Geographic and temporal stability of HIV seroprevalence among pregnant women in Bujumbura, Burundi.
To establish whether HIV seroprevalence in Bujumbura is stable or continuing to increase. HIV seroprevalence data among pregnant women from 1986 were compared with comparable data from 1991-1992. HIV seroprevalence among antenatal clinic attendees at three sites was 10.5, 28.0 and 11.9% in 1986, compared with 7.7, 25.6 and 12.4%, respectively, in 1991-1992. A weighted least squares analysis showed significant differences in HIV seroprevalence between the different sites (chi 2, 71.71; P > 0.0001), but no evidence of any differences between the 1986 and the 1991-1992 prevalence levels (chi 2, 0.51; P = 0.6). Bujumbura appears to be in the endemic phase of the spread of HIV. The stable geographic variation among clinic populations in Bujumbura suggests the need for focused interventions, and a general need for surveillance data to be gathered from numerous sites so to identify those with the highest incidence of HIV infection.


Clinical evaluation of anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (P-15) in the treatment of human infrabony defects.
The purpose of the present study was to compare the clinical outcomes of infrabony periodontal defects following treatment with an anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (ABM/P-15) flow to open flap debridement. Twenty-six patients, each displaying one infrabony defect with probing depth>or=6 mm and vertical radiographic bone loss>or=3 mm participated in the present study. Patients were allocated randomly to be treated with ABM/P-15 flow (test group) or open flap debridement (control group). At baseline and at 12 months after surgery, the following clinical parameters were recorded by a blinded examiner: plaque index, gingival index, probing depth (PD), clinical attachment level (CAL), and gingival recession. Both treatments resulted in significant improvements between baseline and 12 months, in terms of PD reduction and CAL gain (p<0.001). At 12 months following therapy, the test group showed a reduction in mean PD from 7.8+/-1.6 mm to 3.5+/-1.0 mm and a change in mean CAL from 8.5+/-2.1 mm to 4.6+/-1.2 mm, whereas in the control group the mean PD decreased from 7.5+/-0.8 mm to 4.9+/-0.7 mm and mean CAL from 8.2+/-1.2 mm to 6.4+/-1.4 mm. The test group demonstrated significantly greater PD reductions (p=0.002) and CAL gains (p=0.001) compared to the control group. In conclusion, treatment of infrabony periodontal defects with ABM/P-15 flow significantly improved clinical outcomes compared to open flap debridement.


Vas deferens stones.
Reported is a case of stones in the vas deferens that was managed by excision of a segment of the vas.


Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells.
The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.


Partial characterization of a novel endogenous opioid in human cerebrospinal fluid.
Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated "Peak B" has previously been shown to be related to the pain status of chronic pain patients. We now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (less than 1.0 microM) but not at higher (greater than 6.0 microM) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or alpha-chymotrypsin.


Maternal use of antibiotics and the risk of childhood febrile seizures: a Danish population-based cohort.
In a large population-based cohort in Denmark to examine if maternal use of antibiotics during pregnancy, as a marker of infection, increases the risk of febrile seizures in childhood in a large population-based cohort in Denmark. All live-born singletons born in Denmark between January 1, 1996 and September 25, 2004 and who were alive on the 90(th) day of life were identified from the Danish National Birth Registry. Diagnoses of febrile seizures were obtained from the Danish National Hospital Register and maternal use of antibiotics was obtained from the National Register of Medicinal Product Statistics. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazard regression models. We followed 551,518 singletons for up to 5 years and identified a total of 21,779 children with a diagnosis of febrile seizures. Slightly increased hazard ratios were observed among most exposure groups when compared to the unexposed group, ex. HR 1.08 95% CI: 1.05-1.11 for use of any systemic antibiotic during pregnancy. We found weak associations between the use of pharmacologically different antibiotics during pregnancy and febrile seizures in early childhood which may indicate that some infections, or causes or effects of infections, during pregnancy could affect the fetal brain and induce susceptibility to febrile seizures.


Off-track Hill-Sachs lesions do not increase postoperative recurrent instability after arthroscopic Bankart repair with selective Remplissage procedure.
This study aimed to compare clinical outcomes and recurrence rates after arthroscopic Bankart repair with selective Remplissage procedure, between patients with off-track and on-track Hill-Sachs lesions. Patients who underwent arthroscopic Bankart repair with selective Remplissage procedure for recurrent anterior shoulder instability and were followed up for at least 2 years were included. Patients with a glenoid defect greater than 25% were excluded. According to the glenoid track concept, patients were divided into group I (off-track lesions) and group II (on-track lesions). After Bankart repair, an additional Remplissage procedure was performed selectively in patients who sustained engagement of the humeral head. The clinical outcomes and recurrence rates were evaluated. A total of 193 patients (23 in group I and 170 in group II) were enrolled. No significant differences were found in clinical outcomes (n.s.) or recurrence rates (n.s.) between the two groups, despite larger glenoid defects in group I (group I:17.1 ± 6.1%, and group II:13.0 ± 6.4%, P = 0.003). In all patients, the incidence of off-track lesions was not significantly different according to the occurrence of postoperative recurrence (n.s.), whereas the glenoid defect size showed a significant difference (with recurrence: 17.9 ± 3.9%, and without recurrence: 13.2 ± 6.5%, P = 0.002). The presence of an off-track lesion did not alter the clinical outcomes and recurrence rates after arthroscopic Bankart repair with selective Remplissage procedure. The glenoid defect size rather than the presence of an off-track lesion can more reliably predict postoperative recurrence. Arthroscopic Bankart repair with selective Remplissage procedure is considered one surgical option for the treatment of off-track lesions. III.


Studies on fungal polysaccharide. XVII. A new glucuronan "protuberic acid" produced by a fungus Kobayashia nipponica.
A water-soluble glucuronan "protuberic acid", [alpha] 22-D minus 83.6 degrees, was isolated and purified from Kobayashia Nipponica, and its physicochemical properties were investigated. The purified protuberic acid was homogeneous as shown by zone electrophoresis, gel filtration over Sepharose 4B, and ultracentrifugation. The sedimentation coefficient was 1.8 S and its intrinsic viscosity was 1.1 dl/g. By gel filtration the molecular weight was estimated to be about 170 000. The results of periodate oxidation, methylation analysis, and partial acid hydrolysis indicated that this acidic polysaccharide has a linear structure of mainly 1, 4-linkages and containing an acid-labile linkage. Reduced protuberic acid, [alpha] 22-D minus 44 degrees, is also described.


Examination of the Effect of Proton Pump Inhibitors on the Anticancer Activity of Oxaliplatin.
Oxaliplatin (L-OHP) is absorbed by cancer cells via organic cation transporter1-3 (OCT1-3). However, proton pump inhibitors (PPIs) suppress the function of OCT1-3. This study investigated whether PPIs attenuate the antitumor effect of L-OHP. Colorectal cancer patients who received FOLFOX (L-OHP + 5-fluorouracil: 5-FU) + bevacizumab therapy at Nagasaki University Hospital from October 1, 2010 to September 30, 2019 were retrospectively investigated. Patients were categorized into two groups with or without PPIs use. Progression-free survival (PFS) between the two groups was compared using the log-rank test. L-OHP was added to the intestinal epithelial Caco-2 cell line with or without the PPI rabeprazole, and then cell viability was analyzed using the WST-8 cell proliferation assay. The median PFS was 11.4 months in the group with PPIs and 9.7 months in the group without PPIs (p=0.736). No significant effect of 1-10 μM rabeprazole was observed on the antitumor effect of L-OHP. Plasma concentrations of rabeprazole at clinical doses are 1.0-1.3 μM. Even if L-OHP interacts with PPIs, clinical doses of PPIs were considered to have minimal effect on the antitumor effect of L-OHP.


The use of radiological guidelines to achieve a sustained reduction in the number of radiographic examinations of the cervical spine, lumbar spine and knees performed for GPs.
To determine if the use of request guidelines can achieve a sustained reduction in the number of radiographic examinations of the cervical spine, lumbar spine and knee joints performed for general practitioners (GPs). GPs referring to three community hospitals and a district general hospital were circulated with referral guidelines for radiography of the cervical spine, lumbar spine and knee, and all requests for these three examinations were checked. Requests that did not fit the guidelines were returned to the GP with an explanatory letter and a further copy of the guidelines. Where applicable, a large-joint replacement algorithm was also enclosed. If the GP maintained the opinion that the examination was indicated, she or he had the option of supplying further justifying information in writing or speaking to a consultant radiologist. Overall the number of radiographic examinations fell by 68% in the first year, achieving a 79% reduction in the second year. For knees, lumbar spine and cervical spine radiographs the total reductions were 77%, 78% and 86%, respectively. The use of referral guidelines, reinforced by request checking and clinical management algorithms, can produce a dramatic and sustained reduction in the number of radiographs of the cervical spine, lumbar spine and knees performed for GPs.


Determination of the distribution of D-glucuronic acid units within the chain of pig-skin dermatan sulfate near the linkage region.
A method for analyzing the distribution of D-glucuronic acid units within the chain and near the linkage region of dermatan sulfate has been developed. The method consists of a chemical modification of the reducing terminal residue in the polysaccharide by reductive amination with excess 1,2-diaminoethane in the presence of sodium cyanoborohydride, desulfative fragmentation of the polysaccharide, labeled with 2-aminoethylamino (AEA) groups, in hot dimethyl sulfoxide containing 10% of water followed by 2,4-dinitrophenylation of the 2-aminoethylamino group, separation of the 2-(2,4-dinitrophenylamino)ethylamino labeled dermatan fragments from nonlabeled fragments on Octyl-Sepharose CL-4B gel, and determination of the uronic acid composition of the labeled fragments having various chain-length. A preparation of pig-skin dermatan sulfate (Mr 21,000, ratio of GlcA to total uronic acid, 93:500) showed an average distribution pattern of D-glucuronic acid residues near the linkage region of one N-acetylchondrosine unit in the disaccharide sequence 1-5(6) linked to the Xyl----Gal----Gal----GlcA residue, a cluster of 6-8 N-acetyldermosine units in the sequence 6(7)-12(13), and four separate N-acetylchondrosine units between the sequence adjacent to the N-acetyldermosine cluster and the sequence 23 or higher.


