[Etiopathogenesis of aplastic anemia and of the severe form treated with immunosuppression and bone marrow transplantation].
Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in many cases the causative agents remain obscure. Severe aplastic anemia has been treated by immunosuppression and allogeneic marrow transplantation.


Complications of operative vaginal delivery and provider volume and experience.
To evaluate associations between operative vaginal delivery complications and provider experience (operative vaginal delivery volume and time since residency). We included all operative vaginal deliveries between 2008 and 2014 at a tertiary care teaching hospital, stratified into forceps-assisted and vacuum-assisted deliveries. Complications included severe perineal lacerations (3rd and 4th degree) and neonatal injuries (subgaleal/subdural/cerebral hemorrhage, facial nerve injury, and scalp injury), which were identified by International Classification Diagnosis-9 codes. Providers were categorized by operative vaginal delivery volume (mean annual forceps- or vacuum-assisted deliveries over the study interval) and time since residency. Regression analyses were used to compare complication rates by provider volume and time since residency, adjusting for potential confounders, using 0-1 deliveries per year and <5 years since residency as reference groups. Nine hundred and thirty-four forceps and 1074 vacuums occurred. For forceps-assisted deliveries, severe perineal injury was decreased among providers with >10 forceps per year (aOR 0.50 [95%CI 0.30-0.81]) and at 15-19 years (aOR 0.45 [95% CI 0.22-0.94], and ≥25 years (aOR 0.45 [0.27-0.73]) since residency. There were no associations with neonatal injuries. Among vacuum-assisted deliveries, severe perineal injury decreased at ≥25 years since residency (aOR 0.35 [95%CI 0.17-0.74], with no association with provider volume. Neonatal injury decreased at 5-9 years (aOR 0.53 [95%CI 0.30-0.93]), and 15-19 years since residency (aOR 0.53 [95%CI 0.29-0.97]), due to differences in scalp injuries. Neonatal injuries other than scalp injury were rare. Severe perineal lacerations decreased with increasing operative vaginal delivery experience, primarily among forceps-assisted vaginal delivery. Providers >5 years since residency may have lower scalp injury with vacuums, but this cohort was largely underpowered for neonatal injury.


Modeling and optimising dextrose fermentation using a fluorosensor.
Dextrose has been fermented in a Tokyo Rikakikai Fermentor at 32 degree celsius using seven different concentrations of yeast as seeding. The progress of the reaction was followed by measuring the fluorescent signal due to NADH with a Dr. Ingold (Switzerland) fluorosensor which has an excitation wavelength of 360 nm and measurement wavelength of 450 nm. The optimum concentration for this fermentation reaction is 30 percent seeding. At this concentration the biomass growth rate and final biomass concentration are a maximum. The fluorescent voltage vs time data fitted a first order model with an error of less than one percent. Further work on optimising the temperature is in progress.


'Building up safe havens... around the world': users' experiences of living in the community with mental health problems.
Deinstitutionalization moved the focus of psychiatric care away from hospital institutions to community settings. Mental health services are no longer driven by a policy of illness containment, although detention and coercion retain legislative and cultural legitimacy, because the conceptual and practical focus of caring for people in the 1990s is built around journeys to(wards) ordinary 'independent' living. This paper draws upon the experiences of people with enduring mental health problems to explore the positions, roles and therapeutic benefits established by socio-spatial networking in the community. Social isolation and community integration are polar extremes, two very different 'locations' on a 'theoretical' rehabilitation pathway shaping mental health policy and community care practices. The paper assesses these two locations and searches for the middle-ground in practice. It draws on the concept of normality to compare service user and professional perspectives on the rehabilitation process. The paper argues, with optimism, that spaces of rehabilitation are being found 'in the community' but notes that until mental illness is de-stigmatised and society celebrates difference, creating space for 'Mad Pride', the post-asylum landscape must continue to evolve in search of models of good community care practice and potential landscapes of caring. The research presented in the paper was carried out with Rehabilitation and Community Care Services (RCCS) in Nottingham (1994-1997), and is based upon fieldwork observations and in-depth interviews with RCCS staff and 25 service users.


Metabolic integration during the host associations of multicellular animal endoparasites.
The nature of metabolic interaction during parasitic infection was discussed and the concept of metabolic integration outlined. The subjective nature of the integrative argument was noted. The parasite-host relationships of larval trematodes of the genus Schistosoma with their intermediate molluscan hosts, the nematode Trichnella spiralis and cestode Hymenolepis diminuta, with their definitive hosts, as well as the hymenopterous insect parasite, Hyposoter exiguae, with its insect host, Trichoplusia ni, were examined. The significance of the immune system in the establishment of the parasite-host association and the means by which parasites evade host defense were discussed. The involvement of microorganisms or "hyperparasites" during the host associations of multicellular parasites was described. The importance of evolutionary considerations in assessing the nature of metabolic interaction and its significance to the success of the parasite-host relationship was emphasized. The use of teleological assessment and anthropomorphic description was discussed.


Differential age-associated regulation of clusterin expression in prostate lobes of brown Norway rats.
Serum androgen concentrations decline with age in male Brown Norway rats and castration induces apoptosis of luminal secretory epithelial cells in the ventral but not in the dorsal and lateral prostate lobes. Clusterin has been described as an androgen-repressed gene and a protein with either anti- or pro-apoptotic actions. We measured clusterin mRNA and protein levels, the effects of aging and castration on clusterin protein levels and clusterin immunolocalization within the prostatic ductal network in the prostate lobes of young and aged rats. Whereas levels of clusterin mRNA and protein expression measured by RT-PCR and Western blot, respectively, were higher in the ventral and lateral lobes of aged (24 months) compared to young (4 months) rats, no age-dependent differences were observed in the dorsal lobe. Clusterin expression was localized by immunohistochemistry exclusively to the proximal duct segment of young rats, but extended to the distal segment of the ventral and lateral lobes of aged rats. Despite an age-related decrease in serum testosterone concentration, clusterin gene expression was not altered in the dorsal lobe. After castration, levels of clusterin expression increased significantly in the ventral and lateral lobes despite the absence of epithelial cell apoptosis in the latter. In castrated rats, clusterin expression extended throughout the proximal-distal duct regions of the prostate lobes of young and aged rats. Regulation of clusterin expression in the prostate lobes of aging rats appears complex and is neither directly repressed by androgen nor dependent on apoptotic-induced stress.


Fabrication of CoSe2/CoP with rich selenium- and phosphorus-vacancies and heterogeneous interfaces for asymmetric supercapacitors.
CoSe2/CoP with rich Se- and P-vacancies and heterogeneous interfaces (v-CoSe2/CoP) is grown on the surface of nickel foam via a two-step strategy: electrodeposition and NaBH4 reduction, which can be used as the cathode material in asymmetric supercapacitors. The SEM characterization reveals the honeycomb-like structure of the v-CoSe2/CoP, and the results of EPR, XPS and HRTEM reveal the existence of anionic vacancies and heterogeneous interfaces in the v-CoSe2/CoP. The as-fabricated v-CoSe2/CoP exhibits high specific capacitance (3206 mF cm-2 at 1.0 mA cm-2) and cyclic stability (91 % capacitance retention after 2000 cycles). An asymmetric supercapacitor is assembled by using the v-CoSe2/CoP and activated carbon (AC) as cathode and anode materials, respectively, which displays a high energy density of 40.6 Wh kg-1 at the power density of 211.5 W kg-1. The outstanding electrochemical performances of the v-CoSe2/CoP might be ascribed to the synergistic effects of Se- and P-vacancies and the heterogeneous interfaces in the v-CoSe2/CoP.


Oral fluoropyrimidines in the treatment of colorectal cancer.
5-Fluorouracil (5-FU) has been the mainstay of systemic therapy for colorectal cancer since its initial development 40 years ago. Efforts to improve the therapeutic index of 5-FU have included alteration of schedule and addition of biochemical modulators. An understanding of 5-FU mechanisms of action has resulted in major therapeutic advances in the past 10 years; however, a plateau has been reached in the efficacy of 5-FU, mandating a paradigm shift for those involved in colorectal cancer drug development. One direction vigorously pursued is the development of orally administered fluoropyrimidines that maintain or improve upon the effectiveness of intravenous 5-FU. In this paper the preclinical and clinical development of oral fluoropyrimidines and their modulators is reviewed, including UFT, capecitabine, ethynyluracil and S-1.


Streptococcus pneumoniae and Streptococcus pyogenes isolated from a paediatric population in Great Britain and Ireland: the in vitro activity of telithromcycin versus comparators.
To investigate the antimicrobial susceptibility profiles of clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes, isolated from children within Great Britain and Ireland (Northern Ireland and Eire), with particular reference to the new oral ketolide telithromycin. To determine the distribution of macrolide resistance genes within the erythromycin resistant population. MICs were determined using NCCLS microbroth dilution methodology and macrolide resistance mechanisms were investigated using PCR. Penicillin susceptibility was found to be 92.6% in S. pneumoniae isolates ( n=831; 3.7% intermediate, MIC 0.12-1 mg/l, 3.7% resistant, MIC >2.0 mg/l) and 100% in S. pyogenes isolates (n=1333) 8.8% of S. pneumoniae and 2.5% of S. pyogenes isolates demonstrated erythromycin-A resistance (EryA(R)). One hundred percent of S. pneumoniae and 99.8% of S. pyogenes isolates were susceptible to telithromycin (MIC<or=1.0 mg/l). Of the 73 EryA(R) S. pneumoniae isolates tested, 55 (75.3%) were mef (A) positive, 17 (23.3%) erm (B) positive and one isolate (1.4%) was positive for both mechanisms. Of the 34 isolates of EryA(R) S. pyogenes tested, 23 (67.6%) were erm (A) subclass erm (TR) positive, 4 (11.8%) erm (B) and 7 (20.6%) mef (A) positive. This paper presents baseline data on penicillin and macrolide resistance in S. pneumoniae and S. pyogenes isolates in the paediatric population of Great Britain and Ireland. Telithromycin, recently approved for the treatment of community acquired respiratory tract infections (CARTI) in patients over 12 years of age throughout the European community, demonstrated high in vitro activity against these pathogens, including EryA(R) strains.


