Kinetic properties of cation/H(+)-exchange: calcimycin (A23187)-mediated Ca2+/2H(+)-exchange on the bilayer lipid membrane.
The calcimycin (A23187)-mediated electrically silent flux of hydrogen ions coupled with a counter transport of calcium or magnesium ions was measured by the method of local pH changes recording in the unstirred layers near the planar bilayer lipid membrane (BLM). It was shown that: (1) the pH dependence of calcimycin-mediated Ca2+/2H+ exchange had a maximum at pH 7; (2) the apparent Michaelis constant for the alkali earth cations were higher at acidic pH than the corresponding values at alkaline pH; (3) the apparent Michaelis constant for calcium was similar to that for magnesium ions in agreement with calcimycine cation binding constants; (4) the ratio of calcium and magnesium fluxes was independent of pH in the pH range from 5 to 8. (5) the flux was proportional to the calcimycin concentration at pH greater than 6.3 and proportional to the square of the carrier concentration at pH less than 5; (6) the addition of calcium ion chelator EDTA increased the flux significantly. These data were discussed in terms of the model of cation/H(+)-exchange and it was concluded that the dissociation of the cation-carrier complex at the membrane/water interface played an important role in the process of calcimycine operation. The comparison of the kinetic properties of calcimycin with the previously described kinetics of nigericin (Antonenko and Yaguzhinsky (1988) Biol. Membr. (Russian) 5, 718-728) revealed much similarity. On the other hand, a significant difference was found between the mechanism of the nigericin K/Na selectivity and calcimycin Ca/Mg selectivity.


Cervical pessary to prevent preterm birth in women with twin gestation and sonographic short cervix: a multicenter randomized controlled trial (PECEP-Twins).
Spontaneous preterm birth (SPB) is the leading cause of perinatal morbidity and mortality. In twins, the rate of preterm birth is higher than in singletons; interventions to prevent preterm birth are needed in this high-risk population. We sought to test whether a cervical pessary reduces the preterm birth rate in twin pregnancies with sonographic short cervix. A prospective, open-label, multicenter, randomized clinical trial was conducted in 5 hospitals in Spain. The ethics committees of all participating hospitals approved the protocol. The trial was registered as ClinicalTrials.gov, number NCT01242410. Eligible women were scanned in Spain. The primary outcome was SPB <34 weeks of gestation. Neonatal morbidity and mortality were also evaluated. Cervical length was measured in 2287 women; 137 pregnant women with a sonographic cervical length ≤25 mm (of 154 detected with a short cervix) were randomly assigned to receive a cervical pessary or expectant management (1:1 ratio). SPB <34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (11/68 [16.2%] vs 26/66 [39.4%]; relative risk, 0.41; 95% confidence interval, 0.22-0.76). Pessary use was associated with a significant reduction in the rate of birthweight <2500 g (P = .01). No significant differences were observed in composite neonatal morbidity outcome (8/136 [5.9%] vs 12/130 [9.1%]; relative risk, 0.64; 95% confidence interval, 0.27-1.50) or neonatal mortality (none) between the groups. No serious adverse effects associated with the use of a cervical pessary were observed. The insertion of a cervical pessary was associated with a significant reduction in the SPB rate. We propose the use of a cervical pessary for preventing preterm birth in twin pregnancies of mothers with a short cervix.


