Photic and nonphotic effects on the circadian activity rhythm in the diurnal rodent Arvicanthis ansorgei.
The main purpose of the study was to compare behavioural properties of entrainment to photic (30 min; 200lx) and nonphotic (melatonin: 1 h; 100 microg) stimuli in the diurnal rodent Arvicanthis ansorgei. Male animals (n=38) were used, and running wheel activity was recorded. Following entrainment to 12:12 h LD the animals were transferred to DD (dim red light) to freerun before treatment started. A phase response curve (PRC) to light was determined showing a phase delay region in the early subjective night (CT 8-16) and a phase advance region in the late subjective night (CT 18-4). Activity onset defined CT=0. Entrainment to daily phase advance and phase delay light pulses occurred at circadian phases corresponding to the respective phase shift regions of the PRC. Similarly, also entrainment to daily melatonin pulses occurred in two narrow time windows located near the beginning (CT 0) and the end of the subjective day (CT 10), but where light had a phase advance effect melatonin had a phase delay effect and vice versa. These results are consistent with the neurobiological model of Hastings et al. (Chronobiol Int 1998;15:425-445) on the differential effects of photic and nonphotic resetting cues on the circadian pacemaker.


Mechanical restraint--which interventions prevent episodes of mechanical restraint?- a systematic review.
To identify interventions preventing mechanical restraints. Systematic review of international research papers dealing with mechanical restraint. The review combines qualitative and quantitative research in a new way, describing the quality of evidence and the effect of intervention. Implementation of cognitive milieu therapy, combined interventions, and patient-centered care were the three interventions most likely to reduce the number of mechanical restraints. There is a lack of high-quality and effective intervention studies. This leaves patients and metal health professionals with uncertainty when choosing interventions in an attempt to prevent mechanical restraints.


Risk factors and outcomes associated with persistent vancomycin resistant Enterococcal Bacteremia.
Prior studies have identified that vancomycin resistant enterococcus (VRE) bacteremia that persists for four days or more is an independent predictor of mortality. Despite this, there is no published data to identify those patients at highest risk of developing persistent VRE bacteremia. This was a single center, retrospective, case-control study of adult patients with a VRE bloodstream infection (BSI). Case patients were those with persistent bacteremia (≥ 4 days despite VRE-directed therapy) and control patients were those with non-persistent bacteremia. Logistic regression was used to assess risk factors associated with persistent VRE BSIs. Secondary outcomes included in-hospital mortality, recurrent bacteremia, and breakthrough bacteremia. During the study period, 24/108 (22%) patients had persistently positive blood cultures. Risk factors for persistent bacteremia included severe neutropenia (OR 2.13), 4 out of 4 positive index blood cultures (OR 11.29) and lack of source control (OR 11.88). In an unadjusted analysis, no statistically significant differences in in-hospital mortality (58% versus 40%; p = 0.121), recurrent bacteremia (17% versus 6%; p = 0.090), or breakthrough bacteremia (13% versus 7%; p = 0.402) were observed between groups. Patients with severe neutropenia, 4 out of 4 positive index blood culture bottles, and lack of source control were more likely to develop persistent VRE bacteremia despite directed antibiotic treatment.


Risk analysis of early implant loss after immediate breast reconstruction: a review of 14,585 patients.
Early prosthesis loss is an infrequent but serious complication after breast reconstruction. We assessed perioperative risk factors associated with early device loss after immediate breast reconstruction (IBR) using the ACS-NSQIP datasets. We reviewed the 2005 to 2011 ACS-NSQIP databases identifying encounters for CPT codes 19357 and 19340. Patients were identified as experiencing a "loss of graft/prosthetic" based on a standard dataset variable. Patients who experienced a device loss were compared with those who did not with respect to perioperative characteristics. We identified 14,585 patients with an average age of 50.9 ± 10.6 years. A multivariate regression analysis determined that age (>55 years) (odds ratio [OR] 1.66, p = 0.013) (risk score = 1), class II obesity (OR 3.17, p < 0.001) (risk score = 3), class III obesity (OR 2.41, p = 0.014) (risk score = 3), active smoking (OR 2.95, p < 0.001) (risk score = 3), bilateral reconstruction (OR 1.67, p = 0.007) (risk score = 1), and direct-to-implant (DTI) reconstruction (OR 1.69, p = 0.024) (risk score = 1) were associated with early device loss. Odds ratios were used to assign weighted risk scores to each patient, and risk categories were broken into low risk (0 to 1, n = 9,349), intermediate risk (2 to 5, n = 5,001), and high risk (≥ 6, n = 233) groups. The risk of device loss was significantly higher with increased risk score (0.39% vs 1.48% vs 3.86%, p < 0.001). Early device loss following IBR is a complex multifactorial process related to identifiable preoperative risk factors. This study demonstrated that age, obesity, smoking, bilateral procedures, and DTI reconstructions are associated with increased risk of implant loss.


Lipofibromatous hamartoma of the upper extremity: a review of the radiologic findings for 15 patients.
The purpose of this study was to analyze the radiologic characteristics of lipofibromatous hamartomas affecting upper limb peripheral nerves. Although there are pathognomonic features that characterize lipofibromatous hamartoma on MRI, the range of appearances is broad. Sonography appears to show equally characteristic features and may be a useful tool for assessing this condition.


Finger-prick blood collection and computer-assisted enzyme-linked immunosorbent assay for large-scale serological studies on leprosy.
An immunoglobulin M anti-phenolic glycolipid 1 assay was standardized and optimized using specimens of dried blood collected on commercial precut filter paper discs, followed by a computer-assisted enzyme-linked immunosorbent assay (ELISA). The correlation between venepuncture and finger-prick methods, the calibration of the quantity of absorbed blood, and the reproducibility of the ELISA test were excellent. A slight decline of activity was observed when the samples were stored for 3 months at +4 degrees C. Skimmed milk can be used as diluent instead of bovine serum albumin, contributing to lessening the cost of the test. Using the method described, as many as 300 samples can be collected in the field and 480 ELISAs per day can be run in the central laboratory by one trained person.


Characteristics and safety of interventions and procedures performed during catheterisation of patients with congenital heart disease: early report from the national cardiovascular data registry.
The objective of this study was to report procedural characteristics and adverse events on the data collected in the IMproving Paediatric and Adult Congenital Treatment registry. The IMproving Paediatric and Adult Congenital Treatment- registry is a catheterisation registry focussed on paediatric and adult patients with congenital heart disease who are undergoing diagnostic catheterisations and catheter-based interventions. This study reports procedural characteristics and adverse events of patients who have undergone selected catheterisation procedures from January, 2011 to June, 2013. Demographic, clinical, procedural, and institutional data elements were collected at participating centres and entered via either a web-based platform or software provided by the American College of Cardiology-certified vendors, and were collected in a secure, centralised database. For the purpose of this study, procedures that were not classified as one of the 'core' IMproving Paediatric and Adult Congenital Treatment procedures originally chosen for additional data collection were identified and selected for further data analysis. During the time frame of data collection, a total of 8021 cases were classified as other procedures and/or multiple procedures. The most commonly performed case types - isolated or in combination with other procedures - were right ventricular biopsy in 3433 (42.8%), conduit/MPA interventions in 979 (12.3%), and systemic pulmonary artery collateral occlusion in 601 (7.5%). For the whole cohort, adverse events of any severity occurred in 957 (12.0%) cases, whereas major adverse events occurred in 113 (1.4%) cases; six patients (0.1%) died in the catheterisation laboratory. The IMproving Paediatric and Adult Congenital Treatment registry has provided important data on the frequency and spectrum of cardiac catheterisation procedures performed in the present era. For many procedures, more data and work are needed to identify more subtle differences between case categories, especially as it relates to the incidence of major adverse events, and to further develop a risk-adjustment methodology to allow equitable comparisons among institutions.


End-proximal tubule phosphate concentration increases as GFR falls in humans: measurement by means of a lithium clearance-based methodology.
Microscopic nephrocalcinosis secondary to intratubular calcium phosphate (CaP) precipitation is thought to accelerate progression to end-stage renal failure in chronic kidney diseases. In phosphorus (P)-loaded uninephrectomized rats, intratubular CaP crystal formation and progressive tubular damage occurred when end-proximal tubule P concentration (ePTpc) increased above a threshold level. We have calculated ePTpc in humans by urine P and creatinine concentration, with the end-proximal tubule fluid volume calculated either as lithium (Li) clearance (ePTpc-Li) or as a fixed 0.7 fraction of glomerular filtration rate (GFR), as published (ePTpc-70). Healthy people undergoing living transplant kidney donation before (DON-pre, n = 70) and after (DON-post, n = 64) nephrectomy and 25 patients with stage 2-5 CKD were investigated while on regular free diet. ePTpc showed a stepwise increase with decreasing functional renal mass (DON-pre 2.51 ± 0.99 and 1.56 ± 0.47 mg/dL for ePTpc-Li and -70 calculation, respectively; DON-post 3.43 ± 1.14 and 2.18 ± 0.44; CKD 5.68 ± 3.30 and 3.00 ± 1.30, P < .001 for all); ePTpc was inversely correlated with Ccr and directly with PTH, fractional P excretion and excretion (UpV) corrected for GFR (P < .001 for all), but not with Pp. ePTpc-Li and ePTpc-70 were significantly correlated (r = 0.62, P < .001), but ePTpc-70 was lower than the corresponding ePTpc-Li. Levels of ePTpc increased above a suggested dangerous threshold when daily UpV/GFR was higher than about 10 mg/mLCcr. ePTpc progressively increases in humans as functional renal mass falls independently from plasma P levels. Main determinants of ePTpc rise are GFR fall, degree of phosphaturia per unit GFR and P intake corrected for GFR. It may become a novel, potentially useful, indicator to guide management of CKD patients.