Ethanol consumption synergistically increases ultraviolet radiation induced skin damage and immune dysfunction.
Excessive UV radiation disrupts skin homeostasis by multiple mechanisms that extend beyond the simple erythema associated with sunburns including reduction of antioxidants, increased DNA damage, and impairment of skin immune responses. Recreational UV exposure frequently occurs concurrently with excessive ethanol (EtOH). Epidemiological studies suggest a harmful, dose-dependent impact of EtOH in the setting of high UV exposure, leading to increased severity of sunburns relative to those generated in the absence of EtOH. Furthermore, EtOH consumption and UV radiation have multiple overlapping effects on the skin that could account for the epidemiological association. To elucidate the relationship between excessive EtOH ingestion and UV exposures on early skin damage and downstream immune dysfunction. We examined the impact of UVB on local skin damage, including inflammation, sunburned cells, apoptotic cells, melanin and antioxidant levels, DNA damage and immune dysfunction in the presence or absence of EtOH ingestion by combining standard mouse models of EtOH consumption and UVB exposure models. To confirm that the observed changes in mouse skin were relevant to human skin, we investigated the effects of EtOH on UV-induced skin damage with human skin explants. We demonstrated that EtOH consumption and UV exposure act synergistically to increase the severity of local skin damage resulting in impaired melanin responses, reduced antioxidants, greater DNA damage, and immune dysfunction as measured by reduced contact hypersensitivity. The results support incorporation of the risks of combined UV exposure and excessive alcohol consumption into public health campaigns.


Neuroendoscopic management of middle fossa arachnoid cysts.
The purpose of this study is to analyze symptomatic middle fossa arachnoid cysts and describe the advantages of the endoscopic technique to manage those cases that should be resolved surgically. The physiopathology is described, and the clinical manifestations are analyzed. The diagnostic methodology and the surgical indications are presented. The endoscopic surgical technique is described thoroughly, and the advantages of the method are stated based on a series of 28 operated cases. The endoscope of choice has been a rigid endoscope with a 0° lens. All the cases in our series were solved by means of the endoscopic technique. One patient developed meningitis, recovering with antibiotic treatment, and 3 patients developed subdural hygromas: 2 were treated by means of subdural-peritoneal shunting, and the remaining subdural hematoma required surgical drainage. All of the complications reported occurred in patients affected by cysts classified as Galassi type III. There was no mortality. The effectiveness of neuroendoscopic management of middle fossa arachnoid cysts has not yet been superseded by any other surgical treatment. It has been shown to be a simple, reliable, and fast procedure, with a low rate of complications and shorter hospital stay. In general, patients can resume their usual daily activities quite soon.


Prediction of cyclosporine A blood levels: an application of the adaptive-network-based fuzzy inference system (ANFIS) in assisting drug therapy.
Therapeutic drug monitoring (TDM) is a procedure in which the levels of drugs are assayed in various body fluids with the aim of individualizing the dose of critical drugs, such as cyclosporine A. Cyclosporine A assays are performed in blood. We proposed the use of the Takagi and Sugeno-type "adaptive-network-based fuzzy inference system" (ANFIS) to predict the concentration of cyclosporine A in blood samples taken from renal transplantation patients. We implemented the ANFIS model using TDM data collected from 138 patients and 20 input parameters. Input parameters for the model consisted of concurrent use of drugs, blood levels, sampling time, age, gender, and dosing intervals. Fuzzy modeling produced eight rules. The developed ANFIS model exhibited a root mean square error (RMSE) of 0.045 with respect to the training data and an error of 0.057 with respect to the checking data in the MATLAB: environment. ANFIS can effectively assist physicians in choosing best therapeutic drug dose in the clinical setting.


Flexible fitting in 3D-EM guided by the structural variability of protein superfamilies.
A method for flexible fitting of molecular models into three-dimensional electron microscopy (3D-EM) reconstructions at a resolution range of 8-12 A is proposed. The approach uses the evolutionarily related structural variability existing among the protein domains of a given superfamily, according to structural databases such as CATH. A structural alignment of domains belonging to the superfamily, followed by a principal components analysis, is performed, and the first three principal components of the decomposition are explored. Using rigid body transformations for the secondary structure elements (SSEs) plus the cyclic coordinate descent algorithm to close the loops, stereochemically correct models are built for the structure to fit. All of the models are fitted into the 3D-EM map, and the best one is selected based on crosscorrelation measures. This work applies the method to both simulated and experimental data and shows that the flexible fitting was able to produce better results than rigid body fitting.


Systemic sclerosis and the risk of cancer: a nationwide population-based cohort study.
Earlier studies reported an increased cancer risk among patients with systemic sclerosis. Study size limitations and paucity of population-based study designs may have resulted in imprecise risk estimates. To assess cancer risk among patients with systemic sclerosis in a nationwide follow-up study. Patients with a first diagnosis of systemic sclerosis from 1977 to 2006 were identified from the nationwide Danish National Registry of Patients (DNRP), whose records encompass all hospitalizations and outpatient visits. Patients' DNRP records were linked to the Danish Cancer Registry. We compared their cancer incidence with that expected from cancer incidence in the general population, calculating standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Two thousand and forty patients with systemic sclerosis were identified and followed for 16,003 person-years, with a median follow-up time of 6·4 years (interquartile range 2·2-11·5). Among these patients, 222 cases of cancer were identified. The overall SIR for cancer was 1·5 (95% CI 1·3-1·7), with a gender-specific SIR of 2·2 (95% CI 1·7-2·8) for men and 1·3 (95% CI 1·1-1·6) for women. The most frequent cancers were smoking- and alcohol-related cancers including lung cancer (SIR = 1·6, 95% CI 1·2-2·0), haematological cancers (SIR = 2·5, 95% CI 1·5-4·0) and immune-related cancers (SIR = 1·4, 95% CI 1·0-1·9). Systemic sclerosis is a risk factor for cancer, particularly smoking- and alcohol-related cancers. Men with systemic sclerosis generally are at higher cancer risk than women. Both primary and secondary cancer preventive measures are needed in the care of patients with systemic sclerosis.


False-negative cerebrospinal fluid fungal culture results following oral antineoplastic therapy with a 5-fluorouracil derivative.
Cryptococcus neoformans, a common opportunistic pathogen among patients with human immunodeficiency virus (HIV) infection, lymphoproliferative disorders and other conditions causing immunosuppression, can be differentiated from other yeasts using biochemical tests as well as culture results and direct histopathological examination. We present a case of a 78-year-old man with Cryptococcal meningitis and false-negative cerebrospinal fluid culture results following receipt of capecitabine. Patients receiving immunosuppressive agents are at higher risk of developing invasive fungal infections, and all patient medications should be reviewed to identify those with potential antifungal properties.


Identifying predictors of an abnormal computed tomographic scan among patients with a head injury and a Glasgow Coma Scale of 15.
The aim of this study was to determine the proportions of patients with a head injury and a Glasgow Coma Scale of 15 with an abnormal computed tomographic (CT) head scan and to explore its predictors. We conducted a retrospective study on adult patients with such injuries. Patients were risk stratified to undergo a head CT and subsequently discharged or admitted to a neurosurgical (NS) intensive care unit (ICU)/high-dependency (HD) NS or general ward (GW) and observation ward [Emergency Diagnostic and Therapeutic Centre (EDTC)]. The primary outcomes were proportions of abnormal CT results and NS interventions. The secondary outcomes included rates of disposition status, and the distribution and predictors of abnormal CT results. Data were analysed using descriptive statistics. We identified predictors of an abnormal head CT using logistic regression and reported their odds ratios (ORs) and 95% confidence intervals. We reviewed 2038 complete records. A total of 1088 scans were performed; 115 (10.6%) were abnormal. There were 962 (47.2%) discharges and 1076 (52.8%) admissions; six (0.6%) required NS interventions and ICU/HD admission. The proportions of GW admissions (n=1070) were as follows: EDTC 78.0%; NS 18.0%; and medical 4.0%. The proportions of abnormal CT results among these disposition statuses were as follows: NS ICU/HD 6/6 (100%); EDTC 59/835 (7.1%); NS GW 47/188 (25.0%); and medical GW 3/33 (9.1%). We identified three predictors, namely, vomiting [OR 2.23 (1.39-3.58)]; loss of consciousness [OR 1.56 (1.03-2.36)]; and amnesia [OR 2.08 (1.30-3.31)]. Abnormal CT and NS interventions were infrequent in patients with a head injury and a Glasgow Coma Scale of 15. We identified three predictors of abnormal head CTs.


Comparative effects of ammonium and nitrate compounds on Pacific treefrog and African clawed frog embryos.
The effects of ammonium nitrate, ammonium chloride, ammonium sulfate, and sodium nitrate on survival and growth of Pacific treefrog (Pseudacris regilla) and African clawed frog (Xenopus laevis) embryos were determined in static-renewal tests. The 10-day LC50s for the three ammonium compounds for P. regilla ranged from 25.0-32. 4 mg/L NH4 -N. The 10-day sodium nitrate LC50 for P. regilla was 578. 0 mg/L NO3-N. LC50s for X. laevis exposed for 4 or 5 days to the three ammonium compounds ranged from 27.5-60.2 mg/L NH4-N. The sodium nitrate LC50 for X. laevis ranged from 438.4-871.6 mg/L NO3-N. The lowest LOAEL based on length or weight was 6.1 mg/L NH4-N for the two species. The lowest LOAELs for NO3-N were 111.1 mg/L for P. regilla and 56.7 mg/L for X. laevis. Calculated unionized NH3 comprised 0.5-1.8% of measured NH4-N concentrations. Potential harm to amphibian populations could occur if NH4-N and NO3-N in agricultural runoff or drainage impacts sensitive life stages for a sufficiently long period.


