytomegalovirus in glioblastomas and bowel tumors. There is the possible role of herpes simplex virus (HSV) type 2 as carcinogenesis cofactor that initiates the development of dysplasia and maintains it in a stable condition. Epstein - Barr virus (EBV) from a family of the oncogenic DNA viruses is associated with an increasing range of cancers. EBV has been proven to have a role in the development of Burkitts lymphoma, nasopharyngeal carcinoma and gastric cancer. The review outlines the current knowledge on the factors of oncogenesis and the role of some herpesviruses in the etiology of bladder cancer.


Development of a method for reliable power input measurements in conventional and single-use stirred bioreactors at laboratory scale.
Power input is an important engineering and scale-up/down criterion in stirred bioreactors. However, reliably measuring power input in laboratory-scale systems is still challenging. Even though torque measurements have proven to be suitable in pilot scale systems, sensor accuracy, resolution, and errors from relatively high levels of friction inside bearings can become limiting factors at smaller scales. An experimental setup for power input measurements was developed in this study by focusing on stainless steel and single-use bioreactors in the single-digit volume range. The friction losses inside the air bearings were effectively reduced to less than 0.5% of the measurement range of the torque meter. A comparison of dimensionless power numbers determined for a reference Rushton turbine stirrer (NP = 4.17 ± 0.14 for fully turbulent conditions) revealed good agreement with literature data. Hence, the power numbers of several reusable and single-use bioreactors could be determined over a wide range of Reynolds numbers between 100 and >104. Power numbers of between 0.3 and 4.5 (for Re = 104) were determined for the different systems. The rigid plastic vessels showed similar power characteristics to their reusable counterparts. Thus, it was demonstrated that the torque-based technique can be used to reliably measure power input in stirred reusable and single-use bioreactors at the laboratory scale.


Multiple Genome Sequences of Lactobacillus plantarum Strains.
We report here the genome sequences of four Lactobacillus plantarum strains which vary in surface hydrophobicity. Bioinformatic analysis, using additional genomes of Lactobacillus plantarum strains, revealed a possible correlation between the cell wall teichoic acid-type and cell surface hydrophobicity and provide the basis for consecutive analyses.


[Evaluation of anti-HAV IgG on 2 samples of closed populations].
The authors have carried out an epidemiologic research about the diffusion of antibody to hepatitis A antigen in the inhabitants of Ginostra, fraction of Stromboli, and Alicudi Islands (Eolie's arcipelago). We have examined by ELISA 86 human sera. We have detected a percentage of positivity about 82 and 70.6% for two populations. A critic examination of the results with parameters auxiliary (sex, age), showed significant differences of positivity about two different sexs and ages.


Effects of blackberry polysaccharide on the quality improvement of boiled chicken breast.
Blackberry polysaccharide was isolated from blackberry powder with 70% ethanol. The crude polysaccharide was composed of 95.44% glucose, 2.01% arabinose, 1.81% galactose and 0.74% glucuronic acid. Chicken breast meat was only marinated with different concentrations of the isolated blackberry polysaccharide (1 g/kg, 3 g/kg) for 24 h at a ratio of material to liquid of 1:3, and boiled at 80℃ for 1 h. The differences in texture, water distribution and volatile flavor components among different groups (adding 0,1,3 g/kg blackberry polysaccharide) were investigated. The results showed that the addition of blackberry polysaccharide could significantly improve the hardness of chicken breast, the transformation of free water to bound water, the overall flavor characteristics of the control group and the addition of different concentrations of blackberry polysaccharide were significantly different, and the concentration of volatile flavor substances in boiled chicken breast was reduced.


Genomics of antibiotic-resistance prediction in Pseudomonas aeruginosa.
Antibiotic resistance is a worldwide health issue spreading quickly among human and animal pathogens, as well as environmental bacteria. Misuse of antibiotics has an impact on the selection of resistant bacteria, thus contributing to an increase in the occurrence of resistant genotypes that emerge via spontaneous mutation or are acquired by horizontal gene transfer. There is a specific and urgent need not only to detect antimicrobial resistance but also to predict antibiotic resistance in silico. We now have the capability to sequence hundreds of bacterial genomes per week, including assembly and annotation. Novel and forthcoming bioinformatics tools can predict the resistome and the mobilome with a level of sophistication not previously possible. Coupled with bacterial strain collections and databases containing strain metadata, prediction of antibiotic resistance and the potential for virulence are moving rapidly toward a novel approach in molecular epidemiology. Here, we present a model system in antibiotic-resistance prediction, along with its promises and limitations. As it is commonly multidrug resistant, Pseudomonas aeruginosa causes infections that are often difficult to eradicate. We review novel approaches for genotype prediction of antibiotic resistance. We discuss the generation of microbial sequence data for real-time patient management and the prediction of antimicrobial resistance.