Which prediction models best identify additional axillary disease after a positive sentinel node biopsy for breast cancer?
To determine which web-based model best identifies women at low risk of further axillary disease after a positive sentinel lymph node (SLN+) biopsy. 673 women with T1-2cN0M0 SNB+ breast cancer who underwent completion axillary dissection (AxD) were identified. A subgroup not eligible to avoid AxD as part of the Z0011 study was defined (Z0011 exclusion group). Predicted risk of further axillary disease was generated using seven web-based models. "Low risk" was defined as a ≤10% risk of further axillary disease. False negative ("low risk" prediction but AxD+) rates (FNRs), area under the receiver operating characteristic curve (AUC), and Brier score were determined for each model. 6 of 7 models identified "low risk" patients but FNRs ranged from 14 to 30%. The Stanford and Memorial Sloan-Kettering (MSKCC) models had the best FNRs. FNRs were lower with SLN micrometastasis (7-15%) and higher in the Z0011 exclusion group (21-41%). All models under-predicted further nodal disease in low risk patients and over-predicted in higher-risk patients. The Stanford and MSKCC models were able to identify women with SLN micrometastasis with a ≤10% FNR. Models were not able to accurately identify low risk women from a cohort that would have been excluded from Z0011.


A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer.
Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy. Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study. Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested. Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.


Spatial modeling and source identification of PAHs in soils and roadside dusts from Hangzhou, a new first-tier megcity of China.
Soil (n = 100) and roadside dust (n = 97) samples across a new first-tier megacity (Hangzhou, East China) were collected to systematically survey the spatial patterns and sources of 16 priority Polycyclic aromatic hydrocarbons (PAHs). The total PAH (Σ16PAH) concentrations in the surface soils exhibited an average of 329 ± 168 ng/g with a range of 67.7-2950 ng/g. 45 % of soils suffered from the weak - heavy PAH contaminations. By contrast, the average concentration of Σ16PAHs in roadside dusts was approximately three times higher than that found in the soils. Within both soil and dust samples, PAHs with a high molecular weight (HMW, 4-6 rings) were the dominant homologs. Spatial lag models revealed that industrial and traffic-related variables significantly influenced the spatial distribution of PAHs in dusts. Furthermore, a positive matrix factorization model indicated that Σ16PAHs in soils and dusts mainly derived from coal-related production/combustion and automobile exhaust emission (65.0 % and 77.9 %, respectively). The isotopic composition analysis conducted on heavily polluted samples further demonstrated that HMW PAHs in these soils and dusts predominantly originated from coal processing and liquid fossil fuel combustion. Overall, the findings of this study suggest that the intensive urban construction and human activities strongly stimulated PAH accumulations in soils and dusts during the rapid urbanization of Hangzhou.


The influence of stationary phase on pressure-induced retention, selectivity and resolution changes in RP-LC.
This paper reports the influence of a diverse range of stationary phases and differing mobile phase modifiers on pressure-induced retention changes in reversed-phase liquid chromatography (RP-LC). The practical implications of these effects in the Tanaka column characterization using ultra high-performance liquid chromatography (UHPLC) conditions, and implications for HPLC to UHPLC translations in order to increase productivity and resolution are investigated. The stationary and mobile phase combinations responded to a similar degree to elevated pressure; hence, the authors believe that reliable column characterization parameters should be obtainable when UHPLC format columns are evaluated using the Tanaka approach. Analytes exhibited differing pressure-induced retention changes even for only modest increases in pressure (i.e. ΔP(total) 85 bar as shown when one transfers from a 3- to 2-μm particle). The degree of pressure-induced retention changes correlated with the analyte's molar volume and refractivity. The hydrophobicity of the analytes, as measured by logD, only exhibited a weak correlation. Hence, translating a RP-LC methodology from large to smaller particle size material of the same type may result in an increased or decreased selectivity and hence resolution between two analytes depending on their differing response to the pressure-induced retention changes. This potentially has a major impact on LC method development/optimization strategies and LC method translations.


Perfluorinated and chlorinated pollutants as predictors of demographic parameters in an endangered seabird.
Despite global occurrence of several perfluorinated compounds (PFCs) the potential ecological effects of such substances on natural populations are not known. In endangered lesser black-backed gulls (Larus fuscus fuscus) on the Norwegian Coast, the blood concentrations of PFCs were as high as legacy organochlorines (OCs), and here we examined whether PFCs show associations similar to those of OCs to factors potentially affecting population growth, by evaluating relationships between contaminant concentrations and demographic parameters (reproductive performance and the probability of adults returning between breeding seasons). PFCs were not adversely associated with demographic parameters, while the most persistent OCs; notably PCB and p,p'-DDE, were adversely associated with early chick survival, and adult return rate. This study thus suggests that when the concentrations of PFCs and OCs are of similar magnitude in a gull population, OCs are more likely to cause adverse ecological effects.


Severe Corneal Hydrops With Suspected Posterior Stromal Rupture Managed With Ultrathin Descemet-Stripping Automated Endothelial Keratoplasty.
To describe severe acute corneal hydrops in a patient with previously undiagnosed keratoconus, in which anterior segment optical coherence tomography (AS-OCT) revealed a protruding ridge of tissue on either side of Descemet membrane (DM) break, treated successfully with ultrathin Descemet-stripping automated endothelial keratoplasty (UT-DSAEK). A case report. A 32-year-old man presented with severe corneal hydrops in OS. He was treated conservatively with hypertonic saline. Serial AS-OCT revealed persistent edema and haze overlying a break in DM, with a ridge of protruding tissue on either side. Based on these findings, UT-DSAEK was performed. Intraoperatively, the ridge of tissue remained firmly adhered after DM removal and was felt to possibly represent posterior stroma. The patient's uncorrected visual acuity improved to 20/80. Literature review revealed 1 case with similar AS-OCT findings who underwent penetrating keratoplasty; histopathology was reported to show Descemet scrolls on either side of the break, but our analysis of this and other reports suggest that an additional layer of tissue is contained within the scroll along with DM. This case demonstrates severe corneal hydrops in the setting of keratoconus, in which AS-OCT revealed a ridge of protruding tissue on either side of a break in DM. UT-DSAEK led to resolution of corneal edema and improvement in stromal haze and visual acuity. Further research is required to determine the precise role of endothelial keratoplasty and potential role of posterior stromal rupture in some cases of acute corneal hydrops.


Kidney transplantation in small children with live related donors: 20 years of experience.
Kidney transplantation (Tx) with a live related donor is the best option available for the treatment of end-stage renal disease at any age. Modern dialysis has allowed many very young and small children to receive a renal transplant with good results in spite of the limitations of space and the size of the adult kidney. Here, we report our experience with renal Tx with live related donors in this complex group of pediatric patients. From 1978 to 2004 a kidney transplantation was performed in 211 pediatric patients. Of this group, 23 patients between 1 and 10 years of age (16 males and seven females) of less than 17 kg (8.9-16.9 kg) received their first live related donor transplantation between 1985 and 2004. Renal insufficiency was secondary to nephropathy in 11 patients, infravesical obstruction in six and renal dysplasia or renal infarcts in six. Patient and graft survival was 100% and 95.6% with an average follow up of 89.6 months (6-231). There were no vascular or urological complications. Urinary infection in five (21.7%) and acute rejection in three (13%) were the most common complications. One patient has returned to dialysis 11 years after Tx. Young pediatric patients with a low body weight did not suffer a higher percentage of postoperative surgical complications, and the follow-up results are similar to those in older patients. A complex urological malformation has not prevented a living related Tx. These results encourage us to perform this procedure more frequently in younger patients when a live donor is available.


Association of the forced oscillation technique with negative expiratory pressure in COPD.
Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. The negative expiratory pressure (NEP) technique has been the gold standard to detect EFL, while the forced oscillation technique (FOT) has also been reported to detect it. However, the association of FOT with NEP is not fully understood. We assessed whether broadband frequency FOT would predict the presence of EFL measured by NEP. FOT, NEP, and spirometry were performed in 51 patients with COPD. The extent of emphysema was measured by high-resolution computed tomography and scored. Fifteen patients were classified into the EFL-positive group and 36 into the EFL-negative group. In multivariate logistic regression analysis, EFL was independently predicted by emphysema score, forced vital capacity, and whole-breath respiratory system reactance at 5Hz (X5). The receiver operator characteristic curve analysis revealed that inspiratory X5 best predicted EFL-positivity. X5-related forced oscillatory parameters are useful for detecting EFL in the management of COPD.


Colorimetric detection of platelet-derived growth factors through competitive interactions between proteins and functional gold nanoparticles.
We have developed a colorimetric assay-using aptamer modified 13-nm gold nanoparticles (Apt-Au NPs) and fibrinogen adsorbed Au NPs (Fib-Au NPs, 56nm)-for the highly selective and sensitive detection of platelet-derived growth factors (PDGF). Apt-Au NPs and Fib-Au NPs act as recognition and reporting units, respectively. PDGF-binding-aptamer (Apt(PDGF)) and 29-base-long thrombin-binding-aptamer (Apt(thr29)) are conjugated with Au NPs to prepare functional Apt-Au NPs (Apt(PDGF)/Apt(thr29)-Au NPs) for specific interaction with PDGF and thrombin, respectively. Thrombin interacts with Fib-Au NPs in solutions to catalyze the formation of insoluble fibrillar fibrin-Au NPs agglutinates through the polymerization of the unconjugated and conjugated fibrinogen. The activity of thrombin is suppressed once it interacts with the Apt(PDGF)/Apt(thr29)-Au NPs. The suppression decreases due to steric effects through the specific interaction of PDGF with Apt(PDGF), occurring on the surfaces of Apt(PDGF)/Apt(thr29)-Au NPs. Under optimal conditions [Apt(PDGF)/Apt(thr29)-Au NPs (25pM), thrombin (400pM) and Fib-Au NPs (30pM)], the Apt(PDGF)/Apt(thr29)-Au NPs/Fib-Au NPs probe responds linearly to PDGF over the concentration range of 0.5-20nM with a correlation coefficient of 0.96. The limit of detection (LOD, signal-to-noise ratio=3) for each of the three PDGF isoforms is 0.3nM in the presence of bovine serum albumin at 100μM. When using the Apt(PDGF)/Apt(thr29)-Au NPs as selectors for the enrichment of PDGF and for the removal of interferences from cell media, the LOD for PDGF provided by this probe is 35pM. The present probe reveals that the concentration of PDGF in the three cell media is 230 (±20)pM, showing its advantages of simplicity, sensitivity, and specificity.


