Body mass index: a risk factor for 30-day or six-month mortality in patients undergoing aortic valve replacement?
In recent studies, the impact of a low or high body mass index (BMI) on outcome after cardiac surgery has been the subject of controversy. A retrospective study was conducted to determine the influence of BMI on 30-day and six-month mortality after aortic valve replacement (AVR). A multivariable logistic regression was performed on data from 1,241 consecutive patients (mean age 69 +/- 11 years) who underwent AVR either with (n = 514; 41%) or without coronary artery bypass grafting CABG between 2000 and 2003. A wide spectrum of periprocedural variables was collected, including laboratory data as markers for nutritional status and comorbidity. Patients were followed up for six months after AVR (99% complete). Mortality rates after 30 days and after six months were 3.9% (n = 49) and 7.6% (n = 94), respectively. A low BMI was identified as an independent risk factor for 30-day (OR (odds ratio) 0.87; CI (confidence interval) 0.8-0.94) and six-month mortality (OR 0.91; CI 0.86-0.96). The relationship between the logit function and BMI was linear; however, a BMI value of 24 was considered an appropriate cut-off point. Both models containing the BMI linearly or dichotomic were equivalent. As patients with a lower BMI differ in their preoperative risk profile compared to those with a higher BMI, a saturated propensity score estimating the propensity towards having a BMI < 24 was calculated. The propensity score was not significant in the final models for 30-day and six-month mortality (0.24 and 0.73, respectively), and the OR for BMI remained largely unaltered (0.89 and 0.91, respectively). A BMI < 24 is predictive of an increased risk of mortality after AVR, independently of malnutrition, advanced heart disease, or valve size. Further studies are required to investigate the role of adipose tissue in extreme situations and chronic disease. It is mandatory to include BMI in outcome studies after AVR.


Primary Fibroblastic Osteosarcoma of the Lumbar Vertebra on Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.
A 37-year-old man who presented with one year history of lower back and right buttock pain was investigated with contrast enhanced computed tomography (CT), magnetic resonance imaging (MRI), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography which revealed a diagnosis of primary fibroblastic osteosarcoma of the lumbar vertebra. This case highlights the importance of PET/CT imaging.


Guide wire angioplasty balloon catheter: preliminary report.
A new balloon catheter has been developed for angioplasty. The balloon is more flexible and its walls are thinner than those of conventional catheters. It folds down better yet withstands 8-10 atm of pressure. This advance has been married to new guide wire technology, producing a low-profile angioplasty balloon on a 0.038-inch guide wire. It compared favorably with a standard 7-F angioplasty catheter when tested at 4 atm in a rabbit and has been successfully used to dilate ten peripheral stenoses in four patients.


Effects of In Ovo Vitamin D3 Injection on Subsequent Growth of Broilers.
This study was conducted to investigate the influence of in ovo vitamin D3 (Vit D3) administration on growth of broiler chickens when Vit D3 was dissolved in soybean oil. Sixty Ross broiler eggs were incubated at 37.8°C and >60% relative humidity. Distilled water, soybean oil, or Vit D3 (60 IU / 0.5 mL) dissolved in soybean oil, was administered in ovo on Day 18 of incubation. Seven days after hatching, chicks were sexed, and 12 birds (six female and six male) close to the average body weight (BW) of each treatment were selected and their BW continuously recorded until 28 days of age, then sacrificed. Liver and pectoral muscle were collected to determine the mRNA expression of IGF-1 and IGF-1 receptor, and the length of tibia was measured. There were no significant differences in BW, liver weight, or pectoral muscle weight between the groups. However, an interaction was observed between treatments and sexes in the tibia length. In comparison among only males, tibia length in the Vit D3 with oil group was longer than that of the control, but not different from that of the oil group. The same tendency was observed in the hepatic IGF-1 mRNA expression in chicks of either sex, with this effect only being observed after the treatments and not in the control. On the other hand, there was an interaction between treatments and sexes in the mRNA expression of IGF-1 receptor, which was highest in the Vit D3 with oil group in females, but not in males. These results indicated that the in ovo administration of Vit D3 affected IGF-1 receptor mRNA expression without growth.


[Effects of split combined application of organic-inorganic fertilizers on plant growth, 15N absorption, utilization and loss of Gala apple tree].
Fifteen-year-old 'Gala'/M. hupehensis Rehd. trees and 15N trace technique were used to explore the effects of split combined application of organic-inorganic fertilizers on plant growth, 15N absorption, utilization and loss. The main results were as follows: compared to control, combined application of organic-inorganic fertilizers significantly increased the root-shoot ratio, chlorophyll content, total nitrogen content of leaves and mean fruit mass. The effects of split combined application of organic-inorganic fertilizers treatment were more obvious than one time combined application. Combined application of organic-inorganic fertilizers treatment improved the capacity of 15N derived from fertilizer (Ndff) of different organs, with the effects of split combined application of organic-inorganic fertilizers treatment being more significant. The Ndff value of fruits in different treatments were the highest, followed by leaves, biennial branches, fine roots, large roots and perennial branches, and lowest in trunks. Total N content of plant and 15N-urea utilization rate of the split combined application of organic-inorganic fertilizers treatment were 395.39 g and 28.4% respectively, which were obviously higher than the treatments of one time combined application (342.77 g and 21.1%) and no organic fertilizer application (296.41 g and 14.6%), while 15N loss rate was 51.3%, which was obviously lower than the treatments of one time combined application (57.5%) and no organic fertilizer application (60.6%).


Transport of the lipophilic analog minocycline differs from that of tetracycline in susceptible and resistant Escherichia coli strains.
Plasmids which specify resistance to tetracycline offer much less resistance to its more lipophilic analog, minocycline. Resistance to minocycline varies for different plasmids. In the case of plasmid R222 (bearing the class B tetracycline resistance determinant on Tn10), minocycline resistance is comparatively high (10 microgram/ml, or 6% of the tetracycline resistance level). For plasmid pIP7 (bearing the class A determinant), minocycline resistance is only 1% of the tetracycline resistance level. To understand the basis for these differences, we compared the transport of the two tetracyclines by susceptible cells and by resistant cells. Uptake of minocycline by susceptible cells was 10 to 20 times more rapid than uptake of tetracycline and occurred largely via an energy-dependent route. This host-mediated energy-dependent uptake of both analogs was still present in tetracycline-resistant cells. In resistant cells, the same plasmid-mediated active efflux system previously described for tetracycline also exported minocycline. The 15-fold greater susceptibility of tetracycline-resistant R222-bearing cells to minocycline as compared with tetracycline could be explained at least in part by the more rapid influx of minocycline, which more easily overcame the efflux system. The particularly low minocycline resistance offered by pIP7 was due to a weak efflux for minocycline, 10-fold less effective than that mediated by R222. The rate-limiting step for uptake of both analogs appeared to be the outer membrane. That the lipophilic minocycline should cross this membrane more rapidly than tetracycline stands in contrast with other studies which show the outer membrane to be a barrier for entry of lipophilic substances.


Studies of the silencing of baculovirus DNA binding protein.
Baculovirus DNA binding protein (DBP) binds preferentially single-stranded DNA in vitro and colocalizes with viral DNA replication sites. Here, its putative role as viral replication factor has been addressed by RNA interference. Silencing of DBP in Autographa californica multiple nucleopolyhedrovirus-infected cells increased expression of LEF-3, LEF-4, and P35. In contrast, expression of the structural genes coding for P39 and polyhedrin was suppressed while expression of genes coding for P10 and GP64 was unaffected. In the absence of DBP, viral DNA replication sites were formed, indicating replication of viral DNA. Electron microscopy studies, however, revealed a loss of formation of polyhedra and virus envelopment, suggesting that the primary role of DBP is viral formation rather than viral DNA replication.


[The HLA antigen system in married couples with recurrent spontaneous abortions].
Investigations of factors responsible for the disturbance of fetomaternal tolerance during pathological pregnancies and causes of recurrent spontaneous abortions are pointing that HLA antigens play a key role in their development. Rejection of semiallogeneic allograft in this pregnancy disorder is a consequence of interaction between genetic and immunologic phenomena. This article reports results of an investigation of human lymphocyte antigens in 130 couples with recurrent spontaneous abortions and in control group of 57 healthy couples. In both investigated groups the first class of human lymphocyte antigens was detected using microlymphocytotoxicity test by Terasaki. The phenotypic frequencies in the group with recurrent spontaneous abortions were compared with the corresponding results in the control group. We investigated the relative risk for development of this disorder and statistically significant difference of human lympocyte antigen frequencies between both investigated groups. The results of investigation showed that in the group of couples with recurrent spontaneous abortions the relative risk is hihger than 1 for the following human lymphocyte antigens: A2 = (1.53), A9 = (1.149), A10 = (1.07), A29 = (1.70), B18 = (2.24), B40 = (3.31). A significant difference in human lymphocyte antigen frequencies was established for HLA A2, HLA B18 and HLA B40, in comparison with the results of control group. Couples with recurrent spontaneous abortions had a statistically significantly higher rate of identical human lymphocyte antigens among spouses in comparison with the control group, at the level of significance p < 0.05 = 6.32. The results of this investigation showed that human lymphocyte antigens play an etiopathogenic role in development of recurrent spontaneous abortions and that some of these antigens are increasing susceptibility to pregnancy disorders.


In vivo protective performance of N95 respirator and surgical facemask.
The SARS outbreak in 2003 has spawned a major controversy concerning protective performance facemasks for healthcare workers. This study reports a study on in-vivo protective performance of surgical masks and N95 respirators. Typical surgical masks and N95 respirators used in Hong Kong hospitals were tested in comparison with those treated with nano-functional materials (called nano-masks) on various physical properties and in-vivo wear filtration efficiency, as well as usability test in hospitals for surgical masks. Tests on physical properties showed that N95 respirators had significantly lower air permeability and water vapor permeability than surgical masks. The in-vivo filtration tests illustrated that N95 respirators filtered out 97% of potassium chloride (KCl) solution, while surgical masks filtered out 95% of KCl solution. Nano-masks show stronger water repellency and antibacterial activities, but no difference in usability, comparing with normal N95 and surgical masks. Surgical masks can provide in-vivo filtration protection of 95% filtration efficiency. N95 respirators provide higher in-vivo filtration efficiency of 97% with significant reduction of air permeability and water vapor permeability. Compared to normal surgical masks/respirators, the nano-masks can provide additional protective functions in stopping capillary diffusion and antibacterial activities.


