Application of molecular source tracking and mass balance approach to identify potential sources of fecal indicator bacteria in a tropical river.
Microbial source tracking and a mass balance approach were used to identify sources of fecal indicator bacteria (FIB) in the Hanalei River, Kaua'i, Hawai'i. Historically, concentrations enterococci and Clostridium perfringens were significantly higher during storm flows compared to non-storm flows in the Hanalei River, and correlated to total suspended solids in the river. During targeted dry weather studies, the Hanalei River bed sediments and streambank soils were documented to harbor E. coli, enterococci, and the human- and pig-specific fecal markers in Bacteroidales, suggesting that sediments and soils may be potential sources of these microorganisms to the Hanalei river. The human-specific marker in Bacteroidales was four times as likely to be detected in sediment and soil samples as in water samples. Furthermore, the occurrence of host-specific source tracking markers is indicative that a portion of FIB present in the Hanalei River are of fecal origin. A mass balance approach was used to explore causes of observed FIB loadings and losses along different reaches of the river. Resuspension or deposition of FIB-laden river sediments cannot account for changes in E. coli and enterococci concentrations along the river during dry weather. Additionally, losses due to bacterial inactivation were insignificant. Groundwater and ditches draining agricultural and urban lands were shown to provide sufficient FIB fluxes to account for the observed loads along some river reaches. The presence of the human-specific Bacteroidales marker in the river water, sediments and adjacent soils, as well as the presence of the human enterovirus marker in the water, suggests that there is widespread human fecal contamination in the Hanalei River that is likely a result of nearby wastewater disposal systems.


Drugs and sexual behavior.
This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed.


Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines.
Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.


DRAM Weak Cell Characterization for Retention Time.
This work proposes a sequence of tests for detecting refresh weak cells based on data retention time distribution in the main cell array of DRAMs and verify the feasibility of the proposed method through analysis of 30 nm design-rule DRAM cells with Recess Channel Array Transistor (RCAT) and Buried Channel Array Transistor (BCAT). Basic idea of the proposed mechanism is to test with different bias conditions and break down retention failures based on their root causes such as Gate Induced Drain Leakage, sub-threshold leakage and junction leakage. This categorization helps to determine the physical locations of each failure group, enabling precise Physical Failure Analysis (PFA). The characterization of data retention weak cells for 30 nm design rule DRAMs with BCAT and RCAT has been investigated. Most weak cells were classified as GIDL leaky cells in both cases. In the case of BCAT, the distance between the word line and the storage node, caused by the process distribution, is the main origin of weak cells. In the case of RCAT, the sharp corner of the active layer in the storage node is the main cause of weak cells.


Preparation of Monolithic Silica and Polymer Capillary Columns with Ultrahigh Column Efficiencies and Comparisons between van Deemter Plots of Alkylbenzenes on These Two Kinds of Columns.
Monolithic silica and polymer capillary columns with ultrahigh column efficiencies were prepared. Permeability and electrochromatography performances of these two kinds of columns were compared. Monolithic silica columns bear higher permeability than polymer counterparts by two orders of magnitude. Furthermore, the van Deemter plots of alkylbenzenes on these two kinds of columns demonstrate that monolithic silica columns produce much lower plate heights of alkylbenzes than polymer columns do. Within the range of electroosmotic flow (EOF) velocity investigated, no uptrend of plate height with the increase of EOF was observed suggesting the great capacity of fast separation and high efficiency. The plate height of thiourea on monolithic silica columns is as low as 2.67 μm, representing its corresponding column efficiency is over 430,000 plates/m. As far as we know, it is the highest ever column efficiency reported in the literature. Moreover, the separation of butylbenzene isomers was obtained on the monolithic silica column.


Glucose-insulin kinetics of a bioartificial pancreas made of an AN69 hydrogel hollow fiber containing porcine islets and implanted in diabetic mice.
The goal of this study was to determine whether porcine islets encapsulated in hollow fibers made of AN69 copolymer can correct hyperglycemia in diabetic mice and provide normal tolerance to a glucose challenge. In vitro perifusion of hollow fibers demonstrated the rapid kinetics of insulin release in response to glucose. Two fibers containing islets were transplanted into the peritoneal cavity of each of 17 streptozotocin induced diabetic mice. In 11 mice, diabetes was reversed within 3 days with plasma glucose levels decreasing from 19.7 +/- 0.9 (mean +/- SEM) before implantation to 10.9 +/- 0.8 mmol/L. Intraperitoneal glucose tolerance tests were performed in transplanted (n = 7), nondiabetic (n = 15), and diabetic mice (n = 6). A normal glucose pattern was observed in the transplanted diabetic mice. This was achieved in the presence of plasma insulin levels lower than those observed in control nondiabetic mice, suggesting the presence of a state of hypersensitivity to insulin, which was demonstrated in this model by exogenous insulin tolerance tests. In conclusion, encapsulation of islets suspended in ultraculture medium in biocompatible membranes of AN69 can provide xenograft survival, and complete normalization of glucose tolerance can be achieved.


Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial.
Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4-2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Forty-five episodic migraineurs (5-14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. ClinicalTrials.gov, NCT03132233 . Registered on 27 April 2017.


A genetic segmentation of ECG signals.
This paper is concerned with a development of a segmentation technique for electrocardiogram (ECG) signals. Such segmentation is aimed at a lossy signal compression in which each segment can be captured by a simple geometric construct such as, e.g., a linear or quadratic function. The crux of the proposed construct lies in the determination of the optimal segments of data over which they exhibit the highest possible monotonicity (or lowest variability) of the ECG signal. In this sense, the proposed approach generalizes a fundamental and commonly encountered problem of function (data) linearization. The segments are genetically developed using a standard technique of genetic algorithms (GAs). The two fundamental GA constructs, namely a topology of a chromosome and a fitness function governing the optimization process are discussed in detail. The chromosome being coded as a series of floating point numbers contains the endpoints of the segments (segmentation points). The fitness function to be maximized quantifies a level of monotonicity of the ECG data encountered within the segments and takes into consideration differences between the extreme values (minimum and maximum) of its derivatives. As a result of the genetic optimization, we build segments of ECG signals encompassing monotonic (increasing or decreasing) regions of the signal exhibiting a minimal level of variability. A series of experiments dealing with several classes of ECG signals (namely, normal, left bundle branch block beat, and right bundle branch block beat) visualize the effectiveness of the approach and shows the specificity of the linear segments of data. Furthermore, we elaborate on the relationship between the values of the fitness function and the approximation capabilities (quantified by a sum of squared errors between the local model and the data) of the segments of the signal and show that these two descriptors are highly related.


Successful medical treatment of a spinal histoplasmoma.
A woman with previously treated disseminated histoplasmosis was admitted with progressive paraparesis. Magnetic resonance imaging showed multifocal cerebritis and spinal histoplasmoma. She recovered following a second treatment with amphotericin B. This is the fourth reported patient with intramedullary spinal histoplasmoma, and the first demonstrating successful treatment of the lesion with medical therapy alone.


Smallpox vaccine complications: the dermatologist's role in diagnosis and management.
In 2002, the United States implemented a new program for smallpox vaccinations among military personnel using a live vaccinia virus product. Approximately 2.4 million US military service members and health care workers have since been inoculated, with considerable numbers experiencing adverse reactions. Military dermatologists are at the forefront of describing and treating these reactions, from relatively benign generalized vaccinia (GV) and erythema multiforme (EM) to more severe progressive vaccinia (PV) and eczema vaccinatum (EV). A wide range of providers, including civilian dermatologists and primary care providers, also may see such reactions and must be aware of the spectrum of vaccine reactions. Given current world instability (eg, threats of nuclear war, rise of authoritarian regimes) and concerns for bioterrorism attacks, the smallpox vaccine program likely will continue indefinitely. As the brisk military deployment tempo continues, a larger population of new vaccinees will yield more cutaneous reactions and diagnostic challenges.


Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience.
Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinico-pathological subtype of diffuse large B-cell lymphoma (DLBCL). The optimal treatment is unknown, with some studies suggesting a superior outcome with dose-intensive chemotherapy regimens, and the role of radiotherapy remains ill-defined. The British Columbia Cancer Agency lymphoma database was searched and records reviewed to identify those patients presenting with a prominent mediastinal mass and considered to be PMBCL based on the current REAL/WHO classifications. Patients were treated based on era-specific BCCA guidelines (1980-1992 MACOPB/VACOPB; 1992-2001 CHOP-type; 2001-present CHOP-R). Beginning in January 1998 involved-field radiotherapy was recommended to be routinely administered following chemotherapy. Prior to this, use of radiotherapy was individualized in advanced disease. In total, 153 patients with newly diagnosed PMBCL were identified between 28 July 1980 and 30 June 2003. The median age was 37 years (range 13-82) and the majority had stage I/II (74%), bulky mediastinal disease (75%). Overall (OS) and progression-free (PFS) survival at 5 years for the entire cohort were 75% and 69%, respectively. In direct comparison with a cohort of patients with DLBCL (n = 1273), OS (P = 10(-4)) and PFS (P = 0.0001) favored PMBCL. The age-adjusted International Prognostic Index (aaIPI) was not predictive of survival (P = 0.18). Five-year OS in patients < 65 years old treated with MACOPB/VACOPB, CHOP-R and CHOP-type was 87%, 81% and 71% respectively (P = 0.048). In pair-wise survival comparisons, only MACOPB/VACOPB and CHOP-type treated patients were significantly different (P = 0.016). In Cox multiple regression analysis, poor performance status remained the only predictor of survival, with treatment received demonstrating a trend to worse outcome for patients treated with CHOP-type regimens (P = 0.09). In an intention-to-treat analysis comparing the era before radiotherapy was routinely administered with after, there was no significant difference in 5-year PFS (74% versus 62%; P = 0.09) or OS (78% versus 69%; P = 0.14). In this single institution, population-based retrospective study, we found that PMBCL patients have excellent survival rates and a distinct plateau is observed in PFS, in striking comparison to DLBCL. The aaIPI was not predictive of survival in this population, suggesting that other prognostic models may be better suited for risk stratification. Dose-intensified chemotherapy with MACOPB or VACOPB demonstrated a trend to superior outcome over CHOP-type chemotherapy. However, further randomized studies are needed and the impact of rituximab on these comparisons must be considered. Finally, the routine addition of radiotherapy does not improve survival.