Live birth in a 47-million-year-old snake.
Viviparity is a widespread reproductive trait in snakes, although fossil evidence bearing on its evolution is extremely sparse. Here, we report an exceptional specimen of the minute booid snake Messelophis variatus recovered in the paleolake of the Messel Formation (early-middle Eocene, Germany). This gravid female contains at least two embryos located in the posterior third of the trunk region. The morphology, size, and degree of ossification of the cranial and postcranial remains indicate they correspond with late embryos. This specimen documents the first occurrence of viviparity in a fossil snake and extends the temporal distribution of this reproductive strategy in booid snakes by over 47 Ma. The evolution of viviparity in squamates has traditionally been associated with cold climates, but its presence at the dawn of the evolution of booids during early Palaeogene thermal peaks indicates that viviparity may have evolved under different selective pressures in this clade.


Reduced activation to implicit affect induction in euthymic bipolar patients: an fMRI study.
To examine whether euthymic bipolar patients engage similar or contrasting brain regions as healthy subjects when responding to implicit affect induction. The study examined 10 euthymic patients with bipolar I disorder, and 10 age- and gender-matched healthy subjects using event-related functional magnetic resonance imaging (fMRI) while subjects engaged in a modified word-based memory task designed to implicitly evoke negative, positive or no affective change. The activation paradigm involved nominating whether a target word was contained within a previously presented word list using specified response keys. The fMRI task produced significantly greater activation in healthy subjects as compared to patients in response to both negative and positive affect in the anterior and posterior cingulate, medial prefrontal cortex, middle frontal and right parahippocampal gyri. Only negative affect produced significantly greater activation in the postcentral gyrus, inferior parietal lobule, thalamus and putamen and only positive affect achieved the same in the precentral, superior temporal and lingual gyri, precuneus, cuneus, caudate, pons, midbrain and cerebellum. There were no brain regions in which responses were greater in patients as compared to healthy subjects. There were no statistically significant differences between the groups with respect to speed or accuracy. Diminished prefrontal, cingulate, limbic and subcortical neural activity in euthymic bipolar patients as compared to healthy subjects is suggestive of emotional compromise that is independent of cognitive and executive functioning. This finding is of clinical importance and has implications both for the diagnosis and treatment of bipolar disorder. Future studies should aim to replicate these findings and examine the development of bipolar disorder, investigating in particular the effects of medication.


The Effectiveness of Neuromobilization in Patients With Cervical Radiculopathy: A Systematic Review With Meta-Analysis.
Neuromobilization exercises (NE) could be a useful therapeutic tool to induce analgesia and increase function and range of motion (ROM) in patients with musculoskeletal pathologies with neuropathic components; however, the effectiveness of this intervention in patients with cervical radiculopathy (CR) is unknown. To determine the effectiveness of NE in CR on pain, function, and ROM. Systematic review and meta-analysis. An electronic search was performed in the MEDLINE, Scopus, PEDro, and EBSCO databases from inception until June 2022. The authors included randomized clinical trials that evaluated the effectiveness of NE against control groups or other interventions that aimed to treat patients with CR. Seven clinical trials met the eligibility criteria, and for the quantitative synthesis, 5 studies were included. For the studies that compared NE with a control group, the standardized mean difference for pain was -1.33/10 (95% confidence interval [CI], -1.80 to -0.86; P < .01; I2 = 0%), for function with the Neck Disability Index was -1.21/50 (95% CI, -1.67 to -0.75; P < .01; I2 = 0%), and for neck flexion and extensions was 0.66 (95% CI, 0.23 to 1.10; P < .01; I2 = 0%) and 0.47 (95% CI, 0.04 to 0.90; P < .01; I2 = 0%), respectively, with evidence of clinical effectiveness. These findings were based on moderate-quality evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation rating. In studies that compared NE with other interventions, the meta-analysis failed to demonstrate the statistical or clinical superiority of NE. Moderate quality of evidence suggests that NE may be superior to no treatment for pain, function, and ROM in patients with CR. In contrast, NE are not superior to other interventions in the same outcomes, based on low- to very low-quality evidence. More high-quality research is needed to assess the consistency of these results.


[Nature of the relation of acute appendicitis morbidity to meteorological and heliogeophysical factors].
The authors analyzed 2009 appendicitis case records for the period from 1964 to 1973. In a sea climate region an evident season distribution of the apendicitis morbidity was found, with the rise of the incidence rate in January, March and April. The rise of the appendicitis incidence rate during the periods of vast fluctuations of air temperature, increase of air humidity and decrease of actual duration of sun radiance was established. The rise of the incidence of acute appendicitis was also noted during the months of a great and extremely great magnetic storms.


Rapid, one-pot, protein-mediated green synthesis of water-soluble fluorescent nickel nanoclusters for sensitive and selective detection of tartrazine.
In the work, water-soluble bovine serum albumin-protected fluorescent nickel nanoclusters (BSA-NiNCs) are used as fluorescent probes to construct a label-free fluorescence quenching sensor for sensitive and selective detection of tartrazine. The fluorescent BSA-NiNCs are synthesized in one pot using BSA as both the template and reducing agent, and hydrogen peroxide as the additive. The as-prepared NiNCs are characterized by using various analytical techniques like transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, UV-Vis absorption spectroscopy, circular dichroism spectroscopy, and fluorescence spectroscopy. The synthesized BSA-NiNCs have a quantum yield of ca. 8% by using quinine sulfate as a standard. The sensor for tartrazine detection shows a wide linear range of 0.01-3.5 μM, with a low detection limit of 4 nM. The fluorescence quenching very likely results from the combination of the intermolecular interactions and the secondary inner filter effect between BSA-NiNCs and tartrazine. Then, the proposed sensor is successfully employed for tartrazine detection in drink samples, and the results are comparable with those based on a reference HPLC method.


Tissue biopsy monitoring of operational tolerance in liver allograft recipients.
Highly selected, long-surviving, liver allograft recipients with normal/near normal liver injury tests can be weaned from immunosuppression. Baseline biopsies document changes before weaning and can help stratify risk of rejection or dysfunction after weaning; biopsies after weaning are used to study mechanisms of operational tolerance and to monitor for subclinical events. Clinicopathological features associated with successful weaning include a lack of sensitization [negative donor-specific antibodies (DSA) and lack of tissue C4d deposits]; 'inexperienced' recipient immune system with limited potential for cross-reactivity (less immunological memory; infant recipients); noninflamed allograft in those with nonviral, nonimmunological original diseases; upregulation of liver genes associated with iron metabolism; allograft colonization with 'immunosuppressive' cells (Treg and γδ-1>γδ-2); and longer time on immunosuppression, which might signal slow clonal deletion or silencing. The differential diagnosis of histopathological findings detected before and after weaning includes emerging infections, typical and atypical cellular rejection, indolent antibody-mediated rejection, 'autoimmunity', and other causes of progressive fibrosis. Operationally tolerant liver allograft recipients can be successfully managed with very low, and sometimes no immunosuppression, but challenges exist. Newer approaches to tissue pathology and tissue, serum, and cross-platform analytics are needed to predict successful weaning and to monitor for subclinical events.


Detection of genes expressed in primary colon cancers by in situ hybridisation: overexpression of RACK 1.
The isolation of various genes that are expressed in a region specific manner is considered useful for research in molecular pathology. In situ hybridisation (ISH) was used in a screening procedure to isolate these genes efficiently, using colon cancer as a model. Suppression subtractive hybridisation (SSH) between colon cancer tissue samples and corresponding non-cancerous tissues was performed. Genes showing high expression in the cancers were selected using macro-DNA array analysis. As a final screening procedure, conventional ISH was performed to isolate genes expressed specifically in colon cancers. Sixty nine clones were selected by SSH and macro-DNA array analyses. These clones were then analysed by ISH to examine their expression patterns. ISH screening revealed that all the clones screened showed more intense signals in colon cancers than in non-cancerous tissues. Among them, RACK 1, which is a protein kinase C receptor and a homologue of the G protein beta subunit, was expressed intensely in colon cancer cells. RACK 1 expression was evaluated in multiple samples by ISH, and the results confirmed that RACK 1 was universally overexpressed in cells of all 11 colon cancers examined. Many genes, including RACK 1, expressed in colon cancer cells can be isolated efficiently by this method, and their precise expression pattern can be evaluated. These results indicate that ISH is an excellent technique for systemic screening of genes expressed in a region specific manner.


Effect of prostaglandin E1 and indomethacin on responses of longitudinal muscle of guinea-pig ileum to cholecystokinin.
The effect of prostaglandin E1 (PGE1) and indomethacin (IND) cholecystokinin (CCK)-induced contractions of guinea-pig isolated ileum longitudinal muscle were studied. PGE1 (2.8--28 nM) consistently and dose dependently increased the contractions evoked by CCK (indirect muscle stimulation) or by ACh. IND (2.7 microM) decreased the contractions to both compounds and this was reversed with 2.8--7 nM PGE1. Pretreatment of the preparations with phentolamine (2.6 microM) or pretreatment of the animals with reserpine (2 mg/kg i.p. 24 h before killing) did not affect PGE1 potentiation or IND inhibition of CCK-induced contractions. The results indicated that PGE1 potentiated CCK-induced contractions of the longitudinal muscle of guinea-pig ileum by increasing the response to released ACh. Experiments with IND suggested that endogenous PGs may modulate the effect of CCK or related gastrointestinal hormones.