Total syntheses of (-)-fructigenine A and (-)-5-N-acetylardeemin.
The first total synthesis of (-)-fructigenine A and a novel approach to (-)-5-N-acetylardeemin through a common imine intermediate (+)-3 are described. The key steps include highly enantioselective preparation of (+)-3 via domino olefination/isomerization/Claisen rearrangement (OIC) of 5, reductive cyclization (RC), and regioselective oxidation of (-)-4 and a novel assembly of the pyrazino ring of these alkaloids via Ugi three-component reaction/cyclization of (+)-3 with the corresponding amino acid and isonitrile.


High-throughput mapping of the promoters of the mouse olfactory receptor genes reveals a new type of mammalian promoter and provides insight into olfactory receptor gene regulation.
The olfactory receptor (OR) genes are the largest mammalian gene family and are expressed in a monogenic and monoallelic fashion in olfactory neurons. Using a high-throughput approach, we mapped the transcription start sites of 1085 of the 1400 murine OR genes and performed computational analysis that revealed potential transcription factor binding sites shared by the majority of these promoters. Our analysis produced a hierarchical model for OR promoter recognition in which unusually high AT content, a unique epigenetic signature, and a stereotypically positioned O/E site distinguish OR promoters from the rest of the murine promoters. Our computations revealed an intriguing correlation between promoter AT content and evolutionary plasticity, as the most AT-rich promoters regulate rapidly evolving gene families. Within the AT-rich promoter category the position of the TATA-box does not correlate with the transcription start site. Instead, a spike in GC composition might define the exact location of the TSS, introducing the concept of "genomic contrast" in transcriptional regulation. Finally, our experiments show that genomic neighborhood rather than promoter sequence correlates with the probability of different OR genes to be expressed in the same olfactory cell.


[Attention deficit disorder: multidisciplinary observational study over 1 year].
In France, attention deficit disorder (ADHD) has traditionally met with two opposing approaches (biological and psychoanalytic). This conflict led us to conduct a multidisciplinary observational study, on a group of 36 children over a period of 1 year. Thirty-six children with ADHD diagnostic (DSM IV), not treated by MPH were included. Initial "multi-field" evaluation (T0) consisted of: neuro-paediatric consultation (Conners questionnaire, Child Behaviour Checklist, reading and writing scores by French tests); semi-structured child psychiatric interview (DSM-IV axis I), structural hypothesis (CFTMEA), existence of narcissistic fragility, parents/child interactions; neuropsychological standardized evaluation (attention and executive functions); psychodynamic interview and projective tests (Rorscharch, CAT or TAT). A therapeutic project is proposed combining MPH and psychotherapy according to the results. A new evaluation 1 year later (T1) included a consultation and a neuropsychological evaluation. RESULTS T0: All parental questionnaires appreciating attention deficit and hyperactivity/impulsivity were significantly pathological. The neuropsychological evaluation showed usual characteristics of ADHD with individual differences. The psychiatric evaluation revealed the frequency of comorbidity in axis I (23% of children with more than two diagnoses, 57% with anxiety disorder, 23 and 3% with oppositional and conduct disorder). FOLLOW UP (T1): Thirty-one children were re-examined (20 treated by MPH and 11 not treated because of parental refusal or particular psychopathological situations). Psychoanalytical psychotherapy, proposed to 28 children, was undertaken with only 19. An improvement in scores for attention and executive tests was registered only in the treated group. The tests confirm deficits of attention and executive functions without correlation with the scores of questionnaires, underlining the need for a neuropsychological evaluation to objectify attention disorders. Projective tests refine and enrich psychiatric evaluation and showed that half of the children had borderline organization. However, structural hypotheses were heterogeneous, suggesting the need for specific therapeutic projects to be devised according to each child. The treated children were the only ones to improve attention deficit. On the other hand, the scores of anxiety are not improved by MPH, emphasizing the indications of psychotherapy if comorbidity is present. Psychotherapeutic care was carried out only among part of the population, because of parental reservations, exacerbated by differences of opinion among professionals and lack of access. This study is innovative, providing precise data on ADHD from a multidisciplinary perspective. Psychopathological comorbidity is high in this population, so the concept of ADHD cannot be limited to a cognitive point of view. These elements and doubts regarding the efficacy of behavioural therapies suggest the need for a rigorous evaluation of analytical psychotherapies independent of MPH to treat attention deficit.


Evaluating Indoor Air Phthalates and Volatile Organic Compounds in Nail Salons in the Greater New York City Area: A Pilot Study.
The Greater New York City area ranks highest in the United States in the number of nail salon technicians, primarily Asian immigrant women. Nail salon technicians are exposed to toxic phthalates and volatile organic compounds daily in nail salons. The purpose of this pilot study was to measure a mixture of phthalates and volatile organic compounds in nail salons in the Greater New York City area, and to characterize work-related determinants of indoor air quality in these nail salons. Working with four Asian nail salon organizations in the Greater New York City area, we measured indoor air phthalates and volatile organic compounds at 20 nail salons from February to May 2021 using silicone wristbands and passive samplers, respectively. Nail salon characteristics were also examined. We measured six phthalates and 31 volatile organic compounds. Di(2-ethylhexyl) phthalate and Diethyl phthalate had the highest concentrations among the six phthalates measured. Concentrations of toluene, d-limonene, methyl methacrylate, and ethyl methacrylate were higher than that of the rest. Manicure/pedicure tables, the number of customers per day, and application of artificial nail (acrylic) services were positively associated with the levels of phthalates and volatile organic compounds. Given the large number of people employed in the nail industry and the even larger number of customers visiting such establishments, exposures to these toxic chemicals are likely to be widespread.


Lattice vibrations and electronic transitions in the rare-earth metals: yttrium, gadolinium and lutetium.
Lattice vibrations in high-pressure phases of Y, Gd and Lu were studied by Raman spectroscopy. The observed phonon frequencies decrease towards the transitions to the dhcp and fcc phases. There is evidence that the entire structural sequence [Formula: see text] under pressure for the individual regular rare-earth metals and along the lanthanide series at ambient pressure involve softening of certain acoustic and optical phonon modes and of the elastic shear modulus C(44). Comparison is made to transitions between close-packed lattices in other metals, and possible correlations to s-d electron transfer are discussed.


Gastric duplication: a rare cause of massive lower gastrointestinal haemorrhage, chest wall mass, and enterocutaneous fistula.
Gastric duplications are uncommon developmental abnormality reported to present with different clinical scenarios. We present a 2-1/2-year-old Nigerian female who started having intermittent massive lower gastrointestinal haemorrhage at 5 months of age. She subsequently developed a lower chest wall mass and enterocutaneous fistula. She was found to have gastric duplication with fistulous communication with the descending colon, spleen, and lower chest wall. To the best of our knowledge, this is the first paper on gastric duplication resulting in intermittent massive lower gastrointestinal bleeding mainly from splenic capsular erosion and fistula and enterocutaneous fistula resulting from erosion of anterior abdominal wall. Gastric duplication is hence an important rare cause of intermittent massive lower gastrointestinal haemorrhage and spontaneous enterocutaneous fistula in the paediatric population.


Transumbilical single port laparoscopic surgery for the treatment of concomitant disease.
We report our experience of transumbilical single port laparoscopic surgery (TUSPLS) for multiple concomitant intraabdominal pathologies, and assess the feasibility of this technique with several technical tips. Various combined procedures using TUSPLS were performed since April, 2008. All records of concomitant laparoscopic procedures using TUSPLS were searched at three hospitals. Forty-one patients underwent 82 combined procedures using TUSPLS in a single session. The perioperative outcomes of simultaneously performed cholecystectomy and ovarian cystectomy using TUSPLS (n = 14) are compared with those of using CLS (n = 11). The operating time was significantly longer with the TUSPLS method than with the CLS method. However, postoperative convalescent outcomes such as postoperative hospital stay, VAS pain score, and required analgesics showed no differences between the two methods. Also, there were no significant operative complications associated with the two methods. Fewer trocars were used with the TUSPLS method. Combined laparoscopic procedures for various concomitant pathologies in the abdomen can be performed using transumbilical single port laparoscopic surgery without increasing morbidity or hospital stay in patients with acceptable risk.


Regulation of ocular adrenoceptor genes expression by 5-MCA-NAT: implications for glaucoma treatment.
We have demonstrated that 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT), reduces intraocular pressure (IOP) in rabbits. In addition, we have reported a link between hypotensive effect of 5-MCA-NAT and sympathetic nervous system. Moreover, it is known that aqueous humour production is controlled by the activation of adrenoceptors (ADRs) present in the ocular ciliary epithelium. Thus, the aim of this study is to investigate if the hypotensive effect of 5-MCA-NAT is due to a regulation of ciliary ADR genes expression. To confirm this we followed the effect of 5-MCA-NAT on rabbit IOP for 144 consecutive hours. A sustained IOP reduction for up to 72 h (P<0.01) was seen. In addition, changes in ADRB2 and ADRA2A mRNA were measured in cultured rabbit nonpigmented ciliary epithelial cells. After 5-MCA-NAT treatment, a significant downregulation of ADRB2 and upregulation of ADRA2A was observed. These results provide the regulation of ADRs mRNA by 5-MCA-NAT.


[Fast-track recovery for perforated duodenal ulcer].
To study the outcomes of fast-track recovery in patients with perforated duodenal ulcer (PDU). There were 138 patients with PDU who underwent surgical treatment for the period from January 1, 2015 to December 31, 2019. Patients were divided into 3 groups: main group, control group 1 (CG-1) and control group 2 (CG-2). The main group (fast-track group, FT-group) included 51 patients who underwent laparoscopic suturing of PDU followed by enhanced recovery (fast-track). CG-1 comprised 44 patients who underwent open suturing of PDU and conventional perioperative treatment. CG-2 consisted of 43 patients who underwent laparoscopic suturing and conventional perioperative treatment. Complications were assessed using Clavien-Dindo grading system. In the FT group, postoperative complications were observed in 2 patients (3.92%). Anemia of mixed genesis (Clavien-Dindo grade II) was diagnosed in 1 patient and left-sided lower lobe pneumonia in another one (grade II). There were no deaths. Mean length of hospital-stay was 3.86 days. In the 1st control group, the largest number of complications was observed (n=12, 27.27%) including 9 extra-abdominal complications (pulmonary disorders (II) - 7 patients (15.9%); sepsis (IVB) - 1 (2.27%), delirium (IVA) - 1 patient (2.27%), postoperative wound seroma (IIIA) - 1 (2.27%) patient). Intra-abdominal complications consisted of compensated pyloroduodenal stenosis (II) in 1 (2.27%) case, recurrent bleeding from acute gastric and duodenal ulcers (IIIB) in 1 (2.27%) patient. Mortality rate was 4.54% (n=2) in this group (progressive multiple organ failure). Mean length of hospital-stay was 7.56 days. In the 2nd control group, postoperative complications included extra-abdominal (pulmonary disorders (II) - pneumonia in 4 (9.3%) cases, spontaneous pneumothorax (IIIA) in 1 (2.32%) case) and intra-abdominal events (duodenitis (II) in 1 (2.32%) patient and compensated pyloroduodenal stenosis (II) in another 1 (2.32%) patient). There were no lethal outcomes in this group. Mean length of hospital-stay was 6.7 days. Treatment outcomes in patients with perforated duodenal ulcer confirmed an effectiveness of laparoscopic suturing and complete abdominal sanitation. These measures create the prerequisites for fast track recovery in urgent surgical practice. FT-protocol of inpatient management is followed by reduced hospital-stay and less incidence of postoperative complications. Moreover, this approach promotes early and safe discharge of patients.