Osteoimmunology in mucopolysaccharidoses type I, II, VI and VII. Immunological regulation of the osteoarticular system in the course of metabolic inflammation.
Mucopolysaccharidoses (MPSs) are rare genetic diseases caused by a deficient activity of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. These metabolic blocks lead to the accumulation of GAGs in various organs and tissues, resulting in a multisystemic clinical picture. The pathological GAG accumulation begins a cascade of interrelated responses: metabolic, inflammatory and immunological with systemic effects. Metabolic inflammation, secondary to GAG storage, is a significant cause of osteoarticular symptoms in MPS disorders. The aim of this review is to present recent progress in the understanding of the role of inflammatory and immune processes in the pathophysiology of osteoarticular symptoms in MPS disorders and potential therapeutic interventions based on published reports in MPS patients and studies in animal models. The immune and skeletal systems have a number of shared regulatory molecules and many relationships between bone disorders and aberrant immune responses in MPS can be explained by osteoimmunology. The treatment options currently available are not sufficiently effective in the prevention, inhibition and treatment of osteoarticular symptoms in MPS disease. A lot can be learnt from interactions between skeletal and immune systems in autoimmune diseases such as rheumatoid arthritis (RA) and similarities between RA and MPS point to the possibility of using the experience with RA in the treatment of MPS in the future. The use of different anti-inflammatory drugs requires further study, but it seems to be an important direction for new therapeutic options for MPS patients.


Hydroxypropyl‑β‑cyclodextrin attenuates the epithelial‑to‑mesenchymal transition via endoplasmic reticulum stress in MDA‑MB‑231 breast cancer cells.
The epithelial‑to‑mesenchymal transition (EMT) has been reported to serve vital roles in regulating the progress of cancer metastasis. In addition, lipid rafts enriched in sphingolipids and cholesterol serve important roles in physiological and biochemical processes as a signaling platform. The present study explored the effects of hydroxypropyl‑β‑cyclodextrin (HP‑β‑CD), a cholesterol‑depleting agent of lipid rafts, on the transforming growth factor (TGF)‑β/Smad signaling pathway and endoplasmic reticulum (ER) stress in mediating EMT in MDA‑MB‑231 breast cancer cells. HP‑β‑CD treatment inhibited TGF‑β1‑induced EMT, based on increased expression of E‑cadherin and decreased expression of vimentin. HP‑β‑CD reduced the expression of the TGF receptor TβRI and blocked the phosphorylation of Smad2. In addition, HP‑β‑CD increased the expression of ER stress‑related proteins (binding immunoglobulin protein and activating transcription factor 6), but TGF‑β1 could reverse these changes. Sodium 4‑phenylbutyrate, an inhibitor of ER stress, suppressed these effects of HP‑β‑CD on EMT and TGF‑β/Smad signaling pathway inhibition in breast cancer cells. Thus, HP‑β‑CD can block the TGF‑β/Smad signaling pathway via diminishing the expression of TβRI which helps to activate ER stress and attenuate EMT in MDA‑MB‑231 cells, highlighting a potential target of lipid rafts for breast cancer treatment.


[Parathyreoid autoransplantation in secondary hyperparathyreoidism (author's transl)].
Subtotal Parathyreoidectomy offers no problem after surgery, nor after Kidney transplantation. But a recurrence needs extensive investigations for localisation of recurrent hyperplastic glands. The necessary reoperation is loaded with difficulties. After total Parathyreoidectomy hypocalcaemia is a severe complication. Therefore in patients awaiting Kidney transplants in a chronic dialysis program the procedure is not opportune. In 11 patients following total Parathyreoidectomy and autoplastic parathyreoid transplant, we found nearly normal parathyreoid hormone plasma levels. The advantage of this method is: The function of the autoplastic graft is testable and a possible recurrence is easily resectable.


The cAMP-specific phosphodiesterase PDE4D3 is regulated by phosphatidic acid binding. Consequences for cAMP signaling pathway and characterization of a phosphatidic acid binding site.
Hormones and growth factors induce in many cell types the production of phosphatidic acid (PA), which has been proposed to play a role as a second messenger. We have previously shown in an acellular system that PA selectively stimulates certain isoforms of type 4 cAMP-phosphodiesterases (PDE4). Here we studied the effect of endogenous PA on PDE activity of transiently transfected MA10 cells overexpressing the PA-sensitive isoform PDE4D3. Cell treatment with inhibitors of PA degradation, including propranolol, induced an accumulation of endogenous PA accompanied by a stimulation of PDE activity and a significant decrease in both cAMP levels and protein kinase A activity. Furthermore, in FRTL5 cells, which natively express PDE4D3, pretreatment with compounds inducing PA accumulation prevented both cAMP increase and cAMP-responsive element-binding protein phosphorylation triggered by thyroid-stimulating hormone. To determine the mechanism of PDE stimulation by PA, endogenous phospholipids were labeled by preincubating MA10 cells overexpressing PDE4D3 with [(32)P]orthophosphate. Immuno- precipitation experiments showed that PA was specifically bound to PDE4D3, supporting the hypothesis that PDE4D3 activation occurs through direct binding of PA to the protein. PA binding site on PDE4D3 was characterized by engineering deletions of selected regions in the N-terminal regulatory domain of the enzyme. Deletion of amino acid residues 31-59 suppressed both PA-activating effect and PA binding, suggesting that this region rich in basic and hydrophobic residues contains the PA binding site. These observations strongly suggest that endogenous PA can modulate cAMP levels in intact cells, through a direct activation of PDE4D3.


Radiation exposure and mortality risk from CT and PET imaging of patients with malignant lymphoma.
To quantify radiation exposure and mortality risk from computed tomography (CT) and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)F-FDG) in patients with malignant lymphoma (Hodgkin's disease [HD] or non-Hodgkin's lymphoma [NHL]). First, organ doses were assessed for a typical diagnostic work-up in children with HD and adults with NHL. Subsequently, life tables were constructed for assessment of radiation risks, also taking into account the disease-related mortality. In children with HD, cumulative effective dose from medical imaging ranged from 66 mSv (newborn) to 113 mSv (15 years old). In adults with NHL the cumulative effective dose from medical imaging was 97 mSv. Average fractions of radiation-induced deaths for children with HD [without correction for disease-related mortality in brackets] were 0.4% [0.6%] for boys and 0.7% [1.1%] for girls, and for adults with NHL 0.07% [0.28%] for men and 0.09% [0.37%] for women. Taking into account the disease-related reduction in life expectancy of patients with malignant lymphoma results in a higher overall mortality but substantial lower incidence of radiation induced deaths. The modest radiation risk that results from imaging with CT and (18)F-FDG PET can be considered as justified, but imaging should be performed with care, especially in children.


Electrical impedance tomography reconstruction through Simulated Annealing with incomplete evaluation of the objective function.
The EIT reconstruction problem is approached as an optimization problem where the difference between a simulated impedance domain and the observed one is minimized. This optimization problem is often solved by Simulated Annealing (SA), but at a large computational cost due to the expensive evaluation process of the objective function. We propose here, a variation of SA applied to EIT where the objective function is evaluated only partially, while ensuring upper boundaries on the deviation on the behavior of the modified SA. The reconstruction method is evaluated with simulated and experimental data.


Effect of Z-DNA on nucleosome placement.
Histone octamers were reconstituted on plasmids carrying the alternating nucleotide sequence (G-C)15. The plasmids, radioactively labeled at one of two neighboring sites near the (G-C) insert, were digested with micrococcal nuclease. Nucleosome core particles were isolated and the monomer DNA subjected to restriction analysis. Quite different results are obtained if the reconstitution is carried out with relaxed plasmids, in which the (G-C) insert is in the B form, or with supercoiled plasmids, where it is in the Z form. With supercoiled plasmids, there is a marked reduction (compared with relaxed plasmids) in the abundance of labeled monomers, the result of a large decrease in core particles carrying any (G-C) sequence. Some core particles formed on supercoiled (Z) plasmids are positioned either just outside the (G-C) sequence, or with the sequence occupying the terminal position within the core particle. In contrast, monomers obtained from relaxed plasmids incorporate the (G-C) sequence in the B form more or less randomly in the interior of the core particle; species showing discrete positioning make only a minor contribution. We conclude that DNA in the Z form cannot be incorporated within core particles, except at their termini, and that a transition from the B to the Z form in vivo might result in a significantly altered local placement of nucleosomes.


Split Decisions, Split Decisions.
The lead stories in Nature and Science went in opposite directions this week. Science chose outer space, launching into NASA's hotly disputed decision to shelve a planned mission to Pluto. Nature plunged into inner space with a story about a report to the European Commission advising against granting "premature" approval to create human embryos for stem-cell research.


Long-term treatment with low-dose, but not high-dose, guanethidine improves ventricular function and survival of rats with heart failure after myocardial infarction.
We sought to evaluate the effects of various doses of guanethidine, a sympathoinhibitory drug, on ventricular function and survival in chronic heart failure (CHF) after myocardial infarction (MI) in rats. Direct inhibition of sympathetic outflow by a sympathoinhibitory drug might be an effective approach to therapy of CHF. However, recent clinical trials suggest that excessive suppression of sympathetic activity has an adverse effect on outcome. It remains unclear whether the beneficial effects of the sympathoinhibitory drug would be modified by its dosage. Three doses of guanethidine (low-dose [LG], 1 mg/kg/day; medium-dose, 3 mg/kg/day; high-dose, 10 mg/kg/day) were administered via an osmotic mini-pump for 4 weeks. Hemodynamics, left ventricular (LV) diameters, plasma and myocardial norepinephrine (NE) levels, and survival were determined for four weeks after MI. As compared with MI rats receiving vehicle, LG suppressed LV dilation (9.2 +/- 0.9 mm vs. 11.0 +/- 0.8 mm, p < 0.05) and improved LV fractional shortening (25.0 +/- 4.5% vs. 16.4 +/- 4.7%, p < 0.05) in association with a reduction of plasma NE levels (520 +/- 250 pg/ml vs. 1,000 +/- 570 pg/ml, p < 0.05), but not with a significant reduction of noninfarcted myocardial NE levels (154 +/- 71 ng/g vs. 207 +/- 71 ng/g). Low-dose guanethidine reduced 24-h (6%) and 28-day mortality (6%), as compared with untreated MI rats (36% and 52%, respectively). High-dose guanethidine also reduced 24-h mortality (12%) but increased 28-day mortality (91%), in association with a depletion of myocardial NE. Medium-dose guanethidine had no beneficial effects on LV hemodynamics or long-term survival. These results indicate that the dosage of the sympathoinhibitory drug might be quite important for the treatment of CHF.


