How effective is extracorporeal shock wave lithotripsy of ureteral stones with Dornier Lithotripter S EMSE 220F-XXP? A prospective and preliminary assessment.
To report our preliminary series with the Doli S EMSE 220F-XXP, the upgraded version of the previous Dornier Lithotripter S EMSE 220, for treatment of ureteral stones. Since July 2006, a total of 200 patients with ureteral stones were submitted to shock wave lithotripsy (SWL) with Doli S EMSE 220F-XXP. Mean stone size was 9.3 mm (range 6-18 mm). Ureteral stone location was proximal in 75, middle in 34, and distal in 91. Follow-up was carried out at 6 weeks after the treatment, by means of kidney-ureter-bladder (KUB) film and ultrasound, or helical computed tomography (CT). The overall stone-free rate was 89.5%, and the effectiveness quotient was 80. Stratifying by stone site, the stone-free rate was 93.3, 67.6, and 94.5% for proximal, middle, and distal location, respectively. Mean number of sessions per patient was 1.14. Analgesia with intravenous ketorolac or tramadol was required in 42.5% of cases. No significant side-effects were recorded. The new Doli S EMSE 220F-XXP provides similar characteristics to the Doli S EMSE 220 in terms of safety and lack of major complications, when dealing with ureteral stones; the improvement in stone disintegration is particularly evident for distal location, for which the number of pulses and the intensity of treatment can be greatly increased and the upgraded power of the device can be widely applied.


An acidic glycosphingolipid, monosialo-ganglioside GM3, is a potent physiological inducer for monocytic differentiation of human promyelocytic leukemia cell line HL-60 cells.
A remarkable increase in monosialo-ganglioside GM3 was observed during the monocytic differentiation of HL-60 cells induced by 12-0-tetradecanoyl-phorbol-13-acetate(TPA). On the other hand, when the cells were cultured with exogenously-added ganglioside GM3 in serum-free conditions, their differentiation along a monocytic lineage was demonstrated with simultaneous complete growth inhibition. Other gangliosides such as ganglioside GM1 showed no effects on cell differentiation, exhibiting instead stimulatory actions on the cell growth. These results indicate that a physiologically-existent, membranous ganglioside GM3, which specifically increases during monocytic cell differentiation, might play a primary role as a trigger in the monocytic cell differentiation.


In vitro physicochemical characterization of five root canal sealers and their influence on an ex vivo oral multi-species biofilm community.
To evaluate the physicochemical properties of five root canal sealers and assess their effect on an ex vivo dental plaque-derived polymicrobial community. Dental plaque-derived microbial communities were exposed to the sealers (AH Plus [AHP], GuttaFlow Bioseal [GFB], Endoseal MTA [ESM], Bio-C sealer [BCS] and BioRoot RCS [BRR]) for 3, 6 and 18 h. The sealers' effect on the biofilm biomass and metabolic activity was quantified using crystal violet (CV) staining and MTT assay, respectively. Biofilm community composition and morphology were assessed by denaturing gradient gel electrophoresis (DGGE), 16S rRNA sequencing and scanning electron microscopy. The ISO6876:2012 specifications were followed to determine the setting time, radiopacity, flowability and solubility. Obturated acrylic teeth were used to assess the sealers' effect on pH. Surface chemical characterization was performed using SEM with coupled energy-dispersive spectroscopy. Data normality was assessed using the Shapiro-Wilk test. One-way anova and Tukey's tests were used to analyze data from setting time, radiopacity, flowability and solubility. Two-way anova and Dunnett's tests were used for the data analysis from CV, MTT and pH. 16S rRNA sequencing data were analyzed for alpha (Shannon index and Chao analysis) and beta diversity (Bray-Curtis dissimilarities). Differences in community composition were evaluated by analysis of similarity (p < .05). The sealers significantly influenced microbial community composition and morphology. All sealers complied with ISO6876:2012 requirements for setting time, radiopacity and flowability. Although only AHP effectively reduced the biofilm biomass, all sealers, except BRR, reduced biofilm metabolic activity. Despite adequate physical properties, none of the sealers tested prevented biofilm growth. Significant changes in community composition were observed. If observed in vivo, these changes could affect intracanal microbial survival, pathogenicity and treatment outcomes.


Influence of bladder management on epididymo-orchitis in patients with spinal cord injury: clean intermittent catheterization is a risk factor for epididymo-orchitis.
Retrospective study, based on cases of spinal cord injury (SCI). To establish hazard ratios for risk of epididymo-orchitis in SCI. South Korea. A total of 140 male patients injured before 1987 were eligible for this investigation and have been followed up on a yearly basis from January 1987 to December 2003. The average age at which the lesion occurred was 24.8 years old (range, 18-53). The average time since SCI was 16.9 years (range, 1-37). A total of 34 lesions (24.3%) were complete and 106 (75.7%) were incomplete. Over the 17 years, 39 patients (27.9%) were diagnosed with epididymo-orchitis. Epididymo-orchitis was more common for patients with a history of urethral stricture (66.7 versus 25.2%, P=0.014). We also found that epididymo-orchitis was more common for patients on clean intermittent catheterization (CIC) than with indwelling urethral catheterization (42.2% versus 8.3%, P=0.030). In multivariate analysis, patients on CIC had a 7.0-fold higher risk (odds ratio, 6.96; 95% confidence interval, 1.26-38.53; P=0.026); however, a history of urethral stricture lost statistical significance (P=0.074). For other variables, no positive association with epididymo-orchitis was observed. In this study, CIC was an independent risk factor for the development of epididymo-orchitis in patients with SCI. In addition, our findings suggest that urethral stricture may be a contributing factor for the development of epididymo-orchitis in these patients. Correct instructions about CIC are of utmost importance.


Expression of HLA-DR molecules in human gestational choriocarcinoma cell lines and malignant cell lines.
In order to determine whether trophoblast (or gestational choriocarcinoma) expresses the HLA-DR antigen or not, it was analysed using human gestational choriocarcinoma cell lines (GCH-1, GCH-1(m) and TAK-N) by the Northern hybridization method. TYK-nu (human undifferentiated ovarian carcinoma cell line), M-14 (human malignant melanoma cell line), L-14 (human B lymphocyte cell line), and KKNS-1, KKNS-2 and KKNS-3 (three human endometrial carcinoma cell lines) were also examined. Messenger ribonucleic acids (mRNAs) were prepared from 2 X 10(7) cells in each cell line and hybridized by HLA-DR alpha-chain complementary deoxyribonucleic acid (cDNA) probe (pDR alpha-1) and beta-chain cDNA probe (DK-10). Northern hybridization analysis revealed that GCH-1 transcribed at least two kinds of alpha-chain (16s and 23s) and beta-chain mRNA (15s and 23s). TYK-nu transcribed alpha- and beta-chain mRNA, L-14 transcribed only alpha-chain mRNA, and TAK-N appeared to transcribe only a little alpha-chain mRNA. The HLA-DR molecules were not, however, expressed in the other cell lines (GCH-1(m), M-14, KKNS-1, -2 and -3). These results are compared with those obtained by immunocytochemical methods in our laboratory.


[The ultrastructure of epithelial and myoepithelial oncocytes in the human parotid gland (author's transl)].
Oncocytes are well known to occur in the tissue of many organs for over 30 years. Their origin and function are less well known. We observed different types of oncocytes in a human parotid gland with the electron microscope. Besides a hyperplasia of mitochondria they show more or less advanced signs of membrane degeneration of these organelles. On the basis of our findings we discuss oncocyte formation as a special form of cellular aging in an otherwise healthy gland.


Effects of hiatal hernia, reflux esophagitis, and glucagon on the quality of double-contrast esophagram.
The possible effect of hiatal hernia, reflux esophagitis, and glucagon on the quality of the double-contrast esophagram was studied in 177 patients. Overall, the quality of the double-contrast esophageal views were judged poor in 46 (26%) patients and good in 131 (74%). No significant improvement in quality was evident in patients receiving glucagon, or in those with hiatal hernia or documented reflux esophagitis. Although the presence of gastroesophageal reflux or the lowering of esophageal sphincter pressure by glucagon would be expected to promote gaseous reflux from the stomach, no improvement in the quality of the double-contrast views of the esophagus was evident in our study.


Ankle-brachial index predicts renal outcomes and all-cause mortality in high cardiovascular risk population: a nationwide prospective cohort study in CORE project.
Low ankle-brachial index (ABI) related ischemic events are common among individuals with chronic kidney disease (CKD). It is also associated with an increased risk of rapid renal function decline. The presence of peripheral artery disease (PAD) with low ABI among patients with high cardiovascular (CV) risk increases limb loss and mortality. To estimate the association between abnormal ABI and renal endpoints and all-cause mortality. A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. The subjects were divided into 3 groups based on ABI at baseline > 1.3, 0.91-1.3, and ≤ 0.9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine and initiation of dialysis. The secondary outcome was all-cause mortality. Cox regression analysis and Kaplan-Meier curve were performed. A total of 5543 subjects (3005 men and 2538 women) were included. Cox proportional hazards model showed a significant relationship of low ABI (ABI ≤ 0.9) and primary composite outcome and all-cause mortality. Compared with the normal ABI group (ABI 0.91-1.3), subjects with low ABI at baseline significantly had 1.42-fold (95% CI 1.02-1.97) and 2.03-fold (95% CI 1.32-3.13) risk for the primary composite outcome and all-cause mortality, respectively, after adjusting for variable factors. Our study suggested that PAD independently predicts the incidence of renal progression and all-cause mortality among Thai patients with high CV risk.