Long-acting dihydropyridine calcium antagonists. 6. Structure-activity relationships around 4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-2-[(2-hydroxyethoxy)methyl]-5 -(methoxycarbonyl)-6-methyl-1,4-dihydropyridine.
The preparation of 4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-2-[(2-hydroxyethoxy)methyl]-5- (methoxycarbonyl)-6-methyl-1,4-dihydropyridine (2) is described, and its potent calcium antagonist activity on rat aorta (IC50 = 4 x 10(-9) M) and marked tissue selectivity in vitro for vascular smooth muscle over cardiac smooth muscle are established. In order to exploit the excellent in vitro profile of compound 2, a range of analogues were prepared but none were found to have superior calcium antagonist potency and tissue selectivity. Compound 2 has excellent in vivo activity in the anesthetized dog (ED50 = 12 micrograms/kg for reduction of CVR) and a plasma half-life in the conscious dog of 7.2 h. The pharmacokinetic parameters of 2 are compared to those determined for the structurally related compounds amlodipine and felodipine. The plasma clearance for 2 (9.6 mL/min/kg) is similar to that of amlodipine and is consistent with the extended 2-substituent hindering approach to the cytochrome P-450 enzyme responsible for oxidation of the DHP ring to the corresponding pyridine.


Complementary methodologies to identify specific agrobacterium strains.
Serological techniques and restriction enzyme cleavage patterns of total DNA were used to differentiate strains of Agrobacterium spp. Forty-five wild-type and plasmid-cured Agrobacterium strains were tested by immunodiffusion and immunofluorescence against polyclonal antisera to a crude ribosome preparation from Agrobacterium strains K84, U11, B6, A323, NT1, and C58. In immunodiffusion gels, these antisera reacted only with water-phenol extracts of the homologous strain, producing a single, strain-specific precipitin line. In contrast, when the same antisera were used in immunofluorescence staining, cross-reactions occurred with a limited number of heterologous Agrobacterium strains. However, the cross-reacting heterologous cells fluoresced generally less brightly than the homologous cells. When the EcoRI-digested DNA profiles from the same Agrobacterium strains were compared, 34 distinct cleavage patterns were observed. The DNA profiles were the same for all strains sharing a common chromosomal background and correlated with the strain-specific serological reaction. The presence or absence of plasmid DNA did not alter the strain-specific serological reaction or the DNA cleavage patterns. Both the serological reaction and the restriction enzyme digestion of total DNA were complementary to each other. These methods were used successfully to identify A. radiobacter K84 strains which were recovered 6 months after being inoculated to young trees in the field.


Hypothermic pulsatile perfusion: its use in the preservation of pancreases for 24 to 48 hours before islet cell transplantation.
Canine pancreases underwent hypothermic pulsatile perfusion for 24 or 48 hours before islet cell collagenase digestion and intrasplenic autotransplantation. The numbers of dogs surviving longer than two months are as follows: dogs receiving pancreatectomies, 0/10; dogs receiving 24-hour-perfused islet cells, 6/10, dogs receiving 48-hour-perfused islet cells, 4/10; and dogs receiving fresh islet cells, 7/10. Islet cells from 48-hour-perfused pancreases were not as good in reversing hyperglycemia as the islet cells from 24-hour-perfused pancreases. Histologically, the islet cells appeared to be normal in the fresh and 24-hour-perfused pancreases. Thus, hypothermic pulsatile perfusion of pancreas autografts for 24 hours appears to be a safe and reliable method. When this technique is used clinically, special attention should be given to 48-hour-perfused pancreases because the reversal of hyperglycemia sometime is not complete.


Isolation of novel cDNA encompassing the ADU balanced translocation break point in the DiGeorge critical region.
DiGeorge syndrome (DGS) is a developmental field defect of the third and fourth pharyngeal pouches that are associated with congenital heart defects, hypoparathyroidism, cell-mediated immunodeficiency, velopharyngeal insufficiency, and craniofacial anomalities. Approximately 90% of patients exhibit monosomy in the 22q11 region. In order to isolate the critical gene responsible for DGS, the cDNA libraries were screened with a probe containing the ADU balanced translocation break point, that is a locus reported in one patient (ADU) caused by a balanced translocation between chromosomes 22 and 2. Out of 10(6) clones, three independent overlapping clones were isolated, which were assumed to have originated from a single transcript, DGCR7. This transcript contained a 175-aa long open reading frame (ORF), encoding an acidic (pI = 5.81) and a proline-rich peptide, which are often found in the activation domain of several transcription factors. Also, it was predicted to be a nuclear protein. Northern hybridization detected an approx 1.9 kb transcript in all fetal and adult tissues tested, with strong expression in the fetal liver and kidney. In the case of adult tissues, strong expression was also detected in areas such as the heart, skeletal muscle, liver, and kidney.


Measurement of dimethylglycine in biological fluids.
The method of quantitating N,N-dimethylglycine involves cation-exchange high-performance liquid chromatography and detection of dimethylglycine with dimethylglycine dehydrogenase. Dimethylglycine was added to plasma and urine and samples were assayed for dimethylglycine. Plasma and urine to which no dimethylglycine was added were also assayed. Recoveries of added dimethylglycine were 99 to 104% with no endogenous dimethylglycine found in rat plasma or normal human urine. The human plasma used contained a small amount of endogenous dimethylglycine. The cation-exchange chromatography separates dimethylglycine from other compounds which can serve as substrates for dimethylglycine dehydrogenase. Repeatability of the assay is +/- 10%. Using this method we have identified dimethylglycine in the urine of a 1-month-old female human patient.


Enhanced power conversion efficiency of an n-Si/PEDOT:PSS hybrid solar cell using nanostructured silicon and gold nanoparticles.
Herein, the effect of nanostructured silicon and gold nanoparticles (AuNPs) on the power conversion efficiency (PCE) of an n-type silicon/poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (n-Si/PEDOT:PSS) hybrid solar cell was investigated. The Si surface modified with different nanostructures including Si nanopyramids (SiNPs), Si nanoholes (SiNHs) and Si nanowires (SiNWs) was utilized to improve light trapping and photo-carrier collection. The highest power conversion efficiency (PCE) of 8.15% was obtained with the hybrid solar cell employing SiNWs, which is about 8%, 20% and 40% higher compared to the devices using SiNHs, SiNPs and planar Si, respectively. The enhancement is attributed to the low reflectance of the SiNW structures and large PEDOT:PSS/Si interfacial area. In addition, the influence of AuNPs on the hybrid solar cell's performance was examined. The PCE of the SiNW/PEDOT:PSS hybrid solar cell with 0.5 wt% AuNP is 8.89%, which is ca. 9% higher than that of the device without AuNPs (8.15%). This is attributed to the increase in the electrical conductivity and localized surface plasmon resonance of the AuNP-incorporated PEDOT:PSS coating layer.


Synthesis of 1,4-dichloro-1,3-butadienes by rhodium complex catalyzed reaction of terminal alkynes with trichloroacetyl chloride.
Chlorinative dimerization of terminal alkynes with trichloroacetyl chloride as chlorine donor proceeds in the presence of rhodium catalysts to give (Z,Z)-1,4-dichloro-1,3-butadienes stereoselectively. Ligand screening has revealed that reactions using sterically bulky and electron-donating ligands like trimesitylphosphine are high yielding. The reaction is compatible with a range of functional groups to give the title compounds nearly quantitatively in most cases. A mechanistic possibility involving coupling of beta-chloroalken-1-yl intermediate has been discussed.


Chemical equilibrium modeling of organic acids, pH, aluminum, and iron in Swedish surface waters.
A consistent chemical equilibrium model that calculates pH from charge balance constraints and aluminum and iron speciation in the presence of natural organic matter is presented. The model requires input data for total aluminum, iron, organic carbon, fluoride, sulfate, and charge balance ANC. The model is calibrated to pH measurements (n = 322) by adjusting the fraction of active organic matter only, which results in an error of pH prediction on average below 0.2 pH units. The small systematic discrepancy between the analytical results for the monomeric aluminum fractionation and the model results is corrected for separately for two different fractionation techniques (n = 499) and validated on a large number (n = 3419) of geographically widely spread samples all over Sweden. The resulting average error for inorganic monomeric aluminum is around 1 µM. In its present form the model is the first internally consistent modeling approach for Sweden and may now be used as a tool for environmental quality management. Soil gibbsite with a log *Ks of 8.29 at 25°C together with a pH dependent loading function that uses molar Al/C ratios describes the amount of aluminum in solution in the presence of organic matter if the pH is roughly above 6.0.


A comparison of neurotrophic effects of epidermal growth factor and basic fibroblast growth factor in primary cultured neurons from various regions of fetal rat brain.
Effects of recombinant human epidermal growth factor (hEGF) on survival of primary cultured neurons from various regions of fetal rat brain were compared with those of recombinant human basic fibroblast growth factor (hbFGF). Addition of hEGF (0.001-10 ng/ml) in chemically-defined serum-free medium enhanced significantly the survival of cultured neurons from all regions tested, i.e., cerebral cortex, septum, striatum, hippocampus, thalamus, colliculus and cerebellum. However, its effective concentration differed considerably with the regions. The most sensitive regions were the colliculus and cerebellum (minimum effective concentration, 0.001 ng/ml), while the least sensitive was the cerebral cortex (minimum effective concentration, 10 ng/ml). Maximum numbers of surviving neurons in the presence of hEGF were smaller than those of hbFGF in all regions. Maximum effects of hEGF compared with those of hbFGF was greatest in the striatum and smallest in the cerebral cortex. These results suggest that hEGF may exert neurotrophic effects for limited populations of brain neurons. When hEGF (1-10 ng/ml) and hbFGF (0.01-10 ng/ml) were added together, hEGF increased the effects of a lower concentration of hbFGF in an additive manner, but the maximum effects of hbFGF were not potentiated by hEGF in all regions tested. Therefore, mechanisms underlying the effects of hEGF very probably overlap with those of hbFGF.