SgNramp1, a plasma membrane-localized transporter, involves in manganese uptake in Stylosanthes guianensis.
Transporters belonging to the natural resistance-associated macrophage protein (Nramp) family play important roles in metal uptake and homeostasis. Although Nramp members have been functionally characterized in plants, the role of Nramp in the important tropical forage legume Stylosanthes guianensis (stylo) is largely unknown. This study aimed to determine the responses of Nramp genes to metal stresses and investigate its metal transport activity in stylo. Five SgNramp genes were identified from stylo. Expression analysis showed that SgNramp genes exhibited tissue preferential expressions and diverse responses to metal stresses, especially for manganese (Mn), suggesting the involvement of SgNramps in the response of stylo to metal stresses. Of the five SgNramps, SgNramp1 displayed the highest expression in stylo roots. A close correlation between SgNramp1 expression and root Mn concentration was observed among nine stylo cultivars under Mn limited condition. The higher expression of SgNramp1 was correlated with a high Mn uptake in stylo. Subsequent subcellular localization analysis showed that SgNramp1 was localized to the plasma membrane. Furthermore, heterologous expression of SgNramp1 complemented the phenotype of the Mn uptake-defective yeast (Saccharomyces cerevisiae) mutant Δsmf1. Mn concentration in the yeast cells expressing SgNramp1 was higher than that of the empty vector control, suggesting the transport activity of SgNramp1 for Mn in yeast. Taken together, this study reveals that SgNramp1 is a plasma membrane-localized transporter responsible for Mn uptake in stylo.


Shadow pitching deviates ball release position: kinematic analysis in high school baseball pitchers.
Although shadow pitching, commonly called "towel drill," is recommended to improve the throwing motion for the rehabilitation of pitching disorders before the initiation of a throwing program aimed at returning to throwing using a ball, the motion differs from that of normal throwing. Learning improper motion during ball release (BR) may increase shoulder joint forces. Abnormal throwing biomechanics leads to injures. However, there has been no study of shadow pitching focusing on the BR position. The purpose of the present study was to evaluate the BR position and kinematic differences between shadow pitching and normal throwing. In addition, the effect of setting a target guide for BR position on throwing motion was examined in shadow pitching. The participants included in this study were 20 healthy male students who were overhand right-handed pitchers with no pain induced by a throwing motion. Participants performed normal throwing (task 1), shadow pitching using a hand towel (task 2), and shadow pitching by setting a target of the BR position (task 3). A motion capture system was used to evaluate kinematic differences in throwing motions, respectively. Examination items comprised joint angles and the differences in BR position. BR position of task 2 shifted significantly toward the anterior, leftward, and downward directions compared with task 1. The distance of BR position between tasks 1 and 2 was 24 ± 10%. However, task 3 had decreased BR deviation compared with task 2 (the distance between 3 and 1 was 14 ± 7%). Kinematic differences were observed among groups at BR. For shoulder joint, task 2 showed the highest value in abduction and horizontal adduction among groups. In spine flexion, left rotation and thorax flexion, task 2 was significantly higher than task 1. Task 3 showed small differences compared with task 1. The BR position of shadow pitching deviated significantly in the anterior, leftward, and downward directions compared with normal throwing. Furthermore, we demonstrated that the setting of BR target reduces this deviation. Thus, the target of BR position should be set accurately during shadow pitching exercises in the process of rehabilitation.


The optimal discontinuation of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention with drug-eluting stents: A meta-analysis of randomized trials.
Current guidelines recommend prolonged dual antiplatelet therapy (DAPT) for patients with drug-eluting stents (DES) implantation. Nevertheless, optimal discontinuation of DAPT remains a controversy. We performed a meta-analysis of all randomized controlled trials (RCTs) that evaluate optimal discontinuation of DAPT in patients undergoing percutaneous coronary intervention (PCI) with DES. We searched electronic databases including PubMed, Cochrane Library, EMBASE and ClinicalTrials.gov from database RCTs that reported different modes of discontinuation of DAPT in patients with DES. The primary endpoints were all-cause death, cardiovascular death, myocardial infarction (MI) and probably or definite stent thrombosis (ST). Secondary endpoints were repeat revascularization, stroke, major bleeding and net adverse clinical events (NACE). We included 13 RCTs meeting the criteria with a total of 36,749 patients. No significant difference was observed in all-cause death (RR [95% CI]=0.87 [0.75, 1.01], P=0.07, I2=0%), cardiovascular death (RR [95% CI]=0.97 [0.79, 1.19], P=0.76, I2=0%), repeat revascularization (RR [95% CI]=1.07 [0.92, 1.25], P=0.36, I2=0%), and stroke (RR [95% CI]=1.01 [0.80, 1.28], P=0.94, I2=0%). Compared with shorter DAPT, longer DAPT was associated with a significant reduction in MI (RR [95% CI]=1.46 [1.26, 1.69], P<0.00001, I2=28%) and ST (RR [95% CI]=1.93 [1.45, 2.58], P<0.00001, I2=32%), and a significant increase in major bleeding (RR [95% CI]=0.60 [0.49, 0.74], P<0.00001, I2=0%). However, there was no difference in NACE (RR [95% CI]=1.03 [0.91, 1.17], P=0.63, I2=0%). In subgroup analyses based on stent type, we demonstrated that longer DAPT was associated with a significant reduction in thrombotic events (MI and ST) after first-generation DES implantation (RR [95% CI]=2.58 [1.85, 3.58], I2=0%) and everolimus-eluting stents (EES, RR [95% CI]=1.54 [1.12, 2.11], I2=0%). Conversely, there was no difference in thrombotic events in patients with zotarolimus-eluting stents (ZES, RR [95% CI]=1.17 [0.83, 1.63], I2=75%) and biodegradable polymer DES (BP-DES, RR [95% CI]=1.15 [0.74, 1.79]). 1) Compared with shorter DAPT, longer DAPT was associated with a significant reduction in thrombotic events (MI and ST) and a higher rate of major bleeding. 2) By the assessment of the trade-off between thrombotic and hemorrhagic events, shorter DAPT was non-inferior to longer DAPT. 3) The benefit of longer DAPT was significant in patients with first-generation DES and EES and weakened with other second-generation DES (ZES and BP-DES).


Helical CT myelogram: the Ibadan initial experience.
To evaluate our initial experience with Helical Computed Tomography (CT) Myelogram in the investigation of spinal abnormalities. As late as 1980, CT was still regarded as unreliable compared with myelography however, the advent of slip-ring technology in the 1990s, in association with the use of more powerful computers and higher energy x-ray tubes allowed a process known as Helical CT. This revolutionized CT scanning allowing achievement of thinner slices in a single breath-hold. Helical CT myelogram is one of the recent applications with the potential of improving clinical diagnosis in patients with spinal disorders. This is a descriptive study of 56 patients who had a CT myelogram in the first 15 months of operation of a helical CT scanner at Ibadan (January 2004-March 2005). Axial scans were done after a lumbar puncture with injection of 8-10 mls of contrast (iopamidol). Demographic, clinical data and CT findings were analyzed. Patient ages ranged from 3 to 75 years. The highest age frequency was seen in the 4th and 5th decade. 37 (66%) of these patients were males and 19 (34%) were females. The majority of scans, 22 (39.2%) were in the thoracic and thoraco-lumbar regions. Low back pain was the most common indication 26 (32.1%) followed by paraplegia 24 (29.6%). Spinal cord compression and spondylosis represented 34% and 20% of the CT findings respectively. Helical CT myelogram is a valuable investigative tool which demonstrates spinal abnormalities well by providing a good silhouette image of the spinal cord.


Motivational readiness for active commuting by university students: incentives and barriers.
Walking for transport can contribute significantly to health-enhancing physical activity. We examined the associations of stages of motivational readiness for active transport with perceived barriers and incentives to walking to and from university among students. Mail-back surveys were completed by 781 students in a regional university in south-east Queensland. They identified one of eight options on motivational readiness for active commuting, which were then classified as: pre-contemplation; contemplation-preparation; or, action-maintenance. Open-ended questions were used to identify relevant barriers and incentives. Logistic regressions were used to examine the barriers and incentives that distinguished between those at different stages of motivational readiness. Barriers most frequently reported were long travel distances, inconvenience and time constraints. Incentives most frequently reported were shorter travel distance, having more time, supportive infrastructure and better security. Those not considering active commuting (pre-contemplation) were significantly more likely to report shorter travel distance as an incentive compared to those in contemplation-preparation. Those in contemplation-preparation were significantly more likely to report lack of motivation, inadequate infrastructure, shorter travel distance and inconvenience as barriers; and, having more time, supportive infrastructure, social support and incentive programs as encouragement. Different barriers and incentives to walking to or from university exist for students in the different stages of motivational readiness for active commuting. Interventions targeted specifically to stage of motivational readiness may be potentially helpful in increasing activity levels, through active transport.