Intracavitary prophylactic treatment with interferon alpha 2b of patients with superficial bladder cancer is associated with a systemic T-cell activation.
The activation and proliferation of peripheral blood mononuclear cells (PBMNCs) are complex processes involving several surface molecules, cell secretion and response to cytokines. This paper investigates the immunomodulatory effect of prophylactic treatment with interferon alpha 2b (IFN-alpha 2b) upon the blastogenic response of PBMNCs from patients with superficial transitional cell carcinoma (STCC) of the bladder to mitogenic signals that interact with surface molecules [phytohaemagglutinin, PHA and anti-CD3 monoclonal antibodies, (MAbs)]. PBMNCs from the patients were studied prior to the transurethral resection (TUR) of the tumour, during the second month of prophylactic intravesical instillation of IFN-alpha 2b and 3 and 6 months after finishing the instillation treatment. The [3H]thymidine uptake of PBMNCs from 17 patients with STCC of the bladder after 5 days of PHA and anti-CD3 MAb stimulus was found to be significantly lower than that of healthy controls (P < 0.05). The addition of interleukin 2 (IL-2) to the culture medium did not correct this defective proliferative response to PHA and the anti-CD3 MAb. There were no significant differences between IL-2 production in PBMNCs from STCC patients after stimulation with PHA and in PBMNCs from healthy controls (P > 0.05). Patients without evidence of recurrence showed a significantly enhanced proliferative response in PBMNC to PHA and anti-CD3 MAb after intravesical prophylactic treatment with interferon-alpha 2b in the follow-up examinations 3 and 6 months after treatment (P < 0.01). However, three patients had evidence of tumour recurrence, and they showed no enhancement of the PBMNC proliferative response to these mitogens in the same examinations. In conclusion, the prophylactic intracavitary treatment of STCC with IFN-alpha 2b may induce a systemic immunomodulatory effect which is associated to the clinical evolution of the disease.


Validation of skin surface microtopography as a measure of skin photoaging in a subtropical population aged 40 and over.
Evidence suggests that skin surface microtopography is a valid measure of photoaging among young adults, but whether this applies to older adults is unknown. We investigated the association between degree of photoaging as measured by histological dermal elastosis and skin microtopography grades by decade of age from 40 to 89 years in a community sample in Australia. Skin surface replicas and punch biopsies were taken from 664 participants of the Nambour Skin Cancer Study. The association was assessed using ordinal logistic regression with proportional odds assumption, using histological dermal elastosis grades as outcome. There was significant increase in odds of higher skin surface microtopography grades with higher dermal elastosis grades for age groups below 70 years [40 to 49 years: odds ratio (OR) 2.96, 95% confidence interval (CI) 1.68-5.22; 50 to 59 years: OR 3.78, 95% CI 2.28-6.26; 60 to 69 years: OR 2.47, 95% CI 1.41-4.35). The association was not significant for those 70 years or older. Skin surface microtopography grading system is a valid measure of degree of dermal elastosis for middle-aged and older adults up to 69 years but appears not to be valid for adults 70 years or more living in a high sun exposure setting.


Non-toxic concentrations of peroxynitrite commit U937 cells to mitochondrial permeability transition-dependent necrosis that is however prevented by endogenous arachidonic acid.
The present study was aimed at examining the mechanism whereby an otherwise non-toxic concentration of peroxynitrite promotes a rapid necrotic response in U937 cells in which cytosolic phospholipase A(2) is pharmacologically inhibited or genetically depleted. We found that loss of viable cells is appreciable 15min after addition of peroxynitrite, does not further increase at 30min and is mediated by mitochondrial permeability transition (MPT). Both MPT and toxicity were prevented by exogenous arachidonic acid (AA). Various experimental approaches produced results consistent with the notion that the AA-dependent protective mechanism takes place 10-15min after addition of peroxynitrite. The observation that the extent of DNA strand scission induced by peroxynitrite did not vary under conditions of different AA availability suggests that this event is either upstream to mitochondrial dysfunction or irrelevant for cytotoxicity. Collectively, these data indicate that a non-toxic concentration of peroxynitrite commits U937 cells to MTP-dependent necrosis that is however prevented by endogenous AA. Thus, mitochondria are a likely target of the cytoprotective signalling triggered by AA.


Pediatric robot-assisted extravesical ureteral reimplantation (revur) in simple and complex ureter anatomy: Report of a multicenter experience.
Robot-assisted extravesical ureteral reimplantation (REVUR) is a well established approach for surgical treatment of pediatric vesicoureteral reflux (VUR). However, further evidence is needed to confirm its efficacy even in case of complex anatomy. This study aimed to further confirm the evidence that REVUR is safe and effective in both simple and complex ureter anatomy. The charts of all patients with VUR, who received REVUR in 6 different institutions over a 5-year period, were retrospectively reviewed. Patients with both simple and complex ureter anatomy were included. Patient demographics, surgical variables, and post-operative results were assessed. VUR resolution was defined as either being resolved VUR on voiding cystourethrogram (VCUG) or clinically without symptoms during the follow-up. Fifty-seven patients with median age of 6.9 years (range 4.5-12), receiving REVUR in the study period, were included. Eighteen (31.6%) patients had complex anatomy and included prior failed endoscopic injection (n = 13), complete ureteral duplication (n = 2), periureteral diverticulum (n = 2), ectopic megaureter requiring dismembering (n = 1). The median operative time was 155 min for unilateral and 211.5 min for bilateral repairs. The clinical + radiographic VUR resolution rate was 96.5%. Post-operative complications (Clavien 2) included urinary retention following bilateral repair (n = 5, 8.7%), febrile urinary tract infection (UTI) (n = 6, 10.5%) and gross hematuria (n = 3, 5.2%). Comparative analysis between simple and complex cases showed that REVUR was faster in simple cases in both unilateral [p = 0.002] and bilateral repair [p = 0.001] and post-operative urinary retention was more frequent in simple cases [p = 0.004] and in patients with pre-operative bowel and bladder dysfunction (BBD) [p = 0.001] (Table). This series confirmed that the robot-assisted technique was feasible even in cases with complex anatomy using some technical refinements, that justified the longer operative times in both unilateral and bilateral cases. An interesting finding of this study was the correlation emerged between BBD and risk of post-operative urinary retention and VUR persistence. Our results also excluded any significant correlation between complex cases and risk of post-operative urinary retention. The main study limitations included the retrospective and nonrandomized design, the small number of cases and the arbitrary definition of complex anatomy. REVUR was safe and effective for management of VUR in both simple and complex ureter anatomy. Complex REVUR required slightly longer operative times, without significant differences in post-operative mordidity and success rates. Aside from complex anatomy, BBD emerged as the main risk factor associated with surgical failure and post-operative morbidity.


Transcobalamin II, a serum protein reflecting autoimmune disease activity, its plasma dynamics, and the relationship to established serum parameters in systemic lupus erythematosus.
Earlier investigations have shown that the activity of autoimmune diseases appears to correlate with increased levels of the vitamin B12 (cobalamin)-binding serum protein, transcobalamin II (M. Fráter-Schröder et al., Schweìz. Med. Wochensch 110, 1441, 1980; M. Fráter-Schröde et al., Lancet 2, 238, 1978). These preliminary findings were confirmed and extended with regard to SLE in the present prospective study. The correlation of serum levels with the degree of disease activity (determined by clinical scoring of 44 patients with systemic lupus erythematosus (SLE), fulfilling four or more of the American Rheumatoid Association criteria) was shown to be most reliable for transcobalamin II (P less than 0.001), when compared to other serological parameters. An answer to the question "what induces increased levels of transcobalamin II in active SLE?" was sought by injecting 15 SLE patients with cyanocobalamin which influences plasma dynamics of transcobalamin II. Results indicate that transcobalamin II-cobalamin "clearance" is probably unchanged in SLE, and that increased production or stimulation of transcobalamin II secretion may be the cause of elevated plasma levels in active SLE.


Syntheses of 2-[(3,5-dimethyl-4-methoxypyridyl)alkyl]-benzothiazolidine derivatives as a potential gastric H+/K(+)-ATPase inhibitor.
A series of 2-[(3,5-dimethyl-4-methoxypyridyl)alkyl]benzothiazolidine derivatives were synthesized and tested their inhibitory effects on gastric H+/K(+)-ATPase. Compound 4d exhibited potent in vitro inhibitory activity.


Reason for Indispensability of Threonine in Humans and Other Mammals in Comparative Aspect.
The essential amino acid threonine is not synthesized in vertebrates, so it must be obtained from food. During evolution, the decomposition of threonine has changed. Because the decomposition of threonine catalyzed by threonine dehydratase is irreversible, in the present work attention is focused on threonine dehydrogenase to show the inability of this enzyme to synthesize threonine in a reaction that would be the reverse of the reaction of threonine decomposition. The reason why threonine dehydrogenase cannot be used for the biosynthesis of threonine in mammalian tissues is discussed. It is concluded that some quantity of threonine is involved in transamination.


Effects of heavy metals on bacterial community structures in two lead-zinc tailings situated in northwestern China.
We evaluated the variations of bacterial communities in six heavy metal contaminated soils sampled from Yanzi Bian (YZB) and Shanping Cun (SPC) tailings located in northwestern China. Statistical analysis showed that both the heavy metals and soil chemical properties could affect the structure and diversity of the bacterial communities in the tailing soils. Cd, Cu, Zn, Cr, Pb, pH, SOM (soil organic matters), TP (total phosphorus) and TN (total nitrogen) were the main driving factors of the bacterial community variations. As a consequence, the relative abundances of certain bacterial phyla including Proteobacteria, Chloroflexi, Firmicutes, Nitrospirota and Bacteroidota were significantly increased in the tailing soils. Further, we found that the abundance increasement of these phyla were mainly contributed by certain species, such as s__unclassified_g__Thiobacillus (Proteobacteria), s__unclassified_g__Sulfobacillus (Firmicutes) and Leptospirillum ferriphilum (Nitrospirota). Thus, these species were considered to be strongly heavy metal tolerant. Together, our findings will provide a useful insight for further bioremediations of these contaminated areas.