The risk for end-stage renal disease is increased after burn.
Acute kidney injury (AKI) commonly complicates burn. Recently, AKI has been suggested to be causally related to chronic end-stage renal disease (ESRD), but controversial data also exist. Our aim was to study the risk of ESRD after burn in a nationwide analysis. All burn patients undergoing hospitalization between 1998 and 2011 were identified from the National Hospital Discharge Register, and the data were linked with the Finnish Registry for Kidney Diseases, which includes all individuals receiving chronic renal replacement therapy (RRT) in Finland. Altogether 41,179 adults were treated at hospitals for burns in Finland between 1998 and 2011. Of these, 86 had a diagnosis of AKI related to the burn. Forty-three burn survivors had ESRD and RRT initiated related to or after the burn. The overall risk for ESRD after burn was increased (standardized incidence ratio, SIR, 2.40, 95% CI 1.73-3.23) compared with the Finnish population. Standardized incidence ratio was 3.11 (95% CI 1.66-5.32) in women and 1.89 (95% CI 1.27-2.69) in men. Of these 43 patients, 38 had a specific non-burn-related diagnosis of ESRD identified in the registry, and ESRD was deemed unlikely to be directly related to the burn. In five patients, the diagnosis of ESRD was unknown cause of renal failure, and causality of the burn with ESRD was evaluated as plausible. In conclusion, a significantly increased risk of ESRD was recorded after a severe burn. Our results do not support increased incidence of ESRD solely as a consequence of AKI due to burn, but burn may increase the risk of ESRD in patients with pre-existing chronic kidney disease.


Quantitative microsampling for bioanalytical applications related to the SARS-CoV-2 pandemic: Usefulness, benefits and pitfalls.
The multiple pathological effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and its total novelty, mean that currently a lot of diagnostic and therapeutic tools, established and tentative alike, are needed to treat patients in a timely, effective way. In order to make these tools more reliable, faster and more feasible, biological fluid microsampling techniques could provide many advantages. In this review, the most important microsampling techniques are considered (dried matrix spots, volumetric absorptive microsampling, microfluidics and capillary microsampling, solid phase microextraction) and their respective advantages and disadvantages laid out. Moreover, currently available microsampling applications of interest for SARS-CoV-2 therapy are described, in order to make them as much widely known as possible, hopefully providing useful information to researchers and clinicians alike.


Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes.
Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that tandem copies of an alpha-helical fragment from the conserved stem region (helix-A) can be displayed on the protruding spikes structures of a capsid scaffold. The stem region of HA on these designed chimeric nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, mice vaccinated with H1-nanoparticles were protected from lethal challenge with H1N1 influenza virus. By using a nanoparticle library approach with this helix-A nanoparticle design, we show that this vaccine nanoparticle construct design could be applicable to different influenza HA subtypes. Importantly, antibodies elicited by H1, H5, and H7 nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity binding to different HA subtypes. Also, helix-A nanoparticle immunizations were used to isolate mouse monoclonal antibodies that demonstrated heterosubtypic cross-reactivity and provided protection to mice from viral challenge via passive-transfer. This tandem helix-A nanoparticle construct represents a novel design to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.


Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid revascularization.
Impaired revascularization of transplanted islets is a critical problem that leads to progressive islet loss. Since endothelial progenitor cells (EPCs) are known to aid neovascularization, we aimed to enhance islet engraftment by cotransplanting EPCs with islets. Porcine islets, with (islet-EPC group) or without (islet-only group) human cord blood-derived EPCs, were transplanted into diabetic nude mice. The islet-EPC group reached euglycemia by ∼11 days posttransplantation, whereas the islet-only group did not. Also, the islet-EPC group had a higher serum porcine insulin level than the islet-only group. Islets from the islet-EPC group were more rapidly revascularized at the early period of transplantation without increment of final capillary density at the fully revascularized graft. Enhanced revascularization rate in the islet-EPC group was mainly attributed to stimulating vascular endothelial growth factor-A production from the graft. The rapid revascularization by EPC cotransplantation led to better graft perfusion and recovery from hypoxia. EPC cotransplantation was also associated with greater β-cell proliferation, probably by more basement membrane production and hepatocyte growth factor secretion. In conclusion, cotransplantation of EPCs and islets induces better islet engraftment by enhancing the rate of graft revascularization. These findings might provide a directly applicable tool to enhance the efficacy of islet transplantation in clinical practice.


Neuroendocrine effects of leptin.
Leptin, the product of the obesity gene, is a cytokine-like circulating protein acting as a peripheral satiety signal to the hypothalamus. It was initially described as a secreted product of white adipose cells, but more recent data have demonstrated its expression by endocrine and neuroendocrine tissues like the ovary and the hypothalamus, as well as several anterior pituitary cell types. The effects of leptin on body weight homeostasis are mediated via different hypothalamic neurotransmitters regulating appetite and energy expenditure. In addition, leptin participates to the modulation of the activity of the neuroendocrine thyrotrope, somatotrope, corticotrope and gonadotrope axes. These endocrine effects of leptin have progressively emerged as important physiological functions of this molecule. Its role as a permissive factor for puberty and normal reproductive function in adulthood is becoming widely recognized. In addition, leptin participates in the fine tuning of the corticotrope axis. Thus, by signalling body fat stores to the hypothalamus and other endocrine organs, leptin serves as a metabolic integrator of several neuroendocrine functions. The precise site of action and mode of regulation of the gonadotrope and somatotrope axes by leptin are reviewed.


The dipole location shift within the auditory evoked neuromagnetic field components N100m and mismatch negativity (MMNm).
To investigate whether within the latency range of the neuromagnetic mismatch negativity (MMNm) a similar dipole shift can be observed as found in previous studies for the auditory evoked field component N100m. For this purpose selected neuromagnetic data of 29 subjects were analysed in a time window of 15 ms before and 15 ms beyond the peak maximum of both components. In our oddball paradigm, we applied frequency, duration and intensity deviants within one block. The time course of dipole location was analysed by means of a repeated measure analysis of variance (ANOVA). As expected, N100m dipoles shifted significantly from superior to inferior and from posterior to anterior within their latency range. In analogy, the MMNm dipoles of duration and intensity deviants also exhibited a significant shift from posterior to anterior within their latency range. However, the MMNm dipoles of all 3 deviants did not shift significantly from superior to inferior. Concerning this direction, the ANOVA revealed a significant TIME*COMPONENT interaction between the N100m and the MMNm of duration and intensity deviants. The finding of a different time course of N100m and MMNm dipoles does not support the assumption that the MMN represents an amplitude- and latency-modulated auditory N100 response.


PPARs and the placenta.
The discovery of the peroxisome proliferator-activated receptors (PPARs) in 1990s provided new insights in understanding the mechanisms involved in the control of energy homeostasis and in cell differentiation, proliferation, apoptosis and the inflammatory process. The PPARs became thus an exciting therapeutic target for diabetes, metabolic syndrome, atherosclerosis, and cancer. Unexpectedly, genetic studies performed in mice established that PPARgamma are essential for placental development. After a brief description of structural and functional features of PPARs, we will summarize in this review the most recent results concerning expression and the role of PPARs in placenta and of PPARgamma in human trophoblastic cells in particular.


Characteristics of oncology podcasts: Attitudes, speakers, conflicts.
To systematically appraise the content within oncology podcasts and the individuals who speak on them. A cross-sectional study. We obtained a list of 33 current podcasts with substantial oncologic content through queries of predetermined search terms on the Apple Podcast Platform. 98 oncology-related podcast episodes. The perceived attitude of the episode with predetermined categories including "Neutral," "Favorable," or "Negative," the number of conflicts of interest verbally disclosed by individuals featured on oncology podcasts, and the prevalence of general payments among featured physicians. Among 33 oncology podcasts, the median number of episodes was 81 (IQR: 25-129). Ninety-seven percent (n = 32/33) of the podcasts included guests. The median episode run time was 26:50 min (IQR: 18:00 - 41:75). Among the 98 episodes assessed, 47% of episodes (n = 46/98) mentioned oncologic drugs, of which 57% (n = 26) had a neutral disposition, 37% (n = 17) had a favorable disposition and 7% (n = 3) were negative. Across 98 episodes, we identified 194 featured individuals, of which 65% (n = 126) had a medical degree (MD), and 85% (n = 107/126) of these physicians received at least one general payment. Further, 83% (n = 105/126) of physicians did not disclose payments. Within oncology-related podcasts, the majority of conversations about oncologic drugs are perceived as either favorable or neutral, and a majority of individuals featured on podcasts do not disclose conflicts of interest, highlighting potential opportunities for improvement, including the need for standardization of financial conflict of interest disclosure.


Congenital syphilitic hepatitis: a radionuclide study.
A two-month-old girl with congenital syphilitic hepatitis had bizarre liver scintigraphic features showing diminished hepatic uptake of radiocolloid with accentuated pulmonary and bone marrow accumulation. These features were reversible following penicillin therapy and to our knowledge are previously undescribed manifestations of this multisystemic disease.


Alternative origin for "gain-of-function" by mutant SOD enzyme and for conformational change of normal prion protein.
Capillary electrophoresis and ESI-Mass spectrometry methods have revealed that a hydroperoxo-copper(II) complex with (tpa) (=tris(2-pyridylmethyl)amine) reacts with carbonic anhydrase or amyloid beta-peptide (1-40) as a nucleophile to induce the conformational change of the protein structure, while the Cu(bdpg)-complex ((bdpg)=N,N-bis(2-pyridylmethy)-beta-alanineamide) acts as an electrophile toward the proteins to degrade them under the same experimental conditions. This will lead to suggest that enhanced nucleophilic attack by a copper(II)-peroxide adduct to peptide bonding may be one of the serious origins for the "gain-of-function" by mutant superoxide dismutase and for conformational change of normal prion protein.