Nonsurgical Treatment of Acetabular Labral Tears.
Clinical Scenario: Surgical treatment of acetabular labral tears has been explored in multiple studies, while there is a lack of research on the effectiveness of conservative methods. Focused Clinical Question: To what extent can nonsurgical treatment produce symptomatic or functional improvements in athletes with an acetabular labral tear? Summary of Search, Best Evidence Appraised, and Key Findings: The literature was searched for studies of patients with confirmed acetabular labral tears who participated in any level of sport. Four studies were located, all of which were included. Clinical Bottom Line: The research discussed in this review agreed that conservative management of acetabular labral tears produced measurable improvements in pain and function among the athletes studied, including their ability to participate in sport activities. Based on these findings, it appears that conservative management is effective at rehabilitating athletes with acetabular labral tears. However, this method should not be applied to every athlete based on the low strength of current research. Treatment plans should be decided upon on a case-by-case basis. Strength of Recommendation: The studies located were of low quality. The highest Oxford Center for Evidence-Based Medicine Level of Evidence achieved was 4. Higher level studies must be conducted before the conclusions of this research can be applied clinically with assertion. Strength of recommendation is level 3.


Clinical features associated with the jaw winking syndrome.
The jaw winking phenomenon is most often described as blepharoptosis of the upper lid associated with stimulation of the ipsilateral pterygoid muscle. Other clinical features are known to be associated with this entity. They include strabismus, amblyopia and refractive error. A total of 33 patients were identified via a retrospective chart review. The data collected included the presence and type of any associated strabismus, visual acuity during the follow-up period, refractive error at last examination, affected eye, and sex. Strabismus was found in 69.7% of the patients with double elevator palsy being the most common variety. Refractive errors fell within a normal range for this age group. Amblyopia was found in 51.5% and was most commonly associated with strabismus and/or anisometropia. There was a predominance of affected left eyes (57.6%) and females (63.6%). Because of the prevalence of elevation deficiency, one should pay special attention to the extraocular motility pattern when examining a patient with the jaw winking phenomenon. Additionally, one should be aware that amblyopia is common especially in the patients with associated strabismus and/ or anisometropia. The documented association of the jaw winking with Duane syndrome as well as the similar laterality and sex distribution data are an interesting phenomenon.


An effective splitting-and-recombination micromixer with self-rotated contact surface for wide Reynolds number range applications.
It is difficult to mix two liquids on a microfluidic chip because the small dimensions and velocities effectively prevent the turbulence. This paper describes two 2-layer PDMS passive micromixers based on the concept of splitting and recombining the flow that exploits a self-rotated contact surface to increase the concentration gradients to obtain fast and efficient mixing. The designed micromixers were simulated and the mixing performance was assessed. The mixers have shown excellent mixing efficiency over a wide range of Reynolds number. The mixers were reasonably fabricated by multilayer soft lithography, and the experimental measurements were performed to qualify the mixing performance of the realized mixer. The results show that the mixing efficiency for one realized mixer is from 91.8% to 87.7% when the Reynolds number increases from 0.3 to 60, while the corresponding value for another mixer is from 89.4% to 72.9%. It is rather interesting that the main mechanism for the rapid mixing is from diffusion to chaotic advection when the flow rate increases, but the mixing efficiency has not obvious decline. The smart geometry of the mixers with total length of 10.25 mm makes it possible to be integrated with many microfluidic devices for various applications in μ-TAS and Lab-on-a-chip systems.