Klinisch-pathologische Merkmale und histologische Tumorreste in Reexzisionspräparaten unvollständig resezierter Basalzellkarzinome.
Die chirurgische Exzision ist die bedeutendste Therapiemodalität zur Versorgung von Basalzellkarzinomen (BCC). Oft kommt es zu einer unvollständigen Exzision, die eine Reexzision nach sich zieht. Allerdings enthalten Reexzisionspräparate häufig keine Tumorreste, weswegen die Reexzision im Nachhinein überflüssig ist. Ziel unserer Studie ist die Identifikation von klinisch-pathologischen Merkmalen, die mit dem Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten assoziiert sind. 255 unvollständig resezierte BCC von 222 Patienten wurden in diese Fall-Kontroll-Beobachtungsstudie eingeschlossen. Acht klinisch-pathologische Merkmale wurden in einer binären logistischen Regressionsanalyse mit dem Vorhandensein oder Nichtvorhandensein von histologischen Tumorresten in Reexzisionspräparaten korreliert. Ein höheres Alter bei der ersten Exzision und ein BCC in der Rezidiv-Hochrisikozone erwiesen sich als unabhängige Risikofaktoren für das Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten. Die Ergebnisse unserer Studie zeigen, dass eine Reexzision von unvollständig resezierten BCC in der oben genannten Subpopulation definitiv notwendig ist. Für die Nachbehandlung unvollständig resezierter BCC, die sich in der Rezidiv-Niedrigrisikozone jüngerer Patienten befinden, können jedoch auch weniger invasive Therapien wie Imiquimod in Betracht gezogen werden.


Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in the real-world setting.
To assess incidence rates (IRs) of VTE in patients with rheumatoid arthritis (RA) on different DMARDs and DMARD switchers. Adults with RA on a DMARD between 2007 and 2017 were studied in a US claims database. Conventional synthetic DMARD (csDMARD) users, first biologic/targeted synthetic DMARD (b/tsDMARD) users and b/tsDMARD switchers (from a b/tsDMARD to another b/tsDMARD) were followed for inpatient VTE (pulmonary embolism (PE)/deep vein thrombosis (DVT)). Crude and adjusted IR and 95% CIs of VTE were estimated. HRs for VTE were estimated via Cox regression. VTE risk was also evaluated by number of switches between b/tsDMARDs and in patients without a VTE history. The age and sex standardised IR (95% CI) of VTE (per 100 person-years) was 0.86 (0.70 to 1.03), 0.60 (0.52 to 0.68) and 0.58 (0.51 to 0.65) for b/tsDMARD switchers, first b/tsDMARD users and csDMARD users, respectively. After adjustment, b/tsDMARD switchers had an increased risk of VTE, compared with csDMARD users, HRadj (95% CI) being 1.36 (1.16 to 1.58), 1.36 (1.13 to 1.63) and 1.47 (1.18 to 1.83) for VTE, DVT and PE, respectively. Compared with first b/tsDMARD users, the HRadj (95% CI) for VTE was 1.35 (1.15 to 1.60) for first b/tsDMARD switchers and 1.48 (1.19 to 1.85) for second b/tsDMARD switchers. In RA, b/tsDMARD switchers have a higher VTE risk compared with csDMARD users and first b/tsDMARD users. Switching b/tsDMARDs may be a proxy for higher disease severity or poorly controlled RA and an important confounder to consider in obtaining unbiased estimates of VTE risk in observational RA safety studies.


[Is the mother a risk factor for transmission of Helicobacter pylori infection in children between the ages of 6 months and 5 years in Côte d'Ivoire?].
The goals of this study were to determine the prevalence of H. pylori antibodies in children, to establish the relationship between child and mother serostatus, and to identify potential risk factors for contamination. A cross-sectional study was conducted over a 3-month period. All children between 6 months and 5 years of age examined in the Pediatrics Department of the University Hospital Center in Yopougon, Côte d'Ivoire were included after obtaining informed consent from their mothers. Testing for H. pylori antibodies using Pylorix (Acon) was performed in both children and mothers. Based on test results, children were divided into two groups, i.e. case group with H. pylori antibodies and control group without H. pylori antibodies. Case and control groups were compared according to the H. pylori status of their mother and several potential lifestyle and environmental factors. A total of 101 children and 101 mothers were included. The prevalence of H. pylori antibodies was 40.6% in mothers and 24.8% in children. The mean age of children (53% male) was 22.8 +/- 15.6 months (median, 18 months). The mean age of the mothers was 29.6 +/- 5.5 years (range, 19 to 46 years; median, 29 years). Most mothers, i.e., 78.2%, lived in two-parent households but 19% lived in single-parent settings (community or shacks). The number of persons living in the same house ranged from 2 to 20 people (mean, 7.2 +/- 3.8; median, 6 people). Mean monthly household income was 226,188 +/- 161,425 FCFA (range: 30,000 - 750,000 FCFA). In the case group, 80% of children had mothers infected with H. pylori. In the control group, 73.7% of children had non-infected mothers (OR = 11.2, p < 0.001). Median income was less than 150 000 FCA in 76% of families with seropositive children in comparison to 46.1% of families with seronegative children (p = 0.009). This study confirms the early occurrence of H. pylori infection in children. Findings also showed that poor socio-economic condition was a risk factor for infection but the greatest risk factor was living with a mother infected with H. pylori.


Identification of rabbit immunoglobulin latent Ckappa1 allotype genes alters the concept of allelic inheritance.
In the rabbit, expression of immunoglobulin Ckappa1 light chain genes is believed to be under allelic control. Conventionally, four nominal allotypic variants, b4, b5, b6 and b9 have been shown to be co-dominantly expressed at the Ckappa1 gene locus. Analogously, the heavy chain allotypes, VHa1, VHa2 and VHa3, found in the V region, are also believed to be inherited co-dominantly. However, after our earlier discovery of non-allelic or latent allotypes in the serum and on cell surfaces. we subsequently reported that cDNA sequences for latent b5 and b6 were identical to nominal b5 and b6, respectively (Ishaq et al., 1990). The latent b5 cDNAs were from two homozygous b4,b4 rabbits; the latent b6 cDNA was found in a heterozygous b4,b9 rabbit. The cDNA sequences had been obtained from lymph nodes and spleens of rabbits which had been infected with Trypanosoma brucei in order to induce latent allotypes more consistently. In this article, employing spleen DNA from three different T. brucei-infected rabbits, (one, heterozygous b4,b9; two others, homozygous, b4,b4), we initially detected two bands by Southern analysis after Hind III digestion using a 624 base pair Ckappa1 b4 probe derived from a b4,b4 rabbit. However, the probe was non-specific allotypically as it hybridized to b5, b6 and b9 Ckappa1 DNA. Therefore, in order to search for the latent genes, we used allotype-specific oligonucleotides for b5, b6 and b9 to probe DNAs from both normal and T. brucei-infected rabbits by Southern blotting. At the outset, employing a b4 oligonucleotide probe, we detected a single 5.8 Kb segment in two b4,b4 rabbit DNAs after Bg1 II digestion. The findings, using the 624 base pair Ckappa1 b4 probe and the b4 oligomer, agreed with earlier data reported by others. Subsequently, we tested kidney, liver and spleen DNAs from one of these and other rabbits for genomic latent b5, b6 and b9 using these specific oligomeric probes. For each latent allotype, Southern analysis revealed latent-allotype specific DNA segments in the genome. After cosmid cloning and sequencing, latent kappa1, b5, b6 and b9 genes were found to be identical in their coding regions with their nominal counterparts. The genes contained at the 5' end the PyPyXPyAG RNA splice acceptor site found in immunoglobulin and many eukaryotic genes. as well as the termination codon TAG, together with AATAAA and the T-rich sites responsible for cleavage-polyadenylation in the untranslated region downstream from the 3' end. Single cosmid clones representing the b5, b6 and b9 genes were mapped for restriction sites which resulted in identifying putative Jk and enhancer regions. The results thus indicate that latent allotype genes are potentially functional. The data provide evidence that allotypes are not strictly controlled by allelic genes but must be regulated by an hierarchical mechanism which provides for synthesis of allelic allotypes mainly (10-20 mg/ml) together with non-allelic allotypes at lower concentrations (2-20 microg/ml) following activation of the latent genes. These results lay to rest the belief that Ckappa1 latent allotypes are the products of scrambled genes or idiotypic mimicry. Importantly, we now have the possibility of investigating the factors leading to latent allotype gene expression, the Vk and Jk regions associated with the genes, and therefore whether antibody diversity is expanded. We do not know, nor do we imply, that latent allotypes are present in all rabbits. However, since the four conventional Ckappa1 allotypes are present in the genome of several of our tested rabbits, and are presumably functional. we are faced with the probability that rabbit allotypes under certain conditions may in fact behave as isotypes and not allotypes.


Modulating tiller formation in cereal crops by the signalling function of fertilizer nitrogen forms.
Cereal crop yield comprises interrelated components, among which the number of tillers is highly responsive to nitrogen fertilization. We addressed the hypothesis of whether the supply of different nitrogen forms can be employed to manipulate the tiller number in cereal crops. Relative to urea or ammonium, exclusive supply of nitrate increased tiller number in hydroponically-grown barley plants. Thereby, tiller number correlated positively with the root-to-shoot translocation rate of endogenous cytokinins. External supply of a synthetic cytokinin analog further stimulated tillering in nitrate-containing but not in urea-containing nutrient solution. When the cytokinin analog 6-benzylaminopurine riboside was externally supplied to roots, its translocation to shoots was 2.5 times higher in presence of nitrate than in presence of urea or ammonium, suggesting that cytokinin loading into the xylem is affected by different nitrogen forms. We then translated this finding to field scale, cultivated winter wheat in four environments, and confirmed that nitrate fertilization significantly increased tiller number in a dose-dependent manner. As assessed in 22 winter wheat cultivars, nitrogen form-dependent tiller formation was subject to substantial genotypic variation. We conclude that cytokinin-mediated signaling effects of fertilizer nitrogen forms can be employed as a management tool to regulate the tiller number in cereal crops.


Effect of Intralipid on some immunological parameters and leukocyte functions in patients with esophageal and gastric cancer.
This study has been undertaken to investigate if the intravenous (i.v.) infusion of fat emulsions may be associated with impairment of some immunological functions thus increasing the risk of septic complications. Fifteen malnourished patients with advanced gastric or esophageal cancer received for 2 weeks preoperatively and 1 week after surgery an isocaloric and isonitrogenous TPN treatment with Intralipid (group A: n=8) or glucose alone (group B: n=7) as energy substrate. Cluster analysis of 11 nutritional parameters and some tests of the humoral and cellular immunity (IgG, IgM, C3c, Factor B; polymorphonuclear (PMN) cells, total lymphocytes, T and B lymphocyte counts; 'in vitro' PMN chemotaxis, adherence to nylon fibers, phagocytosis of latex particles) were sequentially determined. The incidence and severity of post-operative infections were investigated and a 'sepsis score' was calculated for each patient. Pre- and postoperative TPN were not associated with an improvement of the nutritional status. The humoral and cellular immune parameters showed the same behaviour in patients receiving Intralipid and in controls. The chemotactic activity of PMN cells was constantly normal, granulocyte adherence fluctuated below the normality range in controls, whereas phagocytosis of latex was similar in both groups. Post-operative infectious episodes were less severe in patients receiving Intralipid. Our results do not confirm that Intralipid adversely affects some aspects of the humoral and cellular immune response.