A skin window study of neutrophil migration in subjects with localized juvenile periodontitis.
This study investigated the effect of a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (FMLP), upon skin window migration of neutrophils into filters in 5 patients with a history of localized juvenile periodontitis (LJP) and 8 controls. On 2 occasions, each subject had 2 superficial skin abrasions made on the inner aspect of the forearm. Initial periodontal treatment was carried out on the disease group between the visits. On one skin window filters were placed that were soaked in physiological saline, and on the other filters soaked with FMLP. Leading fronts and cell densities were measured in each filter. At visit 1, LJP subjects had significantly lower leading fronts and cell densities. At visit 2, the differences were insignificant. The leading fronts for the LJP group were significantly improved on the second visit. No difference was observed between saline and FMLP. The findings of this study indicate that neutrophil migration is reduced in LJP patients where treatment is not involved, and that FMLP has no effect on neutrophil migration from the skin windows under the conditions of this study.


Substrate-dependent differences in production of extracellular matrix molecules by squamous carcinoma cells and diploid fibroblasts.
Two human squamous carcinoma cell lines and human diploid fibroblasts were examined for the production of extracellular matrix (ECM) molecules including fibronectin (FN), laminin (LN), and thrombospondin (TSP) when grown on a number of different substrates. The substrates used included glass, plastic, collagen (gelatin), and DEAE-dextran. Levels of TSP as indicated by enzyme-linked immunosorbent assay did not vary significantly as a function of substrate. In contrast, LN levels in the culture medium were significantly decreased when the cells were grown on DEAE-dextran or collagen-linked dextran as compared to the other substrates. FN levels were slightly lower in the culture medium of the cells grown on DEAE-dextran. Biosynthetic labeling followed by immunoprecipitation indicated that the reduction in LN was due, in part, to decreased biosynthesis. Previous studies have indicated that LN influences the behavior of epithelial cells in culture and that the cells, themselves, are a major source of the LN. The differences in LN production noted here indicate that the production of this ECM component is influenced by the substratum on which the cells are grown. These differences could contribute to alterations in biological properties that are known to be influenced by the substratum.


CLEC4s as Potential Therapeutic Targets in Hepatocellular Carcinoma Microenvironment.
Immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) is critical in tumor development. C-type (Ca2+ -dependent) lectin (CLEC) receptors, essential in innate pattern recognition, have potential regulatory effects on immune cell trafficking and modulatory effects on cancer cell activity. However, information on the expression and prognostic value of CLECs in HCC is scanty. Herein, we explored the potential role of CLECs in HCC based on TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, Metascape, TRRUST, and TIMER databases. Results demonstrated a significantly higher mRNA level of CLEC4A and CLEC4L in HCC tissues than normal liver tissues. Contrarily, we found significantly low CLEC4G/H1/H2/M expression in HCC tissues. The IHC analysis revealed the following: Absence of CLEC4A/J/K/M in normal and liver cancer tissues; high CLEC4C expression in HCC tissues; low expression and zero detection of CLEC4D/E/H1/H2/L in HCC tissues and normal tissues, respectively. And the HepG2 and LX-2 were used to verify the expression level of CLEC4s via qRT-PCR in vitro. Furthermore, the expression of CLEC4H1 (ASGR1) and CLEC4H2 (ASGR2) exhibited a significant relation to clinical stages. However, the expression of CLEC4A, CLEC4D, CLEC4E, CLEC4J (FCER2), CLEC4K (CD207), CLEC4G, CLEC4H1, CLEC4M, and CLEC4H2 decreased with tumor progression. Patients expressing higher CLEC4H1/H2 levels had longer overall survival than patients exhibiting lower expression. Moreover, CLEC4A/D/E/J/K/G/H1/M/H2 had significant down-regulated levels of promoter methylation. The expression level of CLEC4s was correlated with the infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophage cells, neutrophil cells, and dendritic cells. Functional analysis revealed the potential role of CLECL4s in virus infection, including COVID-19. Also, hsa-miR-4278 and hsa-miR-324-5p, two potential miRNA targets of CLEC4s, were uncovered. This article demonstrates that CLEC4 is crucial for the development of HCC and is associated with infiltration of various immune cells, providing evidence for new immunotherapy targets in HCC.


Sequence variations of phase-separating proteins and resources for studying biomolecular condensates.
Phase separation (PS) is an important mechanism underlying the formation of biomolecular condensates. Physiological condensates are associated with numerous biological processes, such as transcription, immunity, signaling, and synaptic transmission. Changes in particular amino acids or segments can disturb the protein's phase behavior and interactions with other biomolecules in condensates. It is thus presumed that variations in the phase-separating-prone domains can significantly impact the properties and functions of condensates. The dysfunction of condensates contributes to a number of pathological processes. Pharmacological perturbation of these condensates is proposed as a promising way to restore physiological states. In this review, we characterize the variations observed in PS proteins that lead to aberrant biomolecular compartmentalization. We also showcase recent advancements in bioinformatics of membraneless organelles (MLOs), focusing on available databases useful for screening PS proteins and describing endogenous condensates, guiding researchers to seek the underlying pathogenic mechanisms of biomolecular condensates.


Comparative study of the pollen protein contents in two major varieties of Cupressus arizonica planted in Tehran.
During past few years, the Cupressus arizonica has been abundantly planted in Tehran, causing a significant increase of allergic diseases from the middle of winter to the beginning of spring. The aim of this study was the comparison of pollen protein content in two major varieties of C. arizonica planted in Tehran, including C. arizonica var. arizonica and C. arizonica var. glabra, in order to determine pollen's specificity of each variety and also to find out whether environmental conditions can influence pollen protein contents and its allergenic components. Pollen grains were directly collected from mature male cones of trees planted in different areas of the city. Pollen's proteins were extracted, and were analyzed by SDS PAGE. Total protein content of pollen extracts was measured by Bradford assay. Our investigations revealed noticeable differences in protein content of each variety. Bradford protein assay showed a higher total protein content in C. arizonica var. arizonica pollen extracts. A new major protein, with an approximate molecular weight of about 35 kDa was detected in both varieties. Immunoblotting using the serum of a cypress allergic subject showed that the protein with 35 kDa was also the major allergen of both varieties in pollen extracts. These results showed that there are some intraspecie specificities in Arizona cypress pollens. The major allergen of Cupresuss arizonica pollen, Cup a 1 (45 kDa), has been reported as the most representative protein in pollen extracts of Mediterranean countries, but in our autochthon extracts of both varieties, a protein band at 35 kDa was more representative. These observations seem to indicate that C. arizonica pollen protein content may be influenced by environmental conditions. Moreover, Immunoblot results provided a reliable indication on the allergenic activity of this new major protein band at 35 kDa. The confirmation of these aspects would facilitate the preparation of an effective extract, improving the diagnosis of the allergy to the Cupressus arizonica pollen.


Immunohistochemical localization of thromboxane synthase in human tissues.
Thromboxane A2 is formed mainly in platelets where we have isolated thromboxane synthase as a cytochrome P450-like haemoprotein. A rabbit antiserum prepared against this enzyme was monospecific according to Western blot analysis and was used for immunostaining of human tissues. In liver the Kupffer cells were clearly stained and in the connective tissue, histiocytes and monocytic cells were positive. In lung, alveolar macrophages contained most of the enzyme, whereas Type I and II cells were negative. Kidney mesangial cells were stained and in lymphatic tissue dendritic reticular cells as well as invading macrophages were positive. These were also seen in the crypts of tonsils and surprisingly also the epithelium. Placenta again showed staining of the Hofbauer cells and of the endothelial lining of the vessels. Umbilical cord and uterus only contained weak antigenicity in dendritic cells.


The effect of pretraining sports activity on the incidence of stress fractures among military recruits. A prospective study.
In a prospective study of stress fractures among Israeli infantry recruits, no correlation was found between the recruits' prior participation in sports activities or their aerobic physical fitness and the incidence of stress fractures during basic training. This finding discredits the concept that improving physical fitness prior to basic training can be a prophylactic means of limiting the incidence of stress fractures during subsequent training.


High-Resolution Optical Fiber Shape Sensing of Continuum Robots: A Comparative Study.
Flexible medical instruments, such as Continuum Dexterous Manipulators (CDM), constitute an important class of tools for minimally invasive surgery. Accurate CDM shape reconstruction during surgery is of great importance, yet a challenging task. Fiber Bragg grating (FBG) sensors have demonstrated great potential in shape sensing and consequently tip position estimation of CDMs. However, due to the limited number of sensing locations, these sensors can only accurately recover basic shapes, and become unreliable in the presence of obstacles or many inflection points such as s-bends. Optical Frequency Domain Reflectometry (OFDR), on the other hand, can achieve much higher spatial resolution, and can therefore accurately reconstruct more complex shapes. Additionally, Random Optical Gratings by Ultraviolet laser Exposure (ROGUEs) can be written in the fibers to increase signal to noise ratio of the sensors. In this comparison study, the tip position error is used as a metric to compare both FBG and OFDR shape reconstructions for a 35 mm long CDM developed for orthopedic surgeries, using a pair of stereo cameras as ground truth. Three sets of experiments were conducted to measure the accuracy of each technique in various surgical scenarios. The tip position error for the OFDR (and FBG) technique was found to be 0.32 (0.83) mm in free-bending environment, 0.41 (0.80) mm when interacting with obstacles, and 0.45 (2.27) mm in s-bending. Moreover, the maximum tip position error remains sub-millimeter for the OFDR reconstruction, while it reaches 3.40 mm for FBG reconstruction. These results propose a cost-effective, robust and more accurate alternative to FBG sensors for reconstructing complex CDM shapes.