A-DaGO-Fun: an adaptable Gene Ontology semantic similarity-based functional analysis tool.
Gene Ontology (GO) semantic similarity measures are being used for biological knowledge discovery based on GO annotations by integrating biological information contained in the GO structure into data analyses. To empower users to quickly compute, manipulate and explore these measures, we introduce A-DaGO-Fun (ADaptable Gene Ontology semantic similarity-based Functional analysis). It is a portable software package integrating all known GO information content-based semantic similarity measures and relevant biological applications associated with these measures. A-DaGO-Fun has the advantage not only of handling datasets from the current high-throughput genome-wide applications, but also allowing users to choose the most relevant semantic similarity approach for their biological applications and to adapt a given module to their needs. A-DaGO-Fun is freely available to the research community at http://web.cbio.uct.ac.za/ITGOM/adagofun. It is implemented in Linux using Python under free software (GNU General Public Licence). email@example.com or firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


The detection, treatment, and biology of epithelial ovarian cancer.
Ovarian cancer is particularly insidious in nature. Its ability to go undetected until late stages coupled with its non-descript signs and symptoms make it the seventh leading cause of cancer related deaths in women. Additionally, the lack of sensitive diagnostic tools and resistance to widely accepted chemotherapy regimens make ovarian cancer devastating to patients and families and frustrating to medical practitioners and researchers. Here, we provide an in-depth review of the theories describing the origin of ovarian cancer, molecular factors that influence its growth and development, and standard methods for detection and treatment. Special emphasis is focused on interactions between ovarian tumors and the innate and adaptive immune system and attempts that are currently underway to devise novel immunotherapeutic approaches for the treatment of ovarian tumors.


Treating psychological trauma in first responders: a multi-modal paradigm.
Responding to critical incidents may result in 5.9-22% of first responders developing psychological trauma and posttraumatic stress disorder. These impacts may be physical, mental, and/or behavioral. This population remains at risk, given the daily occurrence of critical incidents. Current treatments, primarily focused on combat and rape victims, have included single and double interventions, which have proven helpful to some but not all victims and one standard of care has remained elusive. However, even though the need is established, research on the treatment interventions of first responders has been limited. Given the multiplicity of impacts from psychological trauma and the inadequacies of responder treatment intervention research thus far, this paper proposes a paradigmatic shift from single/double treatment interventions to a multi-modal approach to first responder victim needs. A conceptual framework based on psychological trauma is presented and possible multi-modal interventions selected from the limited, extant first responder research are utilized to illustrate how the approach would work and to encourage clinical and experimental research into first responder treatment needs.


Anthelmintic activity of European fern extracts against Haemonchus contortus.
Most drugs used in the treatment of helminthiasis in humans and animals have lost their efficacy due to the development of drug-resistance in helminths. Moreover, since anthelmintics, like many pharmaceuticals, are now recognized as hazardous contaminants of the environment, returning to medicinal plants and their products represents an environmentally friendly way to treat helminthiasis. The goal of the present study was to test the anthelminthic activity of methanol extracts of eight selected European ferns from the genera Dryopteris, Athyrium and Blechnum against the nematode Haemonchus contortus, a widespread parasite of small ruminants. Eggs and adults of H. contortus drug-susceptible strain ISE and drug-resistant strain WR were isolated from experimentally infected sheep. The efficacy of fern extracts was assayed using egg hatch test and adults viability test based on ATP-level measurement. Among the ferns tested, only Dryopteris aemula extract (0.2 mg/mL) inhibited eggs hatching by 25% in comparison to control. Athyrium distentifolium, Dryopteris aemula and Dryopteris cambrensis were effective against H. contortus adults. In concentration 0.1 mg/mL, A. distentifolium, D. aemula, D. cambrensis significantly decreased the viability of females from ISE and WR strains to 36.2%, 51.9%, 32.9% and to 35.3%, 27.0%, 23.3%, respectively in comparison to untreated controls. None of the extracts exhibited toxicity in precise cut slices from ovine liver. Polyphenol's analysis identified quercetin, kaempferol, luteolin, 3-hydroxybenzoic acid, caffeic acid, coumaric acid and protocatechuic acid as the major components of these anthelmintically active ferns.


[ Radiological anatomy of the breast].
The macroscopic anatomy of the breast is often not well understood; it is the reason why the radiologic images formation of this organ needs to be explained. This work is based upon anatomical-radiological confrontations, which allow to separate the two main compartments of the gland, the fibroglandular tissue and the adipose tissue, and to study the limits of these two components. Their different proportions are at the origin of different patterns leading to a simple classification of non-pathologic breast X-rays. This classification makes easier the diagnosis of abnormalities, especially of tumoral origin.