The Role of Anesthetic Management in Surgical Site Infections After Pediatric Intestinal Surgery.
Although surgical site infections (SSIs) remain a significant health care issue, a limited number of studies have analyzed risk factors for SSIs in children, particularly the role of intraoperative anesthetic management. Pediatric patients are less likely to have major adult risk factors for SSIs such as smoking and diabetes. Thus children may be more suitable as a cohort for examining the role of intraoperative anesthetics in SSIs. We examined an association between SSI incidence and anesthetic management in children who underwent elective intestinal surgery in a single institution. We performed a retrospective study of 621 patients who underwent elective intestinal surgery under general anesthesia between January 2017 and September 2019, with primary outcome as the incidence of SSIs. We compared patients who were dichotomized in accordance with the median of the sevoflurane dose. We used propensity score (PS) pairwise matching of these patients to avoid selection biases. PS matching yielded 204 pairs of patients. We found that higher doses of sevoflurane were associated with a higher incidence of SSIs (9.8% versus 3.9%, P = 0.019). We adjusted for intraoperative factors that were not included in the PS adjustment factors, and multivariate regression analysis after PS matching showed compatible results (odds ratio: 2.58, 95% confidence interval: 1.11-6.04, P = 0.028). Higher doses of sevoflurane are associated with increased odds of SSIs after pediatric elective intestinal surgery. A randomized controlled study of volatile anesthetic-based versus intravenous anesthetic-based anesthesia will be needed to further determine the role of anesthetic drugs in SSI risk.


Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat.
Sympathetic neurons of SCG are dependent on availability of nerve growth factor (NGF) for their survival. SCG neurons express nicotinic receptors (nAChR) whose expression levels are modulated by nicotine. Nicotine exerts multiple effects on neurons, including neuroprotection, through nAChR binding. Although sympathetic neurons express robust levels of nAChR, a possible neuroprotective role for nicotine in these neurons is not well-understood. Therefore we determined the effect of nicotine exposure on survival of SCG neurons during NGF withdrawal in a well-established cell culture system. NGF was withdrawn in rat neonatal SCG neuron cultures which were then treated with either 10 μM nicotine alone or with nAChR antagonists 0.1 μM α-bungarotoxin (antagonist for α7 subunit bearing nAChR) and 10 μM mecamylamine (non-specific antagonist for ganglionic nAChR) for 48 h. Apoptotic death was determined by TUNEL staining. Cell survival was also determined by MTS assay. Western blot analysis of ERK1/2 was also performed. Our results showed that exposure to 10 μM nicotine significantly reduced apoptotic cell death in SCG neurons resulting from NGF withdrawal as shown by fewer TUNEL positive cells. The MTS assay results also revealed that 10 μM nicotine concentration significantly increased cell survival thus indicating neuroprotective effect of nicotine against cell death resulting from NGF withdrawal. Nicotinic receptor antagonists (bungarotoxin & mecamylamine) attenuated the effect of nicotine's action of neuroprotection. Western blot analysis showed an increased expression of ERK1/2 in nicotine treated cultures suggesting nicotine provided neuroprotection in SCG neurons by increasing the expression of ERK1/2 through nicotinic receptor dependent mechanisms.


2(1H)-quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities.
In order to search for anti-arteriostenotic agents, a series of 2(1H)-quinolinone derivatives was synthesized and evaluated for anti-thrombotic activity and for anti-hyperplastic activity. From this series, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]propoxy]-2 (1H)-quinolinone (1p, OPC-33509) was selected as the best candidate by balancing the efficacy on anti-thrombosis and anti-hyperplasia.


Memory for spatial and temporal order in aphasics and right hemisphere damaged patients.
Sets of five photographs per item were presented successively in five vertically arranged frames to 53 aphasics, 27 right hemisphere damaged (RHD) patients and 18 normal subjects. Following the presentation of the five slides subjects were given a spatial and a temporal recognition task. In the spatial task subjects had to indicate which of two pictures of a probe had been nearer to the top of the vertically arranged set of frames. In the temporal task they had to indicate which of the two pictures of the probe had been presented earlier. Aphasics made significantly more errors than RHD and normals in both the spatial and the temporal task, while RHD were significantly impaired in comparison to the normal controls only in the spatial task.


Chlorination of taurine by myeloperoxidase. Kinetic evidence for an enzyme-bound intermediate.
The chlorination of taurine by the myeloperoxidase-H2O2-Cl- system was investigated under steady state conditions. By systematically varying the pH and the concentrations of H2O2,Cl-, and taurine such that chloride inhibition and the unwanted formation of inactive compound II intermediate are minimized, rate data were found to fit a mechanism involving an enzyme-bound chlorinating intermediate. The mechanism we propose is as follows. [formula: see text] The kinetic parameters determined at pH 4.7 are: k1 = (3.3 +/- 0.2) x 10(7) M-1 S-1, k2 = (2.8 +/- 1.2) x 10(6) M-1 S-1, and k3 = (4.4 +/- 0.2) x 10(5) M-1 S-1. The rate constant for compound I formation (k1) is of the same order of magnitude as the value (1.8 x 10(7) M-1 S-1) obtained using transient state techniques in a previous study by our group. The value of k3 is 2 orders of magnitude greater than the non-enzymatic reaction between HOCl and taurine at the same pH. The results of this study indicate that the chlorination reaction mediated by the myeloperoxidase system in vivo may involve an enzyme intermediate species rather than free HOCl. Not only does this mechanism offer the advantage of substrate specificity but also of speed compared to the non-enzymatic reaction. This mechanism can also explain how the indiscriminate oxidation reactions by HOCl are prevented in the leukocyte. The fast formation of taurine monochloramine, a relatively non-toxic and stable compound compared to HOCl, is consistent with the proposed role of taurine in the neutrophil, that of protecting certain targets including myeloperoxidase from the attack by potent chlorinated oxidants.


Identification of disialosyl paragloboside and O-acetyldisialosyl paragloboside in cerebellum and embryonic cerebrum.
The lacto series of glycolipids are only minor constituents in mammalian CNS and are found mostly during development. Expression of a significant amount (70 micrograms of neuraminic acid/g dry weight) of disialosyl-lacto-N-neotetraosylceramide (LD1) in adult mouse cerebellum is reported for the first time in the nervous system. The structure of this ganglioside was determined by hydrolysis with various glycosidases, immunochemical tests, sugar and fatty acid analyses after permethylation and capillary GLC-mass spectrometry, sugar linkage analysis of permethylated alditol acetates, and fast-atom bombardment-mass spectrometry of the native ganglioside. The structure of LD1 was determined to be NeuAc-NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1-ceramide. The major fatty acid was 18:0, and the long-chain base was C18-sphingenine. Mouse cerebellum also contained O-acetyl-LD1 and several other O-acetylated gangliosides as recognized by monoclonal antibodies ME311 and 3G5. The levels of LD1 and O-acetyl-LD1 in cerebellum increased during postnatal development. During development of the Purkinje cell degeneration mutant, pcd/pcd, the levels of both of these gangliosides in the cerebellum declined with the loss of Purkinje cells, a finding indicating that these gangliosides are primarily associated with Purkinje cells. In the cortex, LD1, O-acetyl-LD1, and O-acetyl GD3, like GD3, are developmentally regulated antigens and are only expressed in the fetal cortex and not to any significant extent in the adult.


Early tracheostomy and active exercise programmes in adult intensive care patients with severe burns.
Tracheostomy is a strategy often employed in patients requiring prolonged intubation in ICU settings. Evidence suggests that earlier tracheostomy and early active exercise are associated with better patient centered outcomes. Severe burn patients often require prolonged ventilatory support due to their critical condition, complex sedation management and multiple operating room visits. It is still unclear the optimal timing for tracheostomy in this population. We conducted a service evaluation where we compared Early Tracheostomy (≤10 days) with Late Tracheostomy (>10 days) in 41 severely burned patients that required prolonged respiratory support. Early Tracheostomy cohort was associated with fewer days of mechanical ventilation (16 vs 33, p = 0.001), shorter hospital length of stay (65 vs 88 days, p = 0.018), earlier first day of active exercise (day 8 vs day 25, p < 0.0001) and higher Functional Assessment for Burns scores upon discharge (32 vs 28, p = 0.016). Early tracheostomy in patients with severe burns is associated with earlier active exercise, fewer days of ventilation, shorter length of hospital stay and better physical functional independence upon discharge from hospital.


Progress of exosome research in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a global chronic autoimmune disease that invades most organs of the body, with kidney injury being the most prominent feature. Exosomes are extracellular vesicles that carry a variety of proteins, lipids and genetic material, participate in the exchange of local and intersystem information, and play an important immunoregulatory role in a variety of autoimmune diseases. At the same time, the use of exosomes as disease biomarkers and drug delivery carriers also shows great application prospects. This article reviews current progress in the application of exosomes in the pathogenesis, diagnosis and treatment of SLE.


Clostridium difficile carriage in healthy pregnant women in China.
Infection with Clostridium difficile has been shown to have particularly poor outcomes for pregnant women, including an increased risk of death. The purpose of this study was to investigate the prevalence, genotypic distribution, and characterization of C. difficile strains isolated from pregnant women without diarrhea in China. As part of this study, 3.7% (37 out of 1009) of samples acquired from pregnant females tested positive for C. difficile. Of these positive samples, 27.0% (10) were toxigenic isolates containing both toxin A and toxin B genes (A+B+), 13.5% (5) of the variant strains contained the toxin B gene (A-B+) only, while the rest were non-toxigenic isolates (59.5%, 22 isolates). Among the non-pregnant women without diarrhea tested, 1.4% (9 of 651) contained toxigenic isolates (all of which were A+B+). Sixteen different sequence types (STs) were isolated during the course of this study. ST-37 (ribotype 017) and ST-54 (ribotype 012) were the most frequent toxigenic types observed in pregnant women. All strains showed susceptibility to the antibiotics metronidazole and vancomycin. The resistance rates of toxigenic C. difficile strains isolated from pregnant females to clindamycin, erythromycin, moxifloxacin, levofloxacin, and rifampicin were 20%, 46.7%, 13.6%, 46.7% and 13.3%, respectively. There was no significant difference between resistance rates of toxigenic and non-toxigenic strains with respect to their susceptibility to these antibiotics. However, when compared with the same data from non-pregnant women, toxigenic strains from pregnant women showed lower resistance rates to clindamycin (P < 0.05).