Standard metabolic rates of Lepisma saccharina and Thermobia domestica: effects of temperature and mass.
Silverfish, Lepisma saccharina L., and firebrats, Thermobia domestica (Packard), are two common thysanuran pests in the urban environment. Both species can survive for extended periods without feeding, suggesting that they have some metabolic modifications compared with other insects which cannot tolerate extended starvation. To investigate potential metabolic modifications and to compare silverfish and firebrats, we measured the standard metabolic rate of both species at five temperatures (10, 20, 25, 30, 40°C) across a range of body masses using closed system respirometry. Temperature had a stronger effect on firebrat mass specific [Formula: see text] (mlg(-1)h(-1)) than on silverfish mass specific [Formula: see text] for adults (>0.00700g: firebrat Q10=2.32, silverfish Q10=2.07) and immatures (<0.00700g: firebrat Q10=2.86, silverfish Q10=2.57). In addition, temperature had a stronger effect on the mass specific [Formula: see text] of immatures than adults for both firebrats and silverfish. Respiratory quotients showed complex relationships with temperature from 10 to 40°C, indicating a change in metabolic substrate with temperature. These results are interpreted with respect to the life histories and environment of both species. Finally, metabolic rates are compared with those of ticks and other arthropods.


[Fixation of the forearm in a neutral position in the treatment of Monteggia's fracture in adults--a report of 77 cases].
Close reduction and fixation neutral position were used for the treatment of 77 cases of fresh adults Monteggia's fracture during 1974-1985. The methods used were extreme flexion plaster fixation to extension fracture, extension plaster fixation to flexion fractures and then change into splint fixation after 2-3 weeks. 77 cases were followed up with an average of 2.5 years and satisfactory results were obtained in 72 cases (93.5%). This article points out the clinical types, the diagnosis and the treatment of manipulation.


Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis.
We examined if empagliflozin was associated with modulation of cardiac autonomic tone among subjects with type 2 diabetes and stable coronary artery disease (CAD) relative to placebo. Using ambulatory 24-h Holter electrocardiographic data prospectively collected from a randomized trial, we compared changes in heart rate variability (HRV) parameters between empagliflozin- and placebo-assigned subjects over a follow-up period of 6 months. Measured HRV domains included: standard deviation (SD) of NN intervals (SDNN), SD of average NN intervals per 5-min (SDANN), root mean square of successive RR interval differences (RMSSD), % successive NN intervals differing >50 ms (ms) (pNN50), low frequency (LF), high frequency (HF) and the LF/HF ratio (LF:HF). Differences in HRV parameters between the 2 groups were compared with analysis of covariance (ANCOVA). Statistical measures of significance were reported as adjusted differences between the 2 groups and their corresponding 95% confidence intervals. Sixty-six subjects completed 24-h Holter monitoring at baseline and 6-months. Over 6 months, the change in HRV was similar between subjects treated with empagliflozin vs. placebo for the following parameters: RMSSD -1.2 ms (-6.0 to 3.6 ms); pNN50 0.5% (-2.6 to 3.6%); VLF -907.8 ms2 (-2388.8 to 573.1 ms2); LF -341 ms2 (-878.7 to 196.7 ms2); HF -33.8 ms2 (-111.1 to 43.5 ms2); LF:HF -0.1 (-0.4 to 0.2). Subjects who received placebo experienced an increase in SDNN 18.6 ms (2.8-34.3 ms) and SDANN 20.2 ms (3.2-37.3 ms) relative to those treated with empagliflozin. Compared to placebo, empagliflozin did not result in changes in autonomic tone among individuals with type 2 diabetes and stable coronary artery disease.


Synthesis of phosphonic analogs of enkephalins. Pentapeptides with COOH replaced by PO3H2 group.
Eight analogs of enkephalins containing the phosphonic analogs of Gly, Leu, Met, Phe and Pro have been synthesized by standard procedures in solution. The key intermediates in the synthesis were pure diastereomers of dialkyl N-L-phenylalanyl/aminoalkanephosphonates obtained from racemic dialkyl aminoalkanephosphonates by coupling with phenylalanine and resolution of the resulting mixture of L, D and L, L dipeptides by means of column chromatography.


Strategies to evade false positives in the in situ analysis of peptide antibiotics in SDS-PAGE gels.
In situ activity assay is one of the promising techniques for the characterization of peptide antibiotics. This assay was carried out for the peptide purified from a new bacterial isolate Paenibacillus alvei and commercial peptide antibiotic polymixin E. Towards this, the routine and new protocols were tried. Interestingly, the unexpected result of these experiments - the "switch over activity" has led us to have further investigations. Here, we have addressed the potential problem in the methodology of in situ assay and demonstrated a fool proof protocol to evade the false positive results.


Improving transfusion safety: implementation of a comprehensive computerized bar code-based tracking system for detecting and preventing errors.
To transfuse blood products safely, health care workers must accurately identify patients, blood samples, and the blood components. A comprehensive bar code-based computerized tracking system was developed and implemented to identify and prevent transfusion errors. A data network, wireless devices, and bar-coded labels were pilot tested before the system was introduced hospitalwide. The system provided a complete audit trail for all transactions. Data from before and after implementation were analyzed. Incident reports decreased from a mean of 41.5 reports per month in the 6 months before the system was implemented to a mean of 7.2 reports per month after implementation. The blood sample rejection rate decreased from 1.82 percent to a mean of 0.17 percent after implementation. Errors detected by the new system were sorted into misscans, skipped steps, wrong steps, and prevented identification errors (PIEs). Misscans and skipped steps were the most common errors in the first 10 months after implementation. During the final transfusion step, PIEs occurred at the rate of about one per month and scans were omitted approximately 1 percent of the time. Therefore, it is estimated that mistransfusions could occur about once every 100 months on average with the new system. The bar code-based computerized tracking system detected and prevented identification and matching errors, thereby reducing the proportion of blood samples rejected and increasing patient safety.


[Alkaloid constituents from silkworm dropping of Bombyx mori].
To extract and isolate chemical constituents from the total alkaloids of silkworm dropping (Can Sha) of Bombyx mori L. Chemical constituents were isolated by column chromatography with macroporous adsorbent resin, ion-exchange resin and sephadex LH 20. The structures of the isolated compounds were determined by spectral means. Three compounds were isolated and identified as 1-deoxynojirimycin (1) , fagomine (2) , and 3-epifagomine (3) on the basis of their 1H-NMR, 13C-NMR spectra and ESIMS data. Compounds 1-3 are isolated and identified from Can Sha for the first time.


Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.
The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14 days later, either CDDP or carboplatin was administered i.c. by CED, followed 24 h later by radiotherapy using either a synchrotron or, subsequently, megavoltage linear accelerators (LINAC). CDDP was administered at a dose of 3 µg in 5 µL, followed 24 h later with an irradiation dose of 15 Gy or carboplatin at a dose of 20 µg in 10 µL, followed 24 h later with 3 fractions of 8 Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180 days with 33% long term survivors (LTS) for CDDP and a MeST > 60 days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72 µg of carboplatin administered by means of Alzet® osmotic pumps over 7 days. This resulted in a MeST of > 180 days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promising survival data ever reported using the F98 glioma model.


Rapid and sensitive detection of E. coli O157:H7 by lateral flow immunoassay and silver enhancement.
The aim of this study was to develop a sensitive lateral flow immunoassay (LFIA) for the rapid detection of Escherichia coli (E. coli) O157:H7, a pathogen contributor to diseases and fatalities worldwide. Au nanoparticles with high stability, uniform size, and shape were synthesized and coated with heterobifunctional PEG polymer with carboxyl groups, and they were bioconjugated to be used as label in sandwich-LFIA. Then, a silver enhancement strategy was developed as an accessible, rapid, and cost-effective approach for signal amplification to reduce the limit of detection (LOD). The optimal results were achieved when a solution of silver nitrate and hydroquinone/citrate buffer was added to the strips for 4 min. This led to a decrease in the visual LOD from 2 × 106 (CFU mL-1) to 2 × 103 (CFU mL-1), resulting in a threefold improvement in sensitivity compared to the conventional LFIA system. The specificity of the system was evaluated by using non-target bacteria (E. coli BL21 and E. coli T515) and its reliability was determined by testing commercial food samples (milk, tap water, and orange juice), demonstrating its effectiveness for quickly detecting pathogenic bacteria in food products.


Experimental intraperitoneal injection of alcohol in rats: Peritoneal findings and histopathology.
This study aimed to evaluate the macroscopic and microscopic peritoneal findings after intraperitoneal injection of alcohol in rats. From January to February 2012, 20 male rats were used in this study: 15 rats received intraperitoneal injection of 0.1 mL 99.9% alcohol (group 1: experiment group) and 5 rats received intraperitoneal injection of 0.1 mL normal saline (group 2: control group). Animals from each group were sacrificed the day after alcohol injection and each week thereafter. Macroscopic and microscopic examinations of the peritonea and abdominal cavity were performed in each rat. There was no significant peritoneal abnormality on macroscopic view, except for a whitish-colored parietal peritoneum around the injection site in 3 animals from group 1. In all but 1 of the animals in group 1, mild to moderate peritoneal inflammation or fibrosis was observed 1 and 2 weeks after alcohol injection. However, the peritoneal abnormality of alcohol injection had dissipated by week 3. Peritoneal abnormalities were not observed in group 2. An intraperitoneal injection of alcohol in rats caused peritoneal inflammation or fibrosis during the first 2 weeks. However, these peritoneal abnormalities were short-lived and had completely disappeared after 3 weeks.


The improvement of hypoxia correlates with neuroanatomic and developmental outcomes: comparison of midterm outcomes in infants with transposition of the great arteries or single-ventricle physiology.
We performed a prospective longitudinal study of the neuroanatomic and developmental changes in infants with transposition of the great arteries (TGA) or single-ventricle (SV) physiology to identify variables in anatomic development of the brain associated with functional impairment. Thirty-three infants with congenital heart defects, 23 with SV and 10 with TGA, were studied at around 1 year old (time 1) and 3 years old (time 2) by magnetic resonance imaging of the brain. Neurodevelomental assessment was performed at the same time. The whole and frontal lobe volumes were significantly reduced in both groups at time 1 compared with normal control subjects (P < .01). However, by time 2 whole and frontal brain volumes were normal in the TGA group but remained significantly smaller (P < .01) in the SV group. In agreement with these findings, the mental development index (MDI) was lower (P < .05) at time 1 in both groups but improved to normal levels at time 2 in the TGA group. In the SV group, both MDI and the psychomotor development index (PDI) were significantly decreased at both time 1 and time 2 (P < .01). These patients continued to experience hypoxia, and multivariate analysis revealed that functional oxygen saturation was significantly associated with PDI. Further, the PDI score correlated with whole and regional brain volumes (P < .05). Neuroanatomic and developmental outcomes improve progressively in infants with TGA, unlike those with SV physiology. Impaired cerebral circulation and hypoxia may have significant effects on brain growth and development in infants with critical congenital heart disease.