Holmium Laser Enucleation of the Prostate vs Robot-Assisted Simple Prostatectomy for Lower Urinary Tract Symptoms in Patients with Extremely Large Prostates ≥200 cc: A Comparative Analysis.
Introduction and Objectives: Robot-assisted simple prostatectomy (RASP) and holmium laser enucleation of the prostate (HoLEP) are both well-established, minimally invasive surgical treatment options for lower urinary tract symptoms caused by benign prostatic enlargement. We have reported the first comparative analysis of both techniques in patients with prostates of ≥200 cc. Materials and Methods: Between 2009 and 2020 a total of 53 patients with a prostate volume of ≥200 cc were surgically treated at OLV Hospital Aalst (Belgium): 31 underwent RASP and 22 underwent HoLEP. Preoperative and postoperative assessments included uroflowmetry with maximum urinary flow rate (Qmax) and postvoid residual volume (PVR), as well as the International Prostate Symptom Score (IPSS) and quality of life (IPSS-QoL). The complication rates were evaluated according to the Clavien-Dindo Classification. Results: Patients treated with RASP had significantly larger prostate volumes compared with HoLEP (median 226 cc vs 204.5 cc, p = 0.004). After a median follow-up of 14 months, both groups showed a significant improvement in the maximum flow rate (+10.60 mL/s vs +10.70 mL/s, p = 0.724) and a reduction of the IPSS score (-12.50 vs -9, p = 0.246) as well as improvement of the QoL (-3 vs -3, p = 0.880). Median operative time was similar in both groups (150 minutes vs 132.5 minutes, p = 0.665). The amount of resected tissue was lower in the RASP group (134.5 g vs 180 g, p = 0.029) and there was no significant difference in postoperative prostate-specific antigen (1.2 ng/mL vs 0.8 ng/mL, p = 0.112). Despite a similar median catheterization time (3 days vs 2 days, p = 0.748), the median hospitalization time was shorter in the HoLEP group (4 days vs 3 days, p = 0.052). Complication rates were similar in both groups (32% vs 36%, p = 0.987). Conclusion: Our results suggest similar outcomes for RASP and HoLEP in patients with very large prostates ≥200 cc. These findings will require external validation at other high-volume centers.


Neuropathic bladder in ankylosing spondylitis with spinal diverticula.
Cauda equina type of syndrome with neuropathic bladder is a rare but known complication of long-standing ankylosing spondylitis. From 1968 until now, diverticula from the subarachnoid space eroding into the bodies of the lumbosacral vertebrae have been reported in 46 cases of ankylosing spondylitis with cauda equina syndrome and neuropathic bladder. We report 3 cases of neuropathic bladder and ankylosing spondylitis with cauda equina symptoms. In 1 of the 3 patients, these rarely encountered spinal diverticula were demonstrated by computerized tomography (CT) scan. The etiology of these diverticula and their treatment are reviewed.


Metallobiochemistry of RNA. Co(NH3)6(3+) as a probe for Mg2+(aq) binding sites.
Co(NH3)6(3+) may serve as a probe of outer sphere complexation by Mg(H2O)6(2+) with RNA. The number of metal binding sites may be quantitatively assessed by optical spectroscopy (55-130, depending on background [K+]). Novel coordination-induced features have been observed in circular dichroism spectra.


Synthesis of retrovirus-like particles in testicular teratocarcinomas.
Two lines of evidence led to the investigation of human teratocarcinoma cells in vitro for oncogenic retroviruses: the observation by electron microscopy of retrovirus-like particles budding from the syncytial trophoblasts of human placentas, and the demonstration that teratocarcinoma patients before treatment show a high serum antibody reactivity against envelope proteins of mammalian retroviruses. In all 5 teratocarcinoma cell lines studied so far, retrovirus-like particles have been detected by electron microscopy. The production of these human teratocarcinoma-derived (HTD)-particles is enhanced by induction procedures known to be effective in animal virus model systems. In parallel, virus induction also increases the level of chorionic gonadotropin in the culture supernatant, demonstrating syncytial trophoblast-like cells in the heterogeneous cell population of teratocarcinomas which could be responsible for HTD-particle production. The origin of these virus-like particles--endogenous or exogenous--as well as their role in the pathogenesis of teratocarcinomas is not known so far. The potential value of serum antibody reactivity in teratocarcinoma patients as a diagnostic marker is discussed.


Myocardial migration by fibroblast progenitor cells is blood pressure dependent in a model of angII myocardial fibrosis.
Activation of the renin-angiotensin system (RAS) is thought to promote myocardial fibrosis. However, it is unclear whether this physiological fibrotic response results from chronic hemodynamic stress or from direct cellular signaling. Male C57B/6 mice were randomly assigned to receive angiotensin II (AngII) (2.0 μg kg(-1) min(-1)), AngII+hydralazine (6.9 μg kg(-1) min(-1)) or saline (control) via osmotic pumps for 7 days. Blood pressure was measured via noninvasive plethysmography. Hearts were harvested and processed for analysis. Cellular infiltration and collagen deposition were analyzed using histological staining. Molecular mediators were assessed using quantitative RT-PCR. As previously described, animals that received AngII developed hypertension and multifocal cellular infiltration by SMA(+)/CD133(+) fibroblast progenitors followed by collagen deposition. The coadministration of hydralazine with AngII completely inhibited the hypertensive effects of AngII (P0.01) and resulted in minimal cellular infiltration and minimal collagen deposition. These findings were in the context of persistent RAS activation, which was evidenced by elevation in serum aldosterone levels in animals that received AngII or AngII+hydralazine compared with animals that received saline. At the molecular level, infusion of AngII resulted in the significant upregulation of profibrotic factors (connective tissue growth factor-7.8±0.7 fold), proinflammatory mediators (TNFα-4.6±0.8 fold; IL-1β-6.4±2.6 fold) and chemokines (CCL2-3.8±1.0 fold; CXCL12-3.2±0.4 fold), which were inhibited when hydralazine was also infused. We provide evidence that myocardial infiltration by fibroblast progenitor cells secondary to AngII and the resultant fibrosis can be prevented by the addition of hydralazine. Furthermore, the beneficial effects of hydralazine were observed while maintaining RAS activation, suggesting that the mechanism of fibrosis is blood pressure dependent.


Synthesis of type 2 human blood-group antigenic determinants. The H, X, and Y haptens and variations of the H type 2 determinant as probes for the combining site of the lectin I of Ulex europaeus.
Chemical syntheses of the human blood-group antigenic determinants derived from N-acetyllactosamine are described; namely, the 6-deoxy derivative, the 4'-epimer, and the 5 H type 2 [alpha LFuc(1 to 2)beta DGal-(1 to 4)beta DGlcNAc], X [beta DGal(1 to 4)[alpha LFuc(1 to 3)[beta DGlcNAc], and Y [alpha LFuc-(1 to 2)beta DGal(1 to 4)[alpha LFuc(1 to 3)]beta DGlcNAc] determinants as glycosides of 8-carboxymethyloctanol. In order to study the binding of the H type 2 determinant with the lectin I of Ulex europaeus, structures designed to specifically alter the hydrophilic and hydrophobic portions of the H type 2 determinant were also prepared; namely, the 6-deoxy derivative, the 4'-epimer, and the 5"-nor-homolog. The use of these structures, together with the H type 1 hapten and the N-deacetylated forms of both the H type 1 and H type 2 determinants, as inhibitors of the agglutination of O red cells by the lectin allowed the conclusion that the binding of the H type 2 determinant is hydrophobic; the binding involves a wedge-like portion of the determinant that is basically hydrophobic, except for the 5-hydroxymethyl group, which is at the tip of the wedge and forms an intramolecular hydrogen-bond with O-5 for acceptance by a hydrophobic cleft at the surface of the lectin. Blocking procedures involving alkoxymethyl groups and new experiences involving glycosylation reactions are described.


Yeast aspartyl-tRNA synthetase binds specifically its own mRNA.
Dimeric class II aspartyl-tRNA synthetase (AspRS) from yeast has a modular architecture and includes an N-terminal appendix of 70 amino acid residues that protrudes from the anticodon-binding module. This extension, of predicted helical structure, is not essential for aminoacylation but contains an RNA-binding motif that promotes non-specific interactions with tRNAs. As shown here, this protein extension can also interact with the 5' end of the AspRS mRNA. In vitro, optimal binding occurs on an mRNA domain comprising part of the 87 nucleotide long 5'UTR and the sequence encoding the N-terminal appendix. At the protein side, only the appendix and the anticodon-binding module participate in the interaction between AspRS and the mRNA domain. Binding is specific, since only tRNA(Asp) can dissociate the complex. In vivo, AspRS also binds specifically this mRNA domain and in doing so triggers a reduced translation of a fused GFP mRNA. From that, a mechanism for the regulation of this eukaryotic aminoacyl-tRNA synthetase is proposed. Implications for aspartylation accuracy in yeast are given.


Evaluating the drug dependency unit.
An evaluation of the St Mary's Drug Dependency Unit is described. Unit staff were interviewed and a retrospective analysis of 156 records was performed. The advent of HIV infection has led to an emphasis on public health priorities in the treatment of drug misuse. However, DDU staff retain a highly individualistic approach to their work. Staff aiming at abstinence within treatment may compromise important advice on harm minimization. The mean delay between first contact and entering treatment was 10 days; 42% of clients failed to complete the initial assessment. The need to extend access to the service is not easy to reconcile with the increasingly specialised support role for such units implied in recent strategy documents. Little is known of the effectiveness of different services for drug misusers. In this study, only 6% of clients were known to have achieved abstinence at one year. The efficiency of the DDU could be improved by closer definition of the unit's goals and target population, regular progress reviews, shortening the assessment procedure and the computerisation of data collection.


Tissue plasminogen activator levels in different types of polycythemia.
The plasma level of tissue plasminogen activator antigen (t-PA-Ag) was examined in 86 patients with polycythemia (29 polycythemia vera, 11 secondary polycythemia and 46 with spurious polycythemia) and 24 healthy volunteers. Tissue plasminogen activator antigen was significantly decreased in patients with polycythemia vera in comparison with healthy controls. On the other hand, in patients with spurious polycythemia and secondary polycythemia t-PA-Ag concentration was significantly increased. There was no significant difference in t-PA-Ag levels in polycythemic patients with or without thromboembolic disease. A significant correlation was detected between t-PA-Ag level and hemoglobin or hematocrit concentration in patients with polycythemia vera (p = 0.02, r = 0.43). However, in patients with secondary polycythemia and spurious polycythemia, no significant correlation between t-PA-Ag and hemoglobin level was found. Plasminogen activator inhibitor (PAI) levels in patients with polycythemia vera and healthy volunteers did not differ significantly.