Multivariate approach to assess the chemical composition of Italian virgin olive oils as a function of variety and harvest period.
Fatty acids, phenolic compounds, and tocopherols of Coratina, Bosana, Semidana, and Tonda di Cagliari virgin olive oils, were measured over a 45-day harvest period. Phenolic composition was the primary factor distinguishing Bosana, Tonda di Cagliari, and Semidana, whereas fatty acids differentiated Coratina and the other cultivars. Harvest period principally influenced oleacein, oleocanthal, oleuropein and ligstroside aglycones, and flavonoids. High phenolic content was observed for Coratina (1039-688 mg/kg) and Bosana (788-592 mg/kg). A drastic decrease in phenolic content was observed in Semidana (529-134 mg/kg) and Tonda di Cagliari (507-142 mg/kg) during the harvest period. These two cultivars also had low MUFA/PUFA (6.0-4.0 and 4.9-3.2 respectively), suggesting that these varieties should be harvested earlier in the season. These results provide information to producers for improved management of the harvesting process, which is strongly affected by varietal factors.


Orthogonal control of dissociation dynamics relative to thermodynamics in a main-chain reversible polymer.
A pair of homologous and soluble reversible polymers display nearly identical solution structures but dramatically different dissociation dynamics (1.0 vs ca. 100 s-1) along their main chains. The polymers are formed by organopalladium-pyridine coordination, and steric effects at the metal center control the dynamics. Importantly, the association constant is not significantly affected by the sterics. The resulting orthogonal control over dissociation kinetics provides a general tool for studying the effects of dynamics independent of thermodynamics in supramolecular systems, particularly main-chain reversible polymers.


Small Airways Disease.
Small airways diseases are best defined pathologically as a diverse group of conditions that primarily involve bronchioles and acartilagenous airways 2 mm or less in diameter, which include membranous bronchioles, respiratory bronchioles, and alveolar ducts. Small airways can be involved with disease primarily or secondarily. The concept of small airways disease varies among specialties, with clinicians generally considering them in terms of terminal airway changes causing airflow obstruction, radiologists considering them in the context of direct signs and indirect signs identified on high-resolution computed tomography scans, and pathologists evaluating them based entirely or almost entirely on the histologic changes present in the bronchioles, with or without associated changes involving bronchi and alveoli. The histologic features of small airways diseases may be confusing because they overlap. There may be incomplete assessment of the histologic process with limited biopsy. Other disease processes may occur along with a small airways disease, and may obscure or confound its histologic features. This article focuses on the histologic changes diagnostic of a variety of primary and secondary small airways diseases. Because the histologic features involve bronchioles, gross findings are often minimal and/or nonspecific. The article provides a nonexhaustive examination of conditions and diseases involving the small airways, focusing on the microscopic features, with emphasis on the limitations of histologic diagnosis and differential diagnosis.


Nation-building policies in Timor-Leste: disaster risk reduction, including climate change adaptation.
Few studies have explored the relationships between nation-building, disaster risk reduction and climate change adaptation. Focusing on small island developing states, this paper examines nation-building in Timor-Leste, a small island developing state that recently achieved independence. Nation-building in Timor-Leste is explored in the context of disaster risk reduction, which necessarily includes climate change adaptation. The study presents a synopsis of Timor-Leste's history and its nation-building efforts as well as an overview of the state of knowledge of disaster risk reduction including climate change adaptation. It also offers an analysis of significant gaps and challenges in terms of vertical and horizontal governance, large donor presence, data availability and the integration of disaster risk reduction and climate change adaptation for nation-building in Timor-Leste. Relevant and applicable lessons are provided from other small island developing states to assist Timor-Leste in identifying its own trajectory out of underdevelopment while it builds on existing strengths.


Comparative Proteomic Analysis Provides New Insights into the Development of Haustorium in Taxillus chinensis (DC.) Danser.
Taxillus chinensis is an important medicinal and parasitic plant that attacks other plants for living. The development of haustorium is a critical process, imperative for successful parasitic invasion. To reveal the mechanisms underlying haustorium development, we performed an iTRAQ-based proteomics analysis which led to the identification of several differentially abundant proteins (DAPs) in fresh seeds (CK), baby (FB), and adult haustoria (FD). A total of 563 and 785 DAPs were identified and quantified in the early and later developmental stages, respectively. Pathway enrichment analysis revealed that the DAPs are mainly associated with metabolic pathways, ribosome, phenylpropanoid biosynthesis, and photosynthesis. In addition, DAPs associated with the phytohormone signaling pathway changed markedly. Furthermore, we evaluated the content of various phytohormones during different stages of haustoria development. These results indicated that phytohormones are very important for haustorium development. qRT-PCR results validated that the mRNA expression levels were consistent with the expression of proteins, suggesting that our results are reliable. This is the first report on haustoria proteomes in the parasitic plant, Taxillus chinensis, to the best of our knowledge. Our findings will enhance our understanding of the molecular mechanism of haustoria development.


Elimination of 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid 9-phosphate synthase activity from human N-acetylneuraminic acid 9-phosphate synthase by a single mutation.
The most commonly occurring sialic acid Neu5Ac (N-acetylneuraminic acid) and its deaminated form, KDN (2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid), participate in many biological functions. The human Neu5Ac-9-P (Neu5Ac 9-phosphate) synthase has the unique ability to catalyse the synthesis of not only Neu5Ac-9-P but also KDN-9-P (KDN 9-phosphate). Both reactions are catalysed by the mechanism of aldol condensation of PEP (phosphoenolpyruvate) with sugar substrates, ManNAc-6-P (N-acetylmannosamine 6-phosphate) or Man-6-P (mannose 6-phosphate). Mouse and putative rat Neu5Ac-9-P synthases, however, do not show KDN-9-P synthase activity, despite sharing high sequence identity (>95%) with the human enzyme. Here, we demonstrate that a single mutation, M42T, in human Neu5Ac-9-P synthase can abolish the KDN-9-P synthase activity completely without compromising the Neu5Ac-9-P synthase activity. Saturation mutagenesis of Met42 of the human Neu5Ac-9-P synthase showed that the substitution with all amino acids except leucine retains only the Neu5Ac-9-P synthase activity at levels comparable with the wild-type enzyme. The M42L mutant, like the wild-type enzyme, showed the additional KDN-9-P synthase activity. In the homology model of human Neu5Ac-9-P synthase, Met42 is located 22 A (1 A=0.1 nm) away from the substrate-binding site and the impact of this distant residue on the enzyme functions is discussed.


Redetermination of despujolsite, Ca(3)Mn(SO(4))(2)(OH)(6)·3H(2)O.
The crystal structure of despujolsite [tricalcium manganese bis-(sulfate) hexahydroxide tri-hydrate], the Ca/Mn member of the fleischerite group, ideally Ca(3)Mn(4+)(SO(4))(2)(OH)(6)·3H(2)O, was previously determined based on X-ray diffraction intensity data from photographs, without H-atom positions located [Gaudefroy et al. (1968 ▶). Bull. Soc. Fr. Minéral. Crystallogr.91, 43-50]. The current study redetermines the structure of despujolsite from a natural specimen, with all H atoms located and with higher precision. The structure of despujolsite is characterized by layers of CaO(8) polyhedra (m.. symmetry) inter-connected by Mn(OH)(6) octa-hedra (32. symmetry) and SO(4) tetra-hedra (3.. symmetry) along [001]. The average Ca-O, Mn-O and S-O bond lengths are 2.489, 1.915, and 1.472 Å, respectively. There are two distinct hydrogen bonds that stabilize the structural set-up. This work represents the first description of hydrogen bonds in the fleischerite group of minerals.


Design and Fabrication of Tubular Micro/Nanomotors via 3D Laser Lithography.
Catalytic tubular micro/nanomachines convert chemical energy from a surrounding aqueous fuel solution into mechanical energy to generate autonomous movements, propelled by the oxygen bubbles decomposed by hydrogen peroxide and expelled from the microtubular cavity. With the development of nanotechnology, micro/nanomotors have attracted more and more interest due to their numerous potential for in vivo and in vitro applications. Here, highly efficient chemical catalytic microtubular motors were fabricated via 3D laser lithography and their motion behavior under the action of driving force in fluids was demonstrated. The frequency of catalytically-generated bubbles ejection was influenced by the geometrical shape of the micro/nanomotor and surrounding chemical fuel environment, resulting in the variation in motion speed. The micro/nanomotors generated with a rocket-like shape displayed a more active motion compared with that of a single tubular micro/nanomotor, providing a wider range of practical micro-/nanoscale applications in the future.


Robust identification of regulatory variants (eQTLs) using a differential expression framework developed for RNA-sequencing.
A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait, and expression quantitative trait loci (eQTL) studies provide important information to help close that gap. However, two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution. Multiple pipelines have been suggested to address this. For instance, the most recent analysis of the human and farm Genotype-Tissue Expression (GTEx) project proposes using trimmed means of M-values (TMM) to normalize the data followed by an inverse normal transformation. In this study, we reasoned that eQTL analysis could be carried out using the same framework used for differential gene expression (DGE), which uses a negative binomial model, a statistical test feasible for count data. Using the GTEx framework, we identified 35 significant eQTLs (P < 5 × 10-8) following the ANOVA model and 39 significant eQTLs (P < 5 × 10-8) following the additive model. Using a differential gene expression framework, we identified 930 and six significant eQTLs (P < 5 × 10-8) following an analytical framework equivalent to the ANOVA and additive model, respectively. When we compared the two approaches, there was no overlap of significant eQTLs between the two frameworks. Because we defined specific contrasts, we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles. Yet, these were not identified by the GTEx framework. Our results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed. Our proposed approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.


[Abnormal psychosocial development and legal responsibility--results of psychopathometric studies].
The introduction (1968) of the legal concept of Grave Abnormal Development of the Personality Amounting to a Disorder into the penal code, made possible criminal deculpation on the basis of psychosocial maldevelopment. On the basis of an intelligence- and personality-diagnostic test-battery (Psychopathometry), the findings obtained in the examination of a sample of culprits on probation under this legal provision, has been compared with a control group homogeneous in respect of the significant parameters. Psychopathometric methods can and should reasonably supplement expertises of this culprits with defective psychosocial development.