[Status of extracellular matrix and adhesion markers in urothelial cancer of the urinary bladder].
39 cases of transitory cell (15 cases of well differentiated, 12-moderately and 12- poorly differentiated) urothelial bladder carcinoma were studied immunohistochemically. Expression of adhesion molecules, collagen, laminin and tenascsin was investigated. Their role in a decrease of a differentiation degree of urothelial carcinoma was revealed. The possibility of the above markers use for individual prognosis is demonstrated.


[Marginal leakage in composite resin restorations in posterior teeth. Effect of material, cavity preparation and enamel conditioning at the cervical level].
The purpose of this "in vitro" study was to investigate the cervical marginal leakage in class II restorations with chemically cured resin (P10) and light-cured resin (P30) in two types of cavities: conventional and adhesive. The effect of acid-etching in this area was also observed. Dentine adhesive Scotchbond was used in all experimental groups. Leakage was evidenced by Rodamina B dye penetration after thermocycling procedure between 10 degrees C and 50 degrees C temperature and analysed by using Zeiss Stereoscopic Magnifying Glass (10 X). According to the results obtained marginal leakage occurred in all experimental groups, with lower percentage for adhesives cavities when enamel acid-etching and light-cured resin P30 was used.


Nemaline myopathy: histological, histochemical and ultrastructural studies.
Histological, histochemical and ultrastructural studies were performed on muscle biopsies from three siblings with congenital nemaline myopathy. Histological studies revealed type I fibre atrophy and type II fibre paucity. Ultrastructural studies of intramuscular nerves showed that the axonal diameters were very narrow compared with the width of myelin lamellae. Granular or membranous osmiophilic material occurred in the adaxonal Schwann cell cytoplasm and had a periodicity of 33--38 A. The neuromuscular junctions showed degenerative features such as glycogen granules or myelin figures in 27.1% of total terminal axons. The secondary synaptic clefts were markedly decreased in number and short in length. Myotendinous junction-like structures were found in 5.5% of the muscle fibres near the neuromuscular junctions, and often near sites of fibre-splitting. Rods in nemaline myopathy might be caused as a result of longitudinal splitting and disruption of fibres due to deficient regeneration of the muscle fibres associated with neurotrophic abnormalities.


Net photosynthesis and transpiration of Pinus montana on east and north facing slopes at alpine timberline.
Potted Pinus montana seedlings, age 4 years, transplanted on adjacent east and north facing slopes 25 m apart at alpine timberline (2,020 m a.s.l.) were measured for net photosynthesis and transpiration under ambient conditions using climatised Koch-Siemens cuvettes. Concurrent recordings were made of air temperature, atmospheric water vapour pressure deficit and illuminance at each site.On a typical summers day the northern aspect averaged 9% less light, 1.8°C cooler air temperatures and 25% lower v.p.d. levels than the eastern aspect. The order of these differences was found to increase in the autumn. Net photosynthetic rates of seedlings on the northern aspect were on average 28% lower than the rates of seedlings on the warmer eastern aspect. Differences in transpiration rates were even greater with north slope seedlings averaging rates 42% lower than east slope seedlings.Maximum CO2 uptake rate per hour of east slope seedlings was 3.2 mg CO2 g-1 d.w.h-1 but average rates when light was not limiting were around 2.0 mg CO2 g-1 d.w.h-1. Corresponding values for the north slope seedlings were 3.0 mg CO2 and 1.8 mg CO2 g-1 d.w.h.-1 respectively.Light intensities below 10 klx, when photosynthesis was strongly limited by light, totalled 48% of available daylight hours on the east slope and more than 50% on the north slope.Net photosynthesis was largely unaffected by air temperature between 10°C and the recorded maximum at either site (24°C east, 20°C north) and there was no apparent response to v.p.d. at levels up to 10 mbar. However the consistently higher net photosynthesis of east slope seedlings under all combinations of weather conditions indicated a possible acclimatisation of seedlings at each site.


The cis-acting 3'-element of rubella virus RNA has DNA promoter activity.
The 3'-terminal region of the rubella virus (RV) positive-strand RNA, referred to here as the cis-acting element (CAE), is implicated in the initiation of negative-strand RNA synthesis. Sequence analysis of the 3'-CAE shows that there is a putative TATA box which is surrounded by G + C-rich sequences. To determine whether this element, in a DNA form, has the capability to initiate transcription, a 3'-end 165-bp NarI-EcoRI fragment from the RV cDNA was cloned upstream from a cat reporter gene. The level of CAT activity was dependent on the presence of the 3'-CAE and the SV40 enhancer. Primer extension analysis of the CAT mRNA showed that the transcription start point is in the RV 3'-CAE, 34 bp downstream from the putative TATA box. DNA-gel shift analysis revealed that three nucleoprotein-specific complexes were formed with the 3'-CAE and the binding sites for these proteins were between bp -64 to -108. The possible promoter function of the RV 3'-CAE is discussed in context to RV persistence.


Recurrent seizures in tramadol intoxication: implications for therapy based on 100 patients.
Tramadol is an atypical opioid analgesic used in the treatment of mild to moderate pain. Despite being a GABA(A) agonist, seizures are a prominent complication with its therapeutic use, abuse or overdose. For patients who have had a tramadol-induced seizure, the likelihood of recurrent seizures and the need for emergent anticonvulsant prophylaxis is unknown. However, treatment of patients with anticonvulsants prophylactically may cause adverse effects and increased morbidity in tramadol poisoning. We studied the outcome and frequency of recurrent seizures in tramadol-intoxicated patients in an attempt to determine the need for prophylactic anticonvulsant therapy. This was a retrospective cohort study of tramadol-intoxicated patients who had at least one seizure. Patients' age, sex, cause(s) of intoxication, route of poisoning, dose or number of capsules or tablets taken, vital signs, other signs or symptoms, numbers of seizures, length of stay, co-ingestions and past medical history were ascertained. Exactly 100 patients met the inclusion criteria. Eighty-two per cent were men, and 50% were between 21 and 30 years old. By our standard clinical protocol, none were treated with seizure prophylaxis after their first seizure. Only 7% had recurrent seizures and all patients recovered without sequelae. Because of the low risk of multiple seizures in tramadol poisoning and the lack of morbidity in patients who do seize, it appears to be unnecessary to administer prophylactic anticonvulsant therapy in patients with tramadol poisoning, even if they have an initial seizure.


Mutation detection for exons 2 to 10 of the polycystic kidney disease 1 (PKD1)-gene by DGGE.
The PKD1-gene encodes a 14 kb transcript spanning a 50 kb genomic interval. Two-thirds of the gene is reiterated at another locus on the same chromosome. Using Long Range PCR with primers in intron 1 and exon 11, 6.8 kb PKD1 specific fragments were generated on genomic DNA. These products were used as templates for nested PCR's to screen exons 2-10 by Denaturing Gradient Gel Electrophoresis (DGGE). Upon analysis of 36 patients, a total of 11 different sequence variants were observed: A nonsense mutation in exon 2, a frameshift mutation in exon 8 and furthermore, two amino acid changes, two silent polymorphisms and five intronic variants.


Hormonal daily variation co-varies with immunity in captive male bullfrogs (Lithobates catesbeianus).
Almost all physiological processes within the organism, including immune parameters and hormones, follow a circadian rhythm. These daily fluctuations are often observed in free-living organisms; however, little is known regarding hormonal and immune daily variations in anurans, particularly under laboratory conditions. This study aimed to investigate the hormonal and immune daily variation in captive-bred Bullfrogs (Lithobates catesbeianus) under constant conditions (21 °C and 12:12 LD cycle). Our results showed a daily variation for plasma corticosterone (CORT), testosterone (T), and melatonin (MEL), as well as for blood leukocyte profile, phagocytic activity, and plasma bacterial killing ability (BKA). Hormonal profile and immune activity were higher at the dark when compared with the light phase; however, monocytes and lymphocytes followed the opposite pattern. Moreover, CORT was positively correlated with phagocytosis percentage of blood cells, BKA, and monocytes, while MEL and T showed a positive correlation with PP. Our results demonstrate the daily covariation of different immune variables and immunomodulatory hormones. These 24 h-day variations and covariation certainly have broad implications and need to be considered for better understanding anuran physiology both in the context of laboratory and field studies.


[The kinetics of hydrolysis of alanine peptide esters and -p-nitroanilides by thermitase, a thermostable serine protease from Thermoactinomyces vulgaris: secondary specificity, influence of temperature and solute].
The kinetic parameters Km and kcat and the resulting proteolytic coefficients kcat/Km for the hydrolysis of blocked alanine peptide esters (X(Ala)nOMe) and -p-nitroanilides (X(Ala)n-pNA) of variable length (n = 1 to 5 alanine residues) by the cationic, microbial serine protease thermitase are determined in order to delineate the number of subsites involved in catalysis. Thermitase has at least five secondary subsites (S1 to S5) being hydrophobic in S1 to S4. Arrhenius plots for both, esterase and amidase activity were biphasic with a break at 30 degrees C, followed by a downward bend. The influence of dimethylformamide, solute for many substrates, on the thermitase-catalyzed esterolysis of Z(Ala)2OMe was also investigated. In contrast to the kcat values being unaffected by 5 to 30% dimethylformamide, the Km values increased logarithmically with enhancing its concentration.


Epidermoid cyst of anterior fontanelle with clear contents.
Epidermal inclusion cysts very rarely occur in the midline in the area of the anterior fontanelle. We report the second case of epidermal inclusion cysts in the midline in the area of the anterior fontanelle in world literature of a 7-month female infant who presented with a slow-growing soft mass located in the midline over the vertex of the head. These lesions with clear contents can have all the features of encephalocele on clinical examination, and imaging will show the exact location, but histopathology will confirm the diagnosis.