Personalisation schemes in social care and inequality: review of the evidence and early theorising.
Personalisation is a growing international policy paradigm that aims to create both improved outcomes for individuals, and reduce fiscal pressures on government, by giving greater choice and control to citizens accessing social services. In personalisation schemes, individuals purchase services from a 'service market' using individual budgets or vouchers given to them by governments. Personalisation schemes have grown in areas such as disability and aged care across Europe, the UK and Australia. There is a wealth of evidence in public health and health care that demonstrates that practically all forms of social services, programs and interventions produce unequal benefit depending on socio-economic position. Research has found that skills required to successfully negotiate service systems leads to disproportionate benefit to the 'middle class. With an unprecedented emphasis on individual skills, personalisation has even greater potential to widen and entrench social inequalities. Despite the increase in numbers of people now accessing services through such schemes, there has been no examination of how different social groups benefit from these schemes, how this widens and entrenches social inequities, and - in turn - what can be done to mitigate this. This article presents a meta-review of the evidence on personalisation and inequality. A qualitative meta-analysis was undertaking of existing research into personalisation schemes in social services to identify whether and how such schemes are impacting different socio-economic groups. No research was identified which seeks to understand the impact of personalisation schemes on inequality. However, a number of 'proxies' for social class were identified, such as education, income, and employment, which had a bearing on outcome. We provide a theoretical framework for understanding why this is occurring, using concepts drawn from Bourdieu. Personalisation schemes are likely to be entrenching, and potentially expanding, social inequalities. More attention needs to be given to this aspect of personal budgets by policymakers and researchers.


Development and characterization of Gal KO porcine bone marrow-derived mesenchymal stem cells.
We demonstrated that neonatal porcine bone marrow-derived mesenchymal stem cell (npBM-MSCs) could improve a critical ischemic limb disease in rat model more efficiently compared with human MSCs. However, since porcine MSC presents galactosyl-alpha 1,3-galactose antigen (Gal antigen), MSC could be eliminated by the xenogeneic rejection. Recently, we established Gal knockout (KO) pigs by a technique of the electroporation of the CRISPR/Cas9 system into vitro-fertilized zygotes. In this study, we hypothesized that MSC from the established Gal KO pigs could further improve the efficacy. Before examining the hypothesis, in this study, we have established and characterized bone marrow-derived MSC from the Gal KO adult pigs (apBM-MSCs). Mononuclear cells (MNCs) were isolated from bone marrow cells of both Gal KO adult pigs and wild-type (WT) adult pigs. MNCs were further manipulated to create Gal KO apBM-MSCs and WT apBM-MSCs. Both MSCs were assessed by their surface markers, the capability of differentiation into adipocytes, osteocytes and chondrocytes, grow speed and colony-forming assay. To assess the efficacy of Gal KO apBM-MSCs, angiogenesis-related genes and immunosuppression-related genes were assessed by cytokine stimulation. Gal KO apBM-MSC showed no Gal antigen on their cell surfaces. Both Gal KO apBM-MSCs and WT apBM-MSCs, presented little or no negative surface markers of MSCs, while they presented positive surface markers of MSCs. Furthermore, Gal KO apBM-MSCs were able to differentiate into adipocytes, osteocytes, and chondrocytes as well as WT apBM-MSCs. There was no difference in doubling time between Gal KO apBM-MSCs and WT apBM-MSCs. Interestingly, the colony-forming efficiency of Gal KO apBM-MSCs was about half that of WT apBM-MSC. However, angiogenesis and immunosuppression-related genes were equally upregulated in both Gal KO apBM-MSCs and WT apBM-MSCs by cytokine stimulation. We created and characterized Gal KO apBM-MSCs which showed similar characteristics and cytokine-induced gene upregulation to the WT apBM-MSCs.


Prevention of intussusception in Peutz-Jeghers syndrome.
Peutz-Jeghers syndrome is a familial disease characterized by mucocutaneous pigmentation and intestinal polyposis. Small-intestinal intussusception is a common complication. Preservation otion technique to prevent intussusception is described.


Test use and assessment practices of school psychologists in the United States: Findings from the 2017 National Survey.
Although several studies have examined the specific instruments and procedures used by school psychologists when conducting comprehensive psychoeducational evaluations, the last one was published over 20 years ago (viz., Wilson & Reschly, 1996). Given the substantial theoretical and practical advances in assessment since then, the purpose of the current study was to examine the test use and assessment practices of contemporary school psychologists in the United States. Data from the 2017 National Survey of Assessment Practices in School Psychology revealed that test use and assessment practices have evolved significantly. Much of this change consists of the substitution of tests and practices with limited reliability and validity with those with greater psychometric support. Results of this study also indicate that school psychologists regularly conduct multi-method assessments to prevent, identify, monitor, and remediate child and adolescent learning difficulties and other presenting problems in the schools.