Cognitive problem solving patterns of medical students correlate with success in diagnostic case solutions.
Problem-solving in terms of clinical reasoning is regarded as a key competence of medical doctors. Little is known about the general cognitive actions underlying the strategies of problem-solving among medical students. In this study, a theory-based model was used and adapted in order to investigate the cognitive actions in which medical students are engaged when dealing with a case and how patterns of these actions are related to the correct solution. Twenty-three medical students worked on three cases on clinical nephrology using the think-aloud method. The transcribed recordings were coded using a theory-based model consisting of eight different cognitive actions. The coded data was analysed using time sequences in a graphical representation software. Furthermore the relationship between the coded data and accuracy of diagnosis was investigated with inferential statistical methods. The observation of all main actions in a case elaboration, including evaluation, representation and integration, was considered a complete model and was found in the majority of cases (56%). This pattern significantly related to the accuracy of the case solution (φ = 0.55; p<.001). Extent of prior knowledge was neither related to the complete model nor to the correct solution. The proposed model is suitable to empirically verify the cognitive actions of problem-solving of medical students. The cognitive actions evaluation, representation and integration are crucial for the complete model and therefore for the accuracy of the solution. The educational implication which may be drawn from this study is to foster students reasoning by focusing on higher level reasoning.


Identification of a novel pyroptosis-related gene signature in human spermatogenic dysfunction.
To reveal the underlying roles that pyroptosis-related genes (PRGs) played in human spermatogenic dysfunction. One discovery set and three validation sets were employed to inspect the previously reported 33 PRGs in the human testis with different status of spermatogenesis. PRGs that differentially expressed in all sets were considered as key differentially expressed pyroptosis-related genes (PR-DEGs). The relationships between key PR-DEGs and samples' clinicopathological, therapeutic, and immune patterns were respectively studied. Single-cell RNA sequencing (scRNS-seq) analyses were conducted to show the expression changes and related mechanisms of key PR-DEGs at a single-cell resolution. CASP4 and GPX4 were identified as two key PR-DEGs. These two genes were significantly dysregulated in spermatogenic dysfunctional samples, but with opposite tendency. CASP4 was negatively correlated with Johnsen scores but positively correlated with follicle-stimulating hormone (FSH) levels (all p < 0.05), while GPX4 exhibited significant positive correlations with Johnsen scores and negative relevance with FSH. For treatments, both molecules showed a prospective value of being predictors for sperm retrieval surgeries. Moreover, CASP4 and GPX4 were potential immunoregulators in the testicular immune microenvironment and showed significant correlations to testicular macrophages and mast cell infiltration. In scRNA-seq analyses, GPX4 was highly expressed in germ cells, which therefore suffered a sharp reduction with the loss of germ cells in spermatogenic dysfunction. On the other hand, CASP4 were basically somatic cell-derived, and the proportion of CASP4-positive Leydig cells significantly increased in disease testes (p = 0.0001). In all, we revealed two key PRGs of human testes that might be functional in spermatogenic dysfunction.


Cytomegalovirus infection in simultaneous pancreas-kidney transplantation.
In this open-label multicenter study, 205 simultaneous pancreas-kidney (SPK) transplant recipients between 1998 and 2000 were randomly assigned to tacrolimus or cyclosporine-microemulsion (ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil and short-term corticosteroids. We report the 3-year data related to the occurrence, severity and effect of cytomegalovirus (CMV) infections. The type of CMV prophylaxis and treatment was at the discretion of the investigator. The overall incidence of CMV infection was 34% with no difference in incidence between the tacrolimus and cyclosporine-ME treatment arms. Statistically significant fewer CMV infections occurred among patients who received ganciclovir (22%) than those who did not receive prophylaxis (42%; P = .0075) or were treated with acyclovir (43%; P = .0066). The CMV infection rate according to donor recipient CMV serological status was: D-/R- group 11%, which was lower than the D-/R+ group at 40% (P = .0035), the D+/R+ group at 37% (P = .0024), or the D+/R- group at 52% (P = .00001). Among the last three groups, the infection rate was lower in patients on ganciclovir than those with no prophylaxis or on acyclovir (22% vs 64%; P = .00001). The incidence of acute rejection episodes was higher among patients without ganciclovir prophylaxis. No difference was observed in actuarial patient, kidney, or pancreas survival rates between patients with versus without infection. Ganciclovir prophylaxis effectively prevented CMV infection in SPK transplant recipients, especially in higher risk groups. An effect of CMV prophylaxis on the incidence of rejection is possible.


The role of the gut in reverse cholesterol transport--focus on the enterocyte.
In the arterial intima, macrophages become cholesterol-enriched foam cells and atherosclerotic lesions are generated. This atherogenic process can be attenuated, prevented, or even reversed by HDL particles capable of initiating a multistep pathway known as the macrophage-specific reverse cholesterol transport. The macrophage-derived cholesterol released to HDL is taken up by the liver, secreted into the bile, and ultimately excreted in the feces. Importantly, the absorptive epithelial cells lining the lumen of the small intestine, the enterocytes, express several membrane-associated proteins which mediate the influx of luminal cholesterol and its subsequent efflux at their apical and basolateral sides. Moreover, generation of intestinal HDL and systemic effects of the gut microbiota recently revealed a direct link between the gut and the cholesterol cargo of peripheral macrophages. This review summarizes experimental evidence establishing that the reverse cholesterol transport pathway which initiates in macrophages is susceptible to modulation in the small intestine. We also describe four paths which govern cholesterol passage across the enterocyte and define a role for the gut in the regulation of reverse cholesterol transport. Understanding the concerted function of these paths may be useful when designing therapeutic strategies aimed at removing cholesterol from the foam cells which occupy atherosclerotic lesions.


Upcycling of recycled minerals from sewage sludge through black soldier fly larvae (Hermetia illucens): Impact on growth and mineral accumulation.
Phosphorous (P) resources are finite. Sewage sludge recyclates (SSR) are not only of interest as plant fertilizer but also as potential source of minerals in animal nutrition. However, besides P and calcium (Ca), SSR contain heavy metals. Under EU legislation, the use of SSR derivatives in animal feed is not permitted, but given the need to improve nutrient recycling, it could be an environmentally sound future mineral source. Black soldier fly larvae (BSFL) convert low-grade biomass into valuable proteins and lipids, and accumulate minerals in their body. It was hypothesized that BSFL modify and increase their mineral content in response to feeding on SSR containing substrates. The objective was to evaluate the upcycling of minerals from SSR into agri-food nutrient cycles through BSFL. Growth, nutrient and mineral composition were compared in BSFL reared either on a modified Gainesville fly diet (FD) or on FD supplemented with either 4% of biochar (FD + BCH) or 3.6% of single-superphosphate (FD + SSP) recyclate (n = 6 BSFL rearing units/group). Larval mass, mineral and nutrient concentrations and yields were determined, and the bioaccumulation factor (BAF) was calculated. The FD + SSP substrate decreased specific growth rate and crude fat of BSFL (P < 0.05) compared to FD. The FD + SSP larvae had higher Ca and P contents and yields but the BAF for Ca was lowest. The FD + BCH larvae increased Ca, iron, cadmium and lead contents compared to FD. Larvae produced on FD + SSP showed lower lead and higher arsenic concentration than on FD + BCH. Frass of FD + BCH had higher heavy metal concentration than FD + SSP and FD (P < 0.05). Except for cadmium and manganese, the larval heavy metal concentration was below the legally permitted upper concentrations for feed. In conclusion, the SSR used could enrich BSFL with Ca and P but at the expense of growth. Due to the accumulation of Cd and Mn, BSFL or products thereof can only be a component of farmed animal feed whereas in BSFL frass heavy metal concentrations remained below the upper limit authorized by EU.


Swenson revisited: a one-stage, transanal pull-through procedure for Hirschsprung's disease.
Hirschsprung's disease is a common cause of neonatal intestinal obstruction. A variety of operations have been used to treat this neurogenic form of bowel obstruction. This report describes an experience with a 1-stage abdominal and transanal pull-through operation in 15 patients with rectosigmoid disease. Fifteen infants with Hirschsprung's disease included 11 boys and 4 girls. Median age at diagnosis was 3 days, and median age of operation was 30 days. Diagnosis was confirmed by rectal biopsy. Biopsies to confirm the transition zone were performed intraabdominally through a left lower quadrant incision. A Swenson pull-through was performed via transanal dissection. There were no instances of anastomotic leaks, wound infections or postoperative bowel obstructions. All patients survived. Two had postoperative enterocolitis. Twelve of 15 patients did well and had 2-3 bowel motions per day. One with Down's syndrome had enterocolitis and required a colostomy. Two were lost to follow up. A one-stage transanal pull-through procedure in infancy is a safe alternative to staged procedures for Hirschsprung's disease.


Compliance, efficacy, and safety of subcutaneous and sublingual immunotherapy in children with allergic rhinitis.
Although previous studies had confirmed the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), respectively, direct head-to-head comparison of SCIT vs SLIT is sparse. We aimed to compare the efficacy, safety, and compliance of SCIT and SLIT in allergic rhinitis (AR) children. This study is a prospective, open-label, and single-center study performed between June 2017 and June 2018. A total of 325 children were grouped into SLIT, Alutard (SCIT1), and NovoHelisen Depot (NHD) (SCIT2) according to the parents' wishes. The adherence and reasons for dropout were recorded. The efficacy of SLIT and SCIT was evaluated by a combined symptom medication score. Adverse events (AEs) were recorded and graded during the whole treatment. The compliance rate was higher in the SCIT group compared with the SLIT group (P < .05). The total nasal symptom score (TNSS), rescue medication score (RMS), and symptom medication score (SMS) after 6-month, 12-month, and 2-year treatment were lower in the SCIT group compared with the SLIT group (P < .05). But the scores between the Alutard and NHD groups were not significantly different. The occurrence of AEs in the SCIT group was significantly higher compared with the SLIT group (P < .05). Our results suggested SCIT is more effective compared with SLIT to a certain degree, whereas SLIT had less AEs compared with SCIT. The AIT routes can be chosen according to personal specific conditions.


