Bilateral choroidal detachment and myopic shift after acetazolamide intake for laser capsulotomy.
To report a case of bilateral choroidal effusion after laser capsulotomy. A healthy 85 years old white woman was referred to our hospital with a diagnosis of posterior capsule opacification in the left eye. The patient was treated with laser capsulotomy and oral acetazolamide was administered after the procedure. The day after, the patient visited the emergency room complaining bilateral blurred vision. A myopic shift and peripheral choroidal detachment was noted in both eyes. Discontinuation of acetazolamide and treatment with topical steroid and cyclopentolate resulted in a significant improvement in visual acuity and the complete resolution of the choroidal detachment in 1 week. To the best of our knowledge, this is the first reported case of choroidal detachment and acute transient myopia following the administration of oral acetazolamide after laser capsulotomy.


Gastric pneumatosis associated with preduodenal portal vein, duodenal atresia, and asplenia.
An 8-day-old newborn presented with non-bilious vomiting, upper abdominal fullness, and failure to pass meconium. Plain radiographs revealed gastric pneumatosis (GP). At operation, he was found to have a non-obstructive preduodenal portal vein, preampullary duodenal atresia, asplenia, and malrotation. The baby was treated by duodeno-duodenostomy without mobilizing the portal vein and correction of the malrotation according to Ladd's procedure. He made an uneventful recovery and the GP resolved spontaneously. The malformative process was believed to have occurred at or soon after the 5th week of gestation, and the GP probably resulted from intramural air tracking through mucosal tears caused by high intragastric pressure.


Obesity in children. Tackling a growing problem.
Childhood and adolescent obesity has increased dramatically over the past 25 years in Australia. Currently over 20% of Australian children are overweight or obese. The National Health and Medical Research Council has recently developed the 'Clinical practice guidelines for the management of overweight and obesity in children and adolescents'. This article discusses the assessment and management of childhood and adolescent overweight and obesity. Children and adolescents with a body mass index over the 85th centile for age are classified overweight and those over the 95th centile, obese. Obesity has significant health consequences for children and adolescents, both in the short term and for their adult life. Family involvement is important in management, particularly in primary aged children. A combination of dietary modification, increased physical activity, decreased sedentary activity and behaviour modification is recommended.


The interaction between serotonin and angiotensin II in the chronically instrumented guinea pig and its alteration by indomethacin.
We examined the effect of a subthreshold infusion of serotonin on the angiotensin II pressor response in the chronically instrumented pregnant and nonpregnant guinea pig before and after administration of a prostaglandin synthesis inhibitor. Arterial blood pressure was significantly lower in the pregnant animal (p = 0.0135). An infusion of serotonin, which failed to alter the blood pressure, pulse, or uterine artery flow velocity, significantly increased the pressor response to angiotensin II infused at 3.5, 7.5, 14.5, and 29 ng/kg/min in both the pregnant (p = 0.0001) and, to a lesser degree, the nonpregnant animal (p = 0.004). Pretreatment with indomethacin heightened the angiotensin pressor effect significantly in the pregnant group (p = 0.0001) and to a near-significant degree in the nonpregnant group (p = 0.074). However, indomethacin enhanced the angiotensin II-serotonin synergism only in the pregnant animal (p = 0.0008). The angiotensin II-serotonin synergism persisted after pretreatment with the sympathetic blocking agent bretylium tosylate. We concluded that serotonin augments the pressor effect of angiotensin II in the pregnant and nonpregnant guinea pig; however, this synergism is potentiated by the inhibition of prostaglandin synthesis only in the pregnant animal.


The effect of aging on phenylephrine response in normal subjects.
With aging, cardiac responses to β-adrenergic stimulation decline but the responses to α1-stimulation are less clear. Moreover, whether aging, in the absence of disease, influences the left ventricular response to an increase in afterload is unclear. This study examined the effect of aging on heart rate (HR), blood pressure (BP), cardiac index (CI) and several left ventricular contractility measurements during α 1-stimulation with a phenylephrine infusion. Subjects were rigorously screened to be normal by history, physical, blood tests, ECG, ETT and echocardiogram. Twelve young (mean 26 years, all male) and 15 aged (69 years, 11 males) subjects were studied during 10 minute infusions of phenylephrine at 0.5 and 1.0 mcg/ kg/min. HR, BP and radionuclide ventriculographic cardiac volumes were measured. Systolic BP increased more in the aged than in the young (22 vs. 13%, p=0.003), while heart rate (16 vs. 21%, p=0.05) fell less. Contractile responses to phenylephrine, including EF, stroke volume index (SVI), stroke work index and left ventricular contractility index were not altered with aging. Systemic vascular resistance (SVR) was higher at baseline and at each infusion rate, but there was no age-associate change in the response to PE. In a healthy normal aged population, a preserved SVI response in the setting of a higher baseline SVR results in an increased SBP response to α1-stimulation. Contractile responses to increased afterload are not altered with aging. Age-associated differences in the response to α1-stimulation are small and are explained by altered baroreflex sensitivity and a stiffer vasculature.


Peptide mimicrying between SARS coronavirus spike protein and human proteins reacts with SARS patient serum.
Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS) is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV). The spike (S) protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927-937) and D08 (residues 942-951) were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490-502) stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.


The underlying heart rhythm in patients with an artificial cardiac pacemaker.
One-hundred forty-two patients with atrioventricular block (AVB) and 61 patients with sick sinus syndrome (SSS) were followed for an average of 50 months after permanent pacemaker insertion. Their underlying heart rhythms (UHR) were evaluated repeatedly by chest wall stimulation (CWS). A deficient UHR was defined as ventricular asystole lasting 4 seconds or longer. The underlying conduction disturbance increased in 14% of AVB patients, decreased in 14%, and remained constant in 68%. The occurrence of Adams-Stokes attacks before pacemaker implantation was associated with a higher incidence of deficient UHR both in AVB and SSS; a deficient UHR was seen more frequently in AVB than in SSS. Among AVB patients (1) atrial fibrillation, flutter or tachycardia and (2) sinus rhythm with incomplete AVB, especially Mobitz 1, when present before pacemaker implantation, were associated with a significantly lower incidence of deficient UHR during subsequent pacing in comparison with other AVB patients. CWS is a non-invasive method which allows the evaluation of UHR and which can contribute to the early recognition of pacemaker-dependent patients.


Expression of the bacteriophage P1 cin recombinase gene from its own and heterologous promoters.
The cin recombinase of bacteriophage P1, a protein that catalyses site-specific DNA inversions, has been identified and its structural gene has been cloned under the control of different promoters. One of the DNA sequences used for the site-specific recombination, cixL, overlaps with the 3' end of the gene, but we show that the presence of this site does not affect cin gene expression from strong promoters. To assay cin activity we have constructed plasmids that carry antibiotic resistance genes within the invertible segment that are transcribed from promoters outside the segment. DNA inversion switches on or off genes for chloramphenicol or kanamycin resistance. These tester plasmids are used to study cin-mediated DNA inversion both in vivo and in vitro.


The geometry of alpha-sheet: Implications for its possible function as amyloid precursor in proteins.
alpha-sheet has been proposed as the main constituent of the prefibrillar intermediate during amyloid formation. Here the helical parameters of the alpha-sheet strand are calculated from average main-chain dihedral angles reported from molecular dynamics simulations. It is an almost linear polypeptide that forms a right-handed helix of about 100 A diameter, with 100 residues and a rise of 30 A per turn. The strands are curved but untwisted, which implies that neighboring strands need not coil to make interstrand hydrogen bonds. This suggests that compared to beta-sheets in native folded proteins, alpha-sheets can be larger and stack more easily to create extensive 3D blocks. It is shown that alpha-sheet is related to a category of structures termed "mirror" structures. Mirror structures have repetitive pairs of main-chain dihedral angles at residues i and i+1 that satisfy the condition phi(i) (+1) = -psi(i), psi(i) (+1) = -phi(i). They are uniquely identified by the two orientations of their peptide planes, specified by phi(i) and psi(i). Their side chains point alternately in opposite directions. Interestingly, their conformations are insensitive to phi(i) and psi(i) in that the pseudo dihedral angle formed by four consecutive C(alpha) atoms is always close to 180 degrees . There are two types: "beta-mirror" and "alpha-mirror" structure; beta-mirror structures relate to beta-sheet by small peptide plane rotations, of less than 90 degrees , while alpha-mirror structures are close to alpha-sheet and relate to beta-sheet by approximately 180 degrees peptide plane flips. Most mirror structures, and in particular the alpha-mirror, form wide helices with diameters 50-70 A. Their gentle curvature, and therefore that of the alpha-sheet, arises from the orientation of successive peptide units causing the difference in the bond angles at the C and N atoms of the peptide unit to gradually change the direction of the chain.


Effect of centchroman on the genital organs of the offspring of rats when administered during lactation or during the neonatal period: a comparative study with ethynylestradiol and diethylstilbestrol.
Lactating rats were treated with centchroman (1.25 mg/kg body wt. p.o.) or ethynylestradiol (100 micrograms/kg p.o.) daily from day 1 of parturition for 21 days and their offspring were autopsied at 60, 90 and 120 days of age. In the offspring nursed by centchroman treated mothers there was no change in ovarian weight. There was a reduction in their uterine weight; while the luminal epithelium presented a stimulated state, the stroma showed immature state in its histological features. The ovarian and uterine weights and their histology in the offspring of ethynylestradiol treated mothers showed no change. The male offspring of both the groups of rats showed an increase in the weight of genital organs and testis histology presented typical adult features. When centchroman was injected s.c. on 5th postnatal day to female rats (500 micrograms/rat), the ovary remained normal but the uterus revealed estrogen deficient state when they were 60 or 90 days old. Neonatal female rats injected with diethylstilbestrol (10 micrograms/rat) on day 5 showed normal ovary while uterus presented features typical of estrogenic stimulation with small areas of luminal epithelium showing squamous metaplastic changes. The results are discussed comparing the centchroman effects with the reported findings in rats treated with steroidal and triphenylethylene estrogenic compounds during lactation or the neonatal period.