Lymphomatoid granulomatosis.
The clinical and pathologic appearance of seven patients with lymphomatoid granulomatosis who had skin lesions when first seen is reviewed. Six patients subsequently developed systemic disease. Although the gross morphology of the skin lesions is variable, the pathology is distinctive. An adequate deep biopsy shows the characteristic lymphohistiocytic infiltrate with variable numbers of atypical cells. Angiodestruction is less evident in the skin compared to other organs. The infiltrate surrounds and invades not only vessels but also nerves and epidermal appendages. The skin biopsy specimen can be differentiated from the lymphomatous infiltrates and Wegener's granulomatosis. Two of the patients who developed systemic disease were diagnosed by skin biopsy but clinicians failed to institute therapy, preferring to wait for other organ involvement. In addition, two patients developed lymphoma, one of which was confirmed at autopsy and one on subcutaneous and bone marrow biopsy 5 years after the initial skin diagnosis. Lymphomatoid granulomatosis can be diagnosed by performing a skin biopsy. Appropriate chemotherapy may result in a high percentage of complete remissions and therefore the dermatopathologist can play an important role in the early diagnosis of this potentially fatal disease.


The aging transcriptome: read between the lines.
The increasing sophistication of gene expression technologies has given rise to the idea that aging could be understood by analyzing transcriptomes. Mapping trajectories of gene expression changes in aging organisms, across different tissues and brain regions has provided insights on how biological functions change with age. However, recent publications suggest that transcriptional regulation itself deteriorates with age. Loss of transcriptional regulation will lead to non-regulated gene expression changes, but current analysis strategies were not designed to disentangle mixtures of regulated and non-regulated changes. Disentangling transcriptional data to distinguish adaptive, regulatory changes, from those that are the consequence of the age-associated deterioration is likely to create an analytical challenge but promises to unlock yet poorly understood aspects of many age-associated transcriptomes.


Diimidazolium Salt HBDIM: An Easily Available, Low-Cost, CageCarbene Precursor with Broad Applications in Transition Metal-Catalyzed Reactions.
The preparation of diimidazolium salt HBDIM 1, a precursor for a di-NHCs ligand, from cheap and easily available agent hexabenzylhexaazaisowurtzitane (HBIW) is reported. Under basic conditions, HBDIM undergoes facile deprotonation to in situ generate CageCarbene, which could efficiently coordinate to transition-metals, such as, Au, Cu or Pd, to give the corresponding bimetallic complexes 2-4. These complexes were isolated and fully characterized, including X-ray diffraction of their single crystals. It was found that the steric hinderance of CageCarbene is similar to that of SIMes but smaller than that of IPr, and electronically, CageCarbene is a strong σ-donator similar to SIMes and a stronger σ-donator than IPr. Further studies showed that complexes 2-4 were highly reactive to catalyze up to 17 reactions. Control experiments utilizing a N-benzyl-substituted monoimidazolium salt showed much lower catalytic reactivity when it was bound to Au or Cu, but exhibited similar reactivity for the Pd complex. Kinetic studies showed that the low reactivity of the monodentate carbene-ligated Au or Cu complex was due to the low stability of the complex under the reaction conditions.


Increased urinary excretion of bilirubin metabolites in association with hyperbilirubinemia after esophagectomy.
This study was conducted to investigate the rationale for postoperative hyperbilirubinemia after major surgery. The serum bilirubin values and urinary excretion of bilirubin metabolites (BM) were monitored in 11 patients who underwent esophagectomy via right thoracotomy for esophageal cancer. Both the serum bilirubin values and the urinary excretion of BM increased postoperatively in all patients. The maximum serum bilirubin level in four patients with septic complications, two of whom developed pneumonia and two, anastomotic leakage (group A), was significantly higher at 5.25+/-4.16 mg/dl than in the remaining patients without septic complications (group B), at 2.11+/-0.07 mg/dl. The peak value of urinary BM was 99.5+/-88.2 micromol/day in group A and 23.5 +/-26.7 micromol/day in group B. The correlation between the level of serum bilirubin and urinary BM excretion was found to be significant. Thus, the metabolism of bilirubin was increased by extensive surgical stress and septic insult.


Frequency domain analysis of contrast echocardiographic images.
Sequences of echocontrastographic images of the dog's myocardium are analysed in the frequency domain for the identification of underperfused areas. Owing to the fact that echo images are contaminated by noise and artifacts, we have applied filtering techniques based on Fourier's methods in sequences of raw frames recorded during perfusion with a contrast agent. Thus we have been able to assess correctly the spatial and temporal distribution of the contrast, i.e. the agent kinetics which parallel the distribution of coronary blood flow, in terms of the time necessary for the flow gradient to reach its maximum value, and to describe such a distribution by a functional image obtained by means of an original procedure.


[Saliva: an important factor in retention of complete dentures].
The saliva plays a profound role in a removable prosthodontic treatment in edentulous patients. Indeed the presence of a thin salivary film is essential to the comfort of the mucosa. The saliva also plays pivotal role for the stomatitis of prothesic etiology, found in significant numbers of complete and partial denture wearers. Additionally, saliva in cause in calcolus deposition and in anomalous hue of removable denture.


Role of physical activity and health-related fitness on self-confidence and interpersonal relations in 14-year-old adolescents from secondary school settings: DADOS study.
The effect of physical activity (PA) and physical fitness (PF) on self-confidence and interpersonal relations in adolescents is uncertain. To analyzed the associations of PA and PF with self-confidence and interpersonal relations in adolescents. A total of 268 (138 boys) adolescents (13.9 ± 0.3 years) from the DADOS study were included in the analysis. PA was evaluated using GENEActiv accelerometers and the health-related PF components by the ALPHA health-related fitness test battery. The levels of self-confidence and interpersonal relations were determined by the Behavior Assessment System for Children Level 3. The associations of PA levels and PF components with self-confidence reported positive associations of moderate-vigorous PA (MVPA), standing long jump, and 20-m shuttle run (shuttle run test) tests (all p < 0.05), and negative association of 4 × 10-m shuttle run test (4 × 10-m test), but only the 4 × 10-m test remained significant in the adjusted model for the whole sample and only in boys (p ≤ 0.01) when analyzed by sex. Regarding interpersonal relations, positive associations of standing long jump and shuttle run test (all p < 0.05), and negative association of 4 × 10-m test were found in all the adolescents. The shuttle run test was associated with interpersonal relations in boys independently of confounders. PA levels were not associated with interpersonal relations. A higher level of lower-limb muscle strength, speed-agility, and cardiorespiratory fitness might improve self-confidence and interpersonal relations in adolescents, but these relationships seem to be influenced by sex, body mass index, and pubertal status. Speed-agility and cardiorespiratory fitness seem to have a stronger impact on boys. MVPA may improve self-confidence in adolescents.


Design principles and applications of a cooled CCD camera for electron microscopy.
Cooled CCD cameras offer a number of advantages in recording electron microscope images with CCDs rather than film which include: immediate availability of the image in a digital format suitable for further computer processing, high dynamic range, excellent linearity and a high detective quantum efficiency for recording electrons. In one important respect however, film has superior properties: the spatial resolution of CCD detectors tested so far (in terms of point spread function or modulation transfer function) are inferior to film and a great deal of our effort has been spent in designing detectors with improved spatial resolution. Various instrumental contributions to spatial resolution have been analysed and in this paper we discuss the contribution of the phosphor-fibre optics system in this measurement. We have evaluated the performance of a number of detector components and parameters, e.g. different phosphors (and a scintillator), optical coupling with lens or fibre optics with various demagnification factors, to improve the detector performance. The camera described in this paper, which is based on this analysis, uses a tapered fibre optics coupling between the phosphor and the CCD and is installed on a Philips CM12 electron microscope equipped to perform cryo-microscopy. The main use of the camera so far has been in recording electron diffraction patterns from two dimensional crystals of bacteriorhodopsin--from wild type and from different trapped states during the photocycle. As one example of the type of data obtained with the CCD camera a two dimensional Fourier projection map from the trapped O-state is also included. With faster computers, it will soon be possible to undertake this type of work on an on-line basis. Also, with improvements in detector size and resolution, CCD detectors, already ideal for diffraction, will be able to compete with film in the recording of high resolution images.


Loss of programmed cell death 4 induces apoptosis by promoting the translation of procaspase-3 mRNA.
The programmed cell death 4 (Pdcd4), a translation inhibitor, plays an essential role in tumor suppression, but its role in apoptosis remains unclear. Here we show that Pdcd4 is a critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA. Pdcd4 protein decreased more rapidly through microRNA-mediated translational repression following apoptotic stimuli than did the activation of procaspase-3, cleavage of poly(ADP)ribose polymerase (PARP) by active caspase-3, and nuclear fragmentation. Strikingly, the loss of Pdcd4 by the specific RNA interference increased procaspase-3 expression, leading to its activation and PARP cleavage even without apoptotic stimuli, and sensitized the cells to apoptosis. Thus, our findings provide insight into a novel mechanism for Pdcd4 as a regulator of apoptosis.