Protein structure probed by polarization spectroscopy. II. A time-resolved fluorescence study of human fibrinogen.
Human fibrinogen in solution was studied by monitoring the time-resolved depolarization of the fluorescence emitted by two spectroscopic labels of which the fluorescence lifetimes differ by an order of magnitude. Contrary to a long-held view, no evidence of molecular flexibility was found in the 10-1000 ns range. In addition, from the rate of the overall rotation, it is proposed that a prolate and symmetric ellipsoid of 47 X 10.5 nm may represent the time-averaged hydrodynamic size and shape of the protein in solution. This rigid and highly hydrated structure (4 g water/g protein) accommodates the latest nodular models obtained from electron microscopy, explains the singular hydrodynamics of fibrinogen and, apparently, it would perform the two main functions of the protein in haemostasis, blood coagulation and platelet aggregation, more efficiently than the flexible molecule.


Protein tyrosine phosphorylation activates rat splenic type II phosphatidylinositol 4-kinase in vitro.
Regulation of phosphatidylinositol 4-kinase (PtdIns 4-kinase) by protein tyrosine phosphorylation has been indirect and the effects of phosphorylation are debatable. Rat splenic type II PtdIns 4-kinase was phosphorylated in vitro with protein tyrosine kinases from Con A stimulated splenic lymphocytes. Stoichiometric analysis showed one mole of phosphate was incorporated per mole of PtdIns 4-kinase. Tyrosine phosphorylation increased the enzyme activity by 3-fold. Kinetic analysis showed a reduction in Km for PtdIns and an increase in Vmax. Dephosphorylation with protein phosphotyrosine phosphatase abolished the activation of PtdIns 4-kinase while protein phosphatase 2A had no effect. Protein tyrosine phosphorylation and activation of PtdIns 4-kinase appear to be tissue specific.


Elevated levels of the 26K human hybridoma growth factor (interleukin 6) in cerebrospinal fluid of patients with acute infection of the central nervous system.
We reported recently that a human protein, previously described as IL-1 inducible 26K factor (26K) or interferon-beta 2, was a potent growth factor for B cell hybridomas in vitro. Subsequently, it appeared that this protein was also identical with the lymphokine B cell stimulatory factor 2. Here we report that the levels of 26K are considerably increased during the early stages of acute infections of the central nervous system. This elevation in 26K titres was not observed in either chronic infections or in non-infectious diseases.


Gene-gene synergistic effect on atopic asthma: tumour necrosis factor-alpha-308 and lymphotoxin-alpha-NcoI in Taiwan's children.
Asthma is now known to be an inflammatory response caused by the release of inflammatory mediators and cytokines. Tumour necrosis factor (TNF) is a potent cytokine in the inflammation response of the airway, and the polymorphisms of TNF genes have been associated with asthma. This study investigated two variants, TNF-alpha-308*2 and lymphotoxin (LT)-alpha-NcoI*1, which may predispose individuals to asthma and atopy pathogenesis. PCR-based assays were performed to determine LT-alpha-NcoI*1 and TNF-alpha-308*2 genotypes among our subjects, with 128 atopic asthmatics and 51 non-atopic asthmatics, 55 atopic controls, and 78 non-atopic controls in this genetic case-control study. The TNF-alpha-308*2 polymorphism increased in subjects with atopic asthma vs. non-atopic controls after adjusting for age distribution (adjusted odds ratios, AOR=2.73, 95% confidence interval, CI=1.16-6.64), but was not associated with non-atopic asthma (AOR=2.40, 95% CI=0.81-7.09). LT-alpha-NcoI*1 did not show an independent association with either atopic asthma or any one phenotype of specific IgE. The synergistic effect between these two genes was conducted, and the interaction between TNF-alpha-308*2 and LT-alpha-NcoI*1 polymorphisms was seen for atopic asthma (OR=2.59, 95% CI=1.10-6.10) when compared with all controls. We have concluded that TNF-alpha-308 may be a risk factor for atopic asthma, whereas the LT-alpha-NcoI polymorphism may modify risk to atopic asthma with TNF-alpha-308.