[Uroinfections and the possibilities of therapy with levofloxacin].
The common occurrence, of inflammatory diseases in the urinary tract and the genitals in men, is quite a reason for identification of the agents and looking for some new chances of therapeutic treatment. For a period of two years (2002-2003) we accomplished 4810 microbiological tests of urine and prostate secretion on patients with uroinfections. The cultures are completed on standard nutrition medium, as the biochemical identification of the strains is accomplished by the systems mini API and "bio Merieux" BBL Crystal, "Becton Dickinson". Meanwhile for a period of one year, 113 patients with different uroinfections are treated and studied. In 16 (14.1%) Levofloxacin (Tavanic-R) is applied i.v. 500mg/daily as in the rest cases 97 (85.9%) Tavanic are applied per oral in different therapeutic doses. The most common agent in our study was the E. Coli, as for the year 2003 we read an increase of the infections caused by E.Coli with 3.4% comparing to the previous one (38.5% to 35.1%). The differentiation of patients treated with Levofloxacin in groups is completed as follows: with acute uncomplicated cystitis--pyelonephritis after ESWL--15.9%; with postoperative uroinfections--20.3%; with chronic post-tuberculosis pyelonephritis--4.4%; and with inflammatory diseases of the male genitals--37.2%.


Comprehensive liamocin biosurfactants analysis by reversed phase liquid chromatography coupled to mass spectrometric and charged-aerosol detection.
Liamocin biosurfactants and structurally related exophilins secreted by the Aureobasidium pullulans (A. pullulans) strain NRRL62031 were firstly analyzed by hyphenation of high-performance liquid chromatography (HPLC) with high-resolution mass spectrometry (HRMS). Ten different analytes were detected and identified by their accurate masses and divided into subclasses according to their different head groups: three liamocins with arabitol as head group, three mannitol liamocins, and four exophilins. A baseline separation of congeners within the subclasses was achieved by reversed phase HPLC on a C18 stationary phase, whereas an overlap of subclasses occurred. The structures were simultaneously confirmed by online tandem mass spectrometry (MS/MS) experiments in positive and negative ionization mode. The assigned polyol head groups and thus the feasibility of this method were confirmed by gas chromatography (GC)-MS data obtained after hydrolysis and derivatization of the liamocins. Based on the varying structural characteristics of liamocins, e.g. the polyol head group (or even none for exophilins) and the degree of acetylation, different detector response in LC-MS was expected, impairing relative quantification of congeners. Therefore, a complementary quantification method was developed using HPLC coupled to charged-aerosol detection (CAD), which allows the determination of the amount of the individual liamocin species without authentic liamocin standards. Hence, the here presented hyphenated techniques facilitate comprehensive analysis of liamocin biosurfactants.


Insulin-loaded nanoparticles based on acetylated cashew gum/chitosan complexes for oral administration and diabetes treatment.
Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.


Intra-operative fluid volume influences postoperative nausea and vomiting after laparoscopic gastric bypass surgery.
Laparoscopic Roux-en-Y gastric bypass (RYGBP) is a commonly performed operation for morbid obesity. A significant number of patients experience postoperative nausea and vomiting (PONV) following this procedure. The aim of this study was to determine the effect, if any, of intra-operative fluid replacement on PONV. Patients who underwent laparoscopic (RYGBP) for morbid obesity during a 12-month period were included in this retrospective analysis. Demographic data including age, gender, and body mass index (BMI) were collected. Perioperative data also included total volume of intra-operative fluids administered, rate of administration, urine output, length of surgery, and incidence of PONV as determined by nursing or anesthesia records in the postanesthesia care unit (PACU). Data were analyzed by t-test. The table below depicts demographic and perioperative data, comparing patients who experienced PONV (n=125) in the PACU with those who did not (n=55). Values are mean +/- standard deviation. PONV is a common complication after laparoscopic RYGB. Patient who did not experience PONV received a larger volume of intravenous fluid at a faster rate than similar patients who complained of PONV.


[Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection].
To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71. A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children. The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01). T allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.


Frontline over ivory tower: key competencies in community-based curricula.
The Royal College of Physicians and Surgeons of Canada mandates that community experiences be incorporated into medicine-based specialties. Presently there is wide variability in community endocrine experiences across Canadian training programs. This is complicated by the paucity of literature providing guidance on what constitutes a 'community' rotation. A modified Delphi technique was used to determine the CanMEDS competencies best taught in a community endocrinology curriculum. The Delphi technique is a qualitative-research method that uses a series of questionnaires sent to a group of experts with controlled feedback provided by the researchers after each survey round. The experts in this study included endocrinology program directors, community endocrinologists, endocrinology residents and recent endocrinology graduates. Thirty four out of 44 competencies rated by the panel were deemed suitable for a community curriculum. The experts considered the "Manager" role best taught in the community, while they considered the community least suitable to learn the "Medical Expert" competency. To our knowledge, this is the first time the content of a community-based subspecialty curriculum was determined using the Delphi process in Canada. These findings suggest that community settings have potential to fill in gaps in residency training in regards to the CanMEDS Manager role. The results will aid program directors in designing competency-based community endocrinology rotations and competency-based community rotations in other medical subspecialty programs.


Recombinant viral vaccines for enzootic bovine leucosis.
Recently published studies on the development and use of recombinant vaccinia virus (VV) vaccines incorporating either the complete envelope (env) gene or only a fragment of the env gene consisting of the coding sequence for the env glycoprotein 51 (gp51) and part of gp30 of the bovine leukaemia virus (BLV) are described. It has been reported that vaccination of sheep with recombinant VV vaccines containing the complete env gene appears to protect sheep against challenge infection with BLV. The evidence for this protection is based on the lack of persistence of high titres of anti-gp51 antibodies compared with unvaccinated BLV infected controls, on the enhanced CD4 proliferative responses to specific BLV gp51 synthetic peptides in the vaccinated sheep, and on the inability to detect BLV pro-virus by polymerase chain reaction in the vaccinated sheep after 4 months following challenge infection compared with continual detection in unvaccinated sheep over a 16 month trial period. It has been suggested that cell-mediated immune responses may be an important aspect of protective immunity against BLV infection and it has been reported that large tracts of amino acid sequences within the env and pol genes are highly conserved in different isolates from different countries which is of importance in designing peptide derived vaccines.


Effect of low-dose aspirin treatment on human platelet aggregation.
1. The effect of aspirin 50 mg/day during 28 days on human platelet aggregation (PAG) induced by ADP and collagen has been studied in 12 healthy volunteers. 2. The results show that aspirin treatment reduces both ADP and collagen-induced PAG (P less than 0.01). 3. Maximal inhibition of PAG appears in the second week of treatment for ADP-induced PAG (41.1%) and in the fourth week for collagen-induced PAG (50.2%). No significant differences exist between the controls taken along the treatment during the 28 days of the study. 4. The data suggest that the low-dose of aspirin tested provides adequate PAG inhibition to be used in the prophylaxis of thromboembolism patients, thus avoiding intolerances to higher dosages.


Pregnancy after uterine fibroid embolization: follow-up of 100 patients embolized using tris-acryl gelatin microspheres.
To evaluate pregnancies in women who had previously undergone uterine fibroid embolization. Prospective study. A city hospital in Spain. A cohort of 100 uterine fibroid embolization patients, 57 of whom wished to preserve their fertility. Uterine arteries were embolized by using 500-1,200 microm tris-acryl gelatin microspheres. After intervention, patient follow-up was performed at 1 week, 3 months, 6 months, and yearly. The number of pregnancies and course of pregnancy. Eleven pregnancies in 10 women (19.2%). The pregnancies resulted in 8 live births, including 4 normal and 4 cesarean deliveries. Early miscarriage occurred in 3 cases (2 patients). None of the 8 newborns was a low-birth weight infant, and gestation lasted >or=37 weeks in all the patients, except for 1 case of a macrosomic fetus delivered at 33 weeks. There were no cases of abnormal placental implantation. Despite the small sample size, uterine artery embolization appears to be viable in young women who still want to become pregnant. Larger series and studies comparing uterine fibroid embolization and myomectomy are needed.


Structure-Dependent Guest Recognition with Flexible Ferrocene-Based Aromatic Oligoamide β-Sheet Mimics.
A series of aromatic oligoamides incorporating an inherently flexible ferrocene dicarboxylic acid unit was synthesized. Solid state, solution, and computational studies on these systems indicated that the aromatic strands can adopt a syn parallel stacked conformation. This results in modular β-sheet-like molecular clefts that display structure-dependent recognition of small polar molecules. NMR and theoretical studies of the host-guest interaction support an in cleft binding mode and allowed the selectivity of the oligomers to be rationalized on the basis of minor changes in functional-group presentation on the edge of the aromatic strands.


Association between SUMF1 polymorphisms and COVID-19 severity.
Evidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19. We found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44-0.88, P = 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90-0.98, P = 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P = 0.015, Generalized Linear Model). In conclusion, our study for the first time identified that rs794185 in SUMF1 gene was associated with the severity of COVID-19.