The power of social media.
Nicky Mansell, one of the recent graduate representatives on BVA Council, looks at some of the pros and cons of social media.


The first record of the invasive mosquito species Aedes albopictus in Chişinӑu, Republic of Moldova, 2020.
In Europe, Aedes albopictus is an important vector of chikungunya virus and Dirofilaria nematodes and has been involved in local autochthonous circulation of dengue and Zika viruses. Due to the ongoing spread, targeted field surveillance at potential points of entry of invasive Aedes mosquitoes was initiated by the Republic of Moldova in 2020 as part of the transboundary "Invasive Aedes Mosquitoes COST-Action project." In 2020, ovitraps were positioned at each of three locations: the border crossing to Romania in Leuşeni (Hancesti region), Chişinӑu International Airport and Chişinӑu Botanical Garden. A total of 188 Aedes spp. eggs were collected at the Chişinӑu International Airport between August and September 2020. Twenty-three adults reared in the laboratory were identified morphologically as Ae. albopictus (Skuse, 1895), and 12 selected specimens were confirmed by molecular barcoding of the cytochrome oxidase subunit I gene region. In addition, one adult Ae. albopictus female at the same site was caught with a manual aspirator. This is the first documented report of Ae. albopictus in the Republic of Moldova. The presence of immature and adult stages indicates the local reproduction of the species in the country. Therefore, it is crucial to extend and strengthen surveillance of the invasive Aedes mosquitoes to prevent Ae. albopictus and other exotic mosquito species from becoming established in the Republic of Moldova.


Epidemiological impact of the human papillomavirus vaccination program on genital warts in Portugal: A retrospective, chart review study.
The quadrivalent human papillomavirus (HPV) vaccine was introduced in the Portuguese National Immunization Program in October 2008, targeting 13-year-old girls. This study aimed at evaluating the impact of HPV vaccination on the epidemiology of genital warts (GWs) in Portugal. Observational, retrospective chart review study conducted at two free-of-charge walk-in sexually transmitted diseases (STD) clinics in Lisbon region. The medical records of all patients attending a first STD consultation at the study centers between May 2006 and December 2017 (observation period) were reviewed. The number of patients diagnosed with GWs and/or chlamydial infection at each year was documented and used to determine yearly prevalence of both conditions throughout the observation period. We broke down the observation period into pre-vaccination (May 2006 to December 2008) and vaccination (January 2009 to December 2017) periods. Most patients were male (69.5%) and aged ≥ 25 years (78.1%). The majority of male patients were men who have sex with women (62.0%). Marked decreases in the prevalence of GWs between the last year of the pre-vaccination period (2008) and the last year of the observation period (2017) were found for female patients aged ≤ 19 and 20-24 years (86.8% and 77.4%, respectively). Lower decreases were observed for male patients of the same age groups (38.5% and 19.3%, respectively). GWs prevalence increased among patients ≥ 25 years (9.7% and 14.7% among female and male patients, respectively). Overall prevalence of chlamydial infection increased by 75.9% between 2008 and 2017. This study contributes to the body of evidence showing that public HPV vaccination programs are effective in reducing the prevalence of GWs among vaccine-eligible patients. HPV vaccination program may significantly reduce the burden associated with GWs in Portugal.


Excited state electric dipole moment of nile blue and brilliant cresyl blue: a comparative study.
A solvatochromic study on the photophysical properties of two cationic oxazine dyes (brilliant cresyl blue and nile blue) was carried out. The electronic absorption and emission spectra of the dyes were recorded in various organic solvents with different polarity. The ground and the excited state dipole moments of the dyes were estimated from solvatochromic shift method. The solvent dependent spectral shifts in absorption and fluorescence spectra were analyzed by the Katritzky and Kamlet-Taft multi-parameter scales. This work is characterized by detailed quantitative studies on the nature and extent of solvent-solute interactions.


Benzalkonium chloride antagonises aminoglycoside antibiotics and promotes evolution of resistance.
Biocide disinfectants are essential tools in infection control, but their use can inadvertently contribute to emergence of antibiotic-resistant bacteria. In this study we systematically examine the effect of the biocide benzalkonium chloride, which is primarily used for surface disinfection but is also present as a preservative in many consumer products, on the activity of aminoglycoside antibiotics in Acinetobacter baumannii. The effect of subinhibitory BAC on aminoglycoside treatment of A. baumannii ATCC17978 was investigated using time-to-kill assays, MIC determination, directed evolution experiments, fluctuation tests and labelled gentamicin accumulation assays. Further MIC determinations and directed evolution experiments were performed with additional Gram-negative ESKAPE pathogens. In A. baumannii ATCC17978, BAC prevents gentamicin killing and drastically increases the frequency at which resistant mutants emerge, through reducing intracellular antibiotic accumulation. BAC also increases the MIC of multiple aminoglycoside antibiotics (kanamycin, tobramycin, streptomycin, gentamicin and amikacin). BAC promotes the emergence of mutants with reduced gentamicin susceptibility in other Gram-negative ESKAPE pathogens but does not always alter the MIC. These effects occur at BAC concentrations which are similar to residual levels in high-use environments, and just below the concentration range for BAC when used as a preservative in eye drops and ear drops. Our results suggest that subinhibitory BAC has the potential to antagonise aminoglycoside activity and promote the emergence of bacterial mutants with reduced susceptibility. We suggest that the extremely widespread use of BAC in clinical and home settings and its long half-life mean there is potential for these interactions to occur in the environment, or in patients who use BAC-containing products while taking aminoglycosides to treat skin, eye or ear infections, although such co-exposure is likely to be rare. We suggest that biocide stewardship is needed to prevent the types of exposure that can contribute to antibiotic resistance. This work was funded by the National Health and Medical Research Council of Australia. The funders had no role in study design, interpretation or decision to publish.


Convergent cross-species pro-cognitive effects of RGH-235, a new potent and selective histamine H3 receptor antagonist/inverse agonist.
The histamine H3 receptor is a favourable target for the treatment of cognitive deficits. Here we report the in vitro and in vivo profile of RGH-235, a new potent, selective, and orally active H3 receptor antagonist/inverse agonist developed by Gedeon Richter Plc. Radioligand binding and functional assays were used for in vitro profiling. Procognitive efficacy was investigated in rodent cognitive tests, in models of attention deficit hyperactive disorder (ADHD) and in cognitive tests of high translational value (rat touch screen visual discrimination test, primate fixed-foreperiod visual reaction time task). Results were supported by pharmacokinetic studies, neurotransmitter release, sleep EEG and dipsogenia. RGH-235 displayed high affinity to H3 receptors (Ki = 3.0-9.2 nM, depending on species), without affinity to H1, H2 or H4 receptors and >100 other targets. RGH-235 was an inverse agonist ([35S] GTPγS binding) and antagonist (pERK1/2 ELISA), showing favourable kinetics, inhibition of the imetit-induced dipsogenia and moderate effects on sleep-wake EEG. RGH-235 stimulated neurotransmitter release both in vitro and in vivo. RGH-235 was active in spontaneously hypertensive rats (SHR), generally considered as a model of ADHD, and revealed a robust pro-cognitive profile both in rodent and primate tests (in 0.3-1 mg/kg) and in models of high translational value (e.g. in a rodent touch screen test and in non-human primates). The multiple and convergent procognitive effects of RGH-235 support the view that beneficial cognitive effects can be linked to antagonism/inverse agonism of H3 receptors.


Therapeutic Efficacy of Mandibular Advancement Devices in Patients with Severe Sleep Apnea: A Preliminary Report.
Obstructive sleep apnea (OSA) is defined as episodes of upper airway obstructions during sleep. The method of choice in conservative treatment of OSA is the use of devices that produce positive airway pressure (CPAP). In patients with mild-moderate form of OSA, intraoral mandibular advancement devices (MAD) are applied. The aim of the study was to evaluate the therapeutic efficacy of MAD in patients with severe OSA who were unable to use CPAP. In this preliminary study three patients from a group of 25 severe OSA sufferers who failed to use CPAP, were included. The three patients underwent a triple polysomnographic (PSG) investigation: on CPAP, before MAD treatment, and during MAD. The patients completed the Epworth Sleepiness Scale questionnaire twice. We found significant improvements of subjective symptoms and PSG-evaluated variables after application of MAD in all three patients in comparison with both baseline and CPAP-recorded data. We conclude that MAD can be an alternative treatment option for severe OSA patients who are non-compliant with CPAP therapy.


First report of Aliarcobacter cryaerophilus in ready-to-cook chicken meat samples from super shops in Bangladesh.
This study aimed to isolate Aliarcobacter cryaerophilus in ready-to-cook poultry meat in Bangladesh. Thirty drumstick samples were collected from super shops in Dhaka city (n = 10), Mymensingh city (n = 10), and Patuakhali town (n = 10). After sample processing, they were cultured in Blood agar media with Campylobacter base using a microfilter (0.42 nm). Suspected colonies were subjected to DNA extraction and PCR assay targeting 16SrRNA genes. Then, sequencing was performed for confirmation. Of 30 samples, 3 (10%) were positive for A. cryaerophilus. Phylogenetic analysis shows that our isolate has strong similarities with one of the isolates from China. The presence of this organism in ready-to-cook poultry meat is a significant concern for consumers as it bears zoonotic importance.


A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model.
Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. ClinicalTrials.gov NCT02522832.


Study of an asymmetric ESR signal in x-irradiated human tooth enamel.
An asymmetric ESR signal and an outer doublet signal centered at g = 2.00 produced in human tooth enamel by X-irradiation have been studied over a temperature range from liquid helium temperature to 380 degrees K. The line shape of the asymmetric signal for an enamel crystallite is Lorentzian at room temperature. The temperature dependence of the integrated intensity of the asymmetric signal suggests that the signal follows a singlet-triplet model with the exchange interaction of 0.022 eV. Below about 60 degrees K the asymmetric signal becomes broad as the temperature is decreased. The ENDOR line of the asymmetric signal shows that there exists interaction between the centers and protons. The temperature dependence of the integrated intensity of the double signal is analogous to that of the asymmetric signal.