Minimally invasive, endoscopic Achilles tendon reconstruction using semitendinosus and gracilis tendons with Endobutton stabilization.
Plantaris tendon, peronus brevis tendon and flexor hallucis longus tendon augmentation, commonly used in Achilles tendon rupture, often lead to weakening of injured foot and they require the immobilization after the surgery. It is essential to develop the technique, which gives no such limitation and allows for immediate functional improvement. We present our method of minimally invasive, endoscopic Achilles tendon reconstruction using semitendinosus and gracilis tendons with Endobutton stabilization. Posterolateral and posteromedial portals were made approximately 3 cm above the posterosuperior part of the calcaneus to clean the area of the Achilles tendon endoscopically. Then the hamstrings are harvested and prepared for the "Endobutton" system. A midline incision of the skin is performed approximately 1 cm above the posterosuperior part of the calcaneus to approach to the posterosuperior part of the calcaneus. Then under fluoroscopy the calcaneus was drilled through using K-wire. The distal end of the graft equipped with an Endobutton loop was entered into the drilled tunnel in the calcaneus. Later, 8 consecutive skin incisions are performed. Proximal ends of the graft were brought out through the native Achilles tendon reaching medial and lateral skin incisions. The final step was to transfer and tie the graft ends through the most proximal skin incision. This minimally invasive, endoscopic technique allows reconstruction of the Achilles tendon using semitendinosus and gracilis tendons with Endobutton stabilization and can be used in so-called "difficult", resistant cases as a "salvage procedure".


Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts.
Transplantation of adult bone marrow-derived mesenchymal stem cells has been proposed as a strategy for cardiac repair following myocardial damage. However, poor cell viability associated with transplantation has limited the reparative capacity of these cells in vivo. In this study, we genetically engineered rat mesenchymal stem cells using ex vivo retroviral transduction to overexpress the prosurvival gene Akt1 (encoding the Akt protein). Transplantation of 5 x 10(6) cells overexpressing Akt into the ischemic rat myocardium inhibited the process of cardiac remodeling by reducing intramyocardial inflammation, collagen deposition and cardiac myocyte hypertrophy, regenerated 80-90% of lost myocardial volume, and completely normalized systolic and diastolic cardiac function. These observed effects were dose (cell number) dependent. Mesenchymal stem cells transduced with Akt1 restored fourfold greater myocardial volume than equal numbers of cells transduced with the reporter gene lacZ. Thus, mesenchymal stem cells genetically enhanced with Akt1 can repair infarcted myocardium, prevent remodeling and nearly normalize cardiac performance.


Time course of proteinuria after living-donor kidney transplantation.
After cadaveric kidney transplantation, preservation-reperfusion damage results in glomerular and tubular proteinuria. There are no data on the time course of proteinuria after living-donor (LD) transplantation. In 10 patients receiving a kidney graft from an LD, the excretion of high molecular weight proteins (albumin, transferrin, and immunoglobulin G) and low molecular weight proteins (beta2-microglobulin and alpha1-microglobulin) was measured at various time points during the first 5 days after transplantation. Immediately after restoration of the circulation, we observed a massive nonselective high molecular weight proteinuria, indicative of glomerular damage. This proteinuria rapidly decreased to slightly elevated values beyond 24 hr after transplantation. Low molecular weight proteinuria, reflecting tubular damage, was also prominent and remained grossly abnormal even at day 5. After LD transplantation, preservation-reperfusion injury causes massive proteinuria during the first 24 hr. Thereafter proteinuria rarely exceeds 1 g per day.


Inhaled nitric oxide for oligohydramnios-induced pulmonary hypoplasia: a report of two cases and review of the literature.
We describe the clinical courses of two premature infants, a male born at 29(4/7) weeks' gestational age after an 8-week period of rupture of membranes (ROM) and severe oligohydramnios, and a female infant born at 31 weeks' gestational age after an 18-week period of ROM and severe oligohydramnios. Within hours after birth, despite intubation and aggressive ventilation, both infants developed fulminant hypoxic respiratory failure. Their clinical courses were consistent with pulmonary hypertension and both infants were transferred for trials of inhaled nitric oxide (iNO). Both infants had dramatic responses to iNO, suggesting that the pulmonary disease seen after prolonged oligohydramnios may have a component of nitric oxide-sensitive pulmonary hypertension. The goals of this article are to (1) review oligohydramnios-induced pulmonary hypoplasia, (2) discuss patients at highest mortality risk, and (3) describe the effects of iNO on pulmonary hypertension in infants with hypoxemia following prolonged ROM and severe oligohydramnios.