Radioactive iodine ablation post differentiated thyroid cancer surgery: an analysis of use and impact of the American Thyroid Association guidelines.
The 2009 American Thyroid Association (ATA) three-tiered risk stratification, and its updated version in 2015, provided clearer guidance on the use of radioactive iodine (RAI) ablation in differentiated thyroid cancer (DTC) patients. This study examines the impact of these guidelines on RAI use in our institution. Patients diagnosed with DTC during three different time periods (group 1: 2002-2006, group 2: 2010-2014 and group 3: 2017-2018) were identified and risk stratified according to the ATA guidelines. RAI use and extent of surgery were compared between the three groups. Categorical variables were analysed using Fisher's exact (2 × 2) and chi-squared (>2 × 2) tests. A total of 415 patients were included (group 1 = 88, group 2 = 215, group 3 = 112). The proportion of patients having total thyroidectomy were 84.6, 84.7 and 69.6% in groups 1, 2 and 3, respectively (P = 0.003). Central lymph node dissection was significantly higher in the more contemporary groups compared to group 1 (9.1 versus 41.9 versus 64.3%, P < 0.001). Overall, fewer patients received RAI in more recent times (76.6 versus 54.8 versus 26.8%, P < 0.001), most evident in the low-risk patients (70 versus 29.1 versus 5.1%, P < 0.001). In the high risk group, the majority received RAI, with no difference between the groups. Comparing DTC patients treated in our unit before and after publications of the 2009 and 2015 ATA guidelines, more nodal surgery was performed with less RAI administered in the latter groups. Better risk stratification according to the ATA guidelines has allowed more judicious use of RAI ablation.


Aggressive surgical approach in patients with adrenal-only metastases from hepatocellular carcinoma enables higher survival rates than standard systemic therapy.
Although guidelines recommend systemic therapy even in patients with limited extrahepatic metastases from hepatocellular carcinoma (HCC), a few recent studies suggested a potential benefit for resection of extrahepatic metastases. However, the benefit of adrenal resection (AR) for adrenal-only metastases (AOM) from HCC was not proved yet. This is the first study to compare long-term outcomes of AR to those of sorafenib in patients with AOM from HCC. The patients with adrenal metastases (AM) from HCC were identified from the electronic records of the institution between January 2002 and December 2018. Those who presented AM and other sites of extrahepatic disease were excluded. Furthermore, the patients with AOM who received other therapies than AR or sorafenib were excluded. A total of 34 patients with AM from HCC were treated. Out of these, 22 patients had AOM, 6 receiving other treatment than AR or sorafenib. Eventually, 8 patients with AOM underwent AR (AR group), while 8 patients were treated with sorafenib (SOR group). The baseline characteristics of the two groups were not significantly different in terms of age, sex, number and size of the primary tumor, timing of AM diagnosis, Child-Pugh and ECOG status. After a median follow-up of 15.5 months, in the AR group, the 1-, 3-, and 5-year overall survival rates (85.7%, 42.9%, and 0%, respectively) were significantly higher than those achieved in the SOR group (62.5%, 0% and 0% at 1-, 3- and 5-year, respectively) (P = 0.009). The median progression-free survival after AR (14 months) was significantly longer than that after sorafenib therapy (6 months, P = 0.002). In patients with AOM from HCC, AR was associated with significantly higher overall and progression-free survival rates than systemic therapy with sorafenib. These results could represent a starting-point for future phase II/III clinical trials.


Anthropogenic and natural methane emissions from a shale gas exploration area of Quebec, Canada.
The increasing number of studies on the determination of natural methane in groundwater of shale gas prospection areas offers a unique opportunity for refining the quantification of natural methane emissions. Here methane emissions, computed from four potential sources, are reported for an area of ca. 16,500km(2) of the St. Lawrence Lowlands, Quebec (Canada), where Utica shales are targeted by the petroleum industry. Methane emissions can be caused by 1) groundwater degassing as a result of groundwater abstraction for domestic and municipal uses; 2) groundwater discharge along rivers; 3) migration to the surface by (macro- and micro-) diffuse seepage; 4) degassing of hydraulic fracturing fluids during first phases of drilling. Methane emissions related to groundwater discharge to rivers (2.47×10(-4) to 9.35×10(-3)Tgyr(-1)) surpass those of diffuse seepage (4.13×10(-6) to 7.14×10(-5)Tgyr(-1)) and groundwater abstraction (6.35×10(-6) to 2.49×10(-4)Tgyr(-1)). The methane emission from the degassing of flowback waters during drilling of the Utica shale over a 10- to 20-year horizon is estimated from 2.55×10(-3) to 1.62×10(-2)Tgyr(-1). These emissions are from one third to sixty-six times the methane emissions from groundwater discharge to rivers. This study shows that different methane emission sources need to be considered in environmental assessments of methane exploitation projects to better understand their impacts.


The interaction of the benzimidazole dye Hoechst 8208 with nucleic acids.
The interaction of Hoechst 8208 (H8208) with DNA and synthetic polynucleotides has been studied by absorption, fluorescence, flow dichroism, circular dichroism (CD), and viscosity measurements. The results are compatible with an intercalative mode of H8208 binding.


[Diagnostic value of heart fatty-acid binding protein in early hospitalized patients with non ST elevation acute coronary syndrome].
Heart fatty-acid-binding protein (FABP) is supposed to be the most sensitive biomarker of myocardial necrosis in patients with Q-wave myocardial infarction (MI) and non-diagnostic ECG during first hours after onset of symptoms. However, diagnostic value of FABP in patients with non-ST elevation acute coronary syndrome (NSTEACS) is not well established. To elucidate diagnostic value of FABP in patients with NSTEACS hospitalized within time interval considered to be too early for a majority of biochemical tests. FABP levels were measured by immunofluorometry (HyTest, Finland) in 44 patients (26 men, mean age 69+/-8.9 years) at admission within 6 hours (median - 2 h) from onset of index attack of angina and in 6, 12, 24 hours after onset of pain. Cut off FABP level was 12 ng/ml. Serum cardiac troponin I was measured for diagnosis of MI on admission and twice during first 24 hours of hospital stay. Cut off TnI level was 0.4 ng/ml. Acute MI was diagnosed by TnI above cut off in 31 patients (70.5%). There were no new-Q-wave MIs. Average ratio of observed serum FABP level to diagnostic cut off value on admission and in 6, 12, 24 hours after onset of pain was higher in patients with MI than in patients with unstable angina (1.01, 1.53, 0.81, 0.66 and 0.78, 0.51, 0.65, 0.56, respectively). The difference was maximally significant in 6 hours after onset of pain (p=0.018). Among patients with MI admission FABP compared with admission TnI more frequently exceeded diagnostic level (in 18 vs 9 patients, respectively, p=0.009). Sensitivity and specificity of admission levels of FABP and TnI for diagnosis of MI were 58 and 85%, 29% and 100%, respectively. In patients with NSTEACS during first 6 hours after pain onset FABP compared with TnI has greater sensitivity for detection of MI and sufficient specificity. FABP can be used as additional diagnostic tool for MI detection in early admitted patients with NSTEACS.


Analysis on short-term change of macular function and the correlates after intravitreal conbercept for CRVO-ME.
To study the short-term change of macular function and the correlates after intravitreal conbercept for CRVO-ME. Prospective, clinical study. Twenty Three patients(23 eyes) were recruited, who were non-ischemia central retinal vein occlusion diagnosed by FFA (fundus fluorescein angiography) and treated with intravitreal conbercept for macular edema, best - corrected visual acuity ( BCVA), central macular thickness(CMT), amplitude density of P1 wave and implicit time of P1,N1 wave from ring 1 and ring 2 of mf-ERG were measured before and 1 week、2 month after treatment. Compared to the baseline, BCVA、CMT、amplitude density of P1 wave and implicit time of P1,N1 wave from ring 1 and ring 2 were greatly improved at 1 W、2 M after treatment; better results were gained at 2 M compared to 1 W; Pearson correlation analysis shows no significantly correlation between the improvement of mf-ERG with the change of BCVA、CMT. The BCVA、the structure and the function of macular were greatly improved after intravitreal conbercept for central retinal vein occlusion induced macular edema; however no significantly correlation between the improvement of the function of macular with the strcture of macular and BCVA.


Can self-reported data accurately describe the prevalence of overweight?
Overweight is an important public health problem affecting around 50% of the population of Wales, resulting in increased risk of illness, premature disability and premature death. The aim of this study was to examine critically the accuracy of self-reported data in describing the prevalence of overweight in Wales. A sample of 1622 adults aged 18 to 64 years was taken from the Welsh Heart Health Survey 1985. In that survey weight and height data were collected on a self-completed questionnaire and by clinical measurement. Mean differences between self-reported and measured weight and height were used as indicators of bias, and the accuracy of BMI and the prevalence of overweight based on this data were analysed. Weight was reported without significant bias in men, but women under-reported their weight by an average of 1.1 kg. Height was over-reported by 1.4 cm in men, and 0.7 cm in women, on average. More than two-thirds of subjects reported to within 2.3 kg and 2.5 cm of their actual weight and height. Reporting was more biased in older and overweight groups. The calculation of body mass index resulted in amplification of bias and underestimation of the prevalence of overweight and obesity in the study sample of 4.5% in men and 6.7% in women. The results have important implications for the use of self-reported data for the scientific measurement of the prevalence of overweight, especially in longitudinal studies, and suggest that further research should be conducted into the stability of reporting bias over time.