Identification of circRNA expression profiles and the potential role of hsa_circ_0006916 in silicosis and pulmonary fibrosis.
Circular RNAs (circRNAs) are emerging as novel regulators in the biological development of various diseases, but their expression profiles, functions and mechanisms in silicosis and pulmonary fibrosis remain largely unexplored. In this study, we constructed a mouse model of pulmonary fibrosis by intratracheal injection of silica particles and then performed transcriptome RNA sequencing of lung tissues. The results showed that 78 circRNAs, 39 miRNAs and 262 mRNAs were differentially expressed. Among them, five circRNAs, three miRNAs and four mRNAs were further selected, and their abnormal expression was verified in mouse fibrotic lung tissues by RT-qPCR assay. The circRNA-associated ceRNA network including 206 ceRNA triplets was constructed based on abnormally expressed circRNAs, miRNAs and mRNAs, and miR-199b-5p, miR-296-5p and miR-708-5p were identified as hub miRNAs connected to circRNAs and mRNAs. Subsequently, GO and KEGG pathway enrichment analyses were performed to detect the potential roles of differentially expressed mRNAs in pulmonary fibrosis, which were mainly involved in immune response, Th17 cell differentiation, NF-κB signaling pathway and PI3K-Akt signaling pathway. Furthermore, we identified that hsa_circ_0006916 was up-regulated in pulmonary fibrosis. To characterize the potential role of hsa_circ_0006916, we transfected siRNA targeting hsa_circ_0006916 into alveolar macrophages and found that knockdown of hsa_circ_0006916 significantly increased the expression levels of M1 molecules IL-1β and TNF-α and reduced the expression level of M2 molecule TGF-β1, indicating that hsa_circ_0006916 may play an important role in the activation of M1-M2 polarization effect in macrophages. Our results provided important evidence on the possible contribution of these abnormal circRNAs to the development of silicosis and pulmonary fibrosis.


A simultaneous demonstration of particular enteric neuronal cell types with the NADH:nitro BT-dehydrogenase reaction and of nerve fibres containing enkephalin-like immunoreactivity in the myenteric plexus of the porcine small intestine.
The myenteric plexus of the porcine small intestine is studied using a combined method for the simultaneous visualization of enteric intramural neuronal cell bodies and peptidergic nerve fibers. As earlier reported, the histochemical method for demonstration of the NADH-dependent dehydrogenase reaction allows the identification of the three neuron types of Dogiel but, in addition, the afore mentioned staining method creates fair conditions in the tissue for the subsequent indirect immunocytochemical visualization of neuropeptides, as demonstrated in this work by means of the indirect immunofluorescence method for enkephalin-like immunoreactivity. Intense fluorescent varicosities of enkephalin-like nerve fibres were found to ramify around dark-blue stained ganglionic cells of type I, type II and type III in a manner suggestive of innervation.


Monitoring of caloric response and outcome in patients with benign paroxysmal positional vertigo.
To analyze the time course of caloric response in patients with Benign Paroxysmal Positional Vertigo (BPPV). Seventy-four individuals with diagnosis of BPPV during Dix-Hallpike (DH) test. A prospective, longitudinal study. A tertiary referral center. Patients were treated by particle repositioning maneuvers according to the affected canal, and the effectiveness was evaluated at 180 and 360 days. Bithermal caloric response was obtained by using 44 and 30 degrees C water irrigations at diagnosis, 6 months, and 1 year after. Canal paresis (CP) and response to DH after treatment. The effectiveness of the treatment for BPPV (absence of vertigo and positional nystagmus during DH) was 65.2% (45 of 69) after 1 year of follow-up. Twenty-five percent of (16 of 64) individuals with BPPV presented CP at diagnosis, 27% (12 of 44) at 6 months, and 16% (9 of 56) 1 year after. One year after, seven individuals with CP showed a normal caloric response, another seven demonstrated persistent CP, and one case developed a bilateral CP. The effectiveness of particle repositioning maneuvers was not significantly different between subjects with or without CP after 1 year of follow-up (odds ratio, 1.31 [95% confidence intervals, 0.35-4.89], p = 0.88). Canal paresis is not associated with a lower outcome to repositioning.


Applying Hierarchy of Expert Performance (HEP) to investigative interview evaluation: strengths, challenges and future directions.
The purpose of this paper is to systematically examine the research literature on the decision of expert interviewers within the theoretical framework of the Hierarchy of Expert Performance (HEP). After providing an overview of the HEP framework, existing research in the investigative interviewing at each of the eight levels of the HEP framework is reviewed. The results identify areas of strength in reliability between experts' observations (Level 2) and of weakness in reliability between experts' conclusions (Level 6). Biases in investigative interview experts' decision making is also revealed at biasability between expert conclusions (Level 8). Moreover, no published data are available in reliability within experts at the level of observations (Level 1) or conclusions (Level 5), biasability within or between expert observations (Level 3 and 4) and biasability within expert conclusions (Level 7). The findings highlight areas where future research and practical endeavour are much needed for the investigative interview.


Purification and reconstitution studies of the nucleoside transporter from pig erythrocytes.
The pig erythrocyte nucleoside transporter has been identified as a band 4.5 polypeptide (Mr 64,000) on the basis of photoaffinity labelling experiments with the nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR). This protein was purified 140-fold by treatment of haemoglobin-free erythrocytes 'ghosts' with EDTA (pH 11.2) to remove extrinsic proteins, extraction of the protein-depleted membranes with n-octyl-glucoside and subsequent gradient-elution ion-exchange chromatography on DEAE-cellulose. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the purified material revealed the presence of only two detectable protein bands, one which co-migrated with the radiolabelled NBMPR-binding protein, and a lower molecular weight species with an Mr of 43,000. The latter protein may be a degradation product of the band 3 anion-exchange transporter. The overall purification of the NBMPR-binding protein with respect to the Mr 64,000 band was 350-fold. Reversible NBMPR-binding to the partially-purified band 4.5 preparation was saturable (apparent Kd 7.2 nM). Adjustment of the chromatography conditions to allow elution of the NBMPR-binding protein along with the majority of solubilised membrane phospholipid reduced the apparent Kd value to 3.0 nM. Purification of reversible NBMPR-binding activity during ion-exchange chromatography was paralleled by an increase in the specific activity of nitrobenzylthioguanosine (NBTGR) -sensitive uridine transport as assayed in proteoliposomes reconstituted by a freeze-thaw-sonication procedure.


Synthetic enhancement in gene interaction: a genetic tool come of age.
Synthetic enhancement, in which one mutation exacerbates the severity of another, is a genetic interaction of increasing importance in biology. This review focuses on the logic of interpreting synthetic enhancement, and begins by comparing the phenomenon with genetic suppression.


Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.
Plasma liver-enzyme tests are widely used in the clinic for the diagnosis of liver diseases and for monitoring the response to drug treatment. There is considerable evidence that human genetic variation influences plasma levels of liver enzymes. However, such genetic variation has not been systematically assessed. In the present study, we performed a genome-wide association study of plasma liver-enzyme levels in three populations (total n = 7715) with replication in three additional cohorts (total n = 4704). We identified two loci influencing plasma levels of alanine-aminotransferase (ALT) (CPN1-ERLIN1-CHUK on chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), and three loci for alkaline phosphatase (ALP) levels (ALPL on chromosome 1, GPLD1 on chromosome 6, and JMJD1C-REEP3 on chromosome 10). In addition, we confirmed the associations between the GGT1 locus and GGT levels and between the ABO locus and ALP levels. None of the ALP-associated SNPs were associated with other liver tests, suggesting intestine and/or bone specificity. The mechanisms underlying the associations may involve cis- or trans-transcriptional effects (some of the identified variants were associated with mRNA transcription in human liver or lymphoblastoid cells), dysfunction of the encoded proteins (caused by missense variations at the functional domains), or other unknown pathways. These findings may help in the interpretation of liver-enzyme tests and provide candidate genes for liver diseases of viral, metabolic, autoimmune, or toxic origin. The specific associations with ALP levels may point to genes for bone or intestinal diseases.


Comparing the effectiveness of two reciprocal reading comprehension interventions for primary school pupils in disadvantaged schools.
Effective reading comprehension teaching is an aspiration of education systems across the world. Teaching incorporating reciprocal reading theory and evidence is an internationally popular approach for improving comprehension. This paper uses two large cluster randomized controlled trials of similar reciprocal reading interventions implemented in different ways to compare their effectiveness. The two interventions had the same teacher professional development, reciprocal reading activities and dosage/exposure, but varied in their implementation, with one delivered as a whole-class ('universal') version for pupils aged 8-9 years and the other a small group ('targeted') version for pupils aged 9-11 years with specific comprehension difficulties. Two large-scale cluster RCTs were conducted in 98 schools with N = 3699 pupils in the universal trial and N = 1523 in the targeted trial. Multi-level models showed significant effects for the targeted version of the intervention on pupil reading comprehension (g = .18) and overall reading (g = .14). No significant effects were found for the whole class version. A sub-group analyses of disadvantaged pupils showed the targeted intervention's effects were even larger on reading comprehension (g = .25). The evidence suggested that this reciprocal reading intervention worked best when implemented in small groups and targeted for pupils with specific comprehension difficulties and particularly for pupils in disadvantaged circumstances. This evaluation shows that even if a reading comprehension intervention is underpinned by strong theory and evidence-based practice, its effectiveness can still depend on implementation choices.


High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia.
To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.