Is tiaprofenic acid different from other NSAIDs with regard to effects on renal function in the elderly?
In a study of the effects of various NSAIDs on renal function in the elderly, indomethacin, tiaprofenic acid and sulindac were administered to patients ranging in age from 54 to 97 years for a period of 3 months. Indomethacin sustained release (25 mg tid) was administered to 66 patients, tiaprofenic acid (200 mg tid) to 54 patients, and sulindac (100 mg tid) to 59 patients. A control group, to whom no NSAIDs were administered, comprised 60 patients. Renal function before and after NSAID administration was compared, the parameters investigated being blood urea nitrogen (BUN), serum creatinine (SCR), and serum beta 2-microglobulin (beta 2-m) concentrations. Patients whose levels of BUN, SCR and beta 2-microglobulin were all within normal ranges at the beginning of the study were considered to have 'normal' renal function; those who showed an abnormal value for at least 1 of the 3 parameters were considered to have 'abnormal' renal function. The administration of indomethacin resulted in a significant increase in the serum creatinine concentration, and in the normal renal function subgroup, a significant increase in BUN. Sulindac administration resulted in a significant increase in BUN and beta 2-microglobulin concentrations, but no significant change in serum creatinine. In comparison, the administration of tiaprofenic acid resulted in no significant changes in any of 3 parameters. An additional study of the effects of 4 weeks' administration of the same NSAIDs on N-acetyl-beta-D-glucosaminidase concentrations in the urine of elderly patients revealed no significant changes with any of the 3 drugs. This suggests that the drugs do not damage the proximal tubules.


Coimbra University Hospitals' bone and tissue bank: twenty-two years of experience.
We report the microbiological contamination rate of sterilely procured 3953 tissue allografts obtained during 22 years of activity for musculoskeletal reconstruction from 1982 to 2003. From 1987 to 2000, allograft retrievals were performed in 191 cadaveric donors and in 323 living donors. In the former group 30 retrievals (15.7%) were excluded based on laboratory criteria. Among living donors 108 femoral heads (33.4%) were also excluded by the same criteria. The microbiological contamination rate of sterilely procured allografts in the operating room was 8.3% for cadaveric donors and 18.2% for living donors. A questionable positive serology for HIV antigen was registered in two non-heart-beating donors. Hepatitis C virus antibodies were positive in two other non-heart-beating donors. Hepatitis B virus serological markers were positive or questionable in more than 11 non-heart-beating donors. In living donors 20 femoral heads were excluded (6.1%) due a positive or questionable hepatitis B virus serology. One femoral head donor showed a positive HTLV-I antibody and another one a positive syphilis serology. No positive serology cases for the HIV antibodies were found. No cases were registered of transmission of viral diseases from the donor to the recipient. Our extremely rigorous criteria led to the exclusion of a considerable number of both donors and allografts.


Shelf life of fresh meat products under LED or fluorescent lighting.
Enhanced pork loin chops, beef longissimus lumborum steaks, semimembranosus steaks (superficial and deep portions), ground beef, and ground turkey were displayed under light emitting diode (LED) and fluorescent (FLS) lighting in two multi-shelf, retail display cases with identical operating parameters. Visual and instrumental color, internal product temperature, case temperature, case cycling, thiobarbituric acid reactive substances (TBARS), and Enterobacteriaceae and aerobic plate counts were evaluated. Under LED, beef products (except the deep portion of beef semimembranosus steaks) showed less (P<0.05) visual discoloration. Pork loin chops had higher (P<0.05) L* values for LED lighting. Other than beef longissimus lumborum steaks, products displayed under LED lights had colder internal temperatures than products under FLS lights (P<0.05). Under LED, pork loin chops, ground turkey, and beef semimembranosus steaks had higher (P<0.05) values for TBARS. LED provides colder case and product temperatures, more case efficiency, and extended color life by at least 0.5d for longissimus and semimembranosus steaks; however, some LED cuts showed increased lipid oxidation.