Predictors of human epidermal growth factor receptor 2 fluorescence in-situ hybridisation amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis.
Eligibility for anti-human epidermal growth factor receptor 2 (HER2) treatments in breast cancer requires a correct HER2 status assessment. Testing guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored as 2+ by immunohistochemistry. This study investigates the correlation between pathological features and FISH amplification in HER2 2+ breast cancer cases. 480 HER2 2+ breast cancer samples were included. The association between tumour grade, hormone receptor status, proliferation index (Ki67) and FISH amplification, using both US Food and Drug Administration (ratio ≥2) and American Society of Clinical Oncologists/College of American Pathologists cut-offs (ratio >2.2) was evaluated. 90.2% of the samples were hormone receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%), 268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio ≥2.0) and 20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1-2 tumours: 34% versus 18% (ratio ≥2.0, p<0.001) and 27% versus 9% (ratio >2.2, p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates than low Ki67 samples: 31% versus 21% (ratio ≥2.0, p=0.022) and 25% versus 12% (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case of grade 3 and high Ki67 with both cut-offs. In this study, high tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2 2+ breast cancer samples.


The p16 (CDKN2A) gene is involved in the growth of neuroblastoma cells and its expression is associated with prognosis of neuroblastoma patients.
We previously reported that loss of heterozygosity (LOH) on chromosome 9p21 correlates with poor prognosis of neuroblastoma and the p16 gene is not expressed in approximately two thirds of neuroblastoma cell lines. Here we demonstrated that p16 expression was induced by 5-aza-2-deoxycytidine treatment in cell lines with 5' CpG island methylation but not in cell lines without methylation. Furthermore, the cell cycle of neuroblastoma cell lines significantly delayed with accumulation of cells in G1 phase by transfection of a wild-type p16 expression vector. These results indicate that p16 is inactivated in part by DNA methylation and its expression is involved in the growth of neuroblastoma cells in vitro. To assess the biological and clinical significance of p16 expression in primary tumors, we undertook immunohistochemical analysis in 74 paraffin sections of neuroblastomas. p16 protein was undetectable in 45 of 74 cases (61%) and lack of p16 expression significantly correlated with poor prognosis of patients and advanced stage of the disease. There was no correlation between loss of p16 expression and N-myc amplification in these tumors. These results indicate that inactivation of the p16 gene is involved in the progression of neuroblastoma independently of N-myc amplification.


Autoimmune Disease in Primary Immunodeficiency: At the Crossroads of Anti-Infective Immunity and Self-Tolerance.
The association of autoimmunity and primary immunodeficiency suggests the existence of mechanistic links between development of the various elements of the immune system and the maintenance of self-tolerance. In this review, various monogenic primary immunodeficiencies (PID) are systematically explored, with a specific focus on the impact of these genetic lesions on tolerance, correlating these defects in tolerance with clinical autoimmune and inflammatory syndromes seen in these PIDs. Common variable immunodeficiency (CVID) is explored, and areas are highlighted in which findings in monogenic PID are beginning to illuminate the mechanisms behind these conditions in CVID.


[Use of coral implants in maxillofacial and otorhinolaryngologic surgery].
The coral, as bio-compatible implant, has been used in several indications: in Otology: for ossicular chain and external auditory canal reconstruction. In Maxillo-facial surgery: for orbital floor, maxillary sinus and jawbone reconstruction. The first results of this study are favorable but coral resorption might be prevent by a careful sealing of the implant deep under the surface layer.


Examining the efficacy and safety of endobiliary radiofrequency ablation for ingrowth occlusion after metal stent placement using a bovine model.
Although endobiliary radiofrequency ablation (RFA) may be an option for the treatment of ingrowth occlusion after self-expandable metal stent (SEMS) deployment, its utility remains uncertain. This study aimed to clarify its utility and safety using bovine liver. A prototype multifunctional RFA catheter and conventional uncovered SEMS were employed in this experimental study. We devised three model types: the ingrowth-ablation, ingrowth-ablation with stent-wire contact (created such that the electrodes were in contact with the metal stent-wire), and standard-ablation models (control). The study outcome was the ablation depth associated with RFA, which was compared among the three models. Thirty-six ablation procedures were conducted (12 for each of the 3 models). In the unipolar mode, the median ablation depth with the stent-wire contact model (1.0 mm) was significantly lower than that of the ingrowth-ablation (2.0 mm, p = 0.005) and standard-ablation models (2.3 mm, p = 0.004). There was no significant difference between the ingrowth-ablation and standard-ablation models (p = 0.563). In the bipolar mode, the median ablation depth with the stent-wire contact model (1.0 mm) was also significantly lower than that of the ingrowth-ablation (2.1 mm, p = 0.008) and standard-ablation models (2.0 mm, p = 0.011), and there was no significant difference between the ingrowth-ablation and standard-ablation models (p = 0.807). Scorching around the stent-wire was not observed in any specimen. In this ex vivo study, endobiliary RFA for ingrowth occlusion can be considered a useful modality, but the ablation effect is diminished when the electrode comes into contact with the stent-wire.


Genomic instability in blood cells from murine model of mucopolysaccharidosis type I.
Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glycosaminoglycans. Some studies have revealed that oxidative stress plays an important role in MPS I. However, the mechanisms by which these alterations occur are still not fully understood. The aim of this study was to analyze genomic instability in blood cells from murine model of MPS I by single cell gel (comet) assay and micronucleus test. The results pointed out genetic damage in blood cells as depicted by the single cell gel (comet) assay results. By contrast, no increase of micronucleated cells were found in mouse blood cells when compared to negative control. Taken together, our results suggest that IDUA deficiency induces genomic damage in blood cells. Certainly, this finding offers new insights into the mechanisms underlying the relation between IDUA deficiency and clinical manifestations that can occur in MPS I patients.


Transcatheter tricuspid valve-in-valve replacement: Making it simpler.
Transcatheter tricuspid valve-in-valve replacement (TTVR) represents an attractive therapeutic option in very high surgical risk patients with degenerated tricuspid bioprostheses. However, the procedural management of these patients might be challenging due to their comorbidities, long lasting heart valve disease and the presence of left-sided mechanical prostheses. Thus, a more "minimally disruptive" procedure would have several potential benefits in such a frail population. We present the cases of four patients admitted for congestive heart failure due to severe degeneration of their tricuspid bioprostheses who were treated with a minimalist TTVR. The protocol combined continuation of the oral anticoagulant treatment with no bridging therapy, the use of a single venous access with local anesthesia, rapid pacing via the stiff right ventricular wire, and transthoracic echocardiographic guidance and assessment, with no need for contrast injection. Our protocol aims at simplifying the TTVR procedure and might be a useful tool to avoid procedural complications and reduce hospital stay.


Predictors of sedentary behavior among colorectal survivors.
Colorectal cancer (CRC) survivors spend approximately 9 h per day in sedentary behavior (SED), despite recommendations to reduce sitting time. The purpose of this study was to examine predictors of SED among CRC survivors over a 1-year duration. Male and female CRC survivors (< 5 years since diagnosis) participated in a 12-week moderate-to-vigorous physical activity randomized controlled trial. To measure SED, participants were given a CSA monitor to wear for three consecutive days (including one weekend day). Additionally, fitness (Treadmill walk test), body composition (bioelectrical impedance analysis) and questionnaires (Profile of Mood States, Exercise Processes of Change and Self-Efficacy for Exercise) were administered. Follow-up assessments were completed at a 3-month, 6-month, and 12-month follow-up. Forty-six colorectal survivors (average age = 57.3 ± 9.7 years) completed the 12-month study. Using latent class models, four classes of SED behavior over time were identified: class 1 (high and sustained SED over time), class 2 (low and sustain SED over time), class 3 (increasing SED over time), and class 4 (high SED through 6-months, followed be a marked decrease at 12-months). Males were more likely to be in class 1, while majority of females were in class 3. Those CRC survivors with a better mood at baseline were in class 2, while those with poor fitness, high body fat, and higher cognitive processes at baseline were in class 3. Identifying the characteristics of survivors who engage in high SED can help healthcare providers to target their efforts to reduce SED.


The effect of emotional freedom technique and music applied to pregnant women who experienced prenatal loss on psychological growth, well-being, and cortisol level: A randomized controlled trial.
Research has shown that application of emotional freedom technique and music ensures psychological growth, increases well-being, and decreases cortisol level. In the study, it was aimed to determine the effect of EFT and music applied to pregnant women who had experienced prenatal loss on their psychological growth, well-being, and cortisol level. The study was conducted as a randomized controlled trial in a city hospital in eastern Türkiye with 159 pregnant women, 53 of whom were in the EFT, 53 in the music group, and 53 in the control group. The study data were collected through Subjective Units of Disturbance Scale (SUDS), Subjective Units of Experience (SUE) Scale, Post Traumatic Growth Inventory (PTGI), and WHO-5 Well-Being Index, and saliva samples were taken for cortisol evaluation. EFT was applied to the women two times every other week; the women in the music group listened to music two times every other week. Throughout the week following the first intervention, the women continued the interventions at home. It was determined that EFT and music significantly decreased the participants' subjective anxiety and salivary cortisol median scores, the lowest anxiety was in the EFT group, and PTGI and WHO-5 Well-Being Index mean scores increased (p < 0.005). Further analyses showed that EFT was more effective in terms of increasing well-being than music (p < 0.001; a > b > c). It was determined that the anxiety levels and salivary cortisol median values of the control group were statistically significantly higher compared to the EFT and music groups (p < 0.001). It was found that EFT and music applied to the women who had experienced prenatal loss decreased anxiety, ensured psychological growth, improved well-being, and decreased salivary cortisol level.


Removal of copper ions from aqueous solutions by a steel-making by-product.
A study is made of the use of a steel-making by-product (rolling mill scale) as a material for removing Cu(2+) ions from aqueous solutions. The influence of contact time, initial copper ion concentration and temperature on removal capability is considered. The removal of Cu(2+) ions from an aqueous solution involves two processes: on the one hand, the adsorption of Cu(2+) ions on the surface of mill scale due to the iron oxides present in the latter; and on the other hand, the cementation of Cu(2+) onto metallic iron contained in the mill scale. Rolling mill scale is seen to be an effective material for the removal of copper ions from aqueous solutions.