[Square-wave polarographic determination of heavy metals in vegetables with special regard to cadmium].
The cadmium contents of 104 foods mostly of vegetable origin (market samples from a highly industrialized area in the GDR) were determined by means of square-wave polarography. The values obtained are in good agreement with literature data about the cadmium contents of foods, and they are not indicative of an increased contamination of the products under investigation compared to other industrialized countries.


First Trimester Mean Arterial Pressure Measured Manually Versus Using an Automated Device and the Prediction of Preeclampsia: A Case-Cohort Study.
First trimester mean arterial blood pressure (MAP) can be used to predict preeclampsia. This study aimed to compare the performance of first trimester MAP measured with an automated device using a standardized technique versus MAP taken manually in a typical clinical setting. A case-cohort study niched into a prospective cohort of pregnant women recruited at 11-14 weeks was performed. MAP was measured with an automated device on both arms until stability was reached. These results were compared with the MAP measured with a manual device at the closest medical visit (between 10 and 15 weeks gestation) and noted in the medical charts. Receiver-operator characteristics curve analyses were used to estimate the predictive values of MAP measured by both techniques. Forty-one women with preeclampsia and 167 control patients were used for the comparisons. MAP measured with an automated device decreased significantly between 11 and 14 weeks gestation (P < 0.001). Moreover, MAP measured with an automated device was a better predictor of preeclampsia (area under the curve 0.70; 95% confidence interval 0.61-0.79) than MAP measured with a manual device in a clinical setting (area under the curve 0.60; 95% confidence interval 0.50-0.70). Taken alone, MAP measured with an automated device was associated with a detection rate of preeclampsia of 34%, for a false-positive rate of 10%. First trimester MAP can predict preeclampsia. This study demonstrated that MAP measured with an automated device using a standardized technique is a better predictor than MAP measured with a manual device.


Association of immune-related pneumonitis with the presence of preexisting interstitial lung disease in patients with non-small lung cancer receiving anti-programmed cell death 1 antibody.
The safety of anti-programmed cell death 1 (PD-1) antibody for patients with preexisting interstitial lung disease (ILD) remains unknown. The aim of this study was to evaluate the dependence of preexisting ILD on anti-PD-1 antibody-induced pneumonitis in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the association of preexisting ILD with the incidence, radiographic pattern, and outcome of pneumonitis in NSCLC patients receiving anti-PD-1 antibody. A total of 331 patients were included in this study. Of these patients, 17 had preexisting ILD. The incidence of pneumonitis was higher among the patients with preexisting ILD than among those without preexisting ILD (29% vs. 10%, P = 0.027). The distributions of the CT appearances at the onset of anti-PD-1 antibody-induced pneumonitis were as follows: for the patients with preexisting ILD, two patients (40%) had diffuse alveolar damage (DAD), one patient each with organizing pneumonia-like (OP), hypersensitivity pneumonitis (HP), and other patterns (20% each); for the patients without preexisting ILD, 19 patients (61%) had OP, 8 (26%) had HP, 3 (10%) had DAD, and 1 (3.2%) had other patterns. The median onset time from the initiation of anti-PD-1 antibody treatment until the development of pneumonitis was 1.3 months (range 0.3-2.1 months) for the patients with preexisting ILD and 2.3 months (range 0.2-14.6 months) for the patients without preexisting ILD. Careful attention to the development of pneumonitis is needed, especially within the first 3 months after the start of anti-PD-1 antibody treatment, when using anti-PD-1 antibody to treat patients with preexisting ILD.


Cytomorphological study of soft tissue neoplasms: role of fluorescent immunocytochemistry in diagnosis.
Exact categorization of soft tissue tumours (STTs) on smears requires application of various ancillary techniques. This study was aimed at evaluating the role of fluorescent immunocytochemistry (FICC) in cyto-diagnosis of 30 STT cases. Thirty cases of soft tissue tumours were included in the present study. All cases were subjected to routine Giemsa and Papanicolaou stain. Extra smears were made and kept for fluorescent immunostaining. A panel of cytoskeletal antibodies, tagged with FITC (Fluorescein isothyocynate), was employed in all these cases. Fluorescent immunostained smears were examined under Zeiss Confocal Laser scanning microscope, using double immunofluorescence (red-green). Finally, all cases were subjected to biopsy and again immunoperoxidase staining. Among the 30 cases in the present study, unaided cytological diagnoses ranged from 'spindle cell' tumour in four (13.3%) cases, benign and malignant spindle cell tumour in 17 (56.6%) cases, to malignant mesenchymal tumour in nine (30%) cases. FICC helped in further correct categorization of 25/30 (83.3%) cases viz. leiomyoma (three), benign neurogenic tumour (six), schwannoma (one), dermatofibrosarcoma protuberans (three), synovial sarcoma (two), rhabdomyosarcoma (two), malignant fibrous histiocytoma (five) and malignant peripheral nerve sheath tumour (three). Aggressive fibromatosis was found to be a missed diagnosis in two cases. Overall concordance between cyto-diagnosis with FICC, and histopathology results was 83.3% (P < 0.05). Fluorescent immunocytochemistry is a significant ancillary technique for making a rapid and specific diagnosis of STT, as required for their timely management. Incorporation of a wide panel of antibody markers with clinico-cytological correlation is recommended in forming an exact diagnosis in these cases.


Quantitative analysis of images in erythropoietin doping control.
The software system GASepo has been developed as a tool to visualise and analyse doping (searching for performance-enhancing drugs in sports) with recombinant erythropoietin (rEpo). Digital images derived from the separation of Epo isoforms in gels by iso-electric focusing followed by double blotting and chemiluminescence detection contain spots (bands) of characteristic shape and positions. For Epo doping control, these have to be analysed and evaluated. A relevant element of the analysis is calculation of the reference cutoff-line (COL) to which the doping positivity criterion is related. Based on analysis of the previous method used, a novel method for the COL calculation was developed and validated. The methodology was based on generation of a partition of the image (lane) being processed into a system of adjacent subimages (blocks) and quantitative characterisation of intensity variability within these blocks by a suitably defined measure. The coordinate of the proper COL position, separating the image part with recombinant Epo bands from the homogeneous background, was calculated by minimisation of the difference function of the measures for two adjacent image blocks. The proposed method was tested on real Epo images and validated on a synthetic phantom of the Epo image. The deviations of the COL position are limited by a 7 pixel-wide corridor. For the cases of noise with standard deviations 2300 and 2600, the deviations did not exceed 2 pixels over the whole range of the lane width values. Testing the method on 50 real Epo images originating from different doping-control laboratories worldwide showed its robust behaviour in Epo images.


Membrane-bound neuraminidases of rat liver. Neuraminidase activity in Golgi apparatus.
The bulk (60 to 65%) of the neuraminidase activity present in rat liver homogenates was found in the M + L (mitochondria plus lysosomes) fraction, The patterns of subcellular distribution were essentially identical whether disialogangliosides or neuramin-lactose (2 yields 3') were utilized as substrates. A new neuraminidase, which hydrolyzes sialyl trisaccharides but which does not act upon glycoproteins and gangliosides, was detected in Golgi apparatus. Unlike the other particulate neuraminidases of rat liver, the Golgi enzyme is stimulated by prior incubation and by the addition of Ca2+ or Zn2+ at 1 mM concentration. Although plasma membrane-rich fractions are often contaminated by Golgi membranes the marked differences in their enzymic properties allowed a clear distinction between the neuraminidases present in these two types of membranes.


[Effect of serotonin and theophylline on generation of rhythmic activity in the buccal ganglia of gastropod mollusks].
Effect of serotonin on generation of the feeding rhythm in buccal ganglia was studied in 8 species from 3 subclasses of gastropod molluscs. Serotonin (10(-5) mol/l) initiated or increased the rhythmical activity in the buccal ganglia. The effect of serotonin was potentiated with theophylline (phosphodiesterase inhibitor).


Signatures of human regulatory T cells: an encounter with old friends and new players.
Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined. To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (Human TReg Chip) based on whole genome transcription data from human and mouse TReg cells. TReg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in TReg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in TReg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human TReg cell function. The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human TReg cells. The Human TReg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate TReg cells under physiologic and diseased conditions.


Over-expression of the overexpressed in lung cancer 1 is associated with poor prognosis in epithelial ovarian cancer.
The overexpressed in lung cancer 1 (OLC1), a novel tumor associated gene, is upregulated in several carcinomas. The purpose of this study was to determine whether increased expression of OLC1 is associated with epithelial ovarian carcinoma (EOC) that diagnosed in patients. OLC1 expression was assayed in 20 normal ovarian and 139 ovarian cancer's specimens by Western blotting and immunohistochemical staining (IHC). Univariate and multivariate analysis were performed to determine the association between OLC1 expression and prognosis. Western blotting analysis demonstrated that OLC1 was overexpressed in ovarian cancers, and immunohistochemistry results revealed that 63 patients had increased level of OLC1. The 5-year overall survival (OS) rates of patients with high OLC1 expression and low OLC1 expression were 24.8% and 75.2%, respectively (hazard ratio: 21.43, 95% CI: 2.54, 7.12, P < 0.0001). The 5-year progression-free survival (PFS) rates were 30.1% for patients in the high-expression group and 69.9% for patients in the low OLC1 expression group (hazard ratio: 17.04, 95% CI: 0.33, 5.96, P < 0.0001). OLC1 over-expression is an important factor in epithelial ovarian carcinoma prognosis and can be a potential biomarker for ovarian carcinoma.


Probing drug action using in vitro pharmacological profiles.
The history of structure-activity relationships in drug design represents a long search for appropriate descriptors of broad biological action at the molecular level. In this context, recent work showing that in vitro pharmacological profiles can be used as exquisite descriptors of the broad biological effects of compounds represents an important breakthrough. Generalization of the methodology could have important implications for drug discovery and development. It might also provide a novel and insightful way to study systems biology.