[Study on the conformational state of Escherichia coli tRNA-Phe in solution by ESR-spectometry without modulation].
ESR-spectrometry without modulation of the magnetic field was used for registering the EST spectral line shape (with shape distortion about 0.1 percent) of spin-labeled Escherichia coli tRNAPhe. The analysis of line shape of two different spin-labels in position 8 (S4U) revealed that tRNAPhe in solution always exists as a mixture of at least two conformers, the equilibria between conformers being dependent on pH, concentration of magnesium and the biological state of tRNA (deacylated, aminoacyl- or peptidyl-tRNA). There are no large structural rearrangements upon aminoacylation or peptidylation of tRNA, the observed small changes of spectral line shape are due to the changes in conformational equilibria.


Expression and Significance of COX-2 and Ki-67 in Hepatolithiasis with Bile Duct Carcinoma.
As an induced enzyme, COX-2 expression is elevated under stimuli from inflammatory mediator or growth factor product. Ki-67, a cell cycle-related proliferative antigen, reflects the tissue proliferative activity. This study analyzed the expressional profile of cyclooxygenase-2 (COX-2) and Ki-67 in hepatolithiasis and bile duct carcinoma tissues, in an attempt to provide evidence for diagnosis and prognosis prediction of disease. A cohort of tissue samples from hepatolithiasis with bile duct carcinoma (N=47) patients were analyzed using immunohistochemical (IHC) staining method for the expression of COX-2 and Ki-67, in parallel with hepatolithiasis (N=44) and normal bile duct tissues (N=30). The relationship between expression pattern of COX-2 and Ki-67 and pathological conditions was also analyzed, in addition to the correlation with positive expression in hepatolithiasis samples. The positive expression rate of COX-2 and Ki-67 in bile duct carcinoma was 76.6% and 80.9%, respectively, and was significantly higher than those in the hepatolithiasis group, which was also higher than the control group. Expression of both COX-2 and Ki-67 is closely related to TNM staging, lymph node metastasis, and differentiation stage. They were also correlated with the mortality rate of patients. Both COX-2 and Ki-67 are abundantly expressed in hepatolithiasis and bile duct carcinoma tissues and may play an important role in the disease occurrence, progression, and metastasis.


An inexpensive spacer for use with metered-dose bronchodilators in young asthmatic children.
A 1-liter soft drink plastic bottle was modified as a spacer for use with a metered-dose bronchodilator. Its efficacy was tested on 22 children aged 3.9-7.5 years who had acute asthma. They were randomly selected to receive aerosolized salbutamol or placebo via the plastic bottle. Children who received the salbutamol showed significantly greater degree of bronchodilation than those who received the placebo. No significant adverse effects were observed. Cylindrical plastic bottles of 1-liter capacity may thus be used as a convenient and cheap spacer to effectively deliver metered-dose bronchodilators to children during acute asthma.


Integrative conjugative elements are widespread in field isolates of Mycoplasma species pathogenic for ruminants.
Comparative genomics have revealed massive horizontal gene transfer (HGT) between Mycoplasma species sharing common ruminant hosts. Further results pointed toward an integrative conjugative element (ICE) as an important contributor of HGT in the small-ruminant-pathogen Mycoplasma agalactiae. To estimate the prevalence of ICEs in ruminant mycoplasmas, we surveyed their occurrence in a collection of 166 field strains representing 4 (sub)species that are recognized as major pathogens. Based on available sequenced genomes, we first defined the conserved, minimal ICE backbone as composed of 4 coding sequences (CDSs) that are evenly distributed and predicted to be essential for ICE chromosomal integration-excision and horizontal transfer. Screening of the strain collection revealed that these 4 CDSs are well represented in ruminant Mycoplasma species, suggesting widespread occurrence of ICEs. Yet their prevalence varies within and among species, with no correlation found with the individual strain history. Extrachromosomal ICE forms were also often detected, suggesting that ICEs are able to circularize in all species, a first and essential step in ICE horizontal transfer. Examination of the junction of the circular forms and comparative sequence analysis of conserved CDSs clearly pointed toward two types of ICE, the hominis and spiroplasma types, most likely differing in their mechanism of excision-integration. Overall, our data indicate the occurrence and maintenance of functional ICEs in a large number of field isolates of ruminant mycoplasmas. These may contribute to genome plasticity and gene exchanges and, presumably, to the emergence of diverse genotypes within pathogenic mycoplasmas of veterinary importance.


Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature.
Increased body fat content correlates with insulin resistance and is a key feature of type 2 diabetes. Excessive intake of fat results in deposition of lipids not only in fat tissue but also in skeletal muscle and liver. Subsequently, both plasma and intracellular concentrations of free fatty acids and their metabolites rise and activate signal transduction pathways, which will induce inflammation and impair insulin signalling. Furthermore, elevated circulating lipids impair endothelial function and fibrinolysis, which contributes to the development of vascular disease. Thus, therapeutic strategies aiming at reduction of (intracellular) lipid availability in skeletal muscle and liver and pharmacological modulation of the signalling pathways activated by increased lipid stores represent promising targets for future treatment of insulin resistance and prevention of its complications. This review focuses on the effects of increased lipid availability on the regulation of glucose metabolism in skeletal muscle and liver as well as on vascular function.


Current significant challenges in the decommissioning and environmental remediation of radioactive facilities: A perspective from outside the nuclear industry.
This paper presents the results of implementing an extrajudicial environmental mediation procedure in the socioenvironmental conflict associated with routine operation of the El Cabril Disposal Facility for low- and medium- activity radioactive waste (Spain). We analyse the socio-ethical perspective of this facility's operation with regard to its nearby residents, detailing the structure and development of the environmental mediation procedure through the participation of society and interested parties who are or may become involved in such a conflict. The research, action, and participation method was used to apply the environmental mediation procedure. This experience provides lessons that could help improve decision-making processes in nuclear or radioactive facility decommissioning projects or in environmental remediation projects dealing with ageing facilities or with those in which nuclear or radioactive accidents/incidents may have occurred.


Direct estimates of cause-specific mortality fractions and rates of under-five deaths in the northern and southern regions of Nigeria by verbal autopsy interview.
Nigeria's under-five mortality rate is the eighth highest in the world. Identifying the causes of under-five deaths is crucial to achieving Sustainable Development Goal 3 by 2030 and improving child survival. National and international bodies collaborated in this study to provide the first ever direct estimates of the causes of under-five mortality in Nigeria. Verbal autopsy interviews were conducted of a representative sample of 986 neonatal and 2,268 1-59 month old deaths from 2008 to 2013 identified by the 2013 Nigeria Demographic and Health Survey. Cause of death was assigned by physician coding and computerized expert algorithms arranged in a hierarchy. National and regional estimates of age distributions, mortality rates and cause proportions, and zonal- and age-specific mortality fractions and rates for leading causes of death were evaluated. More under-fives and 1-59 month olds in the South, respectively, died as neonates (N = 24.1%, S = 32.5%, p<0.001) and at younger ages (p<0.001) than in the North. The leading causes of neonatal and 1-59 month mortality, respectively, were sepsis, birth injury/asphyxia and neonatal pneumonia, and malaria, diarrhea and pneumonia. The preterm delivery (N = 1.2%, S = 3.7%, p = 0.042), pneumonia (N = 15.0%, S = 21.6%, p = 0.004) and malaria (N = 34.7%, S = 42.2%, p = 0.009) fractions were higher in the South, with pneumonia and malaria focused in the South East and South South; while the diarrhea fraction was elevated in the North (N = 24.8%, S = 13.2%, p<0.001). However, the diarrhea, pneumonia and malaria mortality rates were all higher in the North, respectively, by 222.9% (Z = -10.9, p = 0.000), 27.6% (Z = -2.3, p = 0.020) and 50.6% (Z = -5.7, p = 0.000), with the greatest excesses in older children. The findings support that there is an epidemiological transition ongoing in southern Nigeria, suggest the way forward to a similar transition in the North, and can help guide maternal, neonatal and child health programming and their regional and zonal foci within the country.


Amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting 20,000 to 30,000 people in the United States. The mainstay of care of patients affected by this disease is supportive and given the multifaceted nature of their needs is provided most efficiently through multidisciplinary clinics that have shown to prolong survival and improve quality of life. The authors discuss in detail evidence-based management of individuals affected by this condition.