Assisted reproductive technologies and fertility "tourism": examples from global Dubai and the Ivy League.
What motivates the global movements of infertile people searching for assisted reproductive technologies (ARTs)? In this article, we attempt to answer this question by exploring infertile patients' practices of so-called "fertility tourism." Based on ethnographic research carried out with nearly 300 infertile travelers in two major ART centers--one in the global hub of the United Arab Emirates and the other at a major East Coast Ivy League university--we examine a diverse set of reasons for reproductive travel. We argue that reproductive "tourism" should be reconceptualized as reproductive "exile" in that infertile couples feel barred from accessing ARTs in their home countries. Listening to reproductive travel stories is key to understanding infertile couples' transnational "quests for conception." Stories of two couples, one from Lebanon and one from Italy, demonstrate the poignancy of these quests and begin to shed light on the complex calculus of factors governing this global movement of reproductive actors.


Determination of hemoglobin expression patterns in erythroid cells of Rana catesbeiana tadpoles.
1. Rana catesbeiana (bullfrog) tadpoles are heterogeneous in the relative amounts of four major tadpole hemoglobins (Hbs), as well as in the relative amounts of two tadpole red blood cell types in the peripheral blood. 2. Previous work has shown that this heterogeneity is present at all stages of larval development and growth. 3. Although some tadpoles lack one of the Hbs in their peripheral blood (i.e. the electrophoretically slowest form, Td-4), the missing Hb can be found in the erythropoietic organ from which it emanates (the kidneys), indicating that the heterogeneity results from quantitative differences in gene expression. 4. We wished to know whether this in vivo regulation is subject to external environmental perturbation and report that tadpoles of known Hb phenotypes regenerate precisely the pre-anemia Hb profile during early as well as late stages of recovery from phenylhydrazine-induced anemia. 5. These and other results indicate that the in vivo mechanism for regulating the pattern of Hb expression has become firmly determined in the erythropoietic system by the earliest larval stage of development.


Karst groundwater protection: First application of a Pan-European Approach to vulnerability, hazard and risk mapping in the Sierra de Líbar (Southern Spain).
The European COST action 620 proposed a comprehensive approach to karst groundwater protection, comprising methods of intrinsic and specific vulnerability mapping, validation of vulnerability maps, hazard and risk mapping. This paper presents the first application of all components of this Pan-European Approach to the Sierra de Líbar, a karst hydrogeology system in Andalusia, Spain. The intrinsic vulnerability maps take into account the hydrogeological characteristics of the area but are independent from specific contaminant properties. Two specific vulnerability maps were prepared for faecal coliforms and BTEX. These maps take into account the specific properties of these two groups of contaminants and their interaction with the karst hydrogeological system. The vulnerability assessment was validated by means of tracing tests, hydrological, hydrochemical and isotope methods. The hazard map shows the localization of potential contamination sources resulting from human activities, and evaluates those according to their dangerousness. The risk of groundwater contamination depends on the hazards and the vulnerability of the aquifer system. The risk map for the Sierra de Líbar was thus created by overlaying the hazard and vulnerability maps.


Clinical Impact of a Dedicated Trauma Hybrid Operating Room.
Early hemorrhage control is essential to optimal trauma care. Hybrid operating rooms offer early, concomitant performance of advanced angiographic and operative hemostasis techniques, but their clinical impact is unclear. Herein, we present our initial experience with a dedicated, trauma hybrid operating room. This retrospective cohort analysis of 292 adult trauma patients undergoing immediate surgery at a Level I trauma center compared patients managed after implementation of a dedicated, trauma hybrid operating room (n = 186) with historic controls (n = 106). The primary outcomes were time to hemorrhage control (systolic blood pressure ≥ 100 mmHg without ongoing vasopressor or transfusion requirements), early blood product administration, and complication. Patient characteristics were similar between cohorts (age 41 years, 25% female, 38% penetrating trauma). The hybrid cohort had lower initial hemoglobin (10.2 vs 11.1 g/dL, p = 0.001) and a greater proportion of patients undergoing resuscitative endovascular balloon occlusion of the aorta (9% vs 1%, p = 0.007). Cohorts had similar case mixes and intraoperative consultation with cardiothoracic or vascular surgery (13%). Twenty-one percent of all hybrid cases included angiography. The interval between operating room arrival and hemorrhage control was shorter in the hybrid cohort (49 vs 60 minutes, p = 0.005). From 4 to 24 hours after arrival, the hybrid cohort had fewer red cell (0.0 vs 1.0, p = 0.001) and plasma transfusions (0.0 vs 1.0, p < 0.001). The hybrid cohort had fewer infectious complications (15% vs 27%, p = 0.009) and ventilator days (2.0 vs 3.0, p = 0.011), and similar in-hospital mortality (13% vs 10%, p = 0.579). Implementation of a dedicated, trauma hybrid operating room was associated with earlier hemorrhage control and fewer early blood transfusions, infectious complications, and ventilator days.


Hypothalamic neurons innervating fat tissue in the pig express leptin receptor immunoreactivity.
While leptin receptors have been found in both the autonomic ganglion neurons and the hypothalamic nuclei, studies dealing with the projections from the central nervous system to the adipose tissue have been conducted mainly in laboratory animals. Therefore, the purpose of our study was to establish whether hypothalamic neurons are transsynaptically connected to adipose tissue depots in the pig, and if these neurons express leptin receptor immunoreactivity. Pseudorabies virus (PRV; Bartha's K strain) was introduced in perirenal or subcutaneous adipose tissue depots in domestic pigs. On day 9, animals were euthanized and hypothalami were collected and processed immunohistochemically with primary antisera against PRV and leptin receptor (OBR). PRV-labeled neurons were localized in paraventricular nucleus, supraoptic nucleus and arcuate nucleus following injections in both the perirenal and the subcutaneous adipose tissue depots. Ventromedial nucleus, dorsomedial nucleus and preoptic area-labeled neurons were observed after injection of the PRV into the perirenal adipose tissue, while in the lateral hypothalamic area-labeled neurons projected only to the subcutaneous adipose tissue. The majority of the PRV-labeled neurons simultaneously expressed OBR-immunoreactivity. Our results provide the morphological data on multisynaptic projections from hypothalamus to the fat tissue in the pig and demonstrate that these neurons, located in areas involved in reproductive processes and feeding behavior, may regulate fat tissue metabolism.


Dual atrioventricular conduction during an acute inferior myocardial infarction. Electrocardiographic evidence.
A 49-year-old man had electrocardiographic evidence of a dual atrioventricular conduction system which occurred spontaneously during the course of an inferior myocardial infarction. Retrograde concealed conduction involving both conduction systems is proposed as the mechanism to explain the varying patterns of atrioventricular conduction seen.


Elucidating the role of select cytoplasmic proteins in altering diffusion of integrin receptors.
Cytoplasmic proteins that affect integrin diffusion in the cell membrane are identified using a combination of fluorescence recovery after photobleaching (FRAP) and RNA interference. Integrin receptors are essential for many cellular events, and alterations in lateral diffusion are one mechanism for modulating their function. In cells expressing native cytoplasmic protein concentrations and spread on a slide containing integrin extracellular ligand, 45 ± 2% of the integrin is mobile with a time-dependent 5.2 ± 0.9 × 10(-9) cm(2)/s diffusion coefficient at 1 s. The time exponent is 0.90 ± 0.07, indicating integrin diffusion moderately slows at longer times. The role of a specific cytoplasmic protein in altering integrin diffusion is revealed through changes in the FRAP curve after reducing the cytoplasmic protein's expression. Decreased expression of cytoplasmic proteins rhea, focal adhesion kinase (FAK), or steamer duck decreases the integrin mobile fraction. For rhea and FAK, there is a concomitant shift to Brownian (i.e., time-independent) diffusion at reduced concentrations of these proteins. In contrast, when the expression of actin 42A, dreadlocks, paxillin, integrin-linked kinase (ILK), or vinculin is reduced, integrin diffusion generally becomes more constrained with an increase in the integrin mobile fraction. This same change in integrin diffusion is measured in the absence of integrin extracellular ligand. The results indicate breaking the extracellular ligand-integrin-cytoskeletal linkage alters integrin diffusion properties, and, in most cases, there is no correlation between integrin and lipid diffusion properties.


Inflammatory Bowel Disease Phenotype in Pediatric Primary Sclerosing Cholangitis.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that most often occurs in association with inflammatory bowel disease (IBD). We examined whether the activity or colonic distribution of IBD differed in pediatric patients with and without PSC. We compared colonic disease distribution, physician global assessment scores, Mayo endoscopic severity scores, IBD-related hospital admissions, and colonic resection surgery rate in a retrospective cohort of pediatric patients with IBD with and without PSC. We identified 37 patients with PSC-IBD, and 137 non-PSC matched IBD controls. Pancolitis was seen in 89.7 versus 72.4% (P = 0.051) of patients with PSC-IBD and rectal sparing in 24.3 versus 21.6% (P = 0.721) of patients with IBD. Physician global assessment and Mayo scores at presentation and in follow-up were similar in PSC-IBD and IBD. Patients with PSC-IBD had 0.19 admissions per person-year compared with 0.25 in patients with IBD. The incidence rate ratio for admission was 0.75 (95% confidence interval (CI), 0.51-1.08). The 5-year probability of colonic surgery was 16.4% (95% CI, 7.0-36.0) in patients with PSC-IBD and 24.7% (95% CI, 17.7-33.8) in patients with IBD (P = 0.271). In a multivariate model, male sex (hazard ratio [HR] = 2.2 [95% CI, 1.1-4.3]) and the presence of a non-PSC immune-mediated comorbidity {HR = 3.9 (95% CI, 1.5-10.4), but not PSC (HR = 0.5 [95% CI, 0.2-1.3])} or Crohn's disease (HR = 0.5 [95% CI, 0.1-1.5]), were risk factors for colonic surgery in pediatric IBD. Patients with IBD and PSC were more likely to present with pancolitis, but had similar rates of rectal sparing. Patients with IBD showed similar disease activity across a wide range of measures, at presentation and in follow-up, regardless of the presence of PSC.