Corneal photocoagulation with continuous wave and pulsed holmium: YAG radiation.
In this study, the effectiveness of pulsed and continuous wave (CW) holmium: YAG lasers in coagulating in vitro pig corneas was analyzed. With the CW laser, irradiance and exposure time were varied; irradiance, from 162 to 324 W/cm2 and exposure time, from 200 to 800 ms. With the pulsed laser, number of pulses and radiant exposure were varied; number of pulses per lesion, from 4 to 30 and radiant exposure, from 10 to 25 J/cm2. Laser-induced corneal damage was determined by analyzing histological cross sections of each lesion. Depth and diameter of the lesions were plotted against the varying laser parameters. Light and birefringent photomicrographs of typical lesion histology show that the pulsed laser significantly damaged superficial layers of the cornea and could not achieve the coagulation depths produced by the CW laser. Additional histology demonstrates that minimal surface damage (intrastromal coagulation) occurred when the CW laser beam was delivered with a sapphire-tipped contact probe. The results provide empirical data on the sensitivity of each parameter in producing a range of coagulation end points. In addition, the experimental results describe trends between the parameters of either laser and the extent of coagulation.


Interaction of trichloromethyl free radicals with thymine in a model system: a mass spectrometric study.
In previous studies from our laboratory we found that the CCl4 reactive metabolites produced during enzymatic in vitro or in vivo CCl4 biotransformation covalently bind to DNA. Further, chemically produced.CCl3 produce many adducts of unknown structure with the four DNA bases when the reaction proceeds in model systems. In the present work, we describe our attempt to elucidate by GLC/MS the structures of the adducts resulting when chemically generated.CCl3 interact with thymine. The following reaction products were identified: (i) 5-hydroxymethyl uracil; (ii) thymineglycol; (iii) 5-trichloroethyl uracil (tentative) and (iv) two isomeric 5,6-monochloro monohydroxy adducts of thymine (tentative). Reaction products found do not involve thymine positions directly participating in base-pairing processes. However, alterations in thymine structure reported if they occurred in DNA from livers of CCl4 poisoned animals, might potentially have biological significance that remains to be established.


Monocytic delivery of therapeutic oxygen bubbles for dual-modality treatment of tumor hypoxia.
Photodynamic therapy (PDT) is a powerful technique photochemically tailored for activating apoptosis of malignant cells. Although PDT has shown promise in several clinical applications, malignant cells in hypoxic regions are often resistant to PDT due to the transport limitation of therapeutics and the oxygen-dependent nature of PDT. Herein, we present an innovative strategy for overcoming the limits of PDT in tumor hypoxia using bone marrow-derived monocytes as cellular vehicles for co-transport of oxygen and red light activatable photosensitizer, chlorin e6 (Ce6). Superparamagnetic iron oxide nanoparticle/Ce6/oxygen-loaded polymer bubbles were prepared and internalized into tumortropic monocytes. These functional bubbles were found harmless to cellular hosts without external triggers. Nevertheless, the therapeutic monocytes exhibited a superior performance in inhibiting tumor growth on Tramp-C1 tumor-bearing mice (C57BL/6J) upon the treatments of tumors with high frequency magnetic field and red light laser (660 nm). Histological examinations of the tumor sections confirmed the successful cellular transport of therapeutic payloads to tumor hypoxia and the pronounced antitumor effect elicited by combined hyperthermia/photodynamic therapy along with the additional oxygen supply. This work demonstrates that this oxygen/therapeutic co-delivery via tumortropic monocytes toward tumor hypoxia is promising for improving PDT efficacy.


Occurrence and genomic characterization of ESBL-producing Escherichia coli ST29 strains from swine with abundant virulence genes.
Food-production animals were considered to be a major reservoir of antimicrobial-resistant bacteria and clinically relevant pathogens. The potential of commensal Escherichia coli from pigs as a source of opportunistic pathogens associated with extraintestinal infections in humans needs to be assessed. In this study, 13 E. coli isolates from an intensive pig farm in China were analyzed using whole genome sequencing followed by in-depth in silico analysis. Genomic analysis showed comprehensive antimicrobial resistance profiles, with each isolate carrying between 4 and 22 antimicrobial resistance genes. Although these E. coli isolates were assigned to low-virulence phylogroup A and B1, 31 different virulence genes were detected at least once in the 13 sequenced isolates. Extraintestinal pathogenic E. coli-associated virulence genes, including iss, iha, tsh and iroN, were found in commensal E. coli isolates in this study. Of note, a large number of virulence genes (n = 22) were identified in ESBL-producing E. coli sequence type (ST) 29 isolates. Our study revealed the presence of comprehensive antimicrobial resistance and virulence gene profiles in commensal E. coli isolates of pigs. The emerged ESBL-producing E. coli ST 29 isolates harboring a high abundance of VAGs highlighted that this new clonal linage may pose a threat to public health.


Implications of Error-Prone Long-Read Whole-Genome Shotgun Sequencing on Characterizing Reference Microbiomes.
Long-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length and are therefore particularly relevant for microbiome studies. However, owing to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (∼99%) and completeness (∼99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R = 0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results not only demonstrate the feasibility of characterizing complete microbial genomes and populations from error-prone Nanopore sequencing data but also highlight necessary bioinformatics improvements for future metagenomics tool development.


Is Nonoperative Management of Rectal Cancer Feasible?
During the past decade, the treatment of locally advanced rectal cancer (LARC) has become more complex. Total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathologic complete response, resulting in improved long-term oncological outcomes. The feasibility to implement nonoperative management (NOM) depends on solving current challenges such as how to correctly identify the best candidates for a NOM without compromising oncologic safety. NOM should be part of the treatment discussion of LARC, considering increasing rates of clinical complete response, potential quality of life gains, avoidance of surgical morbidity, and patient preferences.


Monocyte-to-Lymphocyte Ratio as a Predictor of Worse Long-Term Survival after Off-Pump Surgical Revascularization-Initial Report.
Background and objective: Coronary artery disease is one of the leading causes of deaths nowadays and the trends in diagnosis and revascularization are still in plateau despite well-known factors. Simple whole blood count parameters may be used to measure inflammatory reactions that are involved in processes of atherosclerosis progression. The aim of our study was to analyse the association between simply available hematologic indices and long-term mortality following off-pump coronary artery bypass grafting (OPCAB). Material and Methods: The study group comprised 129 consecutive patients (16 females and 113 males, mean age 66 ± 6 years) who underwent surgical revascularization with off-pump technique between January 2014 and September 2019. The mean follow-up was 4.7 +/-1.9 years. A receiver operating characteristics curve was applied to estimate demographical and perioperative parameters including MLR for mortality. Results: Cox regression analysis revealed chronic pulmonary obstructive disease (HR = 2.86, 95%CI 1.05-7.78), MLR (HR = 3.81, 95%CI 1.45-10.06) and right coronary artery blood flow (HR = 1.06, 95%CI 1.00-1.10) as significant factors predicting increased mortality risk. In the presented model, the MLR > 1.44 on 1st postoperative day was a significant predictor of late mortality after the OPCAB procedure (HR = 3.82, 95%CI 1.45-10.06). Conclusions: Pronounced inflammatory reaction after off-pump surgery measured by MLR > 1.44 can be regarded as a worse long-term prognostic factor.


Demographic drivers of Norway rat populations from urban slums in Brazil.
The Norway rat is a globally distributed pest, known for its resilience to eradication and control programs. Efficient population control, especially in urban settings, is dependent on knowledge of rat demography and population ecology. We analyzed the relationship between four demographic outcomes, estimated by live-trapping data, and fine-scale environmental features measured at the capture site. Wounds, a proxy for agonistic interactions, were associated with mature individuals. Areas with environmental features favorable to rats, such as open sewers and unpaved earth, were associated with more mature individuals with a better body condition index. The control measures (environmental stressors) are likely to be disrupting the social structure of rat colonies, increasing the frequency and distribution of agonistic interactions, which were common in both sexes and maturity states. The relationship between the favorable environmental conditions and the demographic markers analyzed indicate possible targets for infestation control through environmental manipulation, and could be incorporated into current pest management programs to achieve long-term success. Our study indicate that urban interventions focused on removal of potential resources for rats could be potential long-term solutions by reducing the carrying capacity of the environment. The online version contains supplementary material available at 10.1007/s11252-020-01075-2.


Contributions of saturable active secretion, passive transcellular, and paracellular diffusion to the overall transport of furosemide across adenocarcinoma (Caco-2) cells.
Furosemide permeation across Caco-2 cells was investigated to determine if previously reported directional differences in transport rates are due to a saturable, energy dependent process. In addition, studies were carried out to determine the route of permeation for this drug. By comparing apical (A) to basolateral (B) and B to A directional transport across Caco-2 cells, a saturable, nonlinear component to furosemide transport was observed. Transport in the secretory direction was fit to yield the following apparent parameters K(m) = 63 +/- 28 microM, V(max) = 436 +/- 137 pmol/cm(2)h, and P(app) = 3.7 +/- 0.9 x 10(-7) cm/s. Evidence of energy dependence was demonstrated using both metabolic inhibition, and transport against a diffusion gradient methods. Disruption of tight junctions by use of the calcium chelator, EGTA, caused a significant increase in furosemide transport (twofold and 12-fold increases in B to A and A to B, respectively) indicating the importance of the paracellular route. We conclude that furosemide secretion from Caco-2 cells is the result of saturable active transport and passive diffusion that has a significant paracellular component.


Opiates modify induction of c-fos proto-oncogene in the spinal cord of the rat following noxious stimulation.
The expression of the proto-oncogene c-fos in neurons of the spinal cord dorsal horn of the rat following noxious thermal stimulation was compared in morphine- and ketamine-treated animals. Intravenous injection of morphine reduced the number of c-fos-positive neurons by up to 85% in laminae III-VI and X. This effect was dose dependent and naloxone reversible. The non-competitive N-methyl-D-aspartate (NMDA) antagonist ketamine had no effect. The present data show that morphine suppresses the induction of c-fos. A block of Ca2+ influx through voltage- and ligand (NMDA)-gated channels does not influence c-fos protein synthesis in the dorsal horn of the spinal cord in vivo.