The German Cardiovascular Prevention Study (GCP): design and methods. GCP Study Group.
The German Cardiovascular Prevention Study (GCP) is a multicentre community-based intervention study for the primary prevention of ischaemic heart diseases (ICD-9 410-414) and cerebrovascular diseases (ICD-9 430-438). It comprises a total population of 1.23 million persons in five study regions spread all over the F.R.G. Prevention measures in overlapping campaigns to modify health behaviour and life styles are aimed at the cardiovascular risk factors of cigarette smoking, elevated blood pressure, hypercholesterolaemia, overweight, and physical inactivity over a period of eight years. Age-specific cardiovascular mortality in males and females aged 25-69 years in intervention regions shall be reduced by at least 8% as compared to the mortality experience of the rest of the Federal Republic. Official mortality statistics and incidence data in parts of the study population, together with proxy measures for case fatality, will be incorporated into the evaluation strategy. Risk-factor reduction is being assessed in three health examination surveys at the start, at mid-term and at the end of the study. Further information on the effectiveness of preventive measures is obtained by process evaluation and observation of structural changes in the communities.


A new chemical approach to human ABO histo-blood group type 2 antigens.
A new chemical approach to synthesizing human ABO histo-blood type 2 antigenic determinants was developed. N-Phthaloyl-protected lactosaminyl thioglycoside derived from lactulose via the Heyns rearrangement was employed to obtain a type 2 core disaccharide. Use of this scheme lowered the overall number of reaction steps. Stereoselective construction of the α-galactosaminide/galactoside found in A- and B-antigens, respectively, was achieved by using a unique di-tert-butylsilylene-directed α-glycosylation method. The proposed synthetic scheme provides an alternative to existing procedures for preparing ABO blood group antigens.


The testis in mice infected with Mycobacterium leprae.
Following inoculation either locally or intravenously with Mycobact. leprae of human origin, the histopathology and bacteriology of the testis in experimental mice is described. Normal mice, and mice rendered immunologically deficient by thymectomy and whole-body irradiation, were studied. Attention is drawn to a heavy bacillation of the testis in mice from both groups. Bacilli were found in and beneath the tunica albuginea, but mainly in interstitial cells and in macrophages surrounding the tubules. The percentage of solidly staining bacilli was high, and globi were frequent. The study showed that the testis in mice is particularly favourable for the lodgement and multiplication of Mycobact. laprae following either local or intravenous inoculation. The significance of this in relation to the metabolism of the leprosy bacillus and to the frequent occurrence of testicular damage in the lepromatous male patient is discussed. This work was supported by grants to A. G. M. Weddell and A. C. McDougall from the Medical Research Council and the British Leprosy Relief Association (LEPRA).


Preparation and Electrochemical Characterization of La and Al Co-doped NCM811 Cathode Materials.
LiNi0.8Co0.1Mn0.1O2 (NCM811) became a research hot point because of its low cost, environmental friendliness, and excellent electrochemical performance. However, Li+/Ni2+ intermixing is an essential factor affecting its applicability. Doping could be an important method to improve the electrochemical performance of NCM811-based cathode materials. In this work, La and Al co-doped NCM811 was prepared by a solid-state method. Results from X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) and electrochemical performance were discussed in depth. These showed that when La and Al doping concentrations were 1 and 0.5%, the samples showed the best performance. The as-improved performances were mainly attributed to the reduced Li+/Ni2+ intermixing, suppressed phase transition, and decreased potential polarization and impedance.


Dental health of 12-year-olds in Israel-2002.
To gather epidemiological information on caries prevalence and treatment needs of Israeli 12-year-olds. Prevalence survey of a representative sample of 12-year- olds examined according to WHO Oral Health Survey methods. The mean DMFT was 1.66 (DT = 0.91, MT = 0.03 FT = 0.72), a 40% decline since the previous national survey in 1989. DT and DMFT were lower amongst males (p < 0.01). There were no differences between urban and rural communities. Arab subjects had a higher prevalence, higher DT, MT and DMFT (p < 0.01), but lower FT than the Jewish subjects. In fluoridated areas, the mean DMFT was 1.39 compared to 1.83 in the non-fluoridated areas (p < 0.01). SiC (Significant Caries Index which shows the average DMFT of the third of the population with the highest DMFT) was found to be 4.31. Caries prevalence has declined among 12-year-olds in Israel. However, 53.9% of the children still suffer from caries at this age. There are wide dental health disparities.


Reframing dopamine: A controlled controller at the limbic-motor interface.
Pavlovian influences notoriously interfere with operant behaviour. Evidence suggests this interference sometimes coincides with the release of the neuromodulator dopamine in the nucleus accumbens. Suppressing such interference is one of the targets of cognitive control. Here, using the examples of active avoidance and omission behaviour, we examine the possibility that direct manipulation of the dopamine signal is an instrument of control itself. In particular, when instrumental and Pavlovian influences come into conflict, dopamine levels might be affected by the controlled deployment of a reframing mechanism that recasts the prospect of possible punishment as an opportunity to approach safety, and the prospect of future reward in terms of a possible loss of that reward. We operationalize this reframing mechanism and fit the resulting model to rodent behaviour from two paradigmatic experiments in which accumbens dopamine release was also measured. We show that in addition to matching animals' behaviour, the model predicts dopamine transients that capture some key features of observed dopamine release at the time of discriminative cues, supporting the idea that modulation of this neuromodulator is amongst the repertoire of cognitive control strategies.


Expression of stem cells markers in ocular hemangioblastoma associated with von Hippel-Lindau (VHL) disease.
To better understand the histogenesis of ocular hemangioblastomas associated with von Hippel-Lindau (VHL) disease. We found that co-expression of Epo and EpoR may mediate developmental stagnation and induce proliferation of hemangioblastoma. All lesions were frozen and/or fixed in formalin and embedded in paraffin. The specimens were sectioned and subjected to routine histology, immunohistochemistry and molecular analyses. Avidin-biotin-complex immunoperoxidase was used to evaluate the expression of erythropoietin (Epo), Epo receptor (EpoR), CD31, CD34, CD117, and CD133. Ocular hemangioblastoma cells were microdissected in order to determine expression of Epo and EpoR transcripts using reverse transcription-polymerase chain reaction. Tumorlet-like cells were identified in retinal and optic nerve hemangioblastomas. Co-expression of Epo and EpoR at both protein and messenger levels was detected in many hemangioblastoma cells. In addition, ocular VHL lesions expressed several stem cell markers including CD133 to various degrees. The data suggest that VHL disease-associated ocular hemangioblastomas are comprised of developmentally arrested stem cells including hemangioblasts, endothelial, and neuronal progenitor cells. We found that co-expression of Epo and EpoR may not only mediate developmental stagnation, but may also induce proliferation. Suppression of the growth of AC133/CD133 positive stem cells might be considered as one of the therapeutic targets for VHL-associated hemangioblastoma.


Analyzing computer based patient records: a review of literature.
A wide-ranging literature review of computer-based patient record (CPR) implementation over the past decade reveals that clinical, workflow, administrative, and revenue enhancement benefits of the CPR outweigh barriers and challenges--but only if healthcare organizations redesign certain work processes. Among other key efforts, organizations must train and motivate users to navigate CPR systems, as well as develop a common structured language. Clinicians who used CPRs found that electronic access to clinical information saves time and provides a thorough and efficient way to manage patient information.


High-throughput Growth Measurements of Yeast Exposed to Visible Light.
Light is a double-edged sword: it is essential for life on the planet but also causes cellular damage and death. Consequently, organisms have evolved systems not only for harvesting and converting light energy into chemical energy but also for countering its toxic effects. Despite the omnipresence and importance of such light-dependent effects, there are very few unbiased genetic screens, if any, investigating the mechanistic consequences that visible light has on cells. Baker's yeast, Saccharomyces cerevisiae, is one of the best annotated organisms thanks to several easily available mutant collections and its amenability to high-throughput genetic screening. However, until recently this yeast was thought to lack receptors for visible light, therefore its response to visible light was poorly understood. Nevertheless, a couple of years ago it was discovered that yeast senses light via a novel and unconventional pathway involving a peroxisomal oxidase, hydrogen peroxide, and a particular type of antioxidant protein, called peroxiredoxin. Here, we describe in detail a protocol for scoring yeast genes involved in the resistance to visible light (400-700 nm) on a genome-wide scale. Because cells in dense cultures shield each other from light exposure, resulting in apparent light resistance, our method involves adaptations to reduce inoculum size under conditions amenable to high-throughput screens, to properly be able to identify light-sensitive mutants. We also describe how to measure growth in the presence of light, including two follow-up validation tests. In this way, this method makes it possible to score light-sensitivity on a genome-wide scale with high confidence. Graphic abstract: Overview of strategy for high-throughput determination of yeast growth upon visible light stress.