Cation-activated nucleotidase in cell envelopes of a marine bacterium.
Isolated cell envelopes of a marine bacterium, M.B.3, have been prepared which possess a nonspecific, cation-activated nucleotidase. The cell envelope comprises approximately 35% (dry weight) of the whole cell and contains protein, 60.2%; lipids, 20.7%; hexose, 3.4%; and ribonucleic acid, 4.6%. No deoxyribonucleic acid could be detected in the preparations. The nucleotidase has an essential requirement for Mg(2+); maximum activation at pH 8.0 occurs at a divalent cation concentration of approximately 80 mm. At a Mg(2+) to adenosine 5'-triphosphate (ATP) ratio of 2:1, the enzyme was further stimulated by monovalent cations Na(+), K(+), NH(4) (+), and Li(+). Maximum activity was found at a monovalent ion concentration of approximately 0.3 m. The envelope preparation liberated inorganic orthophosphate (P(i)) from ATP, adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) at similar rates. Thin-layer and ion-exchange chromatography show that when AMP, ADP, and ATP were utilized as substrate, approximately 1, 2, and 3 moles of P(i), respectively, were produced per mole of adenosine. P(i) was also liberated from the 5'-triphosphates of guanosine, uridine, and cytidine. The enzyme preparation did not attack p-nitrophenyl phosphate, beta-glycerophosphate, or inorganic pyrophosphate. Sulfhydryl inhibitors p-chloromercuribenzoate, N-ethyl maleimide, and iodoacetate had little effect upon the nucleotidase activity. Ca(2+) and ethylenediaminetetraacetic acid caused complete inhibition of the system, whereas ouabain had no effect upon the enzyme activity. The concentrations of Na(+) (0.3 m) and Mg(2+) ions (60 to 80 mm) required for maximum ATP-hydrolyzing activity were similar to those concentrations necessary for maintenance of cell integrity and for the prevention of cell lysis.


Review: Risks of disease transmission through semen in cattle.
The purpose of this paper is to review scientific evidence concerning pathogens that could potentially be transmitted via bovine semen. As a result of a careful analysis of the characteristics of infections that may cause transmission of disease through semen, effective control procedures can be identified that provide minimal constraint to the introduction of new bulls into herds for natural breeding and importation of valuable novel genetics through artificial insemination. The potential for transmission through bovine semen and corresponding effective control procedures are described for bovine herpesvirus 1, bovine viral diarrhea virus, bovine leukemia virus, lumpy skin disease virus, bluetongue virus, foot-and-mouth disease virus, and Schmallenberg virus. Brief consideration is also provided regarding the potential for transmission via semen of Tritrichomonas foetus, Campylobacter fetus venerealis, Brucella abortus, Leptospira spp., Histophilus somni, Ureaplasma diversum, Mycobacterium avium subsp. paratuberculosis, Chlamydiaceae, Mycobacterium bovis, Coxiella burnetii, Mycoplasma mycoides ssp. mycoides and Neospora caninum. Thoughtful and systematic control procedures can ensure the safety of introducing new bulls and cryopreserved semen into cattle production systems.


TH1/TH2 cytokine balance in patients with both type 1 diabetes mellitus and asthma.
T1DM and asthma are mediated by opposite arms of the cellular immune system namely T helper (Th)1 and Th2 CD4(+) cells, respectively. Our aim was to characterize the Th1/Th2 cytokine balance in patients with both T1DM and asthma. Forty-four patients, mean age 19 years were matched by gender and age, to 4 paired groups: T1DM and asthma, asthma only, T1DM only and healthy controls. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with disease-specific recombinant antigens; glutamic acid decarboxylase and house dust mite (Der p1 antigen) for T1DM and asthma, respectively, and non-specific mitogens; phytohemaglutinin (PHA), tetanus toxin and anti-CD3 mAb. ELISPOT and ELISA technique were used to determine INF-gamma, IL-2, IL-4, IL-13 and IL-10 expression. Patients with T1DM and asthma demonstrated a similar cytokine pattern but lower Th1/Th2 ratio compared to patients with T1DM only. The Th2 cytokines response to Der p1 was enhanced in patients with both diseases compared to controls. The IL-10 overall secretion was higher in patients with both diseases compared to one disease only. The Th1 and Th2 secretory pattern of patients with T1DM and asthma combines features of both diseases suggesting a unique Th1/Th2 balance.


Predictors of ventriculoperitoneal shunting after spontaneous intraparenchymal hemorrhage.
Intraparenchymal hemorrhage (IPH) is a serious medical condition with high morbidity. Hydrocephalus complicates the course of IPH recovery and frequently necessitates permanent cerebrospinal fluid (CSF) diversion by ventriculoperitoneal shunting (VPS). Risk factors for VPS have not been studied in adults after IPH. This is a nonrandomized retrospective study aimed to determine risk factors for VPS among IPH patients seen at Barrow Neurological Institute over a 2-year period. Chart review collected pertinent demographic and radiological data for all IPH patients. This data underwent statistical analysis to discover those factors associated with VPS requirements. A predictive shunting instrument was then constructed to determine those patients at greatest risk of VPS requirement. Initial Glasgow Coma Scale score < 9 (P = 0.033), abundant blood in the lateral ventricle (P = 0.016), ICP elevations > 25 mmHg (P = 0.016), persistent ICP elevations > 20 mmHg (P = 0.017), and thalamic IPH location (P = 0.009) were associated with VPS on univariate analysis. Thalamic IPH location (P = 0.025) and ICP > 25 mm Hg (P = 0.025) were associated with VPS on multivariate analysis. Application of a predictive shunting instrument to the cohort had positive predictive value of 100% and a negative predictive value of 81%. A predictive shunting instrument utilizing GCS score, lateral ventricle blood, ICP measurement, and the presence of hydrocephalus may predict those patients at risk for VPS or identify those patients requiring additional CSF drainage strategies.


Growth of vegetarian children: The Farm Study.
To examine the effects of a vegetarian diet on child growth, height and weight data of 404 vegetarian children aged 4 months to 10 years who lived in a collective community in Tennessee were studied. Height for age, weight for age, and weight for height were compared with the US growth reference. Birth weights, infant feeding patterns, and parental heights were also evaluated in relation to growth. Most of the height for age, weight for age, and weight for height (n = 833) were within the 25th and 75th percentiles of the US growth reference. The mean height for age and weight for age, however, were slightly less than the median of the reference population. For different age groups, the mean height ranged from 0.2 to 2.1 cm and the mean weight ranged from 0.1 to 1.1 kg less than the reference median. The largest height difference was observed at 1 to 3 years of age and may be partly the result of intrinsic irregularities in the US growth reference at those ages. By 10 years of age, children from The Farm averaged 0.7 cm and 1.1 kg less than the reference median, representing only 0.1 and 0.3 SD from the reference. Thus, these children have adequate attained growth, even though it was modestly less than that of the reference population.


[Surgical treatment of unicentric plasma cell histological type Castleman's disease].
Castleman's disease or angiofollicular lymph hyperplasia is a rare disease with two identified clinical forms. Unicentric or localized form is characterized by isolated growth of lymph nodes, most often in mediastinum, and multicentric form is expressed as systemic disease with spread lymphadenopathy, organomegaly and presence of general symptoms of the disease. Histological types are hyalovascular, plasma-cell and transitive (mixed) cell. This case report shows a woman, 59 years old, with unicentric form of plasma-cell type of Castleman's disease. Unicentric form is usually shown as hyalovascular histological type, extremely rare as plasma-cell type, and transitive (mixed) cell type was never described in literature as localized clinical form. The disease was manifested with chest pain, loss of body weight, exhaustion and weakness of legs. Further diagnostic procedures found the presence of enlarged lymph nodes paratracheally right, in a close contact with vena cava superior. The disease was confirmed by histopathological analysis of bioptated mediastinal lymph node after mediastinoscopy. Surgical treatment included extirpation of enlarged lymph nodes. After the regular postoperative condition, a full therapy effect was confirmed. Unicentric form of Castleman's disease is expressed with enlarged lymph nodes on predilected places, usually in mediastinum. Surgical treatment is best method for the management of the disease and brings a full recovery of patient.


Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective.
The kidney consists of numerous cell types organized into the nephron, which is the basic functional unit of the kidney. Any stimuli that induce loss of these cells can induce kidney damage and renal failure. The cause of renal failure can be intrinsic or extrinsic. Extrinsic causes include cardiovascular disease, obesity, diabetes, sepsis, and lung and liver failure. Intrinsic causes include glomerular nephritis, polycystic kidney disease, renal fibrosis, tubular cell death, and stones. The kidney plays a prominent role in mediating the toxicity of numerous drugs, environmental pollutants and natural substances. Drugs known to be nephrotoxic include several cancer therapeutics, drugs of abuse, antibiotics, and radiocontrast agents. Environmental pollutants known to target the kidney include cadmium, mercury, arsenic, lead, trichloroethylene, bromate, brominated-flame retardants, diglycolic acid, and ethylene glycol. Natural nephrotoxicants include aristolochic acids and mycotoxins such as ochratoxin, fumonisin B1, and citrinin. There are several common characteristics between mechanisms of renal failure induced by nephrotoxicants and extrinsic causes. This common ground exists primarily due to similarities in the molecular mechanisms mediating renal cell death. This review summarizes the current state of the field of nephrotoxicity. It emphasizes integrating our understanding of nephrotoxicity with pathological-induced renal failure. Such approaches are needed to address major questions in the field, which include the diagnosis, prognosis and treatment of both acute and chronic renal failure, and the progression of acute kidney injury to chronic kidney disease.


[Review of the Efficacy of Endoscopic Stenting for Malignant Colorectal Obstruction at Tokyo Metropolitan Ohtsuka Hospital].
The use of self-expandable metallic stent(SEMS)was first authorized by insurance and became available nationwide in Japan in 2012. Insertion of SEMS for colorectal obstruction due to colorectal cancer is useful as a bridge to surgery(BTS)approach and releases stenosis as palliative care. To assess the outcomes of SEMS placement for colorectal obstruction. A total of 14 patients were treated with SEMS between April 2014 and March 2017. We reviewed their medical records to assess the usefulness of SEMS placement and the clinical course. SEMS insertion was effective in 93% of the 14 patients. In 10 patients with BTS, the median interval between SEMS insertion and operation was 16 days, and no severe complications were noted in them. In 4 patients with palliative care, all patients were released from colorectal stenosis. SEMS placement played a satisfactory role in improvement of patient QOL by paying scrupulous attention to a colonic stent retained.