Retinal Microvasculature: A Potential Window Into Heart Failure Prevention.
Endothelial dysfunction and microvascular disease have been shown to play an important role in the development and progression of heart failure (HF). Retinal imaging provides a unique opportunity to noninvasively assess vascular structure and function, vessel features, and microcirculation within the retina. Accumulating evidence suggests that retinal vessel caliber, microvascular features, and vascular characteristics extracted from various imaging modalities are associated with alterations in left ventricular structure and function in stage B HF, as well as incident development of symptomatic HF in the general population. Moreover, dynamic retinal vessel analysis has been shown to differentiate HF patients based on their phenotypes. Given the increasing availability of rapid image acquisition devices (eg, nonmydriatic widefield systems and smartphone-based retinal cameras) and the integration of artificial intelligence-based interrogation/assessment techniques, retinal imaging is a promising noninvasive tool, in conjunction with cardiac imaging and biomarkers, to prevent HF and risk stratify those at risk of developing HF. This review focuses on the current evidence on retinal microvasculature changes, and potential clinical relevance and promising utility of retinal imaging in HF.


Does getting stigma under the skin make it thinner? Emotion regulation as a stress-contingent mediator of stigma and mental health.
Emotion regulation deficits may link stigma to poor mental health, yet existing studies rely on self-reported stigma and do not consider contextual factors. In the present research, we examined associations among cultural stigma (i.e., objective devaluation of others' status), emotion regulation deficits, and poor mental health. In Study 1, we created an index of cultural stigma by asking members of the general public and stigma experts to indicate desired social distance towards 93 stigmatized attributes. In Study 2, emotion regulation deficits mediated the association between cultural stigma and adverse mental health outcomes, including depressive symptoms and alcohol use problems, among individuals endorsing diverse stigmatized identities. The indirect effect of cultural stigma, via emotion regulation, on these outcomes was stronger among those reporting more life stress. These findings highlight the adverse impact of cultural stigma on mental health and its role in potentiating stigmatized individuals' susceptibility to general life stress.


Surgical reversal of prolonged blindness from a metastatic neuroblastoma.
Reports of tumor-related anterior visual pathway blindness that have resolved after surgical decompression are rare. The longest reported duration of tumor-related blindness completely reversed by optic nerve decompression is 3 days. We describe a pediatric patient with 7 days of no light perception who experienced reversal of blindness following tumor resection and optic nerve decompression. A 33-month-old boy presented with a 4-day history of no light perception. Magnetic resonance imaging revealed a mass involving the sphenoid sinus, sella turcica, and clivus with significant optic nerve involvement. Loss of light perception and complete absence of a pupillary light reflex were documented for the next 72 h. A sluggish pupillary light reflex was regained 24 h after instituting intravenous steroids. An urgent bi-frontal craniotomy and optic nerve decompression were performed 7 days after the onset of blindness. Surgical pathology revealed metastatic neuroblastoma. Eleven days after optic nerve decompression, the child was able to count fingers and recognize faces and printed book characters. Prolonged blindness secondary to tumor-related optic nerve compression may be reversible up to 1 week from onset in children presenting with no light perception.


Effects of chemical pretreatments on material solubilization of Areca catechu L. husk: Digestion, biodegradability, and kinetic studies for biogas yield.
This study aimed to understand the pretreatment-aided anaerobic digestion of lignocellulosic residues and to assess the substrate solubilization capacity of pretreatment processes. We evaluated the feasibility of biogas production using chemically pretreated Areca catechu L. (Arecanut husk, AH). AH was pretreated for 24h at two different temperatures-25 °C and 90 °C with four different chemicals viz. H2SO4 (acidic), NaOH (alkaline), H2O2 (oxidative), and ethanol in 1% H2SO4 (organosolv) under each temperature. AH solubilization assessment included analyses of parameters such as volatile solids to total solids (VS:TS) ratio, soluble chemical oxygen demand, total phenolic content, and biomass composition. Alkaline pretreatment of AH at 90 °C resulted in the maximum biogas yield of 683.89mL/gVS, which was 2.3 times more than that obtained using raw AH without pretreatment. Methane content of biogas produced using AH pretreated with 2-10% of NaOH was found to be between 71.53% and 75.06%; methane content of biogas using raw AH was 62.31%. In order to describe the AH degradation patterns, biogas production potential from pretreated AH was evaluated using bacterial kinetic growth models (First-order exponential, logistic, transference, and modified Gompertz models). The modified Gompertz and logistic models (correlation coefficient >0.99) were found to have the best fit of all kinetic models for the cumulative experimental biogas curve. We formulated a multiple linear regression equation depicting the biodegradability index (BI) as a technical tool to determine biomethane production; BI is represented as a function of biomass composition (cellulose, hemicellulose, and lignin), with a high correlation (>0.95). Based on our analyses of AH pretreatment and substrate utilization for biogas production, we propose that the biochemical composition of lignocellulosic residues should be carefully considered to ensure their biodegradability when subjected to anaerobic digestion.


Metabolomic responses in freshwater benthic invertebrate, Chironomus tepperi, exposed to polyethylene microplastics: A two-generational investigation.
The accumulation of microplastics (MPs) in sediments could pose risks to benthic organisms and their progeny. Here, we examined effects on traditional apical endpoints along with changes to whole body metabolite profiles induced by irregular shaped polyethylene MPs (1-45 µm) at environmentally relevant concentrations (125, 250, 500 and 1000 MPs/kg sediment) in Chironomus tepperi using a two-generation exposure regime. Survival and emergence of C. tepperi were negatively affected in the parental generation at the two highest concentrations, whereas endpoints associated with growth were only impacted at 1000 MPs/kg sediment. Metabolites associated with several amino acid and energy metabolism pathways were present at lower abundances at the highest exposure concentration suggesting an overall impact on bioenergetics which relates to the inhibition of food acquisition or nutrient assimilation caused by ingestion of MPs, rather than a traditional receptor-mediated toxicity response. In contrast, no significant effects on apical endpoints were observed in the continuous exposure of first filial generation, and lactic acid was the only metabolite that differed significantly between groups. Larvae in unexposed conditions showed no differences in survival or metabolite profiles suggesting that effects in the parental generation do not carry over to the next filial generation. The findings provide evidence on the underlying impacts of MP ingestion and potential adaption to MP exposure of C. tepperi.


Phosphorylation of the nucleocapsid protein of Hantaan virus by casein kinase II.
Hantaanvirus (HTNV) is the prototype of the genus Hantavirus, which belongs to the family Bunyaviridae. Hantaviruses are carried and transmitted by rodents and are known to cause two serious disease syndromes in humans i.e., hemorrhagic fever with renal syndrome (HFRS) and the hantavirus pulmonary syndrome (HPS). HTNV is an enveloped virus that contains a tripartite genome consisting of three negative-sense RNA segments (L, M, S), and the S and M segment of HTNV, respectively, encode the viral nucleocapsid protein (NP) and envelope glycoproteins. Possible phosphorylation motifs of casein kinase II (CKII) and protein kinase C (PKC) were identified in HTNV NP through bioinformatics searches. Sucrose gradient SDS-PAGE analysis indicated that dephosphorylated HTNV NP migrated faster than non-dephosphorylated NP, suggesting that HTNV NP is phosphorylated in infected Vero E6 cells. Immunoblot anaylsis of HTNV particles with anti-phosphoserine antibody and anti-phosphothreonine antibody after immunoprecipitation showed that viral particles are readily phosphorylated at threonine residues. In vitro kinase assay further showed that HTNV NP is phosphorylated by CK II, but not by PKC. Full length or truncated HTNV NPs expressed in E. coli were phosphorylated in vitro by CKII suggesting that phosphorylation may occur in vivo at multiple sites. Site specific mutagenesis studies suggest that HTNV NP phosphorylation might occur at unknown sites excluding the site-directly mutagenized locations. Taken together, HTNV NP can be phosphorylated mainly at threonine residues in vivo by CK II treatment.


Effects of sad mood on facial emotion recognition in Chinese people.
This study examined the influence of sad mood on the judgment of ambiguous facial emotion expressions among 47 healthy volunteers who had been induced to feel sad (n=13), neutral (n=15), or happy (n=19) emotions by watching video clips. The findings suggest that when the targets were ambiguous, participants who were in a sad mood tended to classify them in the negative emotional categories rather than the positive emotional categories. Also, this observation indicates that emotion-specific negative bias in the judgment of facial expressions is associated with a sad mood. The finding argues against a general impairment in decoding facial expressions. Furthermore, the observed mood-congruent negative bias was best predicted by spatial perception. The findings of this study provide insights into the cognitive processes underlying the interpersonal difficulties experienced by people in a sad mood, which may be predisposing factors in the development of clinical depression.


A novel locus for parietal foramina maps to chromosome 4q21-q23.
Parietal foramina [PFM], inherited usually in an autosomal dominant mode, is an extremely rare developmental defect characterized by a symmetrical, oval hole in the parietal bone. It can be present as either an isolated or a syndromic feature. PFM types 1 and 2 (PFM1 and PFM2) have been found to be caused by mutations in the MSX2 and ALX4 genes, located to chromosomes 5 and 11, respectively. After exclusion of both the above loci in a large Chinese pedigree with autosomal dominant PFM, a genome-wide search revealed a linkage of the PFM to markers at the 4q21-q23 region. The maximum LOD score from two-point linkage analysis is 3.87 for marker D4S2961. Analysis of co-segregated haplotype localized the region to a 20-cM interval that flanks D4S392 and D4S2945. Therefore, we concluded that the PFM in the family is a new PFM locus. Although three genes, BMPR1B, PP1 and IBSP, are located to 4q21-q25 and their functions are related to bone morphogenesis, no mutations were identified by sequencing analysis of their exons.


Restriction fragment length polymorphism (RFLP) heterogeneity of HLA-DQ beta genes associated with DNA fragment identical to the DR1-beta DNA structure.
Restriction fragment length polymorphism (RFLP) analyses of DR1 positive peripheral blood leukocytes DNA was carried out. The Taq I digested DNA was hybridized with cDNA probes for HLA-DR and -DQ beta genes. The DR probe detected fragments commonly observed in the DR1 specificity, whereas a new DQ-beta fragment was detected in some DR1 haplotypes when the DQ-beta probe was used. This fragment had an RFLP pattern identical to the DQ-beta fragment typically associated with most DR2 and some DRw6 specificities.