Understanding paediatric allergic fungal sinusitis: Is it more aggressive?
To study and characterize the features of AFRS in children as compared to adults. 50 consecutive patients of AFRS attending our outpatient department were included in the study from July 2011 to December 2013. They were divided into two groups (A and B) according to age being ≤14 years and >14 years. Clinical history and examination included anterior rhinoscopy, SNOT 20 scores, CT of Nose and PNS (para nasal sinuses) (Lund Mackay scores), diagnostic nasal endoscopy (Kupferberg's grades), punch biopsy from nasal polyp, serum IgE, absolute eosinophil counts (AEC) and Aspergillus skin hypersensitivity test was done in all patients for conformation of AFRS. Bent and Kuhn's criteria were used for diagnosis. Sweat chloride levels were done in all patients of group A. Group A had 12 patients and group B had 38. Mean duration of symptoms was significantly less in children as compared to adults (p<0.05). All patients of both groups had nasal polyposis at presentation. Unilateral disease and multisinus involvement was more common in children (6/12) as compared to adults. Proptosis (2/12) and telecanthus (4/12) was more common in children (group A) as compared to adults (group B). LM (Lund Mackay) scores and serum IgE were significantly high in children as compared to adults. Follow up CT scans showed early evidence of recurrence in children as compared to adults (p<0.05). AFRS was seen to be more aggressive in children with increased fungal load when compared with adults. Typically, AFRS in children was less responsive to treatment with increased recurrence rates.


Embedding Aβ42 in heterogeneous membranes depends on cholesterol asymmetries.
Using a coarse-grained lipid and peptide model, we show that the free energy stabilization of amyloid-β in heterogeneous lipid membranes is predicted to have a dependence on asymmetric distributions of cholesterol compositions across the membrane leaflets. We find that a highly asymmetric cholesterol distribution that is depleted on the exofacial leaflet but enhanced on the cytofacial leaflet of the model lipid membrane thermodynamically favors membrane retention of a fully embedded Aβ peptide. However, in the case of cholesterol redistribution that increases concentration of cholesterol on the exofacial layer, typical of aging or Alzheimer's disease, the free energy favors peptide extrusion of the highly reactive N-terminus into the extracellular space that may be vulnerable to aggregation, oligomerization, or deleterious oxidative reactivity.


[Results of the ciliary body exposure (CBE) in secondary angle closure glaucomas. 2. A histological study (author's transl)].
After treatment of secondary angle closure glaucomas by ciliary body exposure with lamellar scleral resection five eyes had to be enucleated. In view of the histological findings taken from these eyes mode of action and therapeutic value of this operation are considered. The effectiveness of scleral resection seems to be doubtful and there is evidence that permanent regulation of intraocular tension depends mainly on direct diathermy of the ciliary body.


Identification of radioactive materials in moving objects.
Control over the transportation of the radioactive materials crossing the borders of Uzbekistan is actually today not like before, because of increased threat of terrorism and urges of terrorist organizations to use radioactive materials in their terrorist activities. There are many companies producing radiation control systems. All such systems existing nowadays are based on the principles of intensity comparison for radiation detected by the system in the absence of control object and the intensity of the radiation when object appears. This method works well only in the conditions of constant or weakly changing background. However, at significant deviation in the value of background the number of false alarms set off by the systems increases. The present work describes the method for radioactive materials detection in the moving objects independent of the significant background deviations and present radiation monitoring establishment based on this principle.


Glucocorticoid receptor conversion to high affinity nuclear binding and transcription enhancement activity in Chinese hamster ovary cells subjected to heat and chemical stress.
The untransformed glucocorticoid receptor (GR) is a heteromeric complex containing two molecules of the 90-kDa heat shock protein (hsp90) and one molecule of the 56-kDa heat shock protein (hsp56). In the absence of hormone, this complex is found in the cytosolic fraction of cells, and upon hormone-binding the complex dissociates and the GR is recovered in the nuclear pellet fraction. Given the association of heat shock proteins with the cytosolic form of the GR, we have examined the effects of heat shock on GR subcellular localization and transcription enhancement activity in a series of Chinese hamster ovary (CHO) cells which express either low levels of endogenous GR (CHOd cells), high levels of the mouse GR (WCL2 cells), or high levels of mutated mouse GR unable to bind DNA (NB cells). It was found that heat shock treatment of WCL2 cells results in wild-type mouse GR that is recovered almost entirely within the nuclear pellet fraction, a response similar to that seen in hormone-treated cells. In contrast, heat shock treatment of NB cells results in complete loss of GR from the cytosolic fraction, but almost no shift of GR to the nuclear nuclear pellet. These results indicate that heat shock-mediated conversion to high-affinity nuclear binding by the wild-type GR requires a functional DNA-binding domain, and that heat shock will result in loss of GR to proteolysis in the absence of nuclear sequestration. Analysis of MMTV-CAT reporter gene expression in these cells revealed that heat or chemical shock, in comparison to hormone-treatment, results in a small induction of MMTV-CAT expression in the WCL2 cells, but not in the CHOd or NB cells. These results indicate that cellular stress can cause at least a partial induction of hormone-independent GR-mediated gene expression.


Ameliorative effects of diammonium glycyrrhizinate on inflammation in focal cerebral ischemic-reperfusion injury.
The present study investigated the neuroprotective potential of Diammonium Glycyrrhizinate (DG) in focal cerebral ischemic-reperfusion (IR) injury in mice. The middle cerebral artery occlusion (MCAO) model of the mouse was used. Mice were treated with DG (20mg/kg per day, intraperitoneal injection) or saline as control, from the beginning of the reperfusion to 7 days. The focal cerebral IR injury resulted in significant neurological deficits, infarct size, and brain water content (BWC) at 1 day, 3 days and 7 days after MCAO. A significant increase in various inflammatory mediators like interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) and astrocytic glial fibrillary acidic protein (GFAP) was also observed in the IR challenged brains. The DG treatment significantly improved neurofunction, decreased infarct size, and suppressed edema in the focal cerebral IR injury. The neuroprotective effect of DG was found to be associated with significant reduction in the IL-1, TNF-α, COX-2, iNOS, NF-κB and GFAP levels. In summary, this study suggested that DG has a neuroprotective effect on cerebral IR injury and this effect is likely related to DG's anti-inflammatory function.


Effect of retinal nerve fibre loss on the optic nerve head configuration in early glaucoma.
Twenty-nine ocular hypertensive patients with an optic disc haemorrhage, normal optic discs and normal visual fields were followed in this partly retrospective study by means of sequential optic disc stereophotographs and retinal nerve fibre layer (RNFL) photographs for a period of up to 14 years (mean 5.2). During this time early structural glaucoma damage developed in 11 patients (12 eyes). RNFL photographs revealed a nerve fibre loss in 10 of the 12 cases (83%). However, even accurate cup to disc ratio measurements from disc stereophotographs enlarged 20 times showed a measurable increase of horizontal and vertical cup to disc ratios in only 33% and 42% of the pathological cases, respectively. This result indicates that haemorrhage-associated RNFL defects precede measurable changes of the optic disc configuration. Therefore, RNFL photography seems to be a useful and sensitive examination method for the detection of the earliest organic damage in glaucoma.


Assessment of sleep disturbance in oral lichen planus and validation of PSQI: A case-control multicenter study from the SIPMO (Italian Society of Oral Pathology and Medicine).
The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values < 0.001**). Moreover, OLPs had higher scores in the HAM-D, HAM-A, NRS, and T-PRI (p-values < 0.001**). No differences in the PSQI sub-items' scores were found between the K-OLPs and nK-OLPs, although nK-OLPs suffered from higher levels of anxiety, depression, and pain (p-values: HAM-A, 0.007**, HAM-D, 0.009**, NRS, <0.001**, T-PRI, <0.001**). The female gender, anxiety, depression (p-value: 0.007**, 0.001**, 0.020*) and the intensity of pain, anxiety, and depression (p-value: 0.006**, <0.001**, 0.014*) were independent predictors of poor sleep (PSQI > 5) in K-OLPs and nK-OLPs, respectively. The PSQI's validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.


Leukemic Involvement Is a Common Feature in Waldenström Macroglobulinemia at Diagnosis.
Waldenström Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with bone marrow (BM) involvement and IgM monoclonal gammopathy. To date, no studies have focused specifically on peripheral blood (PB) involvement. In this study, 100 patients diagnosed with WM according to the World Health Organization (WHO) criteria were included based on the demonstration of MYD88mut in BM and the availability of PB multiparametric flow cytometry (MFC) analysis. Leukemic involvement by MFC was detected in 50/100 patients. A low percentage of mature small lymphocytes in PB smears was observed in only 15 cases. MYD88mut by AS-qPCR was detected in PB in 65/100 cases. In cases with leukemic expression by MFC, MYD88mut was detected in all cases, and IGH was rearranged in 44/49 cases. In 21/50 patients without PB involvement by MFC, molecular data were consistent with circulating disease (MYD88mut by AS-qPCR 3/50, IGH rearranged 6/50, both 12/50). Therefore, PB involvement by standard techniques was detected in 71/100 patients. MYD88mut was detected in PB by dPCR in 9/29 triple negative cases. Overall, 80% of the patients presented PB involvement by any technique. Our findings support the role of PB MFC in the evaluation of patients with IgM monoclonal gammopathy and provide reliable information on correlation with molecular features. The development of a feasible MFC assay may stand as an objective tool in the classification of mature B cell neoplasms presenting with IgM monoclonal gammopathy.


Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity.
At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient's blood had been almost unexplored. To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients' blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. To sum up, our derived data show, that injury of erythrocytes' redox-status and blood plasma components plays an essential role in development and progression CAP.