Collective thermal diffusion of silica colloids studied by nonlinear optics.
We investigate the collective thermal diffusion of silica charged spheres in Sulpho-Rhodamine B/water solution at different concentrations by measuring time-dependent thermal and Soret lensings. We show a significant concentration-dependence of the thermal diffusion coefficient D(T), not previously reported. Moreover, the results clearly show that both mass diffusion and Soret coefficient are collective quantities being strongly dependent on the particles' packing fraction. Our Z-scan setup allows us to investigate the dynamics of the system at low wave vector, which addresses the influence of the interparticle interactions on the thermal diffusion of the colloids.


Fragmenting the S100B-p53 interaction: combined virtual/biophysical screening approaches to identify ligands.
S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B-p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands. NMR spectroscopic experiments revealed specific binding at the p53 interaction site for a set of these compounds and confirmed their potential for further rational optimization. The X-ray crystal structure determined for one of the binders revealed key intermolecular interactions, thus paving the way for structure-based ligand optimization.


Associations between Medicaid expansion and nurse staffing ratios and hospital readmissions.
To examine the associations between Medicaid expansion and nurse staffing ratios and hospital-wide readmission rates. Secondary data from the 2011-2016 Healthcare Cost Report Information System, the American Hospital Association Annual Survey, and the Hospital Compare data. Difference-in-difference models are used to compare outcomes in hospitals located in states that expanded Medicaid with those located in nonexpansion states. The changes in nurse staffing ratios and hospital-wide readmission rates are calculated in each one of the postexpansion years (2014, 2015, and 2016), compared to pre-expansion. Results indicate that nurse staffing ratios increased, whereas hospital-wide readmission rates declined in expansion states relative to nonexpansion states. Nurse staffing ratios increased by 0.33, 0.42, and 0.46 registered nurses hours per adjusted patient days in 2014, 2015, and 2016 in hospitals located in expansion states, compared with hospitals in nonexpansion states after expansion. This increase was statistically significant (P < .001) in 2015 and 2016, but marginally significant (P = .016) in 2014. Hospital-wide readmission rates statistically significantly decreased by 9, 16, and 18 per 10 000 patients (P < .001) in 2014, 2015, and 2016, respectively, in expansion vs nonexpansion states hospitals after expansion. Medicaid expansion was associated with gradually improved hospitals' nurse staffing ratios and hospital-wide readmission rates from 2014 through 2016. The continued monitoring of quality measures of hospitals can help assess the impact of Medicaid expansion over a longer period of time.


Monocyte infiltration into obese and fibrilized tissues is regulated by PILRα.
Paired immunoglobulin-like type 2 receptor α (PILRα) is an inhibitory receptor that is mainly expressed on myeloid cells, and negatively regulates neutrophil infiltration during inflammation. However, PILRα role on monocyte has not been described. Under both steady-state and inflammatory conditions, monocytes migrate into tissues and differentiate into macrophages. Macrophages in adipose and liver tissues play important roles in tissue homeostasis and pathogenesis of metabolic diseases. Here, we found that PILRα controls monocyte mobility through regulating integrin signaling and inhibiting CD99-CD99 binding. Moreover, we found that Pilra(-/-) mice developed obesity and hepatomegaly with fibrosis, and the numbers of macrophages in adipose and liver tissues are significantly increased in Pilra(-/-) mice. These data suggest that immune inhibitory receptor, PILRα, plays an important role in the prevention of obesity and liver fibrosis.


Antitussive action of nociceptin in the cat.
Experiments were conducted to determine the influence of the specific ORL1 receptor agonist, nociceptin, on the cough reflex in the cat. Cats were anesthetized and allowed to breathe spontaneously. Cough was elicited by mechanical stimulation of the intrathoracic airway. Intravenous administration of nociceptin (0.001-3.0 mg x kg(-1)) inhibited cough number and the magnitude of abdominal muscle electromyogram (EMG) discharge during cough in a dose-dependent manner. Nociceptin had no effect on the magnitude of the inspiratory muscle EMG during cough. These effects of nociceptin were antagonized by pretreatment with the ORL1 receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (J-113397, 0.1 mg x kg(-1), i.v.). We conclude that intravenous nociceptin inhibits cough in the cat.


Cucurbit chlorotic yellows virus p22 suppressor of RNA silencing binds single-, double-stranded long and short interfering RNA molecules in vitro.
Cucurbit chlorotic yellows virus (CCYV) is a new member of the genus Crinivirus (family Closteroviridae) with a bi-partite genome. CCYV RNA 1-encoded p22 has recently been reported to be a weak local suppressor of RNA silencing for which an interaction with cucumber SKP1LB1 through an F-box-like motif was demonstrated to be essential. Using a bacterially expressed maltose-binding protein (MBP) fusion of CCYV p22 in electrophoretic mobility shift assays (EMSA), we have examined in vitro its ability to bind different RNA templates. Our experiments showed that CCYV p22 is able to bind to ss and ds long RNAs, in addition to ss and ds small interfering (si) RNA molecules. CCYV p22 deletion mutants (MBP_CCYV DEL1-4) were produced that covered the entire protein, with MBP_CCYV DEL2 corresponding to the F-box motif and its flanking sequences. None of these deletions abolished the capacity of CCYV p22 to bind ss- and dsRNA molecules. However, deletions affecting the C-terminal half of the protein resulted in decreased binding efficiency for either ss- or dsRNA molecules indicating that essential elements for these interactions are located in this region. Taken together, our data add to current knowledge of the mode of action of suppressors of RNA silencing encoded by genes sited at the 3'-terminus of crinivirus genomic RNA 1, and shed light on the involvement of CCYV p22 in the suppression of RNA silencing and/or in another role in the virus life cycle via RNA binding.


Insulin treatment and the problem of weight gain in type 2 diabetes.
Insulin therapy has been shown to benefit the prognosis in patients with type 2 diabetes, but its initiation and intensification is often delayed through concerns about hypoglycemia and weight gain. In addition, weight gain is linked to the pathophysiology of type 2 diabetes and contributes to the overall risk for adverse cardiovascular outcomes. This article attempts to summarize this issue and examine the options available for weight management. A broad range of literature has been reviewed to distill important, consistent facts about insulin and weight gain and the options available for limiting the problem. Unfortunately, the great benefits of insulin therapy may be potentially undermined by weight gain. Weight gain is physiologically and psychologically undesirable, especially in patients with diabetes who are already overweight. The fear of weight gain with some medications contributes to psychological insulin resistance, which may discourage patients from commencing or following insulin regimens. However, new diabetes treatments and lifestyle interventions can be used to mitigate these problems. The exact choice of insulin and oral medications and weight loss interventions are important considerations in the overall management of patients with type 2 diabetes. Changes in a patient's lifestyle, such as modifications to diet and implementing an exercise program, are first-line treatments for type 2 diabetes and can also counteract insulin-induced weight gain.


Neoadjuvant Modified Short-course Radiotherapy for Stage IV Rectal Cancer.
This study aimed to assess the clinical outcomes of neoadjuvant modified short-course radiotherapy (mSC-RT) for rectal metastatic adenocarcinoma. Data from 14 patients who underwent mSC-RT followed by surgery for primary tumors were retrospectively analyzed. Twelve patients received systemic chemotherapy for 18 weeks. A 2.5 Gy dose twice daily, up to a total dose of 25 Gy in 10 fractions, over 5 consecutive days was administered through mSC-RT. Surgery for primary tumor was performed five weeks (range=3-7 weeks) after mSC-RT. Nine patients underwent adjuvant chemotherapy. The median follow-up was 38.5 months. No patients developed grade ≥3 toxicities before surgery. Three patients developed local failures and 10 died during the follow-up period. The 1-, and 3-year local control rates were 91.7% and 71.3%, respectively. The median overall survival (OS) was 45.1 months. The 1-, and 3-year OS rates were 85.7% and 56.3%, respectively. Patients with stage IVA showed significantly better OS than those with stage IVB disease. mSC-RT followed by delayed surgery was well-tolerated and led to good local control in patients with rectal metastatic adenocarcinoma. mSC-RT could be a treatment option for patients with rectal metastatic adenocarcinoma as it is less likely to lead to cessation of systemic chemotherapy.


Cardioprotective effect of carvedilol: inhibition of apoptosis in H9c2 cardiomyocytes via the TLR4/NF-κB pathway following ischemia/reperfusion injury.
Carvedilol is a non-selective β-blocker used in the treatment of cardiovascular disease, including myocardial ischemia. The aim of the present study was to investigate the molecular mechanisms underlying the effects of carvedilol on simulated ischemia/reperfusion (SI/R)-induced cardiomyocyte apoptosis in vitro. H9c2 cardiomyocytes were incubated with either a vehicle or an ischemic buffer during hypoxia followed by reoxygenation with or without carvedilol. In two additional groups, toll-like receptor 4 (TLR4) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were inhibited by a TLR4 antibody and pyrrolidine dithiocarbamate, respectively. The results revealed that carvedilol markedly decreased SI/R-induced apoptosis in a concentration-dependent manner, as demonstrated by flow-cytometric analysis. This effect was shown to be associated with an increase in the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax) protein ratio and concurrent reductions in the expression levels of TLR4 and NF-κB. These results suggest that carvedilol provides significant cardioprotection against SI/R-induced injury in H9c2 cardiomyocytes, an effect likely to be mediated through the TLR4/NF-κB signaling pathway.


Eight new alleles found in Flanders (Belgium), including the HLA-DRB1*12:24N allele.
Human leukocyte antigen (HLA) high-resolution matching is routinely performed in the case of hematopoietic stem cell transplantation. Misdiagnosis of rare or new variants will result in additional unknown mismatches that can trigger graft versus host disease and/or graft failure. Using a mono allelic sequencing strategy, we obtained >90% first-step sequence-based high-resolution typing results, conforming to the standards set down by the European Federation for Immunogenetics. During this routine analysis, eight new HLA alleles were identified, including one DRB1*12 null variant, DRB1*12:24N and three other coding mutants, resulting in a change of properties of the corresponding antigens.


Outbreak of ocular toxoplasmosis in Coimbatore, India.
Toxoplasma gondii is a protozoan parasite that infects up to a third of the world's population. Infection is mainly acquired by ingestion of food that is contaminated with oocysts. We report an outbreak of ocular toxoplasmosis, which is an acute acquired type rather than reactivation of congenital toxoplasmosis. Our preliminary investigation points to municipal water contamination. This outbreak only proves the need of an effective public health system and health education in curtailing any outbreak.