Can Romney lambs whose scrotums have been shortened by the use of a rubber ring be used as an alternative to vasectomised Perendale rams for inducing early breeding activity in Romney ewe lambs?
To determine if exposure to ram lambs whose scrotums had been shortened by the use of a rubber ring would induce reproductive activity in ewe lambs, and determine if this technique was an effective alternative to vasectomised mature rams. Seven hundred and forty-nine Romney ewe lambs, 7-8 months of age, were randomly assigned to one of three treatment groups. Treatments included exposure for 17 days prior to breeding to either mature vasectomised rams (Vasec), or ram lambs whose scrotums has been shortened via a rubber ring (Ram SS), or not being exposed to either vasectomised or short-scrotum ram lambs (Unteased). Using crayon marks, ewe lambs were identified as having been marked during the first 17 days only, during both 17-day periods, during the second 17 days only, or not marked. Hoggets were weighed on the day of introduction of entire rams. All ewe lambs were diagnosed for pregnancy status using ultrasound. Unteased ewe lambs and those exposed to ram lambs whose scrotums had been shortened by the use of a rubber ring were less (p<0.05) likely to be marked and pregnant to the first 17 days of breeding than ewe lambs exposed to mature vasectomised rams. Twin-bearing ewe lambs were heavier (p<0.05) than their single-bearing counterparts at introduction of the rams. Exposure of ewe lambs to mature vasectomised rams is an effective means of increasing the numbers of ewe lambs bred and pregnant to the first 17 days of breeding. In contrast, a 17-day exposure to ram lambs whose scrotums had been shortened by the use of a rubber ring, at the ratios utilised in the present study, were not a suitable alternative to mature vasectomised rams for inducing early breeding activity in ewe lambs.


Development and Characterization of Polylactic Acid (PLA)-Based Nanocomposites Used for Food Packaging.
The present study is focused on polylactic acid (PLA) blending with bio nanoadditives, such as Tonsil® (clay) and Aerosil®, to obtain nanocomposites for a new generation of food packaging. The basic composition was enhanced using Sorbitan oleate (E494) and Proviplast as plasticizers, increasing the composite samples' stability and their mechanical strength. Four mixtures were prepared: S1 with Tonsil®; S2 with Aerosil®; S3 with Aerosil® + Proviplast; and S4 with Sabosorb. They were complexly characterized by FT-IR spectroscopy, differential scanning calorimetry, mechanical tests on different temperatures, and absorption of the saline solution. FTIR shows a proper embedding of the filler component into the polymer matrix and DSC presents a good stability at the living body temperature for all prepared samples. Micro and nanostructural aspects were evidenced by SEM and AFM microscopy, revealing that S3 has the most compact and uniform filler distribution and S4 has the most irregular one. Thus, S3 evidenced the best diametral tensile strength and S4 evidenced the weakest values. All samples present the best bending strength at 18 °C and fair values at 4 °C, with the best values being obtained for the S1 sample and the worst for S4. The lack of mechanical strength of the S4 sample is compensated by its best resistance at liquid penetration, while S1 is more affected by the liquid infiltrations. Finally, results show that PLA composites are suitable for biodegradable and disposable food packages, and the desired properties could be achieved by proper adjustment of the filler proportions.


DYX1C1 is required for axonemal dynein assembly and ciliary motility.
DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2-4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start-codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary motility defects. In humans, we identified recessive loss-of-function DYX1C1 mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4).


Development of a Novel Diagnostic Biomarker Set for Rheumatoid Arthritis Using a Proteomics Approach.
Rheumatoid arthritis (RA) is an autoimmune disease that starts with inflammation of the synovial membrane. Studies have been conducted to develop methods for efficient diagnosis of RA and to identify the mechanisms underlying RA development. Blood samples can be useful for detecting disturbance of homeostasis in patients with RA. Nanoliquid chromatography-tandem mass spectrometry (LC-MS/MS) is an efficient proteomics approach to analyze blood sample and quantify serum proteins. Serum samples of 18 healthy controls and 18 patients with RA were analyzed by LC-MS/MS. Selected candidate biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) using sera from 43 healthy controls and 44 patients with RA. Thirty-eight proteins were significantly differentially expressed by more than 2-fold in healthy controls and patients with RA. Based on a literature survey, we selected six candidate RA biomarkers. ELISA was used to evaluate whether these proteins effectively allow distinguishing patients with RA from healthy controls and monitoring drug efficacy. SAA4, gelsolin, and vitamin D-binding protein were validated as potential biomarkers of RA for screening and drug efficacy monitoring of RA. We identified a panel of three biomarkers for RA which has potential for application in RA diagnosis and drug efficacy monitoring. Further, our findings will aid in understanding the pathogenesis of RA.


Comparison of the effects of salmeterol and formoterol in patients with severe asthma.
Several studies have demonstrated the superiority of salmeterol and formoterol to either regular treatment with albuterol or placebo. However, to date there have been no trials comparing the efficacy of salmeterol and formoterol in patients with severe asthma. We undertook a randomized, placebo-controlled, crossover study to compare 4 weeks of treatment with inhaled formoterol (12 microg twice daily) or salmeterol (50 microg twice daily) in patients with severe asthma whose conditions were not being adequately controlled by therapy with high doses of inhaled corticosteroids (i.e., > or = 1,500 microg daily) or with regular oral corticosteroid treatment. Morning pretreatment peak expiratory flow (PEF) during the last 14 days of the treatment period was the primary outcome variable. Patients recorded morning and evening pretreatment PEF, daytime and nighttime symptom scores, and any use of rescue medication. Spirometry and bronchial reversibility were performed after each treatment. Forty-two nonsmoking patients (29 women; mean age, 45 +/- 2 years; mean [+/- SEM] FEV(1), 61.8 +/- 3.4% of predicted) took part in the trial, and 27 patients completed the trial. The mean morning PEF was greater in patients receiving formoterol (mean increase, 14.4 L/min; 95% confidence interval [CI]. 0.2 to 28.6) or salmeterol (mean increase, 14.8 L/min; 95% CI, 0.5 to 29.1) compared with those receiving placebo, but there was no difference between these treatments. There were no significant treatment effects for any of the secondary outcome variables (i.e., FEV(1,) FVC, mean evening PEF, mean daytime symptom score, or nighttime symptom score). We conclude that the long-acting beta(2)-agonists salmeterol and formoterol improve morning PEF in patients with severe asthma, but that there is no difference in efficacy between the two drugs.


Exploring genetic modifiers of Gaucher disease: The next horizon.
Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from mutations in the gene GBA1 that lead to a deficiency in the enzyme glucocerebrosidase. Accumulation of the enzyme's substrates, glucosylceramide and glucosylsphingosine, results in symptoms ranging from skeletal and visceral involvement to neurological manifestations. Nonetheless, there is significant variability in clinical presentations amongst patients, with limited correlation between genotype and phenotype. Contributing to this clinical variation are genetic modifiers that influence the phenotypic outcome of the disorder. In this review, we explore the role of genetic modifiers in Mendelian disorders and describe methods to facilitate their discovery. In addition, we provide examples of candidate modifiers of Gaucher disease, explore their relevance in the development of potential therapeutics, and discuss the impact of GBA1 and modifying mutations on other more common diseases like Parkinson disease. Identifying these important modulators of Gaucher phenotype may ultimately unravel the complex relationship between genotype and phenotype and lead to improved counseling and treatments.


Antidepressant efficacy of electroconvulsive therapy is associated with a reduction of the innate cellular immune activity in the cerebrospinal fluid in patients with depression.
A bidirectional link between the antidepressant effects of electroconvulsive therapy (ECT) and the modulation of the immune system has been proposed. To elucidate the interplay between antidepressant treatment and macrophage/microglia activation in humans, we performed a study on the effects of the antidepressant treatment by ECT on markers of macrophage/microglia activation in patients with depression. We measured six different markers (IL-6, neopterin, sCD14, sCD163 MIF and MCP1) of macrophage/microglia activation in the cerebrospinal fluid (CSF) and blood of 12 patients with a severe, treatment-resistant depressive episode before and after a course of ECT. Some markers in the CSF of remitters were reduced after the ECT course and differed from non-remitters, but no differences were found before and after ECT independently from the antidepressant efficacy. CSF baseline levels of some markers could predict the reduction of depressive psychopathology during ECT. Higher CSF levels indicating increased macrophage/microglia activation at baseline predicted a better treatment response to ECT. Although the sample size was small, our data suggest that macrophages/microglia are involved in the pathophysiology of major depression and that antidepressant efficacy by ECT might be partly explained by the modulation of the innate immune system within the brain.


The missing link: does tunnelling nanotube-based supercellularity provide a new understanding of chronic and lifestyle diseases?
Tunnelling nanotubes (TNTs) are increasingly recognized as central players in a multitude of cellular mechanisms and diseases. Although their existence and functions in animal organisms are still elusive, emerging evidence suggests that they are involved in developmental processes, tissue regeneration, viral infections or pathogen transfer, stem cell differentiation, immune responses as well as initiation and progression of neurodegenerative disorders and cancer (see Sisakhtnezhad & Khosravi 2015 Eur. J. Cell Biol. 94, 429-443. (doi:10.1016/j.ejcb.2015.06.010)). A broader field of vision, including their striking functional and structural resemblance with nanotube-mediated phenomena found throughout the phylogenetic tree, from plants down to bacteria, points to a universal, conserved and tightly regulated mechanism of cellular assemblies. Based on our initial definition of TNTs as open-ended channels mediating membrane continuity between connected cells (Rustom et al. 2004 Science 303, 1007-1010. (doi:10.1126/science.1093133)), it is suggested that animal tissues represent supercellular assemblies that-besides opening discrete communication pathways-balance diverse stress factors caused by pathological changes or fluctuating physiological and environmental conditions, such as oxidative stress or nutrient shortage. By combining current knowledge about nanotube formation, intercellular transfer and communication phenomena as well as associated molecular pathways, a model evolves, predicting that the linkage between reactive oxygen species, TNT-based supercellularity and the intercellular shuttling of materials will have significant impact on diverse body functions, such as cell survival, redox/metabolic homeostasis and mitochondrial heteroplasmy. It implies that TNTs are intimately linked to the physiological and pathological state of animal cells and represent a central joint element of diverse diseases, such as neurodegenerative disorders, diabetes or cancer.