Abundance of phosphorylated Apis mellifera CREB in the honeybee's mushroom body inner compact cells varies with age.
Hymenopteran eusociality has been proposed to be associated with the activity of the transcription factor CREB (cAMP-response element binding protein). The honeybee (Apis mellifera) is a eusocial insect displaying a pronounced age-dependent division of labor. In honeybee brains, CREB-dependent genes are regulated in an age-dependent manner, indicating that there might be a role for neuronal honeybee CREB (Apis mellifera CREB, or AmCREB) in the bee's division of labor. In this study, we further explore this hypothesis by asking where in the honeybee brain AmCREB-dependent processes might take place and whether they vary with age in these brain regions. CREB is activated following phosphorylation at a conserved serine residue. An increase of phosphorylated CREB is therefore regarded as an indicator of CREB-dependent transcriptional activation. Thus, we here examine the localization of phosphorylated AmCREB (pAmCREB) in the brain and its age-dependent variability. We report prominent pAmCREB staining in a subpopulation of intrinsic neurons of the mushroom bodies. In these neurons, the inner compact cells (IC), pAmCREB is located in the nuclei, axons, and dendrites. In the central bee brain, the IC somata and their dendritic region, we observed an age-dependent increase of pAmCREB. Our results demonstrate the IC to be candidate neurons involved in age-dependent division of labor. We hypothesize that the IC display a high level of CREB-dependent transcription that might be related to neuronal and behavioral plasticity underlying a bee's foraging behavior.


Natural history of primary biliary cirrhosis.
Primary biliary cirrhosis is an insidious disease that progresses through the clinical phases: preclinical, asymptomatic, symptomatic, and liver insufficiency. The outlook of patients diagnosed with PBC has improved significantly over the past 2 decades because more patients are being diagnosed earlier in the disease process and being treated with UDCA. A need remains to better define and predict the course of symptomatic and asymptomatic patients on and off UDCA in order to better evaluate outcomes of clinical trials.


Paroxysmal supraventricular tachycardia during theophylline therapy in a premature infant.
An episode of supraventricular tachycardia occurred in an infant born at 31 weeks' gestation after three days of therapy with theophylline 3.5 mg/kg every six hours. The infant had a plasma theophylline half-life of 24.7 hours and a low plasma theophylline clearance of 12.7 ml/kg/hour. The plasma theophylline concentration at the time of the arrhythmia was about 42 mg/l. The extent of drug accumulation with these kinetic characteristics is emphasized. Serious adverse effects due to theophylline may occur with few signs of symptoms of impending toxicity. Plasma theophylline concentration measurements are valuable in avoiding such toxicity.


Major histocompatibility complex non-restricted presentation to CD4+ T lymphocytes of Mycobacterium leprae heat-shock protein 65 antigen by macrophages transfected with the mycobacterial gene.
When the immunodominant 65,000 MW heat-shock protein of Mycobacterium leprae (ML65hsp) was expressed from the transfected mycobacterial gene in the mouse macrophage cell line J774.G8, the antigen was recognized by specifically sensitized CD4+ splenocytes in association with major histocompatibility complex (MHC) class II and CD4. Inhibition by monensin, leupeptin and chloroquine but not brefeldin A indicated dependence of presentation upon endosomal antigen processing. Although direct access of the endogenously synthesized antigen to the endosomal pathway of presentation, without extracellular release followed by endocytosis, could not be discounted, antigen was present in supernatants of the transfected cells in a form that could be presented by fixed macrophages and a form that required further processing for presentation. Each of three monoclonal antibodies (mAb) specific for widely separated linear amino acid epitopes of the antigen strongly inhibited recognition, suggesting steric interference with antigen-presenting cell (APC)-T cell interaction. Tests with splenocytes from vaccinated congenic mice indicated that recognition was not restricted by MHC haplotype. The significance and mechanism of this apparent MHC context-independent interaction of the presented antigen with specific T-cell receptor (TcR) remain to be explored.


IL 3 and IL 6 do not induce bone resorption in vitro.
Bone resorption in vitro and in vivo can be induced by interleukin 1 (IL 1) and tumor necrosis factor (TNF), both of which are potent inflammatory cytokines. Additionally, there are other factors produced by cells which can active osteoclasts. Because diverse factors are involved in bone resorption, we examined the role of two other inflammatory cytokines, IL 3 and IL 6. IL 3 has been shown to induce the formation of osteoclast-like cells from precursors, while IL 6 is a potent mediator of inflammatory responses. Osteoclast activity in neonatal mouse calvaria was measured as 45Ca released into the supernatant fluid following a 48 hr incubation period with cytokine. Our results show that while parathyroid hormone (PTH) and IL 1 are potent inducers of bone resorption, neither IL 3 nor IL 6 displayed such activity.


Proliferation characteristics of erythroblasts in chronic renal failure.
Proliferation of bone marrow erythroblasts in patients with chronic renal disease was studied by combined application of cytophotometric measurement of the DNA content and 3H-TdR labeling in vitro. A striking decrease of 3H-TdR labeling was found in most of the cases. The proportion of diploid (G0 + G1) as well as of tetraploid unlabeled cells (G2) was increased. The data suggest a disturbed induction of DNA synthesis of resting cells as well as an arrest of cells in G2 being responsable for ineffective cell production in this disease.


Engineered high content of ricinoleic acid in fission yeast Schizosaccharomyces pombe.
In an effort to produce ricinoleic acid (12-hydroxy-octadeca-cis-9-enoic acid: C18:1-OH) as a petrochemical replacement in a variety of industrial processes, we introduced Claviceps purpurea oleate ∆12-hydroxylase gene (CpFAH12) to Schizosaccharomyces pombe, putting it under the control of inducible nmt1 promoter. Since Fah12p is able to convert oleic acid to ricinoleic acid, we thought that S. pombe, in which around 75% of total fatty acid (FA) is oleic acid, would accordingly be an ideal microorganism for high production of ricinoleic acid. Unfortunately, at the normal growth temperature of 30 °C, S. pombe cells harboring CpFAH12 grew poorly when the CpFAH12 gene expression was induced, perhaps implicating ricinoleic acid as toxic in S. pombe. However, in line with a likely thermoinstability of Fah12p, there was almost no growth inhibition at 37 °C or, by contrast with 30 °C and lower temperatures, ricinoleic acid accumulation. Accordingly, various optimization steps led to a regime with preliminary growth at 37 °C followed by a 5-day incubation at 20 °C, and the level of ricinoleic acid reached 137.4 μg/ml of culture that corresponded to 52.6% of total FA.


Predictive value of ASCVD risk score for mortality and major adverse cardiovascular events in the year following a COVID-19 infection among US Veterans.
Morbidity and mortality following COVID-19 infection may be influenced by baseline atherosclerotic cardiovascular disease (ASCVD) risk, yet limited data are available to identify those at highest risk. We examined the association between baseline ASCVD risk with mortality and major adverse cardiovascular events (MACE) in the year following COVID-19 infection. We evaluated a nationwide retrospective cohort of US Veterans free of ASCVD who were tested for COVID-19. The primary outcome was absolute risk of all-cause mortality in the year following a COVID-19 test among those hospitalized vs. not stratified by baseline VA-ASCVD risk scores. Secondarily, risk of MACE was examined. There were 393,683 Veterans tested for COVID-19 and 72,840 tested positive. Mean age was 57 years, 86% were male, and 68% were white. Within 30 days following infection, hospitalized Veterans with VA-ASCVD scores >20% had an absolute risk of death of 24.6% vs. 9.7% (P ≤0.0001) for those who tested positive and negative for COVID-19 respectively. In the year following infection, risk of mortality attenuated with no difference in risk after 60 days. The absolute risk of MACE was similar for Veterans who tested positive or negative for COVID-19. Veterans without clinical ASCVD experienced an increased absolute risk of death within 30 days of a COVID-19 infection compared to Veterans with the same VA-ASCVD risk score who tested negative, but this risk attenuated after 60 days. Whether cardiovascular preventive medications can lower the risk of mortality and MACE in the acute period following COVID-19 infection should be evaluated.


Critical steps in clinical shotgun metagenomics for the concomitant detection and typing of microbial pathogens.
High throughput sequencing has been proposed as a one-stop solution for diagnostics and molecular typing directly from patient samples, allowing timely and appropriate implementation of measures for treatment, infection prevention and control. However, it is unclear how the variety of available methods impacts the end results. We applied shotgun metagenomics on diverse types of patient samples using three different methods to deplete human DNA prior to DNA extraction. Libraries were prepared and sequenced with Illumina chemistry. Data was analyzed using methods likely to be available in clinical microbiology laboratories using genomics. The results of microbial identification were compared to standard culture-based microbiological methods. On average, 75% of the reads corresponded to human DNA, being a major determinant in the analysis outcome. None of the kits was clearly superior suggesting that the initial ratio between host and microbial DNA or other sample characteristics were the major determinants of the proportion of microbial reads. Most pathogens identified by culture were also identified through metagenomics, but substantial differences were noted between the taxonomic classification tools. In two cases the high number of human reads resulted in insufficient sequencing depth of bacterial DNA for identification. In three samples, we could infer the probable multilocus sequence type of the most abundant species. The tools and databases used for taxonomic classification and antimicrobial resistance identification had a key impact on the results, recommending that efforts need to be aimed at standardization of the analysis methods if metagenomics is to be used routinely in clinical microbiology.


Histamine is correlated with liver fibrosis in biliary atresia.
Biliary atresia (BA) is a severe neonatal cholestasis disease that is caused by obstruction of extra bile ducts. Liver fibrosis progresses dramatically in BA, and the underlying molecular mechanism is largely unknown. Amino acids and biogenic amines were quantified by targeted metabolomic methods in livers of 52 infants with BA and 16 infants with neonatal hepatitis syndrome (NHS). Normal adjacent nontumor liver tissues from 5 hepatoblastoma infants were used as controls. Orthogonal partial least-squares discriminant analysis was used to identify the differences between BA, NHS, and control tissues. Histamine metabolism enzymes and receptors were analyzed by immunohistochemistry and Western blot. The orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and the controls using amino acid and biogenic amine profiles. Histamine was significantly increased in the livers of BA infants and was positively correlated with the severity of fibrosis. This finding was supported by the elevated l-histidine decarboxylase and reduced monoamine oxidase type B expressions in the BA infants with severe fibrosis. Furthermore, histamine receptor H1 was observed in the cholangiocytes of BA livers. Histamine was positively correlated with fibrosis and may be a potential target to prevent liver fibrosis in BA.