Biological effects of Tire and Road Wear Particles (TRWP) assessed by in vitro and in vivo studies - A systematic review.
Air quality is a critical issue because even small amounts of air pollutants can cause significant adverse health effects. Road traffic is a major contributor to air pollution both through aerosols from exhaust emissions (EE) and non-exhaust emissions (NEE). The latter result from mechanical abrasion of brakes and tires, erosion of road surfaces and resuspension of road dust into the atmosphere by passing traffic. EE have been extensively characterized and have declined over time due to mitigation measures. By contrast, NEE have been less studied, are not tightly regulated and there are limited data on their toxicity. Thus, NEE relative part has become prevalent, potentially making of these emissions a major human health concern. The aim of this systematic review was to provide an overview of the current state of knowledge on the biological effects of NEE. We paid particular attention to the toxicological effects of Tire and Road Wear Particles (TRWP) induced in vitro and in vivo in mammalian models. To this end, we performed a bibliographic search in two databases (PubMed and Web of Science). Of the 400 papers, 22 were found to be relevant and included in our analysis, confirming that the assessment of the TRWP toxicity in mammalian models is still limited. This review also reports that oxidative stress and inflammation are the main mechanisms underlying the toxicity of TRWP.


Suspension feeding of anuran larvae at low concentrations of Chlorella algae (Amphibia, Anura).
Ingestion and filtering rates in larval Xenopus laevis, Bufo calamita, Rana temporia and Bufo bufo fed suspensions of Chlorella fusca were investigated. Concentrations were measured with a Coulter Counter. (1) For all species, filtration occurred at concentrations far below those reported by other authors for Rana sylvatica feeding on Chlorella pyrenoidosa. For Bufo bufo, only larvae near metamorphosis showed ingestion at low particle concentrations. Since buccopharyngeal ventilation continues even in the absence of food particles, this threshold feeding behaviour in the younger larvae must be due to different mechanisms to those found in Daphnia and Calanus studied by other authors: probably reduction of the buccal pumping rate and the mucus production of the filter apparatus. (2) For B. calamita, R. temporaria and X. laevis the highest suspension feeding efficiency was at early tadpole stages, corresponding with the high growth rate of these stages. (3) The life histories of the species provide the basis for understanding their different retention efficiencies and functional responses.


International adoption: a personal perspective.
The personal perspective of an international adoptee from Korea based on her own experiences is described in this article.


Oral contraceptive use in women at increased risk of breast/ovarian cancer: knowledge and attitudes.
Several of the health benefits and risks associated with the combined oral contraceptive pill (COCP) are particularly relevant to women at risk of hereditary breast and/or ovarian cancer. Eighty-three past female patients of an Australian hereditary cancer clinic aged 18-50 years completed a self-report questionnaire to assess their contraceptive practices, knowledge and information needs (44% response rate). Ninety-two percent of participants had previously used the COCP, with a mean knowledge score of 3.63 out of 8. Nearly 40% reported that their family history of cancer was one reason they discontinued/avoided using the COCP. Women reported receiving insufficient COCP information and preferred a targeted information leaflet to answer their questions. Although recall bias may have affected some women, there is a clear need to improve the consistency of information delivered to women at risk of hereditary breast and/or ovarian cancer, to ensure informed contraceptive choices are made.


Application of Lanthanide Shift Reagent to the 1H-NMR Assignments of Acridone Alkaloids.
This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids (1-3) and pyranoacridone alkaloids (4-6). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm)3. Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm)3 to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry.


Effect of ischemia reperfusion on sodium-dependent phosphate transport in renal brush border membranes.
The effect of ischemia induced acute renal failure (ARF) on the transport of phosphate (Pi) after early (15-30 min) and prolonged (60 min) ischemia in the brush border membrane vesicles (BBMV) from rat renal cortex was studied. Sodium-dependent transport of Pi declined significantly and progressively due to ischemia. Western blot analysis of BBM from ischemic rats showed decreased expression of NaPi-2. A compensatory increase was observed in Pi uptake in BBMV from contralateral kidneys. There was no significant difference in NaPi-2 expression between BBMV from sham and contralateral kidneys. Early blood reperfusion for 15 min after 30 min ischemia caused further decline in Pi uptake. Prolonged reperfusion for 120 min caused partial reversal of transport activities in 30-min ischemic rats. However, no improvement in the transport of Pi was observed in 60-min ischemic rats after 120 min of blood reperfusion. Kinetic studies showed that the effect of ischemia and blood reperfusion was dependent on the Vmax of the Na-Pi transporter. Western blot analysis showed increased expression of NaPi-2 in the BBMs from ischemia-reperfusion animals. Further, a shift in the association of Na ions to transport one molecule of Pi was observed under different extracellular Na concentrations [Na]o. Feeding rats with low Pi diet and/or treatment with thyroid hormone (T3) prior to ischemia resulted in increased basal Pi transport. Ischemia caused similar decline in Pi transport in BBM from LPD and/or T3 animals. However, recovery in these animals was faster than the normal Pi diet fed (NPD) animals. The study suggests a change in the intrinsic properties of the Na-Pi transporter in rat kidneys due to ischemia. The study also indicates that treatment with T3 and feeding LPD prior to ischemia caused faster recovery of phosphate uptake due to ischemia-reperfusion injury.


Skin perfusion assessed by contrast ultrasound predicts tissue survival in a free flap model.
The purpose of this study was to assess perfusion in a free skin flap model using contrast-enhanced ultrasound (CEU), and to determine if the extent of perfusion early after venous occlusion predicted long-term flap survival. Perfusion was assessed in an autologous abdominal skin flap and adjacent healthy skin in rats using CEU imaging before venous occlusion and following reflow. Perfusion assessment was possible in all flaps and quantitative measurements of microvascular blood volume (BV) and blood velocity were expressed as a ratio to that in the healthy skin. Proximal flap BV 18 h after venous occlusion was significantly greater in those that survived (n = 4) vs. those that became necrotic (n = 6) (BV ratio 0.8 +/- 0.1 vs. 0.2 +/- 0.1, p = 0.0001). A BV ratio of 0.5 predicted graft viability with a sensitivity and specificity of 100%. Microvascular blood velocity at 18 h was similar in grafts that survived and those that became necrotic. Qualitative assessment of perfusion by a "blinded" observer correlated well with quantitative data and predicted flap outcome in all cases. We conclude that skin perfusion can be assessed with CEU. Perfusion 18 h following a secondary ischemic insult in a free flap accurately predicts subsequent tissue survival in this model.


GABA-mediated potentiation of amine release from nigrostriatal dopamine neurones in vitro.
The uptake and release of 3H-dopamine was studied in slices of corpus striatum and substantia nigra in the presence of nialamide. High potassium triggered the outflow of tritium in both brain structures and this release was potentiated by GABA in a dose related fashion, whereas the spontaneous overflow of radioactivity was unchanged. This action of GABA was mimicked by the GABA-T antagonists aminooxyacetic acid and ethanolamine-O-sulphate, but not by the GABA analogues muscimol, 3-aminopropanesulphonic acid, gamma-hydroxybutyrate or beta-(p-chlorophenyl)-GABA. The response to GABA was not blocked by picotoxin, which itself facilitated the evoked release of 3H-dopamine, nor by bicuculline or the omission of calcium ions from the bathing medium. GABA facilitation of K+-evoked 3H-dopamine release was increased significantly on reducing tissue thickness and following prolonged incubation with GABA. GABA also potentiated the depolarization induced outflow of 3H-noradrenaline, 3H-5-hydroxytryptamine and 3H-histamine without affecting their initial accumulation. Veratridine, amphetamine and cold dopamine also raised the output of 3H-dopamine, but none of these releases was altered by GABA. The uptake of 3H-dopamine, but not that of 14C-GABA, was considerably attenuated in 6-hydroxydopamine lesioned corpora striata. The possible mechanism(s) of this stimulatory action of GABA is discussed.


Riboflavin transport and metabolism in humans.
Recent studies elucidated how riboflavin transporters and FAD forming enzymes work in humans and create a coordinated flavin network ensuring the maintenance of cellular flavoproteome. Alteration of this network may be causative of severe metabolic disorders such as multiple acyl-CoA dehydrogenase deficiency (MADD) or Brown-Vialetto-van Laere syndrome. A crucial step in the maintenance of FAD homeostasis is riboflavin uptake by plasma and mitochondrial membranes. Therefore, studies on recently identified human plasma membrane riboflavin transporters are presented, together with those in which still unidentified mitochondrial riboflavin transporter(s) have been described. A main goal of future research is to fill the gaps still existing as for some transcriptional, functional and structural details of human FAD synthases (FADS) encoded by FLAD1 gene, a novel "redox sensing" enzyme. In the frame of the hypothesis that FADS, acting as a "FAD chaperone", could play a crucial role in the biogenesis of mitochondrial flavo-proteome, several basic functional aspects of flavin cofactor delivery to cognate apo-flavoenzyme are also briefly dealt with. The establishment of model organisms performing altered FAD homeostasis will improve the molecular description of human pathologies. The molecular and functional studies of transporters and enzymes herereported, provide guidelines for improving therapies which may have beneficial effects on the altered metabolism.