Experimental demonstration of secure 100 Gb/s IMDD transmission over a 50 km SSMF using a quantum noise stream cipher and optical coarse-to-fine modulation.
In this paper, we experimentally demonstrate a secure 100 Gb/s 214-level intensity modulation and direct detection transmission over a 50 km standard single-mode fiber (SSMF) using a quantum noise stream cipher (QNSC) technique and 8-bit digital to analog converters. Optical coarse-to-fine modulation (CTFM) has been proposed to simultaneously enhance the security and overcome the weakness of low modulation depth in the traditional CTFM scheme. The optical power instead of the radio-frequency signal power is adjusted to satisfy the required peak-to-peak relation for CTFM, and thus the coarse and fine modulation has the same modulation depth. Two optical CTFM schemes based on an optical coupler and a polarizing beam combiner (PBC) are proposed and their pros and cons are analyzed and compared. Considering the trade-off of transmission performance and security performance, the optical CTFM scheme based on PBC is preferred in our experiment. 214-level pulse amplitude modulation (PAM) is achieved using two dual-drive Mach-Zehnder modulators (DD-MZM). Simultaneously, each DD-MZM is also used to achieve single-sideband (SSB) modulation to eliminate the power fading induced by fiber dispersion. By these means, 100 Gb/s 214-level PAM-QNSC signal transmission over 50 km SSMF with the bit error rate below the 7% overhead hard-decision forward error correction threshold of 3.8×10-3 is achieved. The results validate that the proposed scheme is effective to realize low-cost, high-speed, and highly secure optical transmission in the data center.


Iron-loaded carbon black prepared via chemical vapor deposition as an efficient peroxydisulfate activator for the removal of rhodamine B from water.
The excessive use of organic pollutants like organic dyes, which enter the water environment, has led to a significant environmental problem. Finding an efficient method to degrade these pollutants is urgent due to their detrimental effects on aquatic organisms and human health. Carbon-based catalysts are emerging as highly promising and efficient alternatives to metal catalysts in Fenton-like systems. They serve as persulfate activators, effectively eliminating recalcitrant organic pollutants from wastewater. In this study, iron-loaded carbon black (Fe-CB) was synthesized from tire waste using chemical vapor deposition (CVD). Fe-CB exhibited high efficiency as an activator of peroxydisulfate (PDS), facilitating the effective degradation and mineralization of rhodamine B (RhB) in water. A batch experiment and series characterization were conducted to study the morphology, composition, stability, and catalytic activity of Fe-CB in a Fenton-like system. The results showed that, at circumneutral pH, the degradation and mineralization efficiency of 20 mg L-1 RhB reached 92% and 48% respectively within 60 minutes. Fe-CB exhibited excellent reusability and low metal leaching over five cycles while maintaining almost the same efficiency. The degradation kinetics of RhB was found to follow a pseudo-first-order model. Scavenging tests revealed that the dominant role was played by sulfate (SO4-˙) and superoxide (O2-˙) radicals, whereas hydroxyl radicals (OH˙) and singlet oxygen (1O2) played a minor role in the degradation process. This study elucidates the detailed mechanism of PDS activation by Fe-CB, resulting in the generation of reactive oxygen species. It highlights the effectiveness of Fe-CB/PDS in a Fenton-like system for the treatment of water polluted with organic dye contaminants. The research provides valuable insights into the potential application of carbon black derived from tire waste for environmental remediation.


FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome.
Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification. The assay was optimised and validated on single lymphoblasts isolated from fragile X reference cell lines, and applied to a simulated PGD case and a clinical in vitro fertilisation (IVF)-PGD case. In the simulated PGD case, definitive diagnosis of the expected results was achieved for all 'embryos'. In the clinical IVF-PGD case, delivery of a healthy baby girl was achieved after transfer of an expansion-negative blastocyst. FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos. Together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.


Distribution and size of thalamic neurons projecting to layer I of the auditory cortical fields of the cat compared to those projecting to layer IV.
The distribution of thalamocortical neurons projecting to layer I of the cat auditory cortical fields was examined by the horseradish peroxidase (HRP) method. After HRP injection into layer I of the primary auditory cortex (AI), HRP-labeled neuronal cell bodies were distributed mainly in the medial, dorsal, and ventrolateral divisions of the medial geniculate nucleus (MGN) and suprageniculate nucleus (Sg), and additionally in the lateral and medial divisions of the posterior group of the thalamus (Pol and Pom), lateroposterior thalamic nucleus (Lp), and nucleus of the brachium of the inferior colliculus (BIN). After HRP injection into layer I of the second auditory cortex (AII), labeled neurons were seen mainly in the medial, dorsal, and ventrolateral divisions of the MGN and Sg and additionally in the Pom, Lp, and BIN. After HRP injection into layer I of the anterior auditory field (AAF), labeled neurons were located mainly in the medial and dorsal divisions of the MGN, Sg, Pol, and BIN, and additionally in the ventrolateral divisions of the MGN, Pom, and Lp. After HRP injection into layer I of the dorsal part of the posterior ectosylvian gyrus (Epd), labeled neurons were observed chiefly in the medial and dorsal divisions of the MGN, Sg, and Lp and additionally in the ventrolateral division of the MGN, Pom, and BIN. After HRP injection into layer I of the ventral part of the posterior ectosylvian gyrus (Epv), labeled neurons were distributed chiefly in the medial and dorsal divisions of the MGN and Pol and additionally in the ventrolateral division of the MGN, Sg, and BIN. Thus no labeled neurons were found in the ventral division of the MGN after HRP injection into layer I of all auditory cortical fields examined in the present study. The average soma diameters of neurons that were labeled after HRP injection into layer I were statistically smaller than those of neurons that were labeled after HRP injection into layer IV.


Linear response, multi-order grating interferometry using a reversal shearing imaging system.
Linear response, multi-order grating interferometry is proposed to measure grating displacement. The system, a combination of a reversal shearing interferometer and an imaging system, enables calculating multi-order, integrated intensity signals with a linear waveform response. A theoretical multi-order model for the linear response signal analysis is presented with a Fourier series expansion. The results of the experiment, which prove the validity of the theoretical model, indicate a linear response to displacement with a linearity of 98.7% and a resolution of 10 nm. We conclude that the proposed method enables the development of a new class of potent linear response grating interferometry for displacement metrology.


Could endogenous substrates of drug-metabolizing enzymes influence constitutive physiology and drug target responsiveness?
Integration of genomic data from pharmacokinetic pathways and drug targets is an emerging trend in bioinformatics, but is there a clear separation of pharmacokinetic pathways and drug targets? Should we also consider the potential interactions of endogenous substrates of drug-metabolizing enzymes with receptors and other molecular drug targets as we combine pharmacogenomic datasets? We discuss these overarching questions through a specific pharmacogenomic case study of the cytochrome P450 (CYP)2D6, serotonin and dopamine triad. Importantly, CYP2D6 may contribute to the regeneration of serotonin from 5-methoxytryptamine by virtue of its catalytic function as a 5-methoxyindolethylamine O-demethylase. Furthermore, serotonergic neurons provide a regulatory feedback on dopaminergic neurotransmission. Hence, we hypothesize that independent of its role as a pharmacokinetic gene, CYP2D6 may nuance the regulation of serotonergic and dopaminergic neurophysiology. Additionally, we reflect upon the contribution of hyperspecialization in biomedicine to the present disconnect between research on pharmacokinetics and drug targets, and the potential for remedying this important gap through informed dialogue among clinical pharmacologists, human geneticists, bioethicists and applied social scientists.


Periploca sepium Bunge as a model plant for rubber biosynthesis study.
Periploca sepium Bunge (Chinese silk vine) is a woody climbing vine belonging to the family Asclepiadaceae. It originally comes from Northwest China. Periploca resembles the Para-rubber tree, Hevea brasiliensis, regarding a similar body plan to produce a milky exudate containing rubber latex. The Periploca plant was assessed as a rubber-producing plant by rubber structure elucidation and its molecular weight distribution. A rubber fraction purified from the milky exudate was subjected to 1H NMR analysis, and a characteristic signal derived from cis-polyisoprene was observed. In addition, when the molecular weight distribution of rubber components in the exudate was measured (using size-exclusion chromatography), the number-average molecular weight (Mn), weight-average molecular weight (Mw), and polydispersity (Mw/Mn) were estimated to be Mn = 1.3 x 10(5), Mw = 4.1 x 10(5), and Mw/Mn = 3.1, respectively. Furthermore, the presence of polyisoprene, with Mn = 4.0 x 10(4), Mw = 7.6 x 10(4), and Mw/Mn = 2.5, was also confirmed in plantlets obtained from shoots as a result of tissue culture.