Green Extraction-Assisted Pseudo-Targeted Profile of Alkaloids in Lotus Seed Epicarp Based on UPLC-QTOF MS with IDA.
Lotus seed epicarp, a byproduct of lotus, is commonly discarded directly or burned in the cropland, resulting in waste of resources and environmental pollution. In this work, a green ultrasonic-assisted extraction method with ethyl lactate as the extraction solvent was established to extract alkaloids from lotus seed epicarp. The extraction conditions were optimized by response surface methodology. Under the optimal extraction conditions, the extraction of alkaloids from 1 g lotus seed epicarp was accomplished with only 10 mL of extraction solvent within 15 min. Combined with ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry with information-dependent acquisition mode, a total of 42 alkaloids were annotated in the lotus seed epicarp extracts. Among them, 39 alkaloids were reported in lotus seed epicarp for the first time. According to quantitative analysis, the distributions and trends of alkaloids in the lotus seed epicarp were found to be similar to those of lotus leaves. The five growth stages of lotus seed epicarp could be successfully distinguished based on the ten representative alkaloids. This study demonstrates that ultrasonic-assisted extraction with ethyl lactate as extractant solvent was efficient in the extraction of alkaloids from lotus seed epicarp, which is a potential renewable resource of bioactive ingredients.


The complications of full-pelvic irradiation with particular emphasis to external beam therapy.
62 Patients with uterine carcinoma of cervix treated with high-dose large-volume full-pelvic irradiation given through co-axial-opposing pair portals over the anterior and posterior pelvis. Of these patients, 29 also received a single course of intracavitary radium supplementary to external beam irradiation. Only the severe complications which required surgical intervention have been analyzed, In the group of 33 patients who received only external irradiation, 4 developed such complications (12.1%).The overall incidence of those complications was about 19.3%. It is concluded that the treatment with hidh-dose large-volume full-pelvic irradiation technique, utilizing two opposing parallel pelvic portals, carries an incidence of morbidity 3-4 times the acceptable level and should be discouraged. Alternative techniques are discussed.


Targeting Tyrosinase: Development and Structural Insights of Novel Inhibitors Bearing Arylpiperidine and Arylpiperazine Fragments.
The inhibition of tyrosinase (Ty, EC 188.8.131.52) represents an efficient strategy of decreasing melanogenesis and skin hyperpigmentation. A combination of crystallographic and docking studies on two different tyrosinases, that from Bacillus megaterium (TyBm) and that from a mushroom (TyM), has contributed to increasing our knowledge about their structural information and translating that information to the most druggable human Ty (TyH) isozyme. In particular, we designed and synthesized a series of 1-(4-fluorobenzyl)piperazine and 1-(4-fluorobenzyl)piperidine derivatives showing inhibitory activities on TyM at micromolar ranges and more potency than that of the reference compound, kojic acid. The crystal structures of TyBm with inhibitor 3 (IC50 value of 25.11 μM) and 16 (IC50 value of 5.25 μM) were solved, confirming the binding poses hypothesized by in silico studies and revealing the main molecular determinants for the binding recognition of the inhibitors.


Beta radiation excited thermoluminescence of solid-state synthesized SrZrO3 phosphors.
In this work, we report on the solid-state reaction synthesis of SrZrO3 phosphors, and their beta particle irradiation excited thermoluminescence (TL) characterization. X-ray diffraction data confirmed the obtention of the orthorhombic phase of SrZrO3. Through computational glow curve deconvolution, the whole glow curve was resolved into six individual first order kinetics peaks. This is the first report concerning the usefulness of SrZrO3 as TL dosimeter. The synthesized phosphors exhibit TL emission from below 100 °C up to above 300 °C, being the most intense TL between 200 and 300 °C, as well as a remarkable reproducibility of the TL response in repeated irradiation-TL readout cycles.


Dynamic Testing for Evaluation of Adrenal and Gonadal Function in Pediatric and Adult Endocrinology: An Overview.
Dynamic tests are often considered as the backbone of endocrinology. These tests involve the use of an exogenous agent to manipulate the body's hormonal milieu for the diagnosis and characterization of an endocrine disorder. They are especially helpful in the evaluation of certain endocrine conditions, such as disorders of growth and pubertal maturation and disorders of sex development. A great deal of heterogeneity exists across clinicians with regard to the usage, methodology, and interpretation of these tests. This review outlines various dynamic tests used to evaluate adrenal and gonadal function in pediatric and adult endocrinology, along with their clinical application and interpretation.


Suitability of epididymal and testicular ultrasonography and computerized image analysis for assessment of current and future semen quality in the ram.
Breeding soundness evaluation (BSE) is the primary assessment for determining the reproductive potential of male animals. This method, however, cannot be used to evaluate semen frequently or to predict future semen quality. Computerized analysis of ultrasonographic images provides information on histophysiological changes in male reproductive organs. We hypothesized that: (i) semen parameters would correlate with ultrasonographic characteristics of the distal region (cauda) of the epididymis and (ii) testicular ultrasound images and/or circulating testosterone concentration would predict future semen quality in the ram. Six adult rams underwent BSE and scrotal ultrasonography approximately 60 d apart (average duration of the spermatogenic cycle) both during the breeding (December and February) and non-breeding (June and August) seasons. An inverse correlation was found between pixel intensity (numerical pixel values) of the epididymes and percentage of sperm in semen with normal morphology (r = -0.46, P < 0.05). Pixel heterogeneity (standard deviation of pixel values) correlated negatively with percentage of sperm with normal morphology (r = -0.42, P < 0.05) and directly with percentage of spermatozoa with abnormal tails (r = 0.43, P < 0.05). Pixel heterogeneity of testicular parenchyma obtained approximately 60 d prior to semen evaluation inversely correlated with percentage of sperm with normal morphology (r = -0.73, P < 0.01) and sperm progressive motility (r = -0.76, P < 0.01), and directly with percentage of sperm with abnormal tails (r = 0.72, P < 0.01) and loose heads (r = 0.79, P < 0.01). We concluded that scrotal ultrasonography combined with computer-assisted analyses of epididymal and testicular echotexture in the ram was a valuable method for determining certain current and future semen parameters, respectively.


Comparison of bio-hydrogen production yield capacity between asynchronous and simultaneous saccharification and fermentation processes from agricultural residue by mixed anaerobic cultures.
Taken common agricultural residues as substrate, dark fermentation bio-hydrogen yield capacity from asynchronous saccharification and fermentation (ASF) and simultaneous saccharification and fermentation (SSF) was investigated. The highest hydrogen yield of 472.75mL was achieved with corncob using ASF. Hydrogen yield from corn straw, rice straw, corncob and sorghum stalk by SSF were 20.54%,10.31%,13.99% and 5.92% higher than ASF, respectively. The experimental data fitted well to the modified Gompertz model. SSF offered a distinct advantage over ASF with respect to reducing overall process time (60h of SSF, 108h of ASF). Meanwhile, SSF performed better than SSF with respect to shortening the lag-stage. The major metabolites of anaerobic fermentation hydrogen production by ASF and SSF were butyric acid and acetic acid.


Photodynamic treatment and H2O2-induced oxidative stress result in different patterns of cellular protein oxidation.
Photodynamic treatment (PDT) is an emerging therapeutic procedure for the management of cancer, based on the use of photosensitizers, compounds that generate highly reactive oxygen species (ROS) on irradiation with visible light. The ROS generated may oxidize a variety of biomolecules within the cell, loaded with a photosensitizer. The high reactivity of these ROS restricts their radius of action to 5-20 nm from the site of their generation. We studied oxidation of intracellular proteins during PDT using the ROS-sensitive probe acetyl-tyramine-fluorescein (acetylTyr-Fluo). This probe labels cellular proteins, which become oxidized at tyrosine residues under the conditions of oxidative stress in a reaction similar to dityrosine formation. The fluorescein-labeled proteins can be visualized after gel electrophoresis and subsequent Western blotting using the antibody against fluorescein. We found that PDT of rat or human fibroblasts, loaded with the photosensitizer Hypocrellin A, resulted in labeling of a set of intracellular proteins that was different from that observed on treatment of the cells with H2O2. This difference in labeling patterns was confirmed by 2D electrophoresis, showing that a limited, yet distinctly different, set of proteins is oxidized under either condition of oxidative stress. By matching the Western blot with the silver-stained protein map, we infer that alpha-tubulin and beta-tubulin are targets of PDT-induced protein oxidation. H2O2 treatment resulted in labeling of endoplasmic reticulum proteins. Under conditions in which the extent of protein oxidation was comparable, PDT caused massive apoptosis, whereas H2O2 treatment had no effect on cell survival. This suggests that the oxidative stress generated by PDT with Hypocrellin A activates apoptotic pathways, which are insensitive to H2O2 treatment. We hypothesize that the pattern of protein oxidation observed with Hypocrellin A reflects the intracellular localization of the photosensitizer. The application of acetylTyr-Fluo may be useful for characterizing protein targets of oxidation by PDT with various photosensitizers.


A Catalytic Microwave Process for Superfast Preparation of High-Quality Reduced Graphene Oxide.
Herein we report that a small amount of graphite can unexpectedly act as the catalyst to greatly promote the microwave exfoliation and reduction of graphite oxide in ambient air. The reaction can be finished in a few seconds in contrast to more than ten minutes without catalyst. The catalytic microwave exfoliated graphite oxide (CMEGO) is of higher quality than the traditional microwave exfoliated graphite oxide, including a much higher exfoliation degree with thinner graphene sheets and higher specific surface area (886 m2 g-1 vs. 466 m2 g-1 ), a much larger C/O ratio (19.4 vs. 6.3) and a higher lattice crystallinity, as well as significantly improved electrical conductivity (53180 S m-1 vs. 5140 S m-1 ). The CMEGO is used as anode for lithium-ion battery (LIB) and sodium-ion battery (SIB), and delivers ultrahigh reversible capacities, remarkable rate capabilities, and superior cycling stabilities in both LIB and SIB.


Characterization of the physiological substrate for lipopolysaccharide heptosyltransferases I and II.
L-Glycero-D-manno-heptopyranose is a characteristic compound of many lipopolysaccharide (LPS) core structures of Gram-negative bacteria. In Escherichia coli two heptosyltransferases, namely WaaC and WaaF, are known to transfer L-glycero-D-manno-heptopyranose to Re-LPS and Rd(2)-LPS, respectively. It had been proposed that both reactions involve ADPL-glycero-D-manno-heptose as a sugar donor; however, the structure of this nucleotide sugar had never been completely elucidated. In the present study, ADPL-glycero-D-manno-heptose was isolated from a heptosyltransferase-deficient E. coli mutant, and its structure was determined by nuclear magnetic resonance spectroscopy and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry as ADPL-glycero-beta-D-manno-heptopyranose. This compound represented the sole constituent of the bacterial extract that was accepted as a sugar donor by heptosyltransferases I and II in vitro.