The burden of a brain tumor: guiding patient centric care in neuro-oncology.
Brain tumor patients report an overwhelming sense of uncertainty when navigating the course of their terminal disease. Historically, organizational experts and/or treating physicians have established neuro-oncology programs. However, given the disease burden and incurable nature of current medical treatments, patient-centric care should be prioritized alongside institutional and academic objectives. Integrating patient perspectives into interdisciplinary programmatic development can improve comprehensive care and empower patients to advocate for their own quality healthcare needs. Data was derived from four focus groups with adult brain tumor patients (N = 15; Mage = 46 years, 53% female). A trained moderator led each 90-min group and posed semi-structured questions regarding patients' care needs throughout their neuro-oncological disease trajectory. Emphasis was placed on quality of life and psychological distress reduction for both patients and their loved ones. Common themes were identified via thematic content analysis using NVivo software. A high inter-rater reliability (Mkappa = 0.92, range= 0.85-0.93) was achieved. Six distinct themes emerged, where the frequency of each theme ranged from 12.5 to 23.3%. Specifically, patients discussed relational concerns, navigation of interdisciplinary care, neurobehavioral impacts, emotional responses to stressors, existential concerns, and caregiver support. A discussion of themes follows. It is imperative that we include the patient perspective in the development of neuro-oncology programs; considering the quality of survival in addition to quantity. Neuro-oncology quality care themes identified were relational concerns, navigating interdisciplinary care, neurobehavioral impact, emotional response to stressors, existential concerns, and caregiver support. A paramount concentration for comprehensive neuro-oncology programs must include patients' quality needs.


N-mineralization of formaldehyde-releasing N-compounds.
The mineralization of several N-compounds, such as MMU, DMU, and HMT, as well as their respective nitrificide action, have been investigated. It has been proved that the amount of available formaldehyde, as well as its rate of release, are responsible for the specific action of these compounds on the N-mineralization process. Factors affecting the rate of release, namely molecular structure, solubility, and temperature, are discussed as well. Importance of these N-compounds as slow-release N-fertilizers based on a new molecular-microbiological approach is described.


Examining the protective role of the posterior elements of the spine against endplate fractures in a porcine model.
Previous studies have shown that the posterior elements/facet joints provide strength to the overall functional spine unit (FSU) by taking 3-25% of vertical compressive load off the intervertebral disc (IVD). However, little is known regarding whether this offloading has a protective effect against endplate fracture. Therefore, the purpose of this study was to investigate if the posterior elements provide a protective role to the endplate in porcine cervical spines under fracture-inducing conditions. Twenty-two cervical porcine FSUs (C5/6 level) were randomized into two groups: 1) a control group which had their posterior elements left intact (n = 11); 2) an experimental group which had the posterior elements removed (n = 11). Each FSU underwent a previously reported rapid IVD pressurization protocol in order to create endplate fractures. Briefly, hydraulic fluid was rapidly injected into the IVD via a standard inflation needle inserted through the anterior annulus which was connected to a hydraulic pump and pressure transducer. Post pressurization, each FSU was dissected to determine the presence and size of endplate fracture. Peak pressurization and rate of pressurization were not found to differ between intact and cut specimens (p = 0.313 and 0.101, respectively). In contrast, significantly, more cut FSUs sustained an endplate fracture (11/11) compared to intact FSUs (5/11); p = 0.012. Further, cut FSUs resulted in a fracture area 1.91 times greater in size compared to the fractures seen in the intact FSUs (p = 0.011). Therefore, posterior elements appear to decrease the risk and severity of endplate fracture.


Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.
Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.


Retrospective: Patricia S. Goldman-Rakic, pioneer in neuroscience and co-founder of the journal, Cerebral Cortex.
Patricia Goldman-Rakic (1937-2003), the co-founder of this journal, was a pioneering neuroscientist who made transformational discoveries about the prefrontal cortex and the neurobiological basis of working memory. Her research served as the foundation for cognitive neuroscience, and paved the path for women in science. Her multidisciplinary approach created a new paradigm, where the scientific question, rather than a single method, was paramount to the investigation. The current review provides a brief summary of her extraordinary life and scientific contributions.


Body mass index and height in relation to brain tumor risk in a Japanese population.
Although height and body mass index (BMI) are reported to be positively associated with several common cancers, evidence regarding their association with brain tumor risk remains sparse, particularly in Asian populations. In this study, we analyzed the association between height and BMI and brain tumor risk in a Japanese population using a large population-based prospective cohort study. A total of 102,925 participants (48,213 men and 54,712 women) enrolled in the Japan Public Health Center-based Prospective Study were followed from baseline, namely 1990 for cohort I and 1993 for cohort II, until 2012. Information on participants' dietary and lifestyle habits, including height and body weight, was collected through survey questionnaires administered at baseline. We used the Cox proportional hazards regression model to estimate hazard ratios and 95% confidence intervals (CIs) for brain tumor incidence, with adjustment for potential confounding variables. During an average follow-up of 18.1 years, 157 (70 men and 87 women) cases of brain tumor were newly diagnosed. BMI showed a statistically insignificant positive association with the risk of brain tumor. In addition, statistically significant positive trends were seen for men and meningioma, with multivariable-adjusted hazard ratios for a BMI of 27.5 to less than 40 versus 18.5 to less than 23 kg per m2 of 2.14 (95% CI = 0.99-4.59) (P = 0.03) and 1.98 (95% CI = 0.84-4.67) (P = 0.046), respectively. In contrast, height showed no clear association with brain tumor risk, overall or in subgroup analysis. Compared with a BMI of 18 to less than 23.5 kg per m2, a higher BMI was associated with higher risk of brain tumor, particularly in men and with meningioma.


Mythology to reality: case report on a giant cutaneous horn of the scalp in an African American female.
We present a case study of a patient with a rare and disfiguring dermatologic condition known as cornu cutaneum, or giant cutaneous horn (GCH). While this condition has been well described in people of European and Asian ancestry, its presence in African populations is perceived to be rare and has not been reported in the literature until recently. We present the case of cornu cutaneum in a woman of African descent, contributing to the recent evidence that this condition may not be as rare in African populations as believed. Etiologic factors, epidemiology and management are also reviewed.


[Determinants of asthma among children and adolescents in Germany. Results of the German Health and Examination Survey for Children and Adolescents (KiGGS)].
In this study, associations between current asthma and possible determinants were studied using data of the German Health Interview and Examination Survey for Children and Adolescents ("Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland," KiGGS). In this nationwide cross-sectional survey, 17,461 subjects aged 0-17 years were examined between 2003 and 2006. Data collection included a medical examination of the child, an interview of the parents, and written questionnaires. Apart from prevalence estimates, multivariate logistic regression analyses were performed. Increasing age and male sex, previous atopic diseases of the child, a positive family history of allergic diseases and low birth weight were significant risk factors of asthma, as were overweight and moldy walls in the residence. Breast feeding was not associated with a reduced risk of asthma. Low age at delivery of the mother and living in rural or provincial regions were shown to be protected. Overall, this study suggests that allergies of the parents and previous atopic disease of the child are the strongest determinants of asthma. However, environmental factors (mold on walls, living in rural and provincial towns) and lifestyle factors could also modify asthma risk.


Enzyme induction by daunorubicin in neonatal heart cells in culture.
The effect of the antineoplastic agent daunorubicin on beating heart cells from neonatal rats was investigated with respect to cell damage and induction of enzymes possibly involved in drug metabolism. Of the enzymes assayed DT-diaphorase and glutathione-S-transferase showed a two-to-four fold increase in activity: higher concentrations of daunorubicin inactivated glutathione-S-transferase. Daunorubicin toxicity increased in the presence of dicoumarol, a specific inhibitor of DT-diaphorase. These results indicate that both DT-diaphorase and glutathione-S-transferase may be involved in the metabolism of daunorubicin.


Sensitive Structural Control of Macrocycle Threading by a Fluorescent Squaraine Dye Flanked by Polymer Chains.
A macrocyclic tetralactam is threaded by a complementary squaraine dye that is flanked by two polyethylene glycol chains to produce a pseudorotaxane complex with favorable near-infrared fluorescence properties. The association thermodynamics and kinetics were measured for a homologous series of squaraines with different N-alkyl substituents at both ends of the dye. The results show that subtle changes in substituent steric size have profound effects on threading kinetics without greatly altering the very high association constant.


An investigation of modifying effects of single nucleotide polymorphisms in metabolism-related genes on the relationship between peripheral nerve function and mercury levels in urine and hair.
Mercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n=515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves was recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl-mercury exposure were also collected. Subjects included 244 dentists (47.4%) and 269 non-dentists (52.2%; mostly dental hygienists and dental assistants). The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the US general population (0.95 μg/L and 0.47 μg/g, respectively). In multivariate linear models predicting nerve function adjusting for covariates, only 3 out of a total of 504 models showed stable and statistically significant interaction of SNPs with mercury biomarkers. Overall, given the possibility of false positives, the results suggested little evidence of effect modification of the SNPs on the relationship between mercury biomarkers with peripheral nerve function at exposure levels that are relevant to the general US population.


Multiblock chemometrics for the discrimination of three extra virgin olive oil varieties.
To discriminate samples from three varieties of Tunisian extra virgin olive oils, weighted and non-weighted multiblock partial least squares - discriminant analysis (MB-PLS1-DA) models were compared to PLS1-DA models using data obtained by gas chromatography (GC), or global composition through mid-infrared spectra (MIR). Models performances were determined using percentages of sensitivity, specificity and total correct classification. The choice of threshold level for the interpretation of PLS1-DA results was considered. PLS1-DA models using GC data gave better results than those using MIR data. Even with the most conservative threshold, PLS1-DA on GC data allowed very good predictions for Chemlali variety (99% correct classification), but had more difficulty to discriminate Chetoui and Oueslati samples (95% and 84% correct classification respectively). Non-weighted MB-PLS1-DA models benefiting from the synergy between the two sources of data were more discriminative than simple PLS1-DA, yielding better prediction for Chetoui and Oueslati varieties (98% and 90% correct classification respectively).