The association of cortisol curve features with incident diabetes among whites and African Americans: The CARDIA study.
A flatter diurnal cortisol curve has been associated with incident diabetes among older white adults. However, this relationship has not been examined among middle-aged individuals or African Americans [AA]. We analyzed the longitudinal association of baseline diurnal cortisol curve features with incident diabetes over a 10 year period in a cohort of AA and white participants who were, on average, 40 years old. Salivary cortisol was collected immediately post-awakening, then subsequently 45 min, 2.5 h, 8 h, and 12 h later, as well as at bedtime. Cortisol curve features included wake-up cortisol; cortisol awakening response (CAR); early, late, and overall decline slopes; bedtime cortisol; and 16 -h area under the curve (AUC). Salivary cortisol (nmol/L) was log-transformed due to positively skewed distributions. Diabetes was defined as fasting plasma glucose ≥ 126 mg/dL or taking diabetes medication. Logistic regression models were used to investigate the association of log-transformed cortisol curve features with incident diabetes. The analysis was stratified by race and adjusted for age, sex, education, depressive symptoms, smoking status, beta-blocker and steroid medication use and BMI. Among 376 AA and 333 white participants (mean age 40 years), 67 incident diabetes cases occurred over 10 years. After full adjustment for additional covariates, a 1-unit log increase in CAR was associated with a 53 % lower odds of incident diabetes among whites (Odds Ratio [OR] 0.47, 95 % CI: 0.24, 0.90). A 1-SD increase in late decline slope was associated with a 416 % higher odds of incident diabetes among whites (OR 5.16, 95 % CI: 1.32, 20.20). There were no significant associations in AAs. A robust CAR and flatter late decline slope are associated with lower and higher odds of incident diabetes, respectively, among younger to middle-aged whites and may provide a future target for diabetes prevention in this population.


[Clinical relevance of immunochemical determination of pancreatic lipase in chronic pancreatitis].
The determination of basal pancreatic serum enzymes is of little value in the diagnosis of chronic pancreatitis. The organ specificity of a recently introduced immunochemical method of determining pancreatic lipase is guaranteed. The diagnostic value of the basal and stimulated serum-lipase determination by the immunochemical assay in chronic pancreatitis was investigated on 84 patients and controls. In 46 patients with chronic pancreatitis the serum increase of pancreatic lipase after secretin stimulation (1 U/kg) was significantly (P less than 0.01) higher than the pancreatic lipase increase in patients with non-pancreatic intestinal disorders and in healthy controls. Patients with chronic pancreatitis deserve to be classified in subgroups, according to the degree of the exocrine pancreatic insufficiency established by means of the secretin-ceruletide test. Of the patients with chronic pancreatitis and a slight to moderate exocrine pancreatic insufficiency 87% show an abnormal serum pancreatic-lipase increase and differ significantly (P less than 0.01) from patients with severe exocrine insufficiency who exhibit an increase of the pancreatic serum lipase only in exceptional cases. Specificity is limited, since an abnormal serum lipase increase after stimulation is found in 20% of controls.


Exploring a deep learning neural architecture for closed Literature-based discovery.
Scientific literature presents a wealth of information yet to be explored. As the number of researchers increase with each passing year and publications are released, this contributes to an era where specialized fields of research are becoming more prevalent. As this trend continues, this further propagates the separation of interdisciplinary publications and makes keeping up to date with literature a laborious task. Literature-based discovery (LBD) aims to mitigate these concerns by promoting information sharing among non-interacting literature while extracting potentially meaningful information. Furthermore, recent advances in neural network architectures and data representation techniques have fueled their respective research communities in achieving state-of-the-art performance in many downstream tasks. However, studies of neural network-based methods for LBD remain to be explored. We introduce and explore a deep learning neural network-based approach for LBD. Additionally, we investigate various approaches to represent terms as concepts and analyze the affect of feature scaling representations into our model. We compare the evaluation performance of our method on five hallmarks of cancer datasets utilized for closed discovery. Our results show the chosen representation as input into our model affects evaluation performance. We found feature scaling our input representations increases evaluation performance and decreases the necessary number of epochs needed to achieve model generalization. We also explore two approaches to represent model output. We found reducing the model's output to capturing a subset of concepts improved evaluation performance at the cost of model generalizability. We also compare the efficacy of our method on the five hallmarks of cancer datasets to a set of randomly chosen relations between concepts. We found these experiments confirm our method's suitability for LBD.


Electrodialysis with porous membrane for bioproduct separation: Technology, features, and progress.
Electrodialysis with porous membrane (EDPM) is a recently developed membrane separation process, in which one or more porous filtration membranes stacked in an electrodialysis cell. It is a promising technology for separation, purification or concentration of bioactive components for it associates the excellent properties of electrodialysis (ED), porous filtration membrane, and electrophoresis. There are a number of studies having attempted to optimize the performance of EDPM processing, however, it still has some limitations involving low productivity with one pair of separation unit, membrane fouling and few applications on the fractionation of components with high molecular weight. This paper offers a comprehensive overview of recent studies devoted to EDPM, including principles, configurations, mathematical model regarding mass transfer, process performance optimization, membrane fouling and applications in as much detail as possible. In addition, a collection of other separation technologies based on electrophoresis at a preparative scale are presented to illustrate their limitations on the large-scale application. Some drawbacks of EDPM have been put forward. To achieve full scale applications of EDPM, there are still many issues to overcome. Finally, an outlook for prospective development of EDPM technology is given.


Cerebral blood flow and metabolism in hypertensive patients with cerebral infarction.
The authors investigated, by positron emission tomography, the effect of long-standing hypertension on cerebral blood flow (CBF) and oxygen metabolism in patients with chronic atherothrombotic brain infarction. In the nonbrain infarct (non-BI) group (n = 13, mean age: sixty-two years), the regional CBF (rCBF) was decreased significantly with a rise in the mean arterial blood pressure (MABP) in the cerebral cortexes (r = -0.575) and the deep gray matter (r = -0.451), whereas the regional cerebral metabolic rate for oxygen (rCMRO2) remained unchanged. In the brain infarct (BI) group (n = 22, mean age: fifty-eight years), however, the rCBF as well as the rCMRO2 were reduced even in the normotensive patients and thus did not correlate with the MABP. These results suggest that long-standing hypertension per se causes a reduction in the rCBF but not in the oxygen metabolism with a compensatory increase in the oxygen extraction fraction. On the other hand, patients with brain infarction, even normotensives, show a diffuse decrease in cerebral circulation and metabolism, which is probably due to the more severe sclerotic changes that take place in the cerebral vessels.


More pain, more gain: Blocking the opioid system boosts adaptive cognitive control.
The ability to adaptively increase cognitive control in response to cognitive challenges is crucial for goal-directed behavior. Recent findings suggest that aversive arousal triggers adaptive increases of control, but the neurochemical mechanisms underlying these effects remain unclear. Given the known contributions of the opioid system to hedonic states, we investigated whether blocking this system increases adaptive control modulations. To do so, we conducted a double-blind, placebo-controlled psychopharmacological study (n=52 females) involving a Stroop-like task. Specifically, we assessed the effect of naltrexone, an opioid blocker most selective to the mu-opioid system, on two measures of adaptive control that are thought to depend differentially on aversive arousal: post-error slowing and conflict adaptation. Consistent with our hypothesis, relative to placebo, naltrexone increased post-error slowing without influencing conflict adaptation. This finding not only supports the view that aversive arousal triggers adaptive control but also reveals a novel role for the opioid system in modulating such effects.


Impact of colistin sulfate treatment of broilers on the presence of resistant bacteria and resistance genes in stored or composted manure.
The application of manure may result in contamination of the environment with antimicrobials, antimicrobial-resistant bacteria, resistance genes and plasmids. The aim of this study was to investigate the impact of the administration of colistin and of manure management on (i) the presence of colistin-resistant Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and (ii) the prevalence of various antimicrobial resistance genes in feces and in composted or stored manure. One flock of chickens was treated with colistin at the recommended dosage and a second flock was kept as an untreated control. Samples of feces, litter and stored or composted manure from both flocks were collected for isolation and determination of the colistin-susceptibility of E. coli, K. pneumoniae and P. aeruginosa and quantification of genes coding for resistance to different antimicrobials. The persistence of plasmids in stored or composted manure from colistin-treated broilers was also evaluated by plasmid capturing experiments. Results revealed that colistin administration to chickens had no apparent impact on the antimicrobial resistance of the dominant Enterobacteriaceae and P. aeruginosa populations in the chicken gut. Composting stimulated an apparently limited decrease in genes coding for resistance to different antimicrobial families. Importantly, it was shown that even after six weeks of composting or storage, plasmids carrying antimicrobial resistance genes could still be transferred to a recipient E. coli. In conclusion, composting is insufficient to completely eliminate the risk of spreading antimicrobial resistance through chicken manure.


Home Monitoring of Cardiac Devices in the Era of COVID-19.
Despite the promise of remote patient monitoring (RPM), this technology remained underutilized secondary to a lack of data transparency and systems issues until the COVID-19 pandemic ushered in a new era of telehealth and virtual solutions out of necessity. This review will explore the data supporting the use of RPM via both implantable and wearable devices in the field of cardiology and the role of home monitoring using RPM in the era of COVID-19. RPM using implantable cardiac devices is a safe alternative to in-person only visits which leads to enhanced patient satisfaction and improved clinical outcomes. Consumer-grade wearable sensors have drastically expanded RPM capabilities from just the sickest cardiac patients to the entire population aiding in early diagnosis and real-time disease management. Home monitoring enabled by automated alert systems tailored specifically to the needs of the patient by the provider will be the cornerstone of a more continuous, patent-centric healthcare model.


Determination of 23 pesticide residues in leafy vegetables using gas chromatography-ion trap mass spectrometry and analyte protectants.
A gas chromatographic method was developed for simultaneously determining residues of 12 insecticides (acrinathrin, bifenthrin, carbofuran, cyfluthrin, lambda-cyhalothrin, cypermethrin, chlorfenvinphos, deltamethrin, esfenvalerate, fenamiphos, methiocarb and tau-fluvalinate) and 11 fungicides (cyprodinil, fludioxonil, iprodione, metalaxyl, penconazole, pyrimethanil, procymidone tebuconazole, triadimefon, triadimenol and vinclozolin) in leafy vegetables. Samples were extracted with acetonitrile and cleaned-up with graphitized carbon black/primary secondary amine (GCB/PSA) solid-phase extraction (SPE) cartridges using acetonitrile:toluene (3:1, v/v) as eluent. The eluate was finally evaporated and redissolved with 0.5 mL of acetone containing the internal standards (pentachlorobenzene and fenpropathrin) and three analyte protectants (3-ethoxy-1,2-propanediol, d-sorbitol and l-gulonic acid gamma-lactone). The addition of analyte protectants allows to avoid the matrix-induced response enhancement effect on quantitation process with absolute recoveries ca. 100%. Precision (expressed as relative standard deviation) was lower than 10% for all pesticides and finally, limits of detection were also 10-20 times lower than maxima residue levels (MRLs) established by European Regulation. The proposed method was applied to determine pesticide residues in commercial leafy vegetables (lettuce, Swiss chard and spinach) purchased from markets in Orense (NW Spain). Pesticide residues were detected in 84% of the total samples (63 from 75 samples) and pesticide concentrations were higher than MRL in 18 samples.