Predation risk and the structure of freshwater zooplankton communities.
Many predators inflict substantial mortality on their prey. The prey respond to these selective pressures with changes in their spatial and temporal overlap with the predator (density risk responses), or with changes in their vulnerability to the predator (prey vulnerability responses). Here we develop a simple predation model that permits quantification of the basic response types of the prey in nature. We then test the hypothesis that prey response will be proportional to the intensity of the predation mortality relative to all other sources of mortality and decreased natality acting on the prey. A significant regression relationship is obtained for the prey vulnerability response but not for any of the density risk responses. The individual response values and regression statistics are used to interpret the relative importance of the different response types and to assess the predator's influence on prey community structure.


Thoracoscopic resection of a giant mediastinal parathyroid cyst.
Parathyroid cysts are a rare situation, unusually in the mediastinum. The preoperative diagnosis could be more difficult in some atypical topographies and imaging characteristics in particular in case of huge mediastinal cyst. In the following years traditionally, in case of intrathoracic parathyroid cysts, sternotomy or thoracotomy have been the preferred approaches. We report a case of an older patient with a huge mediastinal parathyroid cyst removed successfully using videothoracoscopy.


Maintenance of High Cytochrome P450 Expression in HepaRG Cell Spheroids in DMSO-Free Medium.
We studied the effects of DMSO and fibroblasts during HepaRG cell spheroid formation and conditions of their subsequent culturing on the levels of mRNA of the major cytochromes P450. A protocol of spheroid formation from differentiated HepaRG cells and their culturing in serum- and DMSO-free medium is developed.


Neurological manifestations of Fabry disease in female carriers.
A family is described in which a 33-year-old man has classic X-linked recessive Fabry disease. His 2 sisters were discovered to be heterozygous carriers of the Fabry gene and to have both episodic and permanent neurological deficits including vertigo, tinnitus, long tract motor signs, and bladder incontinence. The most concise explanation for these findings is that the sisters manifest central nervous system complications of the Fabry carrier state. This family provides additional evidence that female carriers of rare X-linked recessive disorders may exhibit serious consequences of the disease, presumably related to tissue variability in expression of mutant enzyme activity.


Rho/Rho kinase pathway regulates maintenance of the differentiated tubular epithelial cell phenotype on laminin-1.
Maintenance of a polarized tubular epithelium by appropriate intracellular signaling and extracellular matrix is critical both in normal renal function as well as in acute and chronic tubular injury. We examined the hypothesis that maintenance of a differentiated epithelial phenotype on the basement membrane glycoprotein laminin-1 is controlled by the Rho/Rho kinase pathway. Using the tubular epithelial cell lines LLC-PK1 and MDCK which were cultured on laminin-1 vs. collagen IV, we analyzed cell morphology and motility (cohort migration assay) as well as expression of differentiation and dedifferentiation markers (immunofluorescence microscopy). Cohort migration of LLC-PK1 cells was significantly slowed down on laminin-1 (10.7 +/- 2.2 m.u. (migratory units)) compared with collagen IV (16.6 +/- 2.3 m.u.; BSA control: 2.8 +/- 2.5 m.u.). Inhibition of the Rho/Rho kinase pathway by C3 exotoxin (1 mug/ml) or the Rho kinase inhibitor Y27632 (10 microM) significantly augmented cohort migration on laminin-1 (14.5 +/- 1.4 and 16.0 +/- 1.8 m.u. vs. 10.7 +/- 2.2 m.u.). In parallel to the increased migratory activity, inhibition of the Rho/Rho kinase pathway resulted in a more mesenchymal phenotype of LLC-PK1 cells on laminin-1 with increased formation of lamellopodia and filopodia, distinct loss of focal contacts and stress fibers, upregulation of the dedifferentiation marker vimentin, and loss of cell-cell contacts with translocation of beta-catenin from the adherens junctions to the cytosol and nucleus. Similarly, cohort migration of MDCK cells was retarded on laminin-1 when compared with collagen IV, and addition of the Rho kinase inhibitor Y27632 resulted in enhanced motility and a change in cell morphology. The study demonstrates that the Rho/Rho kinase pathway is required to maintain a non-migratory epithelial phenotype of cultured renal tubular LLC-PK1 and MDCK cells on the basement membrane glycoprotein laminin-1.


Role of CBL Mutations in Cancer and Non-Malignant Phenotype.
CBL plays a key role in different cell pathways, mainly related to cancer onset and progression, hematopoietic development and T cell receptor regulation. Somatic CBL mutations have been reported in a variety of malignancies, ranging from acute myeloid leukemia to lung cancer. Growing evidence have defined the clinical spectrum of germline CBL mutations configuring the so-called CBL syndrome; a cancer-predisposing condition that also includes multisystemic involvement characterized by variable phenotypic expression and expressivity. This review provides a comprehensive overview of the molecular mechanisms in which CBL exerts its function and describes the clinical manifestation of CBL mutations in humans.


Recovery of indium from LCD screens of discarded cell phones.
Advances in technological development have resulted in high consumption of electrical and electronic equipment (EEE), amongst which are cell phones, which have LCD (liquid crystal display) screens as one of their main components. These multilayer screens are composed of different materials, some with high added value, as in the case of the indium present in the form of indium tin oxide (ITO, or tin-doped indium oxide). Indium is a precious metal with relatively limited natural reserves (Dodbida et al., 2012), so it can be profitable to recover it from discarded LCD screens. The objective of this study was to develop a complete process for recovering indium from LCD screens. Firstly, the screens were manually removed from cell phones. In the next step, a pretreatment was developed for removal of the polarizing film from the glass of the LCD panels, because the adherence of this film to the glass complicated the comminution process. The choice of mill was based on tests using different equipment (knife mill, hammer mill, and ball mill) to disintegrate the LCD screens, either before or after removal of the polarizing film. In the leaching process, it was possible to extract 96.4 wt.% of the indium under the following conditions: 1.0M H2SO4, 1:50 solid/liquid ratio, 90°C, 1h, and stirring at 500 rpm. The results showed that the best experimental conditions enabled extraction of 613 mg of indium/kg of LCD powder. Finally, precipitation of the indium with NH4OH was tested at different pH values, and 99.8 wt.% precipitation was achieved at pH 7.4.


Survival of children diagnosed with acute lymphoblastic leukemia in 1977-82 in Connecticut.
There was no evidence for an increase in survival among all all cases (N = 104) diagnosed between 1977-82 with acute lymphoblastic leukemia (ALL) at age less than 15 years and reported to the population-based Connecticut Tumor Registry (CTR). Hazard rates were consistently higher in males vs females during the second year after diagnosis, especially in males diagnosed after 1977-78. Registry data on prognostic factors, including white blood cell (WBC) count at diagnosis and Down's syndrome (DS), and initial treatment were used to interpret survival data by sex and year of diagnosis. A statistically significant sex difference in 4-year survival among cases diagnosed in 1979-80 was related to an unusually high survival rate (i.e. 100%) in females and the occurrence of two male DS cases. Further studies are needed on sex-specific survival rates among ALL cases diagnosed after 1977-78 in population-based cancer registries, which could be improved by more complete collection of data on immunophenotype and validation of data on relapses.


Impact of repeated percutaneous coronary intervention on long-term survival after subsequent coronary artery bypass surgery.
In the current stent era, aggressive repeated percutaneous coronary intervention (PCI) has become more common. The aim of this study was to investigate the impact of previous repeated PCI on the subsequent coronary artery bypass grafting (CABG). Between January 1990 and January 2008, a total of 894 patients underwent first-time isolated elective CABG. Among the 894 patients, 515 patients had had no PCI (group A), 179 patients had had single PCI (Group B), and 200 patients had had multiple PCI (2-15 times, mean 3.6 ± 2.3 times) (group C) before CABG. These groups were compared in terms of early and late clinical results. Preoperative left ventricular ejection fraction was significantly higher in group A (group A;58 ± 13%, group B;54 ± 12%, and group C;54 ± 12%). Number of bypass grafts was significantly smaller in group C (A:3.3 ± 1.0, B 3.4 ± 0.9, C 3.1 ± 1.0). Although there was no statistically significant difference among the groups, in-hospital mortality in group C was higher than that in group A and B (A:1.6%, B:1.1%, C:3.5%, p = 0.16). Survival analysis by Kaplan-Meier method (mean follow-up: 58 ± 43 methods) revealed that freedom from all-cause death and cardiac death was significantly lower in group C in comparison with group A. Freedom from cardiac event was significantly higher in group C than that in group A. Multivariate analysis identified a number of previous PCI as an independent risk factor for cardiac death. Repeated PCI increased risk for long-term prognosis of subsequent CABG.


Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire.
The life cycle of endogenous retroviruses (ERVs), also called long terminal repeat (LTR) retrotransposons, begins with transcription by RNA polymerase II followed by reverse transcription and re-integration into the host genome. While most ERVs are relics of ancient integration events, "young" proviruses competent for retrotransposition-found in many mammals, but not humans-represent an ongoing threat to host fitness. As a consequence, several restriction pathways have evolved to suppress their activity at both transcriptional and post-transcriptional stages of the viral life cycle. Nevertheless, accumulating evidence has revealed that LTR sequences derived from distantly related ERVs have been exapted as regulatory sequences for many host genes in a wide range of cell types throughout mammalian evolution. Here, we focus on emerging themes from recent studies cataloging the diversity of ERV LTRs acting as important transcriptional regulatory elements in mammals and explore the molecular features that likely account for LTR exaptation in developmental and tissue-specific gene regulation.