Management of perforated gastric carcinoma: a report of 16 cases and review of world literature.
Perforated gastric carcinoma is rare; however, it is a serious condition associated with complications. To understand the proper management of this disease and to characterize its clinical course we reviewed available data on 16 patients with perforated gastric carcinoma. We collected data on the age and sex of the patients as well as operative findings and histological features of the primary tumor. The depth of invasion and presence of lymph node metastasis were also recorded. The Union Internationale Contre Cancer stage, extent of resection, and surgical method used were reviewed. We also reviewed published information on the management of perforated gastric carcinoma. The carcinoma was stage I in three cases, stage II in one case, stage III in three cases, and stage IV in nine cases. Many patients had distant metastases. Fourteen patients underwent gastrectomy. Two patients whose preoperative condition was poor died of surgery-related complications, but patients with early-stage carcinoma underwent an R0 resection (resection of the primary tumor with negative margins) and had minimal complications. We conclude that the outcome of patients who were able to undergo radical surgery was good and correlated with the stage of cancer. It is important to perform gastrectomy rather than repair the perforation first, and a proper lymphadenectomy should follow--thus a two-step surgery when necessary.


Dietary Niacin and Open-Angle Glaucoma: The Korean National Health and Nutrition Examination Survey.
Glaucoma is a leading cause of loss of sight. High intraocular pressure (IOP) is the most critical risk factor. However, glaucoma develops even within a normal IOP range. Normal tension glaucoma (NTG) is more common in Asia, whereas high tension glaucoma is more common in Western countries. The pathogenesis of glaucoma, especially NTG, is poorly understood. We evaluated the correlation between dietary nutrient intake and glaucoma using data from subjects ≥40 years old from the ongoing, nationwide, population-based study, the Korean National Health and Nutrition Examination Survey V (2008-2012). Dietary intake was determined using the 24 h recall method. Fiber (g/day), ash (g/day), calcium (mg/day), phosphorus (mg/day), iron (mg/day), sodium (mg/day), potassium (mg/day), β-Carotene (μg/day), retinol (μg/day), vitamin A (μg Retinol Equivalents/day), thiamine (mg/day), riboflavin (mg/day), niacin (mg/day), and vitamin C (mg/day) were included in nutrient intake data. All nutrient intake was divided into quartiles. The mean IOP did not differ according to quartiles from any nutrients (all p > 0.05). After adjusting for age, gender, income status, education level, smoking, alcohol consumption, physical activity, diabetes, hypertension, IOP, and total energy, the intake of niacin was associated with glaucoma (p = 0.013). Among subjects with IOP ≤ 21 mmHg, only niacin was related to glaucoma in a multivariate analysis (p = 0.022). Dietary nutrient intake was associated with open-angle glaucoma independent of IOP. Individuals with NTG showed lower intake of niacin among nutrients. This finding suggests the possibility that proper diet counseling may be another modifiable factor, aside from IOP, particularly among patients with NTG.


Lanreotide in the treatment of patients with thyroid eye disease.
Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Five patients, three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using 111 In DTPA-D-Phe1-octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The five patients who comprised the treatment group received 0.04 g LRT i.m. once every 2 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for 3 months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to be given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results.


Depletion of ZBTB38 potentiates the effects of DNA demethylating agents in cancer cells via CDKN1C mRNA up-regulation.
DNA methyltransferase inhibitor (DNMTi) treatments have been used for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and have shown promising beneficial effects in some other types of cancers. Here, we demonstrate that the transcriptional repressor ZBTB38 is a critical regulator of the cellular response to DNMTi. Treatments with 5-azacytidine, or its derivatives decitabine and zebularine, lead to down-regulation of ZBTB38 protein expression in cancer cells, in parallel with cellular damage. The depletion of ZBTB38 by RNA interference enhances the toxicity of DNMTi in cell lines from leukemia and from various solid tumor types. Further we observed that inactivation of ZBTB38 causes the up-regulation of CDKN1C mRNA, a previously described indirect target of DNMTi. We show that CDKN1C is a key actor of DNMTi toxicity in cells lacking ZBTB38. Finally, in patients with MDS a high level of CDKN1C mRNA expression before treatment correlates with a better clinical response to a drug regimen combining 5-azacytidine and histone deacetylase inhibitors. Collectively, our results suggest that the ZBTB38 protein is a target of DNMTi and that its depletion potentiates the toxicity of DNMT inhibitors in cancer cells, providing new opportunities to enhance the response to DNMT inhibitor therapies in patients with MDS and other cancers.


Regiodependent luminescence quenching of biotinylated N-sulfonyl-acridinium-9-carboxamides by avidin.
[reaction: see text] Biotin was conjugated to chemiluminescent N-sulfonylacridinium-9-carboxamides at the N-10 or 9-position carboxamide. Upon binding to avidin, the light output of the N-10 derivative (8) was quenched up to 92% upon triggering with basic peroxide, while the 9-position carboxamide conjugate (9) was quenched only 33%. The utility of this effect was demonstrated in a model homogeneous chemiluminescence assay.


Video-assisted thoracoscopic surgery for primary spontaneous pneumothorax.
Video-assisted thoracoscopic surgery (VATS) has been suggested as the most appropriate choice for spontaneous pneumothorax. Thirty-two patients (30 males, two females, age range from 16 to 42) with primary spontaneous pneumothorax (PSP) are reported. All had mechanical pleurodesis with Marlex mesh. Blebs or bullae could be identified in 24 patients (75%). All bullae over 2 cm were either excised (11 patients) or ligated (five patients). The median operating time was 45 min. There was minimal postoperative discomfort and the median postoperative hospital stay was 4 days. There was one minor wound infection and one recurrence (mean follow up of 11 months). It is concluded that VATS is a quick, safe and effective approach for the treatment of PSP. Long-term results will better define its true merit in thoracic surgery.


Lime pretreatment of switchgrass.
Lime (calcium hydroxide) was used as a pretreatment agent to enhance the enzymatic digestibility of switchgrass. After studying many conditions, the recommended pretreatment conditions are: time = 2 h, temperature = 100 degrees C and 120 degrees C, lime loading = 0.1 g Ca(OH)(2)/g dry biomass, water loading = 9 mL/g dry biomass. Studies on the effect of particle size indicate that there was little benefit of grinding below 20 mesh; even coarse particles (4-10 mesh) digested well. Using the recommended pretreatment conditions, the 3-d reducing sugar yield was five times that of untreated switchgrass, the 3-d total sugar (glucose + xylose) yield was seven times, the 3-d glucose yield was five times, and the 3-d xylose yield was 21 times. A material balance study showed that little glucan (approx 10%) was solubilized as a result of the lime pretreatment, whereas about 26% of xylan and 29% of lignin became solubilized.


Bacterial endocarditis after cardiac catheterization.
Bacterial endocarditis is a rare complication of cardiac catheterization. We present the history of a patient who developed fatal, acute bacterial endocarditis following diagnostic cardiac catheterization. The implications regarding antibiotic prophylaxis and catheterization technique are discussed.


Evaluation of SPf66 malaria vaccine efficacy in Brazil.
This paper reports the efficacy results of the randomized, placebo-controlled, field trial of SPf66 malaria vaccine in Costa Marques, Rondonia, Brazil. This region is characterized by the seasonal distribution of Plasmodium falciparum and P. vivax infections, and the recent occupation by migrants from nonendemic areas. A total of 800 individuals of both sexes, ranging in age from seven to 60 years, were included in the study. Of the initial cohort, 572 participants completed the vaccination schedule. Clinical and parasitologic evaluations were obtained by active and passive searches on a periodic basis. The overall protective efficacy against P. falciparum infections was -1.6% (-32.9% to 22.4%), and 14.1% (-17.0% to 36.9%) for the first episode. The overall protective efficacy for P. vivax infections was -19.7% (-44.8% to 1.03%), and -10.8% (-41.1% to 12.8%) for the first episode. No statistical evidence of an overall significant protective effect of SPf66 malaria vaccine against P. falciparum and P. vivax malaria was obtained in this trial.


Blueberry muffin rash secondary to hereditary spherocytosis.
The term blueberry muffin rash is used to describe the clinical presentation of dermal extramedullary hematopoiesis. The common culprits of this rash include a TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes) infection or hematologic dyscrasia. Association of this rash with hereditary spherocytosis is extremely rare. We present a unique case of a neonate born with a blueberry muffin rash secondary to hereditary spherocytosis.


Oxygen-doped antimonene monolayer as a promising anchoring material for lithium-sulfur batteries: a first-principles study.
To effectively mitigate the dissolution of lithium polysulfides (Li2Sx) in the electrolyte, the search for an effective anchoring material is crucial. In this study, we employed density functional theory (DFT) computations to investigate the adsorption behavior of long-chain Li2Sx species on an O-doped antimonene monolayer. Our results demonstrate that the O-doped antimonene mono-layer exhibits stronger adsorption for long-chain Li2Sx species compared to the pristine antimonene monolayer, resulting in enhanced adsorption energies. This improved adsorption effectively curtails the dissolution of lithium polysulfides and preserves the structural integrity of the Li2Sx species. The charge transfer analysis also revealed the strong chemical interactions between the Li2Sx species and the O-doped antimonene monolayer. These findings suggest that the O-doped anti-monene monolayer holds promise as an effective anchoring material for enhancing the performance of lithium-sulfur batteries.