Modulation of cytokine production by carnitine.
The ability of carnitine congeners to modulate cytokine production by human peripheral blood mononuclear cells (PBMC) was investigated. Modulation of cytokine production by PBMC of young (30 years of age or younger) and old (70 years of age or older) normal donors was first compared. The PBMC were collected over Ficoll-Hypaque and incubated in the presence of various concentrations of acetyl L-carnitine for 24 h. Subsequently the supernatants were collected and examined for cytokine production. The presence of cytokines in tissue culture supernatants was examined by ELISA. The cytokines measured included IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, TNFalpha, GM-CSF, and IFNgamma. The results showed that at 50 mug/ml of acetyl L-carnitine the most significant response was obtained for TNFalpha. In this regard four of five young donors responded, but only one of five old donors responded. More recently these studies were expanded to examine the ability of L-carnitine to modulate cytokine production at higher doses, 200 and 400 mug/ml, in young donors. The results of these studies showed that in addition to TNFalpha, significant production of IL-1beta and IL-6 was observed. These preliminary studies provide evidence that carnitine may modulate immune functions through the production of selected cytokines.


Incidental pregnancy luteoma associated with ectopic tubo-ovarian pregnancy: evidence in favor of origin from theca interna of an atretic follicle.
An incidental pregnancy luteoma was identified microscopically in an ovary submitted for ruptured ectopic tubo-ovarian pregnancy. The lesion consisted of a localized, non-encapsulated proliferation of thecal cells in the wall of an atretic follicle and had all the pathologic features of the typical late pregnancy luteoma. This finding is presented to support the origin of the pregnancy luteoma from the theca interna of atretic follicles.


Distribution and breeding sites of Aedes aegypti and Aedes albopictus in 32 urban/peri-urban districts of Mozambique: implication for assessing the risk of arbovirus outbreaks.
Aedes-borne arboviruses have emerged as an important public health problem worldwide and, in Mozambique, the number of cases and its geographical spread have been growing. However, information on the occurrence, distribution and ecology of Aedes aegypti and Ae. albopictus mosquitoes remain poorly known in the country. Between March and April 2016, a cross-sectional study was conducted in 32 districts in Mozambique to determine the distribution and breeding sites of Ae. aegypti and Ae. albopictus. Larvae and pupae were collected from a total of 2,807 water-holding containers using pipette, dipper, funnel and sweeping procedures, depending on the container type and location. Both outdoor and indoor water-holding containers were inspected. The immature forms were reared to adults and the identifications of the mosquito species was carried out with a stereomicroscope using a taxonomic key. Aedes aegypti was found in every district sampled, while Ae. albopictus was only found in Moatize district, situated in Tete Province in the central part of the country. Six hundred and twenty-eight of 2,807 (22.4%) containers were positive for Ae. aegypti but only one (0.03%) was positive for Ae. albopictus. The Container Index (CI) of Aedes was highest in densely populated suburban areas of the central region (260/604; 43.0%), followed by suburban areas in northern areas (228/617; 36.9%) whilst the lowest proportion was found in urbanized southern areas (140/1586; 8.8%). The highest CI of Aedes was found in used tires (448/1268; 35.3%), cement tanks (20/62; 32.3%) and drums (21/95; 22.1%). Data from our study showed that Ae. aegypti is present nation-wide, since it occurred in every sampled district, whilst Ae. albopictus had a limited distribution. Therefore, the risk of transmission of dengue and chikungunya is likely to have been underestimated in Mozambique. This study highlights the need for the establishment of a national entomological surveillance program for Aedes spp. in Mozambique in order to gain a better understanding about vector bionomics and to support the development of informed effective vector control strategies.


Inhibition of ovulation by low-dose monophasic contraceptive containing gestodene.
Ovulation inhibition by the monophasic oral contraceptive containing 75 ug of gestodene and 30 ug of ethinyl estradiol was evaluated in 25 healthy volunteers for five cycles: a pretreatment cycle, three treatment cycles, and a posttreatment cycle. Serum luteinizing and follicle- stimulating hormones, estradiol, and progesterone levels were measured on days 8 through 17; progesterone was measured once, around day 21. Pelvic ultrasound examinations were performed on cycle days 8 to 17, luteinizing and follicle-stimulating hormone levels reached values on the lower limit of detection. Luteal activity was not detected in treated cycles. Follicular activity, which was reflected by estradiol levels, was mot strongly depressed during the first treated cycle. Pelvic ultrasound examinations confirmed excellent inhibition of follicular maturation. Restoration of ovarian function in the posttreatment cycle was excellent and showed a midcycle hormonal profile identical to the pretrial cycle.


[A description of early hydrocephalus with macrocephaly, cerebral palsy, epilepsy, intellectual disability, and growth retardation by Norwegian novelist Amalie Skram (1846-1905)].
In her novel «S.G. Myre» written in 1890, Norwegian author Amalie Skram describes Hans (Hansemann) Tønnesen, a 16-year-old boy with an enormous head, convulsions, and a rudimentary command of language. He is bullied by children in the street and is held in low esteem by his mother, who refers to him as a beast, crazy, or «a cross». Presumably, the boy has hydrocephalus with macrocephaly, epilepsy, and mental retardation. His retarded growth, small teeth and cracked skin suggest growth hormone deficiency resulting from his hydrocephalus. A couple of interesting details, such as his «splaying his fingers and moving them in various directions to make himself understood» and his «becoming red with exertion and grimacing terribly» when trying to speak, suggest extrapyramidal, dyskinetic cerebral palsy. He may also be deaf. A cousin of Skram's shared several of these traits and is a likely model for Hansemann. A question that occurs to a modern reader is to what degree Hansemann is mentally retarded, or whether he is wrongly perceived as such because of his physical challenges and his communication problems.


Inpatient Rehabilitation Facility Patients' Functional Abilities and Validity Testing of the Standardized Self-Care and Mobility Data Elements.
To describe the abilities of Medicare patients in inpatient rehabilitation facilities (IRFs) at admission and discharge using the standardized self-care and mobility data elements and examine the validity of the data elements. These data are used in the Center for Medicare & Medicaid's IRF payment and quality reporting programs. Descriptive study reporting IRF patients' self-care and mobility scores. We also examined content validity and the associations between admission scores and length of stay (LOS), discharge scores and discharge destination, and change scores and the number of comorbidities. Patients discharged from 1129 IRFs in 2017. IRF Medicare fee-for-service and Medicare Advantage patient stays (N = 493,209). Not applicable. Self-care and mobility item scores, IRF LOS, discharge destination, and categories of the number of comorbidities. For each self-care and mobility activity, patients in IRFs overall made substantial improvements in function between admission and discharge. For example, the percentage of patients independent with eating and toilet transfers increased from 29.04% to 66.68% and 0.80% to 39.87%, respectively, between admission and discharge. Activities represented in the standardized data elements are included in other functional assessment instruments addressing content validity. Analyses showed a monotonic relationship between admission scores and LOS and between discharge scores and discharge to community percentages with only a few exceptions. Self-care and mobility scale change scores decreased as the number of comorbidities increased across categories. Patients in IRFs overall show functional improvement across each of the activities as defined by the standardized self-care and mobility data elements. The results showing the associations between patient functioning and 3 metrics (LOS, discharge to community rates, and number of comorbidities) support the validity of the data elements measuring functional abilities in the IRF Medicare population.


Reliability and Validity Evidence for Health Care-Seeking Behavior Questionnaire on Sexual Health Among Filipino Men: A Confirmatory Factor Analysis.
Background and Purpose: Healthcare-seeking behavior is an issue affecting the promotion of sexual health among Filipino men. However, tools to measure healthcare-seeking behaviors among men, in general, are scarce. This study aimed to find evidence of validity and reliability of the Health Care-Seeking Behavior Questionnaire (HCSBQ). Methods: A cross-sectional online survey was conducted among N = 464 Filipino men. Linear Structural Relations (LISREL®) was used for statistical analysis. Results: The HCSBQ demonstrates validity and reliability after data analysis. The overall Cronbach's alpha of 0.94 shows excellent internal consistency. The exploratory factor analysis revealed three latent variables, namely, interactional, intellectual, and active and decision-making. Cronbach's alpha for each latent variable is 0.91, 0.84, and 0.88, respectively. A confirmatory factor analysis shows an excellent goodness-of-fit indices (Adjusted Goodness-of-Fit Index [AGFI] = .95; Goodness-of-Fit Index [GFI] = .97; Comparative Fit Index [CFI] = .99; Incremental Fit Index [IFI] = .99; Expected Cross Validation Index [ECVI] = .45; and Root Mean Square Error of Approximation [RMSEA] = .03). Conclusions: The HCSBQ is a valid and reliable tool to measure healthcare-seeking behaviors among Filipino men.


Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy.
Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. To assess the long-term safety and efficacy of zonisamide in children and adolescents. Zonisamide-naïve patients (n=109, aged 3-15 years, weight >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=4 seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1mg/kg/day, increased by 2 mg/kg/day every 1-2 weeks at the investigator's discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. The mean dose received was 8.5 mg/kg/day. Of the 109 children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant (p=0.033) median reduction in 'all seizure' frequency of 2.60 seizures per week was observed. Additionally, a significant (p=0.029) median reduction of 1.80 seizures/week in 'complex partial' seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes.


S-nitrosoglutathione functionalized polydopamine nanoparticles incorporated into chitosan/gelatin hydrogel films with NIR-controlled photothermal/NO-releasing therapy for enhanced wound healing.
Nitric oxide (NO) has aroused wide interest in the treating infected wounds due to its characteristic functionalities. However, its utilization is limited due to its volatile properties, high reactivity, direct potential toxicity, and byproducts of NO donors limited its application. Herein, endogenously NO donor S-nitrosoglutathione (GSNO) was connected covalently to polydopamine nanoparticles (PDA-GSNO NPs) to minimize the loss of NO in aqueous medium. Meanwhile, near-infrared (NIR)-controlled NO release and photothermal therapy (PTT) was obtained through the photothermal conversion by PDA. Then chitosan (CS)/gelatin (GE) biocomposite hydrogel films with preferable biocompatibility, surface hydrophilicity, hydroabsorptivity, and mechanical adhesive properties were constructed. By embedding PDA-GSNO NPs into the films, a multifunctional wound dressing was fabricated. Under NIR light irradiation, the combination of PTT, NO-releasing, and CS antibacterial agents can strengthen the in vitro antimicrobial efficacy and in vivo wound healing activities. Meanwhile, the obtained wound dressing presented good biocompatibility. This work outlines an approach for combating bacterial infections and demonstrating the possibility for synergistic NO-releasing wound healing.