Differential effects of infralimbic cortical lesions on temperature and locomotor activity responses to feeding in rats.
The time of food availability induces important behavioral and metabolic adaptations. Animals subjected to feeding restricted to a few daytime hours show increased locomotor activity and body temperature in anticipation of mealtime. In addition, animals under ad libitum feeding show a marked postprandial raise in body temperature and in thermogenesis. The areas of the brain commanding these responses to food are partially known. We investigated in the rat the role of the infralimbic area, located in the medial prefrontal cortex, and considered a visceral-autonomic motor area, in the responses to ad libitum or restricted feeding schedule. We performed infralimbic cortex excitotoxic lesions using injections of ibotenic acid, and measured body temperature and locomotor activity by telemetry in rats under ad libitum and restricted feeding conditions. We found that bilateral infralimbic area lesions prevented both the anticipatory and the postprandial increases in core temperature, decreased mean temperature by nearly 0.3 degrees C during both light/dark phases, and increased daily temperature variability. In contrast, the lesion caused a rapid induction of the anticipatory locomotor activity. These results show that behavioral and metabolic responses to the time of food availability are commanded separately and that the infralimbic area is a key structure to adjust the body temperature to an upcoming meal.


Syntactics of interpretation of negation: a developmental study.
Two cues are considered as syntactic indicators of the focus of a sentential negation in 7- and 10-year-olds and adults. One is the articles; it is proposed that an indefinite noun phrase is taken within the scope of a negative and a definite noun phrase outside it. A second cue is position. Based on R. S. Jackendoff's (1969, Foundations of Language, 5, 218-241) and P. A. Hornby's (1971, Child Development, 42, 1975-1988) work, subjects may be expected to take the second noun within the focus of sentential negatives regardless of the articles. In Experiments 1 and 2, subjects made picture selections for sentences of the form A/the Noun1 isn't V-ing the/a Noun2 and their passives. In Experiment 3, 10-year-olds describe the scenes of the sentences of the prior experiments. Noun position and article independently influenced the focus of the negation with age trends. Developmental differences in the uses of the articles are related to the acquisition of mastery of these linguistic markers.


[Renal involvement in Sjögren's syndrome].
Primary Sjögren syndrome is an autoimmune disorder characterized by lymphoplasmacytic infiltration of the exocrine (salivary and lachrymal) glands resulting in sicca symptoms (dryness). Systemic complications can occur in primary Sjögren syndrome, but renal involvement is rare, affecting<10% patients. The most frequent form of nephropathy in primary Sjögren syndrome is tubulointerstitial nephritis, where infiltration of the kidney by plasma cells is a key feature and shows similarity to the lymphoplasmacytic infiltration of the salivary glands. Electrolyte disturbances may occur in primary Sjögren syndrome, such as renal distal tubular acidosis, diabetes insipidus, Gitelman syndrome, or Fanconi syndrome. Glomerular involvement is less frequently detected in patients with primary Sjögren syndrome, but can take the form of membranoproliferative glomerulonephritis secondary to cryoglobulinaemia. The renal prognosis in patients with primary Sjögren syndrome and TIN or glomerular disease is usually good, but the risk of chronic kidney disease remains significant for some patients. Appropriate screening must be performed at least once a year in patients with systemic primary Sjögren syndrome in order to facilitate the early detection of renal complications. In this Review, we discuss the epidemiology, pathophysiology, differential diagnosis, and treatment of renal disease in primary Sjögren syndrome.


Sonodegradation of halomethane mixtures in chlorinated drinking water.
Ultrasonic degradation of halomethane mixtures, with very low initial concentration in chlorinated drinking water was investigated. It was observed that the removal efficiencies of four halomethanes after 1 h ultrasonic irradiation followed the increasing order: CHCl(3) < CHBr(2)Cl < CHBrCl(2) < CCl(4) and the degradation reactions of the halomethanes were well described by the pseudo-first-order kinetics model. Molecular polarity was found to be an important factor controlling the sonodegradation of halomethane mixtures. Increasing acoustic intensity enhanced the removal of halomethanes in chlorinated drinking water. In addition, ultrasonic irradiation led to a slightly decrease of pH and TOC of chlorinated drinking water.


Cognitive dysfunction after acute lacunar infarct.
Vascular dementia and vascular cognitive impairment have attracted more attention recently due to their association with increased risk of death and institutionalization. The purpose of the present study was to detect and identify the characteristics of cognitive impairments during the early stage of lacunar stroke. The subjects consisted of 23 consecutive first-ever acute lacunar infarction patients who were admitted to the Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, from November 2001 to October 2002. The National Institutes of Health Stroke Scale and Cognitive Abilities Screening Instrument (CASI) were used to evaluate stroke severity and cognitive function, and assessments were performed by a neurologist and psychologist, within 10 days of stroke onset. Of the 23 patients, 21 (91.3%) had CASI scores below their respective cutoff values and all patients had cognitive impairment in at least one cognitive domain in CASI. There were no significant correlations between CASI abnormality (below the cutoff value) and patient age, education, or the interval from stroke onset. Recent memory impairment was the most often impaired cognitive domain on CASI (19 patients, 82.6%). There were significant correlations between recent memory and "attention or concentration"(correlation coefficient, 0.52; p < 0.05), and "abstraction and judgment" (correlation coefficient, 0.44; p < 0.05). The correlations between recent memory and other domains were not significant. It was concluded that cognitive impairment after acute lacunar infarct is quite common and recent memory is the most often impaired cognitive domain. This may have been caused by the location of the specific lesion as well as by the impairment in "attention or concentration" or "abstraction and judgment".


Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case.
Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.


Evaluation of antidiabetic activity of biologically synthesized silver nanoparticles using Pouteria sapota in streptozotocin-induced diabetic rats.
Medicinal plants and green synthesis of silver nanoparticles (AgNPs) have proven to be good sources of agents effective in the treatment of diabetes mellitus. The present study focused on the green synthesis of AgNPs from the aqueous leaf extract of Pouteria sapota in order to evaluate the in vitro and in vivo antidiabetic properties of this extract and the synthesized AgNPs. The AgNPs were biologically synthesized under ambient conditions from an aqueous leaf extract of P. sapota using the hot percolation method and were characterized using spectroscopic methods, X-ray diffraction, and scanning electron microscopy. The in vitro antidiabetic activity of the aqueous leaf extract and AgNPs was confirmed by non-enzymatic glycosylation of hemoglobin, glucose uptake by yeast cells following exposure of cells to 5 or 10 mmol/L glucose solution, and inhibition of α-amylase. Further, in vivo antidiabetic activity was assessed in streptozotocin-induced rats. Rats were treated with aqueous leaf extract (100 mg/kg) or AgNPs (10 mg/kg) for 28 days. Following treatment, rats were killed for biochemical and histopathological analysis of kidney and liver samples. A significant reduction in blood sugar levels was noted in rats treated with leaf extract or AgNPs. Results of in vitro and in vivo analyses in rats treated with leaf extract or AgNPs show that both the extract and the biologically synthesized AgNPs have antidiabetic activity. The aqueous leaf extract of P. sapota and AgNPs exhibited efficient antidiabetic activity in the rat model of diabetes and therefore could have potential for development for medical applications in the future.


Sarcopenia and adverse health-related outcomes: An umbrella review of meta-analyses of observational studies.
The purpose of this umbrella review was to assess the associations between sarcopenia and adverse health-related outcomes. An umbrella review of meta-analyses of observational studies. Patients with sarcopenia and controls without sarcopenia were included. The PubMed, Web of Science and Embase were searched for relevant systematic review and meta-analysis. AMSTAR and GRADE system were used for methodological quality and evidence quality assessments, respectively. Totally 54 outcomes extracted from 30 meta-analyses were analyzed. Twenty out of 21 prognostic outcomes indicated that sarcopenia was significantly associated with poorer prognosis of gastric cancer, hepatocellular cancer, urothelial cancer, head and neck cancer, hematological malignancy, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, esophageal cancer, and ovarian cancer. Besides, 10 out of 16 postoperative outcomes suggested that sarcopenia significantly increased the risk of multiple postoperative complications and prolonged the length of hospitalization of patients with digestive cancer. In age-related outcomes, sarcopenia significantly increased the risk of dysphagia, cognitive impairment, fractures, falls, hospitalization, and all-cause mortality of elderly populations. Moreover, sarcopenia was also associated with higher level of albuminuria, risk of depression, and several metabolic diseases. Sarcopenia significantly affected a wide range of adverse health-related outcomes, particularly in patients of tumor and elderly populations. Because evidences of most outcomes were rated as "low" and "very low," more prospective cohort studies are required in the future.


Possible function of the c-myc product: promotion of cellular DNA replication.
We have recently cloned a plasmid, pARS65, containing the sequences derived from mouse liver DNA which can autonomously replicate in mouse and human cells (Ariga et al., 1987). In this report, we show that replication of pARS65 in HL-60 cells can be inhibited by co-transfection with anti-c-myc antibody. In an in-vitro replication system using HL-60 nuclear extract, pARS65 functioned as a template. This in-vitro replication was also blocked by addition of anti-c-myc antibody. Specific binding activity of the c-myc product to pARS65 was detected by an immunobinding assay, suggesting that the c-myc protein promotes DNA replication through binding to the initiation site of replication. This has been substantiated using the antibody to help isolate a human DNA segment that can autonomously replicate in the cells.


3D tracking of mating events in wild swarms of the malaria mosquito Anopheles gambiae.
We describe an automated tracking system that allows us to reconstruct the 3D kinematics of individual mosquitoes in swarms of Anopheles gambiae. The inputs to the tracking system are video streams recorded from a stereo camera system. The tracker uses a two-pass procedure to automatically localize and track mosquitoes within the swarm. A human-in-the-loop step verifies the estimates and connects broken tracks. The tracker performance is illustrated using footage of mating events filmed in Mali in August 2010.


Anomerization and hydrolysis of lactose by beta-galactosidase from Saccharomyces lactis.
Beta-Galactosidase from Saccharomyces lactis was found to be able to catalyze both the anomerization of alpha-lactose and the hydrolysis of beta-lactose; the rate of hydrolysis appeared to be four times higher with a 1:1 mixture of alpha and beta lactose than with a freshly prepared solution of alpha-lactose. The enzyme was also found to be unable to hydrolyze alpha-lactose. Thus, it appears that beta-galactosidase from S. lactis has its hydrolytic activity on lactose adapted only to the naturally more abundant beta-lactose.