Fourier space approach for convolutional neural network (CNN) electrocardiogram (ECG) classification: A proof-of-concept study.
There has been a proliferation of machine learning (ML) electrocardiogram (ECG) classification algorithms reaching > 85% accuracy for various cardiac pathologies. Although the accuracy within institutions might be high, models trained at one institution might not be generalizable enough for accurate detection when deployed in other institutions due to differences in type of signal acquisition, sampling frequency, time of acquisition, device noise characteristics and number of leads. In this proof-of-concept study, we leverage the publicly available PTB-XL dataset to investigate the use of time-domain (TD) and frequency-domain (FD) convolutional neural networks (CNN) to detect myocardial infarction (MI), ST/T-wave changes (STTC), atrial fibrillation (AFIB) and sinus arrhythmia (SARRH). To simulate interinstitutional deployment, the TD and FD implementations were also compared on adapted test sets using different sampling frequencies 50 Hz, 100 Hz and 250 Hz, and acquisition times of 5 s and 10s at 100 Hz sampling frequency from the training dataset. When tested on the original sampling frequency and duration, the FD approach showed comparable results to TD for MI (0.92 FD - 0.93 TD AUROC) and STTC (0.94 FD - 0.95 TD AUROC), and better performance for AFIB (0.99 FD - 0.86 TD AUROC) and SARRH (0.91 FD - 0.65 TD AUROC). Although both methods were robust to changes in sampling frequency, changes in acquisition time were detrimental to the TD MI and STTC AUROCs, at 0.72 and 0.58 respectively. Alternatively, the FD approach was able to maintain the same level of performance, and, therefore, showed better potential for interinstitutional deployment.


Machine learning discriminates P2X7-mediated intracellular calcium sparks in human-induced pluripotent stem cell-derived neural stem cells.
Adenosine triphosphate (ATP) is an extracellular signaling molecule that mainly affects the pathophysiological situation in the body and can be sensed by purinergic receptors, including ionotropic P2X7. Neuronal stem cells (NSCs) remain in adult neuronal tissues and can contribute to physiological processes via activation by evoked pathophysiological situations. In this study, we revealed that human-induced pluripotent stem cell-derived NSCs (iNSCs) have ATP-sensing ability primarily via the purinergic and ionotropic receptor P2X7. Next, to develop a machine learning (ML)-based screening system for food-derived neuronal effective substances and their effective doses, we collected ATP-triggered calcium responses of iNSCs pretreated with several substances and doses. Finally, we discovered that ML was performed using composite images, each containing nine waveform images, to achieve a better ML model (MLM) with higher precision. Our MLM can correctly sort subtle unidentified changes in waveforms produced by pretreated iNSCs with each substance and/or dose into the positive group, with common mRNA expression changes belonging to the gene ontology signatures.


Quarantine during COVID-19 outbreak: Changes in diet and physical activity increase the risk of cardiovascular disease.
CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.


Oversizing of self-expanding Nitinol vascular stents - A biomechanical investigation in the superficial femoral artery.
Despite being commonly employed to treat peripheral artery disease, self-expanding Nitinol stents are still associated with relatively high incidence of failure in the mid- and long-term due to in-stent restenosis or fatigue fracture. The practice of stent oversizing is necessary to obtain suitable lumen gain and apposition to the vessel wall, though it is regarded as a potential cause of negative clinical outcomes when mis-sizing occurs. The objective of this study was to develop a computational model to provide a better understanding of the structural effects of stent sizing in a patient-specific scenario, considering oversizing ratio OS, defined as the stent nominal diameter to the average vessel diameter, between 1.0 and 1.8. It was found that OS < 1.2 resulted in problematic short-term outcomes, with poor lumen gain and significant strut malapposition. Oversizing ratios that were in the range 1.2 ≤ OS ≤ 1.4 provided the optimum biomechanical performance following implantation, with improved lumen gain, reduced incomplete stent apposition and favourable predicted long-term fatigue performance. Excessive oversizing, OS > 1.4, did not provide any further benefit in outcomes, showing limited increases in lumen gain and unfavourable long-term performance, with higher mean strain values predicted from the fatigue analysis. Therefore, our findings predict that the optimal oversizing ratio for self-expanding Nitinol stents is in the range of 1.2 ≤ OS ≤ 1.4, which is similar to clinical observations, with this study providing detailed insight into the biomechanical basis for this.


Catalytic Enantioselective Synthesis of Tetrahydocarbazoles and Exocyclic Pictet-Spengler-Type Reactions.
A synthetic strategy for the synthesis of chiral tetrahydrocarbazoles (THCAs) has been developed. The strategy relies on two types of 6-exo-trig cyclization of 3-substituted indole substrates. Enantioselective domino Friedel-Crafts-type reactions leading to THCAs can be catalyzed by chiral phosphoric acid derivatives (with up to >99% ee), and the first examples of exocyclic Pictet-Spengler reactions to form THCAs are reported.


Endovascular stenting for the management of port-a-cath associated superior vena cava syndrome.
Port-a-cath systems are often essential for the administration of long-term chemotherapy in the treatment of malignancies because they improve venous access, but they are associated with complications, mainly thrombosis of central veins. In the present report, we describe a case of right subclavian and superior vena cava port-a-cath-related thrombosis causing superior vena cava syndrome (SVCS) in a patient affected by Hodgkin's disease. The patient underwent percutaneous revascularization with stent positioning, experiencing immediate relief of symptoms. Endovascular procedures for the treatment of nonmalignant SVCS seem to represent a challenging therapeutic option.


Effect of chronic oral nicotine on dopaminergic function in the MPTP-treated mouse.
Although epidemiological studies have suggested a lower incidence of Parkinson's disease in cigarette smokers, repeated exposure to cigarette smoke or nicotine does not protect against neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since there is some evidence that nicotinic antagonists, nicotine, and neurotransmitters may have tropic effects on neurite outgrowth, the present study examined the effects of chronic nicotine administration for 16 weeks (in drinking water; 5 mg/kg consumed per day) on the rate of terminal recovery after striatal lesioning with MPTP (2 x 30 mg/kg, s.c.). Terminal recovery, as measured by the rate of recovery in the level of striatal dopamine, was not affected by nicotine. Monoamine oxidase-B activity was not reduced by MPTP, nor did nicotine affect its activity in striatal homogenates.


Prevalent cocaine use and myocardial infarction.
Studies have reported a possible link between cocaine use and risk for cardiovascular events. The aim of this study was to examine the association between self-reported cocaine use and physician-diagnosed myocardial infarction (MI) in the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994. Odds ratios (ORs) were estimated using logistic regression models adjusted for age and additionally for gender, race, and other MI risk factors, which accounted for the complex sampling design. In the group aged 18 to 59 years, there was no statistically significant association between any exposure to cocaine and MI (age-adjusted OR 1.56, 95% confidence interval [CI] 0.44 to 5.50, p = 0.48; multivariate-adjusted OR 1.06, 95% CI 0.30 to 3.73, p = 0.92). Participants who reported using cocaine >10 times had a nonsignificant higher prevalence of MI (age-adjusted OR 3.13, 95% CI 0.80 to 12.25, p = 0.10; multivariate-adjusted OR 1.84, 95% CI 0.46 to 7.29, p = 0.40). However, participants aged 18 to 45 years who reported >10 occasions of cocaine use had a significantly elevated prevalence of MI in age-adjusted models (OR 4.60, 95% CI 1.12 to 18.88, p = 0.035). The association was attenuated in multivariate-adjusted models (OR 3.84, 95% CI 0.98 to 15.07, p = 0.054). The lifetime prevalence of cocaine use increased from 14% in NHANES III to 19% in NHANES 2005-2006. In conclusion, these data support a substantial association between cocaine use and MI; the temporal trend in cocaine use may increase the occurrence of MI, particularly in younger populations.


Thrombin-induced neuronal protection: role of the mitogen activated protein kinase/ribosomal protein S6 kinase pathway.
Our previous studies have found that intracerebral pretreatment with a low dose of thrombin (thrombin preconditioning, TPC) reduces infarct volume and attenuates brain edema after focal cerebral ischemia. In this study, we examined whether TPC protects against the neuronal death induced by oxygen glucose deprivation (OGD), and whether the protection is through thrombin receptors and the p44/42 mitogen activated protein kinases (MAPK)/ribosomal protein S6 kinases (p70 S6K) pathway. Expression of protease-activated receptors (PARs) mRNA was detected in cultured primary rat neurons and thrombin upregulated PAR-1 and PAR-4 mRNA expression. TPC reduced OGD-induced neuronal death (e.g. dead cells: 52.5 ± 5.4% vs. 72.3 ± 7.2% in the control group, n=6, p<0.01). Agonists of PAR-1 and PAR-4 mimicked the effects of thrombin and reduced OGD-induced neuronal death. Pretreatment with thrombin or PAR agonists induced the upregulation of activated p44/42 MAPK and p70S6K (Thr 421/Ser 424). PD98059, an inhibitor of p44/42 MAPK kinase, blocked thrombin-induced upregulation of activated p44/42 MAPK and p70S6K. It also reduced TPC-induced neuronal protection (e.g. dead cells: 68.2 ± 5.2% vs. 56.9 ± 4.6% in vehicle+TPC group, n=6, p<0.05). These results suggest that TPC-induced ischemic tolerance is through activation of thrombin receptors and the p44/42 MAPK/p70S6K pathway.


The relationship between schizophrenia and essential fatty acid and eicosanoid metabolism.
Essential fatty acids (EFAs) and their eicosanoid derivatives are important constituents of the brain and regulators of neuronal function. There is direct and indirect evidence of impaired metabolism of prostaglandin (PG)E1 in schizophrenia. There is also direct evidence of abnormal EFA biochemistry with plasma phospholipids from five populations and brain phospholipids from another all showing reduced levels of linoleic acid and elevated levels of 22-carbon EFAs of both n-6 and n-3 series. Clinical trials of PGE1 and of the PGE1 precursors, gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DGLA) have shown modest therapeutic effects. In view of lack of therapeutic process involving drugs based on the dopamine concept of schizophrenia, it is time for new approaches based on the EFA/PG concept to be evaluated thoroughly.