Buccal Mucosa Tube Graft for Failed Hypospadias Repair: Worth it or Not?
To report the outcome of buccal mucosa tube graft (BMTG) over time in correcting failed hypospadias. We conducted a retrospective analysis, reviewing charts of all 69 patients who underwent BMTG to repair hypospadias between January 2005 and October 2016. Twenty-one patients were excluded, leaving 48 eligible study subjects. In patients with penile curvatures, corrective procedures (including urethral division, corporoplasty, and local skin flap) took place prior to grafting. Mean age at surgery was 8.96 years, and mean duration of follow-up was 73.10 ± 30.31 months. A mean of 1.88 previous surgeries was recorded. During follow-up, only 7 patients (14.5%) were complication free. The other 41 patients required at least 1 additional procedure. Stricture-free rates were 50%, 35.4%, and 27% at 1, 3, and 12 months after BMTG, respectively. Among 37 patients with postoperative stricture, 25 were treated only by endoscopic procedures. Single operation prior to BMTG (P= .004) and usage of larger catheter size (>8Fr) (P = .029) were confirmed significant factors associated with better stricture-free survival after BMTG by log-rank test. After several additional procedures, 46 patients (95.8%) reported normal urination with mean maximal urinary flow of 9.55 mL/s and post-void residual of 16.08 mL for at least 12 months on last visit. BMTG after failed hypospadias repair seems prone to complications, primarily urethral stricture. However, a large number of patients with postoperative stricture could be treated simply by endoscopic procedures. Given the better results of staged approach, BMTG should be only applied to highly selected patients with failed hypospadias.


Effects of lead acetate on testicular function and caspase-3 expression with respect to the protective effect of cinnamon in albino rats.
The aim of this study was to investigate the protective effects of cinnamon on lead acetate induced reproductive toxicities in rats. Thirty-two male rats were randomly divided into 4 groups, 8 rats in each. Control rats received distilled water, while treated rats received lead acetate (30 mg/kg), cinnamon (250 mg/kg) and lead acetate and cinnamon (30 mg/kg and 250 mg/kg) for 60 days by gavage tube. In cinnamon treated rats, the relative weights of testes, epididymis, seminal and prostate glands were significantly (P < 0.05) increased compared with that in lead acetate treated rats. Sperm cell concentration and viability were significantly (P < 0.05) reduced, while sperm abnormalities were significantly (P < 0.05) increased in lead treated rats. The superoxide dismutase (SOD) and catalase activities were significantly reduced (P < 0.001) in lead acetate treated rats compared to the other groups, while the addition of cinnamon to lead acetate improved the level of SOD compared to the lead treated group. There was a marked reduction (P < 0.001) in the expression of androgen receptor and significant (P < 0.001) increase in the level of caspase-3 protein expression in the testis of lead treated rats. In conclusion, cinnamon exhibited protective effect on reproductive system by inhibiting lead acetate induced oxidative stress and excessive cell apoptosis.


Rapid screening of the entire mitochondrial DNA for low-level heteroplasmic mutations.
Alterations of the mitochondrial DNA (mtDNA) are implicated in various pathological conditions. In this study, we used denaturing high performance liquid chromatography (DHPLC) as a method to rapidly screen the entire mtDNA for mutations. Overlapping DNA fragments, amplified by one single cycling protocol from frozen pre-formulated PCR mixes, were subjected to DHPLC analysis. Single DHPLC injections of fragments yielded straightforward interpretation of results with a detection limit down to 1% mtDNA heteroplasmy. Furthermore, collection and re-amplification of low degree heteroduplex peak-fractions allowed sequence analysis of mtDNA mutations down to the detection limit of the DHPLC method. In order to demonstrate that the method has diagnostic value, we analyzed and confirmed known mtDNA mutations in patient samples.


Somatosensory-evoked magnetic fields following stimulation of the tongue in humans.
To clarify the characteristics relating to the temporal dynamics of the tongue primary somatosensory cortex (SI). We fabricated individual intraoral devices and recorded somatosensory-evoked magnetic fields (SEFs) from 10 normal subjects. The tongue was stimulated with a concentrated bipolar electrode in four areas: the right and left antero-lateral margins, and the right and left postero-lateral margins. The primary component was recorded about 19 ms post-stimulation. Six components, termed 1M, 2M, 3M, 4M, 5M, and 6M, respectively, were found within 130 ms of the stimulation. These activities were detected in hemispheres both contralateral and ipsilateral to the stimulation, and were estimated to be located around the tongue SI. In addition, the latency of the contralateral hemisphere was significantly shorter than that of the ipsilateral hemisphere for all components, independent of the area stimulated. Tactile stimulation of the tongue-elicited activity in the tongue SI in both hemispheres. This is the first study to investigate the brain responses evoked by stimulating different areas of the tongue, using magnetoencephalography.


Autologous Stem Cell Rescue recipient with neutrophil tissue delivery detected prior to blood engraftment: a case report.
Neutrophil recovery after autologous hematopoietic cell transplantation (auto-HCT) is affirmed with achievement of an Absolute Neutrophil Count (ANC) of ≥500/uL. There is growing evidence that neutrophils may be observed despite undetectable peripheral ANC counts following autologous hematopoietic cell transplant and are preferentially delivered to sites of inflammation. We report an interesting case that confirms neutrophil tissue delivery to the skin two days prior to evidence of blood engraftment after an auto-HCT.


Papillary tumor of the heart: incidental finding at surgery.
A large papillary endocardial "tumor" of the heart was resected during surgery for closure of an interventricular septal defect in an adult. The theories of pathogenesis of papillary "tumors" of the heart are briefly reviewed. To our knowledge, this is the first report of a papillary tumor resected at surgery.


Fatal COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome Is Associated with Incomplete Alveolar Type 1 Epithelial Cell Differentiation from the Transitional State without Fibrosis.
Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; recovery requires epithelial regeneration. During physiological regeneration in mice, type 2 AECs (AEC2s) proliferate, exit the cell cycle, transiently assume a transitional state, then differentiate into type 1 AECs (AEC1s); in humans, persistence of the transitional state is associated with pulmonary fibrosis. It is unknown whether transitional cells emerge and differentiate into AEC1s without fibrosis in human ARDS and why transitional cells differentiate into AEC1s during physiological regeneration but persist in fibrosis. We hypothesized that incomplete but ongoing AEC1 differentiation from transitional cells without fibrosis may underlie persistent barrier permeability and acute respiratory failure in ARDS. Immunostaining of postmortem ARDS lungs revealed abundant transitional cells without fibrosis. They were typically cuboidal or partially spread, sometimes flat, and occasionally expressed AEC1 markers. Immunostaining and/or single-cell RNA sequencing revealed that transitional cells in mouse models of physiological regeneration, ARDS, and fibrosis express markers of cell cycle exit but only in fibrosis express a specific senescence marker. Thus, in severe, fatal early ARDS, AEC1 differentiation from transitional cells is incomplete, underlying persistent barrier permeability and respiratory failure but ongoing without fibrosis; senescence of transitional cells may be associated with pulmonary fibrosis.


Production of eleutherosides in in vitro regenerated embryos and plantlets of Eleutherococcus chiisanensis.
High frequency somatic embryogenesis of Eleutheorcoccus chiisanensis was achieved through suspension culture of embryogenic cells in hormone-free Murashige and Skoog liquid medium supplemented with 30 g sucrose l-1. Cotyledonary somatic embryos were germinated and converted into plantlets using 20 microM: gibberellic acid which were then grown in a 10 l airlift bioreactor. HPLC analysis revealed the accumulation of eleutheroside B, E and E1 in the embryos and plantlets. Thus mass production of embryos and plantlets of E. chiisanensis can be achieved in liquid cultures and the biomass produced may become an alternative source of eleutherosides.


[Solidarity and financing in the statutory health insurance system sin West Germany during the 1960s and 1970s].
Until the early seventies escalating costs in the health care sector were accepted as being a necessary consequence of social progress. However, this view has since begun to shift. Due to the recession in the mid-seventies, mounting health expenditures now loomed as a threat to the economy. Rather than social progress, the issue now was measures to curb the rising costs and increase-insurance revenues. Rising health care contributions initiated by the government coalition of Social Democrats and the Liberal Party marked this change of perspective in health policy that led to restraints in the principle of solidarity within the statutory health insurance system and, as a result, to a renewed privatisation of health expenditures. Since then patients who had health insurance were obliged to pay a larger share of their health expenses.


A novel bioluminescent NanoLuc yeast-estrogen screen biosensor (nanoYES) with a compact wireless camera for effect-based detection of endocrine-disrupting chemicals.
The presence of chemicals with estrogenic activity in surface, groundwater, and drinking water poses serious concerns for potential threats to human health and aquatic life. At present, no sensitive portable devices are available for the rapid monitoring of such contamination. Here, we propose a cell-based mobile platform that exploits a newly developed bioluminescent yeast-estrogen screen (nanoYES) and a low-cost compact camera as light detector. Saccharomyces cerevisiae cells were genetically engineered with a yeast codon-optimized variant of NanoLuc luciferase (yNLucP) under the regulation of human estrogen receptor α activation. Ready-to-use 3D-printed cartridges with immobilized cells were prepared by optimizing a new procedure that enables to produce alginate slices with good reproducibility. A portable device was obtained exploiting a compact camera and wireless connectivity enabling a rapid and quantitative evaluation (1-h incubation at room temperature) of total estrogenic activity in small sample volumes (50 μL) with a LOD of 0.08 nM for 17β-estradiol. The developed portable analytical platform was applied for the evaluation of water samples spiked with different chemicals known to have estrogen-like activity. Thanks to the high sensitivity of the newly developed yeast biosensor and the possibility to wireless connect the camera with any smartphone model, the developed configuration is more versatile than previously reported smartphone-based devices, and could find application for on-site analysis of endocrine disruptors. Graphical abstract Wireless effect-based detection of endocrine-disrupting chemicals with nanoYES platform.