The backward phase flow method for the Eulerian finite time Lyapunov exponent computations.
We propose a simple Eulerian approach to compute the moderate to long time flow map for approximating the Lyapunov exponent of a (periodic or aperiodic) dynamical system. The idea is to generalize a recently proposed backward phase flow method which is specially designed for long time level set propagation. Unlike the original phase flow method or the backward phase flow method, which is applicable only to autonomous systems, the current approach can also be applied to any time-dependent (periodic or aperiodic) flow. We will discuss the stability of the proposed method. Numerical examples will be given to demonstrate the effectiveness of the algorithm.


Microbial biomass: an economical alternative for removal of heavy metals from waste water.
Today indiscriminate and uncontrolled discharge of metal contaminated industrial effluents into the environment has become an issue of major concern. Heavy metals, being non-biodegradable and persistent, beyond a permissible concentration form unspecific compounds inside the cells thereby causing cellular toxicity. The only alternative to remove them from the wastewater is by immobilizing them. The conventional methods adopted earlier for this purpose included chemical precipitation, oxidation, reduction, filtration, electrochemical treatment, evaporation, adsorption and ion-exchange resins. These methods require high energy inputs especially when it refers to dilute solutions. Here microbial biomass offers an economical option for removing heavy metals by the phenomenon of biosorption. Non-living or dead biomass sequester metal(s) on their cell surface due to certain reactive groups available like carboxyl, amine, imidazole, phosphate, sulphydryl, sulfate and hydroxyl. The process can be made economical by procuring spent biomass from industry or naturally available bulk biomass. A batch or a continuous process of removal of heavy metals directly from effluents can be developed in a fixed bed reactor using the immobilized biomass. Further biosorption potential of the biomass can be improved by various physical and chemical treatments. The availability of variety of microbial biomass and their metal binding potential makes it a economical and sustainable option for developing effluent treatment process for removal and recovery of heavy metals.


Orbital reconstruction: bone-anchored implants.
The authors present their experience on reconstruction by extraoral bone-anchored implants technique, showing two patients from a total of 13, treated for orbital reconstruction. They were selected from 66 patients treated for reconstruction of orbit, ear and nose using this technique by the staff of the Department of Plastic and Reconstructive Surgery of the University of Tor Vergata, Rome, Italy. They underwent orbital emptying due to cancer pathology. Surgical technique is described in detail; its final purpose being positioning of titanium fixtures on the orbital borders, necessary to anchor the silicone epithesis. The advantages and potential limits of this technique are exposed, exposing the important role of patient's compliance. The importance of preliminary study on the patients is also emphasized and includes clinical evaluation and instrumental examination for surgical planning, completed by a photographic study in the three standard projections.Satisfactory aesthetic results were obtained by the use of this technique and the authors believe it may represent a valid option; complementary to more traditional ones, but is a first choice in patients who cannot endure major surgery or in case of failure of traditional techniques.


Vaginal cancer with multiple liver and pulmonary metastases that achieved long-term survival.
Primary vaginal cancer represents only 1% to 2% of malignant neoplasm of the female genital tract. Here, we report a 68-year-old woman who showed a vaginal tumor extending to urethra and clitoris, a 10 cm-sized mass in left adnexa and multiple metastases in lung and liver. Vaginal biopsy showed squamous cell carcinoma of vagina and she was diagnosed as International Federation of Gynecology and Obstetrics stage IVB vaginal cancer. Palliative surgery including left salpingectomy, tumorectomy, and clitoris mass excision was performed. Concurrent chemoradiation therapy (CCRT) with six cycles of 5-fluorouracil and cisplatin was administered. The patient had a complete remission of 20 months after treatment. At a 40-month follow-up, there was no evidence of local recurrence or distant metastasis. We can suggest that CCRT is very effective in treating primary squamous cell carcinoma of the vagina, not only in locally advanced but also systemically involved vaginal cancer in selected cases.


Cancer prevention in the workplace and natural environment. A review of etiology, research design, and methods of risk reduction.
Guidelines for developing programs in cancer prevention and reduction of risk related to occupational and environmental carcinogens are provided in this review, which includes a summary of experimental and epidemiologic research designs for assessing potential etiologic agents, an overview of known occupational and environmental carcinogens, and a summary of general approaches to risk reduction. This review includes human cancer risks in the workplace and in the natural environment, which encompasses air pollution, water pollution, and hazardous waste disposal. Fourteen tables present the following: (1) established and probable carcinogens that may be encountered in the workplace, as contaminants of air or water, or as hazardous waste; (2) regulated carcinogens; (3) primary sources of exposure; (4) research designs; and (5) risk reduction methods. The interactive effects of multiple exposures are discussed as they relate to etiology and prevention. The importance of federal regulation is emphasized, as well as the need to understand the potential for cancer prevention in the context of broader economic, political and social issues.


Parkinsonism and Anderson Fabry's disease: a case report.
We describe and present a videotape of a 57-year-old woman admitted to our Neurological Clinic at 46 years of age due to extrapyramidal manifestations suggesting Parkinson's disease (PD) and with a brain magnetic resonance imaging scan showing multi-infarctual leukoencephalopathy. Various investigations led to the diagnosis of Anderson Fabry's disease (AFD). We discuss the possibility of correlation between the patient's parkinsonism and AFD.


Preoperative assessment of thyroid nodules: role of ultrasonography and fine needle aspiration biopsy followed by cytology.
To evaluate the preoperative assessment of thyroid nodules using ultrasound studies and cytology of nodular aspirates. 2,468 patients with thyroid nodules were examined from 1999 to 2005. All patients were clinically examined and underwent ultrasonography followed by fine-needle aspiration biopsy (FNAB) and cytology. Nodules larger than 10 mm were classified ultrasonographically in a 4-tier system and received a score according to the criterion of possible malignancy. Cytological examinations were conducted independently by 2 cytologists and classified as benign (score 1), indeterminate (score 2), suspicious (score 3), and malignant (score 6). Combining both scores, an index was generated that would indicate a higher probability of malignancy (benign, doubtful, suspicious, and malignant). Thyroid surgery was performed in 274 patients. Of those, 115 patients had a score of 2 to 5 and only 8 had a histological diagnosis of thyroid cancer (6.9%). For patients with a score of 5 (n = 51), 11.5% had a malignant lesion, and 51% of the 61 patients with a score of 6 had confirmed thyroid cancer. Of the 98 patients with a combined score of 7 to 10, 99% had a histological confirmation of malignancy. The index score had a sensitivity of 94.1% and specificity of 77.5%. The overall accuracy was 85.8%. Therefore, we concluded that this methodology may improve the preoperative diagnosis of thyroid cancer in nodules larger than 10 mm. Association with other methods such as color Doppler echography, serum TSH concentration, galectin-3 expression analysis, and FDG/PET scan would be useful in avoiding the higher costs of thyroid surgical procedures.


[Incidence of cancer in migrants: data of the Lombardy tumor registry].
Epidemiological studies of migrants have played an important role in evaluating the environmental and genetic components of cancer aetiology. Italian regions were grouped into five areas: North-West, North-East, Central, South and Lombardia. Incidences of cancer in migrants from South and North-East of Italy, in the province of Varese, have been compared with the incidence of Lombardia-born population, using data collected from the Cancer Registry of Lombardia for 12 years (1976-1987). Incidence comparisons were made using the Standardized Incidence Ratio (SIR). Subjects emigrated from the North-East show SIR higher than the Lombardia-born for lung and oesophageal cancer (smoking and alcohol related cancers). SIR for lip and nasopharyngeal cancers were higher in South-born. Cancer of breast, stomach and colon have low SIRs in subjects migrated from the South and, to a even lower extent, in subjects migrated from the North-East. Several others cancers tended, in general, to have lower rates in migrants from South than in native-born in Lombardia.


Take One for the Team? Influence of Team and Individual Sport Participation on High School Athlete Substance Use Patterns.
The current web-based survey investigated the association between team or individual sport participation (or both) and self-reported alcohol and tobacco use among high school athletes (N=1, 275) transitioning to college. Peak Blood Alcohol Concentration, weekly drinking, and alcohol-related problems were significantly lower among athletes in individual sports compared to other groups. Athletes competing in both team and individual sports reported greater lifetime tobacco use and combined alcohol/tobacco use compared to individual or team sports alone. Preventive strategies targeting HS athletes in general and those participating in team sports in particular may be useful in minimizing future alcohol use and related problems.


Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host.
The development and use of murine myeloid progenitor cell lines that are conditionally immortalized through expression of HoxB8 has provided a valuable tool for studies of neutrophil biology. Recent work has extended the utility of HoxB8-conditional progenitors to the in vivo setting via their transplantation into irradiated mice. Here, we describe the isolation of HoxB8-conditional progenitor cell lines that are unique in their ability to engraft in the naïve host in the absence of conditioning of the hematopoietic niche. Our results indicate that HoxB8-conditional progenitors engraft in a β1 integrin-dependent manner and transiently generate donor-derived mature neutrophils. Furthermore, we show that neutrophils derived in vivo from transplanted HoxB8-conditional progenitors are mobilized to the periphery and recruited to sites of inflammation in a manner that depends on the C-X-C chemokine receptor 2 and β2 integrins, the same mechanisms that have been described for recruitment of endogenous primary neutrophils. Together, our studies advance the understanding of HoxB8-conditional neutrophil progenitors and describe an innovative tool that, by virtue of its ability to engraft in the naïve host, will facilitate mechanistic in vivo experimentation on neutrophils.