Precarious Work Schedules and Sleep: A Study of Unionized Full-Time Workers.
Unlike precarious employment which is temporary and insecure, with inadequate pay, benefits, and legal protections, precarious work schedules can affect workers with permanent full-time jobs in sectors where employment has historically been secure, well-compensated, and even unionized. Precarious work schedules - characterized by long shifts, non-daytime hours, intensity and unsocial work hours - are increasingly prevalent. Relations between precarious work schedules and poor health are not well understood, and less is known about how to attenuate this relation. We examined the indirect effects of precarious work schedules on fatigue and depressive symptoms through sleep quantity. Two moderators - schedule flexibility and sleep quality - were examined as buffers of these associations. Workers from the Departments of Correction and Transportation in a northeast state (N = 222) took surveys and reported on demographics, work schedule characteristics, schedule flexibility, sleep quality and quantity, fatigue, and depressive symptoms. Results revealed that precarious work schedules had indirect effects on fatigue and depressive symptoms through sleep quantity. Schedule flexibility moderated the relation between precarious work schedules and sleep quantity, such that workers with greater schedule flexibility had more hours of sleep. Sleep quality moderated the association between sleep quantity and fatigue and depressive symptoms, such that workers reported greater fatigue and depressive symptoms when they had poorer sleep quality. Findings have direct applicability for developing initiatives that enhance Total Worker Health® through individual and organizational changes. The online version contains supplementary material available at 10.1007/s41542-022-00114-y.


To what extent do people living with HIV, people on pre-exposure prophylaxis, doctors and pharmacists endorse 90-day dispensing of antiretroviral therapy in France?
The WHO 95-95-95 targets for 2030 do not imply that people living with HIV (PLHIV) achieve a good quality of life. The current 30-day dispensing interval for antiretroviral (ART) burdens the healthcare system. Lengthening dispensing intervals could alleviate this burden as well as enhance patient well-being. To capture perceptions on 90-day dispensing interval (90D) for ART from the perspective of PLHIV, people on pre-exposure prophylaxis (PrEP), doctors, and pharmacists. Multi-centre observational survey led in France from 16 to 20 October 2020, among doctors agreeing to participate via regional coordinated care organisations for HIV, all PLHIV or people on PrEP consulting these outpatient-clinic doctors, and pharmacists doing ART dispensing. The survey was completed by 220 doctors who saw 1087 people (999 PLHIV; 88 on PrEP) and 176 pharmacists from 55 centres. Among the PLHIV, 855 (85.6%, 95% CI: 83.2%-87.7%) and among the patients on PrEP, 70 (79.5%, 95% CI: 69.6%-87.4%) stated they would be interested in 90D. All in all, patients who were more likely to endorse 90D are those who opt exclusively for hospital dispensing (OR 3.22 [1.57-6.58]) and who rotate between hospital and community pharmacy dispensing (OR 3.29 [1.15-9.32]). Patients who were less likely to endorse 90-D were those who consult in a city located outside the 3 French high HIV prevalence regions (OR 0.66 [0.44-0.99]), receive 2 vs 1 pill QD regimens (OR 0.53 [0.31-0.91]), and anticipate at least one vs no limitation to 90D (OR 0.27 [0.17-0.42]). 90D was perceived as possible by 152 pharmacists (86.4%), including 8 (5%) without restriction, and 219 doctors (99.6%), including 42 (19.2%) regardless of PLHIV's immunovirologic status or social conditions (health insurance coverage, access to housing or accommodation, access to rights, resources). Comparison of the benefits and limitations of a 90-day ART dispensing interval as perceived by PLHIV and people on PrEP, doctors and pharmacists shows that doctors anticipate a higher number of benefits than people on ART and/or pharmacists, chiefly that 90D would be more convenient and create less risk of drug shortages and that patients would gain autonomy and a better quality of life. Pharmacists were found to clearly perceive the economic benefits (90D would be less expensive) but anticipate more drawbacks than doctors and the people on ART themselves: more administrative burdens, more non-dispensing if doses get lost, harder to track adherence and more drug-drug interaction issues, and more work as they shall have to warn the patient of potential risks of shortages due to the cost of the stock. A clear majority of PLHIV, people on PrEP, doctors, and pharmacists endorsed 90D of ART. Most patients thought that 90D would be a good option, whereas most pharmacists and doctors thought that eligibility for 90D dispensing should depend on immunovirologic factors and social condition criteria. Moreover, pharmacists thought it would be necessary to commit regulatory resources and a better follow-up on adherence and drug-drug interactions.


Key Metabolic Functions of β-Arrestins: Studies with Novel Mouse Models.
β-Arrestin-1 and -2 are intracellular proteins that are able to inhibit signaling via G protein-coupled receptors (GPCRs). However, both proteins can also modulate cellular functions in a G protein-independent fashion. During the past few years, studies with mutant mice selectivity lacking β-arrestin-1 and/or -2 in metabolically important cell types have led to novel insights into the mechanisms through which β-arrestins regulate key metabolic processes in vivo, including whole-body glucose and energy homeostasis. The novel information gained from these studies should inform the development of novel drugs, including β-arrestin- or G protein-biased GPCR ligands, that could prove useful for the therapy of several important pathophysiological conditions, including type 2 diabetes and obesity.


Incidence of oronasal fistulae and velopharyngeal insufficiency after cleft palate repair: an audit of 211 children born between 1990 and 2004.
We present an audit of primary cleft palate surgery at our unit, including rates of oronasal fistula development, speech outcomes, and rates of velopharyngeal insufficiency requiring secondary surgery. A retrospective study of patients with all cleft palate types, born between January 1990 and December 2004, who underwent primary palatoplasty at Middlemore Hospital, Auckland, New Zealand. The study included 211 patients, collectively operated on by five different surgeons. The overall rate of true fistula development was 12.8% over a mean follow-up period of 4 years 10 months. The incidence of true fistulae that required surgical repair was 8.1%. Fistula rates were higher for more severe degrees of clefting but were not affected by gender or type of surgical repair. Overall, 31.8% of the study population had some degree of hypernasality following primary palatoplasty. Secondary surgery for velopharyngeal insufficiency was required in 13.3% of patients. Following surgical correction of velopharyngeal insufficiency, no patients were reported to have appreciable hypernasality and 21.7% were reported to have mild hypernasality, a result comparable to previously published audits. The requirement for secondary surgery was higher in patients with more severe clefts. Our results are comparable to other recent studies. We believe that highly coordinated cleft care helps ensure such outcomes. These data provide a benchmark against which we can measure future performance in our attempts to improve outcomes of cleft repair.


Patient influenza vaccination reduces the risk of hospital-acquired influenza: An incident test negative-case control study in Lyon university hospital, France (2004-2020).
Literature is limited on the impact of patient vaccination on the risk of hospital-acquired influenza (HAI). This test negative case-control study nested in a surveillance program aimed at evaluating the effectiveness of influenza vaccination in reducing the risk of HAI in hospitalized patients during 15 influenza seasons (2004-05 to 2019-20). HAI cases were those who developed influenza like illness (ILI) symptoms at least 72 h after hospitalization and had a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Controls were those with ILI symptoms and a negative RT-PCR test. A nasal swab as well as socio-demographic, clinical data and information on influenza vaccination were collected. Of the 296 patients included, 67 were confirmed HAI cases. Influenza vaccine coverage was significantly higher among controls compared to HAI cases (p = 0.002). The risk of HAI was reduced by almost 60 % in vaccinated patients. A better control of HAI can be achieved by vaccinating hospitalized patients.


Myosin light chain kinase modulates hypotonicity-induced Ca2+ entry and Cl- channel activity in human cervical cancer cells.
Hypotonicity-induced Ca2+ entry is a critical signal for the normal regulatory volume decrease in human cervical cancer cells. The aim of this study was to explore the role of myosin light chain kinase (MLCK) in the regulation of hypotonicity-induced Ca2+ signalling and Cl- channel activity. Blockade of MLCK activity by MLCK(11-19) amide, a substrate-specific peptide inhibitor, markedly attenuated hypotonicity-induced Ca2+ entry. A similar result was obtained with ML-7, a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK. More than 85% of the activity of the volume-regulated Cl- channel was suppressed when intracellular Ca2+ was buffered to near zero in the absence of extracellular Ca2+, suggesting that hypotonicity-induced Ca2+ signalling is important for the activation of the volume-regulated Cl- channel. Intracellular dialysis with MLCK(11-19) amide or ML-7 concentration-dependently reduced the amplitude and rate of activation of the volume-regulated Cl- channel. Swelling-activated taurine transport was also inhibited concentration dependently by ML-7 and MLCK(11-19) amide with IC(50) values of 6.4 and 2.0 microM, respectively. Hypotonicity induced MLC phosphorylation which was mediated totally by MLCK and depended on Ca2+ entry. However, phosphorylated MLC per se was not involved critically in the regulation of Ca2+ entry and activation of volume-sensitive organic osmolyte/anion channels (VSOAC). We propose that MLCK has a novel function in regulating the activation of VSOAC by mediating Ca2+ entry in response to hypotonicity. This function of MLCK on Ca2+ signalling does not correlate with MLC phosphorylation.


Late osteoarticular lesions following meningococcemia with disseminated intravascular coagulation.
Nineteen children, who had been admitted to the Pediatric Hospital of Coimbra with severe meningococcal infection with DIC, were submitted to clinical and radiological examination, an average of 4.2 years after hospitalization, in order to demonstrate late skeletal lesions. Patellar dystrophy, to our knowledge previously unreported, was found in 4 children, all of whom had overlying cutaneous scarring.