Hypercalcaemia, parathyroid hormone-related protein and malignancy.
Hypercalcaemia is the most common serious metabolic complication of malignancy. Recent advances have significantly increased our understanding of the pathophysiology of hypercalcaemia of malignancy and revealed the importance of parathyroid hormone-related protein (PTHrP) in a wide range of physiological and pathological processes. This review examines the pathophysiology of hypercalcaemia of malignancy, focusing on the role of PTHrP before discussing further pathological and physiological processes in which PTHrP may be implicated, and the impact of this knowledge on the management of malignant disease.


Apoptosis and JNK activation are differentially regulated by Fas expression level in renal tubular epithelial cells.
In chronic renal disease, renal tubular epithelial cell (RTC) Fas expression is up-regulated, leading to apoptotic RTC deletion and tubular atrophy. In vitro, cytokine- or hypoxia-induced up-regulation of Fas expression is associated with RTC apoptosis. In contrast, constitutively expressed, low level RTC Fas does not mediate apoptosis, suggesting that Fas may be coupled to expression level-dependent RTC signaling pathways. Fas is known to signal through JNK in many systems, but the requirement of JNK activation for apoptosis remains controversial. To determine if RTC Fas regulates JNK activity and apoptosis, human RTC were transfected with graded concentrations of a eukaryotic expression vector for murine Fas. Apoptosis was measured by annexin V, TUNEL and PARP cleavage assays. JNK activity was determined by immune complex kinase assay and/or immunoblots with phospho-specific JNK antibodies, in the presence or absence of co-expressed dominant negative JNK constructs. Fas antibody stimulation of RTC with high Fas expression levels (to model RTC phenotype in renal disease) caused a tenfold increase in apoptosis, while RTC with low level Fas expression (to model normal RTC phenotype) were apoptosis-resistant. Fas ligation activated JNK in RTC expressing low levels of Fas, but not in apoptosis-sensitive RTC with increased Fas expression. Dominant negative JNK co-expression failed to inhibit apoptosis in RTC expressing high levels of Fas, suggesting that JNK is neither necessary, nor sufficient, for Fas-dependent apoptosis. At high levels of expression, RTC Fas promotes apoptosis in a JNK-independent manner. At low basal expression, Fas induces JNK activation, but not apoptosis, consistent with novel roles for RTC Fas as a mediator of cell stress or chronic inflammation.


Metals Differentially Activate Ovarian Cancer G Protein-Coupled Receptor 1 in Various Species.
Human, mouse, and zebrafish ovarian cancer G protein-coupled receptors (OGR1s) are activated by both metals and extracellular protons. In the present study, we examined whether pig, rat, chicken, and Xenopus OGR1 homologs could sense and be activated by protons and metals. We found that all homologs stimulated serum response element (SRE)-driven promoter activities when they are stimulated by protons. On the other hand, metals differentially activated the homologs. The results using chimeric receptors of human and zebrafish OGR1s indicate that the specificity of the metal-induced activation lies in the extracellular region. These results suggest that protons are an evolutionally conserved agonist of OGR1. However, the types of metals that activated the receptor differed among the homologs.


Deciphering the structural framework of glycine receptor anchoring by gephyrin.
Glycine is the major inhibitory neurotransmitter in the spinal cord and brain stem. Gephyrin is required to achieve a high concentration of glycine receptors (GlyRs) in the postsynaptic membrane, which is crucial for efficient glycinergic signal transduction. The interaction between gephyrin and the GlyR involves the E-domain of gephyrin and a cytoplasmic loop located between transmembrane segments three and four of the GlyR beta subunit. Here, we present crystal structures of the gephyrin E-domain with and without the GlyR beta-loop at 2.4 and 2.7 A resolutions, respectively. The GlyR beta-loop is bound in a symmetric 'key and lock' fashion to each E-domain monomer in a pocket adjacent to the dimer interface. Structure-guided mutagenesis followed by in vitro binding and in vivo colocalization assays demonstrate that a hydrophobic interaction formed by Phe 330 of gephyrin and Phe 398 and Ile 400 of the GlyR beta-loop is crucial for binding.


The role of selective estrogen receptor modulators (SERMs) in postmenopausal health.
Concerns about long-term therapy with HRT have recently highlighted interest in a class of compounds active in the estrogen receptor, but with selectivity in their actions, known as the selective estrogen receptor modulators (SERMs). Tamoxifen is recognized as the first widely marketed SERM, but its selectivity focuses interest on its approved indications: the treatment and prevention of breast cancer. Raloxifene has been approved in most countries of the world for the treatment and prevention of osteoporosis, and it displays a pattern of actions highly matched to the needs and concerns of many postmenopausal women. Further study of current and future SERMs promises to open new vistas in patient-specific management of the field of postmenopausal health.


Tip-Enhanced Raman Scattering Imaging of Single- to Few-Layer Ti3C2Tx MXene.
MXenes are among the most widely researched materials due to a unique combination of high electronic conductivity and hydrophilic surface, confined in a 2D structure. Therefore, comprehensive characterization of individual MXene flakes is of great importance. Here we report on nanoscale Raman imaging of single-layer and few-layer flakes of Ti3C2Tx MXene deposited on a gold substrate using tip-enhanced Raman scattering (TERS). TERS spectra of MXene monolayers are dominated by an intense peak at around 201 cm-1 and two well-defined peaks at around 126 and 725 cm-1. Absolute intensities of these peaks decrease with increasing number of layers, though the relative intensity of the 126 and 725 cm-1 bands as compared to the 201 cm-1 band increases. The peak positions of the main MXene bands do not significantly change in flakes of different number of layers, suggesting weak coupling between the MXene layers. In addition, we observed stiffening of the 201 cm-1 vibration over the wrinkles in MXene flakes. Using TERS for nanoscale spectroscopic characterization of Ti3C2Tx allows fast Raman mapping with deep subdiffraction resolution at the laser power density on the sample about an order of magnitude lower as compared to confocal Raman measurements. Finally, we demonstrate very high environmental stability of stoichiometric single-layer MXenes and show that the intensity of TERS response from the single- and few-layer flakes of Ti3C2Tx can be used to track early stages of degradation, well before significant morphological changes appear.


Time trends in antithrombotic management of patients with atrial fibrillation treated with coronary stents: Results from TALENT-AF (The internAtionaL stENT - Atrial Fibrillation study) multicenter registry.
Antithrombotic management of patients with atrial fibrillation (AF) requiring percutaneous coronary intervention (PCI) is highly variable; limited evidence-based guidelines exist to influence practice. Patient characteristics and availability of novel drugs may have contributed to practice variability. We undertook an international multicenter retrospective registry of AF patients treated with PCI. The primary measures of interest were antiplatelet and OAC prescriptions at discharge. We compared temporal trends between Prior (2010-2012) and Recent (2013-2015) cohorts and investigated variables associated with OAC prescription. We identified 488 cases (140 Prior, 348 Recent). Median CHADS2 and HAS-BLED scores were 2 (IQR, 1-3) and 2 (IQR, 2-3). Clinical characteristics were similar between cohorts, with high (85%) prevalence of ACS. More patients in the Recent cohort, compared with Prior, received OAC (56.9% vs 44.3%; P = 0.01) and NOAC (27.3% vs 3.6%; P < 0.01) at baseline. Triple therapy at discharge was not different between the cohorts. Clinical presentation with ACS and consequent use of potent P2Y12 inhibitors were associated with reduced odds of OAC prescription at discharge (OR: 0.57, P = 0.045 and OR: 0.38, P = 0.023, respectively). Despite little change over time in clinical characteristics of AF patients undergoing PCI, significantly more patients received OAC at presentation. However, triple therapy was not more frequent in the Recent cohort, and ACS presentation was associated with lack of OAC at discharge. We underscore the need for trial evidence and use of updated guidelines to assist clinicians in balancing ischemic and bleeding risks.


Exhaled nitric oxide in asthma: variability, relation to asthma severity, and peripheral blood lymphocyte cytokine expression.
Exhaled nitric oxide has been used as a means of indirectly measuring the underlying inflammation in asthma. The objectives of the study were to measure exhaled nitric oxide levels in asthma patients and healthy volunteers, to study peripheral blood lymphocyte cytokine expression, and to study the relationship between exhaled nitric oxide and intracellular cytokine expression. Exhaled nitric oxide was elevated in patients with moderate to severe asthma and with treatment decreased in the first week reaching to a near normal level by 4 weeks. Elevated exhaled nitric oxide was associated with decreased IL-4 and IL-13 cytokine expression by CD8 lymphocytes.


Investigation of cystic left ventricular masses with echocardiography and magnetic resonance imaging.
We report on two patients who had cystic masses located in the left ventricle associated with findings of congestive heart failure. Both echocardiography and magnetic resonance imaging (MRI) were helpful in identifying features of these masses. Echocardiography was used to guide percutaneous transarterial catheter drainage of the mass in one patient.


Segmentation and Analysis of Corpus Callosum in Alzheimer MR Images using Total Variation Based Diffusion Filter and Level Set Method.
Alzheimer's Disease (AD) is a common form of dementia that affects gray and white matter structures of brain. Manifestation of AD leads to cognitive deficits such as memory impairment problems, ability to think and difficulties in performing day to day activities. Although the etiology of this disease is unclear, imaging biomarkers are highly useful in the early diagnosis of AD. Magnetic resonance imaging is an indispensible non-invasive imaging modality that reflects both the geometry and pathology of the brain. Corpus Callosum (CC) is the largest white matter structure as well as the main inter-hemispheric fiber connection that undergoes regional alterations due to AD. Therefore, segmentation and feature extraction are predominantly essential to characterize the CC atrophy. In this work, an attempt has been made to segment CC using edge based level set method. Prior to segmentation, the images are pre-processed using Total Variation (TV) based diffusion filtering to enhance the edge information. Shape based geometric features are extracted from the segmented CC images to analyze the CC atrophy. Results show that the edge based level set method is able to segment CC in both the normal and AD images. TV based diffusion filtering has performed uniform region specific smoothing thereby preserving the texture and small scale details of the image. Consequently, the edge map of CC in both the normal and AD are apparently sharp and distinct with continuous boundaries. This facilitates the final contour to correctly segment CC from the nearby structures. The extracted geometric features such as area, perimeter and minor axis are found to have the percentage difference of 5.97%, 22.22% and 9.52% respectively in the demarcation of AD subjects. As callosal atrophy is significant in the diagnosis of AD, this study seems to be clinically useful.