I (Don't) want to consume counterfeit medicines: exploratory study on the antecedents of consumer attitudes toward counterfeit medicines.
Substandard and falsified medicine (SFM) sales (an estimated > $200 billion) has become one of the worlds' fastest growing criminal enterprises. It presents an enormous public health and safety challenge. While the developed world is not precluded from this challenge, studies focus on low-income countries. They emphasize supply chain processes, technological, and legal mechanisms, paying less attention to consumer judgment and decision-making aspects. With attention to the demand side of the counterfeit medicines challenge, this survey of U.S. consumers (n = 427) sheds light on some of the social, psychological, and normative factors that underlie consumers' attitudes, risk perceptions, and purchase intentions. Consumers who (a) self-report that they know about the problem, (b) are older, (c) view counterfeit medicine consumption as ethical, and (d) think their significant others would approve of them using such products are more inclined to perceive lower risks and have favorable purchase intentions. Risk averseness is also inversely related to the predicted outcomes. Perceived benefit of SFMs is a factor but has no effect when risk perception and aversion, attitudes, and subjective norms are factored into the model that predicts purchase intentions. The results of this study indicate that consumer knowledge (albeit in an unexpected direction), people's expectations about what will impress their significant others, their ethical judgments about selling and consuming counterfeits, and their risk-aversion are associated with their decision-making about counterfeit medicines. The study offers insights into a demand-side approach to addressing SFM consumption in the U.S. Implications for public health, consumer safety, and brand advocacy education are discussed.


Molecular and biochemical markers for monitoring dynamic shifts of cellulolytic protozoa in Reticulitermes flavipes.
Lower termites rely on cellulolytic protozoa to aid in the digestion of their wood-based diet. However, despite the major contribution of protozoa to the lower termite digestive system, few techniques have been developed to monitor shifts in protozoan populations. This study investigated whether quantitative real-time PCR (qRT-PCR) and/or cellulase enzyme assays can be used to monitor changes of cellulolytic protozoan populations in the lower termite, Reticulitermes flavipes (Kollar). Previously developed cellulase primer sets were used to test for changes in cellulase gene expression, while three different cellulase enzyme assays were used to assess changes in cellulase enzyme activity. The results from this study indicate that qRT-PCR is a reliable method to monitor shifts in cellulolytic protozoan populations. Specifically, qRT-PCR can serve as a useful monitoring technique during high-throughput screening of novel termite control agents such as cellulase inhibitors, and help to answer questions relating to whether or not such control agents impact cellulolytic protozoan populations.


Umbilical artery Doppler waveform indices from normal pregnant women are related to vasodilatation of placental chorionic plate small arteries.
Blood flow control within the fetoplacental circulation is poorly understood despite the essential role of the placenta in pregnancy. Our study compared an in vitro assessment of placental chorionic plate small artery function with in vivo measures of umbilical artery blood flow. Umbilical artery Doppler waveform analysis was performed on women (N=8) with uncomplicated pregnancies within 24 hours of delivery. Small arteries (n=25) were dissected from the placental chorionic plate from biopsies at term and studied using parallel wire myography. Chorionic plate arteries developed maintained constrictions to the thromboxane-mimetic U46619. Nitric oxide (NO) donation with the endothelial-independent agent sodium nitroprusside elicited significant relaxation compared to paired control vessels. This vasodilatation correlated significantly with both pulsatility and resistance indices measured in the umbilical artery. We conclude that Doppler indices in the umbilical artery are inversely proportional to the maximal relaxation achieved by chorionic plate small arteries in response to a NO donor.


C-reactive protein levels in normal tension glaucoma.
To determine C-reactive protein (CRP) levels in patients with normal tension glaucoma (NTG). This study included 20 cases with NTG and 30 controls, with no history of ocular disease. Plasma CRP levels of all the study participants were determined using a highly sensitive CRP kit. Twenty cases (11 males, 9 females, mean age 69 +/- 5 years) with NTG and 30 age-matched controls (15 males, 15 females, mean age 68 +/- 6) were evaluated. Both groups had similar demographic parameters (age, sex, BMI). Plasma CRP levels were significantly higher in the NTG cases than in controls (median [range], 3.20 [0.17-8.4] mg/dL compared with 0.5 [0.1-3.2], P < 0.001). The mean plasma CRP level was significantly elevated in the NTG cases compared with the controls (3.21 +/- 0.6 mg/dL and 0.85 +/- 0.17 mg/dL, respectively, P < 0 0.01). Our findings suggest that higher CRP levels may be associated with NTG. It is possible that a vascular inflammatory process is involved in the etiology of this glaucoma.


Local dynamics of pharmaceutical powder fluidization using high speed long distance microscopy and particle image velocimetry.
The local dynamics of fluidized pharmaceutical carrier powders in a turbulent channel flow was studied using particle image velocimetry (PIV) and High-speed, long-distance microscopy (HS-LDM). Four different lactose powders which have been used as a drug carrier in dry powder inhalers were used in this study. These powders have median powder particle diameters ranging between 61 and 121 μm. Air flow velocities ranging between 13.3 m/s and 66.7 m/s were examined. In addition, the effect of grid blockage ratio (ranging from ~25% to ~40% of the area of channel cross-section) was also investigated. Results show that the high-speed, long-distance microscopy (HS-LDM) technique was able to capture the mean velocity of the particles, and the results corresponded well with the PIV measurements. Results from the high-speed, long-distance microscopy (HS-LDM) method also demonstrate that the span of particle velocity closely follows that of the particle size distribution both for cohesive and non-cohesive powders. This study contributes towards an improved understanding of pharmaceutical carrier dynamics in turbulent channel flows and demonstrates how advanced image processing can be used to capture local particle dynamics.


Management of rectal injuries sustained during laparoscopic radical prostatectomy.
To report on a treatment algorithm for the management of rectal injures. Rectal injuries during laparoscopic radical prostatectomy (LRP) are rare. In the first 200 cases of LRP performed at our institution, 2 (1%) rectal injuries occurred. Our experience prompted collaboration with our colorectal surgery colleagues to develop a treatment algorithm for the management of such injuries. We report on the management of rectal injuries sustained during LRP at our institution. We describe the intraoperative laparoscopic repair of a rectal tear using a 2-layer interrupted closure with absorbable suture. The conservative, nonoperative, management of a rectourethral fistula in a patient who presented after LRP is also described. Collaboration with our colorectal surgery colleagues resulted in the formulation of a treatment algorithm for intraoperative and postoperative presentations of rectal injury during LRP. The algorithm is presented. Of the first 200 cases of LRP at our institution 2 (1%) were complicated by rectal injury. Injuries recognized intraoperatively should be managed laparoscopically if the operating surgeon is adept at intracorporeal suturing. Small rectourethral fistulas can be managed conservatively with urinary catheterization or diversion and antibiotics as needed. Rarely, rectal injuries sustained during LRP will require fecal diversion; injuries that fail to heal despite fecal diversion require operative repair. Rectal injuries incurred during LRP are rare but must be managed successfully to minimize morbidity. Rectal tears recognized intraoperatively can be managed laparoscopically. The development of a rectourethral fistula is a potential complication of LRP. Most fistulas can be managed conservatively with urinary catheterization or diversion. Rarely, rectal injuries that occur during LRP require fecal diversion or definitive operative repair.


Asthma and allergy in Turkish university students: Two cross-sectional surveys 5 years apart.
prevalence of asthma and allergic diseases is increasing worldwide. We investigated the first-year university students to a) determine prevalence of asthma, and allergic diseases, b) compare prevalence with a similar study conducted in 1994, and c) investigate determinants of asthma, current wheeze and seasonal rhinitis. an ECRHS based questionnaire was distributed to 5,406 students and completed by 4,639 (response: 85.3 %) in september 1999. Information from the students residing in Turkey was used in the analyses (1,800 boys, 2,712 girls). prevalence % of asthma (symptom and/or medicine), current wheeze and seasonal rhinitis were 2.1, 6.9 and 12.7 in boys, and 2.5, 7.2 and 14.5 in girls. Current smoking, pet ownership and family atopy was reported more frecuently in 1999 than 1994. Cough and seasonal rhinitis increased almost twofold. Asthma diagnosis and attack rate was similar in 1999 and 1994. Family atopy, pet in childhood, smoking and passive smoking in childhood increased the risk of asthma, and current wheeze. Family atopy, passive smoking and current pet ownership increased the risk of seasonal rhinitis. increased rate of smoking and pet ownership could contribute to the increased prevalence of asthma and allergic diseases in the last 5 years.


The survival of inoperable breast cancer treated with radiotherapy and radiotherapy followed by mastectomy.
Forty-five patients with locally advanced breast carcinoma were treated by radiotherapy. Twelve of them became operable and were operated. After 3 and 4 years in comparable clinical stage the rate of metastases in the nonoperated group was 78.6% and in the operated 75%. The survival after 3 and 4 years in comparable clinical stages was similar. In more advanced stages the survival was worse. Considering the trauma of mastectomy and the similar survival obtained in our material, an international trial should be performed to decide whether inoperable breast cancer becoming operable after radiotherapy should be operated.


Low-grade renal cell carcinoma arising from the lower nephron: a case report with immunohistochemical, histochemical and ultrastructural studies.
Most renal cell carcinomas (RCC) are composed of clear cells with sinusoid-like vasculatures and originate from the proximal tubule. On the other hand, collecting duct carcinoma (CDC) and chromophobe RCC are thought to originate from the lower nephron. In the present study, we present a case of unusual RCC. The patient was a 68-year-old Japanese woman who had developed general fatigue with hematuria. Computed tomography revealed a left renal tumor suggesting sarcoma. The resected tumor was located in the renal parenchyma, measuring 12 x 10 x 8 cm in size. Histologically, the tumor consisted principally of cuboidal cells forming parallel or radiating arrays, continuous with the spindle-shaped cells. Most parts of the tumor showed hemorrhagic necrosis. Immunohistochemically, tumor cells were positive for high molecular weight cytokeratins, vinculin, vimentin, CD15 and epithelial membrane antigen, and showed affinities with some kinds of lectins. N- and E-cadherins and beta-catenin were diffusely positive in tumor cells. Nuclear positivity for Ki-67 and p53 protein were approximately 2.0 and 1.7%, respectively. Considering its morphological and histochemical natures, this tumor is considered to have originated from the lower nephron, which is unique for a tumor of low-grade malignancy.