A strategy-purifying wastewater with waste materials: Zn2+ modified waste red mud as recoverable adsorbents with an enhanced removal capacity of congo red.
The strategy, called purifying wastewater with waste materials (PWWM), can simultaneously improve the secondary utilization of industrial waste materials and in turn, reduce environmental pollution. However, the PWWM strategy has still not been extensively used because of its low purification efficiency of organic pollutants and extremely difficult secondary utilization process. Herein, we use zinc aluminum silicate (ZAS) to modify waste granular red mud (GRM) to form a recoverable adsorbent, called ZAS/GRM adsorbent. The ZAS has been found to exhibit exceptional adsorption performance with the ability to firmly anchor onto the surface of GRM, in which heavy metal ions can effectively solidify and reduce their outflow. Furthermore, many voids have been tactfully designed in the ZAS/GRM adsorbents by using a water vapor project, which provide more active sites for congo red (CR) organic dye, thereby remarkably improving the removal efficiency of CR. From our purification of CR, we find that the CR adsorption capacity of the ZAS/GRM adsorbent is 3.509 mg g-1, which is four times higher than pure GRM (0.820 mg g-1). This study demonstrates our PWWM strategy is highly effective and can inspire more research on waste reuse.


Dried Blood Spot Self-Sampling by Guardians of Children With Epilepsy Is Feasible: Comparison With Plasma for Multiple Antiepileptic Drugs.
Dried blood spot (DBS) is an attractive matrix alternative to plasma for the measurement of antiepileptic drug concentrations with the possibility of self-sampling at home. The aim of this study was to evaluate whether DBS concentrations from a children population could be used as an alternative to plasma concentrations in a clinical routine laboratory. Children with epilepsy using carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA) had capillary blood collected for routine plasma analysis. DBS samples were collected by guardians or nurses, and the quality of sampling was compared between the groups. DBS samples were analyzed with liquid chromatography-tandem mass spectrometry methods and plasma samples with immunochemical methods. In the comparison between DBS and plasma concentrations, previously analyzed sample data were pooled with data in this study and resulted in 190 comparison pairs. A bioanalytical cross-validation according to European Medicines Agency was performed. Clinicians evaluated the results to understand if a DBS concentration was linked to a different clinical dose recommendation for the patient in comparison with plasma concentrations. Comparison of DBS sample quality showed that 2.3% of the capillary DBS collected by guardians were rejected and 8.0% of the capillary DBS collected by nurses. For DBS, a conversion factor of 0.85 for CBZ and 1.65 for VPA was applied for the comparison with plasma. LTG and LEV results were directly comparable. In the cross-validation, 88% of CBZ, 75% of LTG, 74% of LEV, and 94% of VPA comparisons were within 20% of the difference of the mean, although LEV had a few major differences (+31% to -40%). In 4 of the 190 comparisons, the clinical evaluation indicated a risk of conflicting decisions regarding the need for dose adjustment when using DBS concentrations. However, the risk of negative patient outcomes was considered negligible. Our study demonstrates that a combination of bioanalytical cross-validation and clinical evaluation is an effective way to describe the applicability of DBS as an alternative to plasma, taking into account how therapeutic drug monitoring is used in specific patient groups. For LTG, converted CBZ and VPA, DBS is a feasible alternative for self-sampling at home. DBS for LEV can only be recommended for nonadherence queries due to the high variability of the plasma/DBS concentration ratios.


Synthesis of the (1→6)-linked thiodisaccharide of galactofuranose: inhibitory activity against a β-galactofuranosidase.
A new (1→6)-linked thiodisaccharide formed by two galactofuranosyl units has been synthesized. Methyl (methyl α,β-D-galactofuranosid)uronate was employed as the starting compound, which was per-O-silylated with TBSCl and reduced with LiAlH4 to afford methyl 2,3,5-tri-O-tert-butyldimethylsilyl-β-D-galactofuranoside (2β) as a key precursor for the preparation of methyl per-O-tert-butyldimethylsilyl-6-thio-β-D-galactofuranoside (12). The free thiol group of 12 was glycosylated and the product O-deprotected to afford the target β-D-Galf-S-(1→6)-β-d-Galf-OMe (14). The conformations of this thiodisaccharide were preliminarily studied using combined theoretical calculations and NMR data. Furthermore, the glycomimetic 14 showed to be a competitive inhibitor of the β-galactofuranosidase from Penicillum fellutanum (K(i)=3.62 mM).


Yersinia pestis is viable with endotoxin composed of only lipid A.
Lipopolysaccharide (LPS) is the major outer membrane component of gram-negative bacteria. The minimal LPS structure for viability of Escherichia coli and Salmonella enterica serovar Typhimurium is lipid A glycosylated with 3-deoxy-D-manno-octulosonic acid (Kdo) residues. Here we show that another member of the Enterobacteriaceae, Yersinia pestis, can survive without Kdo in its LPS.


Reimplantation of an extruded osteoarticular segment of the femur: Case series and in vitro study in a rat model.
The treatment of open femur fractures with reimplantation of large extruded segments remains one of the most difficult clinical management scenarios. The situation is even complicated when the extruded segments contains a large osteoarticular segment and no consensus exist about the efficient sterilization. We successfully managed five cases of open femur fracture by reimplantation of a large osteoarticular segment. While the outcomes were favourable, we performed an in vitro investigation in a rat model to determine whether the bone segment preparation strategy was optimal. After meticulous debridement and sterilization with povidone-iodine scrub/orthopaedic antibiotic solution, osteoarticular segments of the femur were reimplanted successfully in five patients with Gustilo-Anderson IIIa-IIIb fractures. Furthermore, in vitro study performed to assess the relative efficacy of various methods of sterilization employed osteoarticular segments of rat femurs. After contamination, osteoarticular segments were treated via one of the following protocols: (1) saline rinse; (2) povidone-iodine scrub and saline rinse; (3) povidone-iodine scrub and autoclaving; (4) povidone-iodine scrub and immersion in antibiotic solution; (5) povidone-iodine scrub and immersion in povidone-iodine solution; or (6) povidone-iodine scrub and gamma-irradiation. The osteoarticular segments were then cultured and finally evaluated for infection and morphological changes. At the mean 40 month follow-up, there were no infection in the patients and the fractures achieved completed union. For the basic research, only approaches involving povidone-iodine scrub with autoclaving or antibiotic solution immersion were 100% effective in eliminating bacterial growth. Furthermore, povidone-iodine scrub with antibiotic solution immersion preserved the articular surface morphology. Our study suggests that reimplantation of extruded osteoarticular segments of long bone may represent a feasible alternative to amputation. This is the first description of such a technique and its long-term outcomes in the clinical setting, which were corroborated with the outcomes of in vitro investigation in a rat model, concluding that contaminated extruded osteoarticular segments can be adequately sterilized for reimplantation by cleaning with povidone-iodine scrub followed by brief soaking in antibiotic solution. However, it remains unclear whether the antibacterial efficacy of different sterilizations noted in vitro is reflected in vivo, warranting further research.


The scavenger receptor BI and its ligand, HDL: partners in crime against HCV neutralizing antibodies.
Better knowledge of the viral and host factors that determine HCV clearance vs. persistence at the acute stage of infection is needed in order to improve antiviral therapy and develop efficient vaccines. Spontaneous HCV clearance is associated with a strong, early and broad cellular immune response. Yet, several observations suggest that antibody-mediated neutralisation occurs during HCV infection in vivo and that polyclonal antibodies to HCV can be protective. The recent development of HCV infection assays has confirmed that sera from HCV-infected patients neutralise infection in vitro. Recent studies have demonstrated that Nt-antibodies, of narrow specificity, are induced during the early phase of infection and could play a role in controlling viral infection or clearance. Yet, high-titre, broadly cross-reacting Nt-antibodies are readily detected in chronically infected patients, suggesting that their effectiveness is limited in patients who do not resolve the disease. The factors that mitigate the impact of the Nt-antibody response need to be clarified. Here we review some essential features of the Nt-antibody responses to HCV. We then discuss an original mechanism that HCV may use in vivo to attenuate Nt-antibodies, which involves the hyper-variable region-1 of the HCV-E2 glycoprotein, high-density lipoprotein (HDL) and the physiologic activity of the scavenger receptor BI, a receptor shared by both HCV and HDL.


Does motilin regulate canine interdigestive gastric motility?
Our objective was to determine whether motilin increases the frequency of cyclic interdigestive motor activity in the canine proximal stomach. In 4 conscious dogs with autotransplanted proximal gastric pouches and gastrointestinal electrodes, intravenous infusions of motilin (0.6 microgram/kg body wt/hr) increased the frequency of the interdigestive cycles by 30% both in the pouch and in the main gastrointestinal tract. However, the 3-min interval between the end of a cycle in the pouch and the end of a cycle in the duodenum was unchanged by motilin. In control experiments, without motilin infusion, the concentration of endogenous motilin in the plasma during the intense contractile phase of the cycles (overall mean 385 pg/ml) was greater in each dog (P less than 0.01) than the concentration during the quiescent phase (overall mean, 256 pg/ml). The concentration of plasma motilin was also greater in the contractile phase (mean, 717 pg/ml) than in the quiescent phase (mean, 587 pg/ml) during exogenous infusions of motilin in two of three dogs (P less than 0.01). We concluded that motilin increased the frequency of cyclic interdigestive motor activity in the canine proximal stomach and that the increase was not dependent on intact proximal gastric extrinsic innervation.