2,4-Dimeth-oxy-6-[(E)-2-(4-meth-oxy-phenyl)ethen-yl]benzaldehyde.
There are two conformationally similar mol-ecules in the asymmetric unit of he title compound, C18H18O4, in which the dihedral angles between the benzene rings are 23.54 (12) and 31.11 (12)°. In the crystal, C-H⋯π inter-actions (minimum H⋯ring centroid distance = 2.66 Å) link the mol-ecules into a layered structure extending down a.


Evidence of a precursor-product relationship between vitellogenin and toposome, a glycoprotein complex mediating cell adhesion.
Toposome, a large and oligomeric glycoprotein complex isolated from mesenchyme-blastula embryos, was defined as a cell-adhesion molecule expressing positional information specificities during sea urchin embryogenesis. This report describes the biochemical and functional characterization of the toposome precursor from sea urchin coelomic fluids of both male and female organisms. The molecule is isolated in the form of a 22S particle which has an apparent molecular mass of 200 kDa. An intermediate form is present in yolk granules of unfertilized eggs with a molecular mass of 180 kDa. The 200 kDa and 180 kDa polypeptides are defined as toposome precursors by Western blot and immunoprecipitation analyses using polyclonal and monoclonal toposome-specific antibodies. Comparison of the 200 kDa polypeptide and mesenchyme-blastula toposome by partial-proteolysis peptide-mapping shows that they are related in a precursor-product relationship. A morphogenetic cell-aggregation assay shows that toposome precursors promote cell adhesion of dissociated blastula cells, suggesting that processing is not required for the cell-adhesion function. The studies reported here present the first evidence that cell adhesion molecules first appear in the form of a 200 kDa polypeptide, previously named vitellogenin, and to which only a function as major-yolk-protein precursor has been ascribed.


IL-33 gene variants and protein expression in pediatric Tunisian asthmatic patients.
Interleukin-33 (IL-33) is one of the last discovered members of the human IL-1 family. It is involved in the pathogenesis of many inflammatory diseases. This study investigates the relationship between IL33 gene variants and serum protein levels with the development of childhood asthma. We analyzed in this case-control study the distribution of two IL33 polymorphisms, rs7044343 and rs1342326, within 200 Tunisian children, using predefined Taqman genotyping assays. IL-33 serum levels were assessed by commercial sandwich Enzyme-linked immunosorbent assay (ELISA). The presence of rs1342326 polymorphism was significantly associated with a lower risk of asthma development. The CC [OR=0.20, CI (0.08-0.50)] and AC [OR=0.24, CI (0.11-0.49)] genotypes, as well as the C-allele [OR=0.40; CI: 0.26-0.61, P=0.00001] were associated significantly with a decreased asthma risk. However, the C-allele was more frequent in severe asthma patients than in milder ones. No association was found between rs7044343 variant and asthma. The level of IL-33 in sera was significantly increased in asthmatic children [1.48±0.47pg/mL] compared to controls [0.70±0.18pg/mL; P<0.001]. Furthermore, this increase of IL-33 was associated with the presence of rs1342326 C allele. The IL33 rs1342326 polymorphism was associated with a lower childhood asthma risk in the Tunisian population and a higher IL-33 protein expression.


The Lateral Column.
Lower extremity biomechanics is the cornerstone of podiatric medicine and surgery. The foot and ankle act as the interface between the ground and proximal segments, mediating internal and external moments Although the medial longitudinal arch has been widely researched, the details of the lateral longitudinal arch are less extensively delineated. The purpose of this review is to analyze the biomechanics of the lateral column as it relates to lower extremity biomechanics and function.


Two new species of Pupulina van Beneden, 1892 (Copepoda: Siphonostomatoida: Caligidae) from mobulid rays off South Africa.
The caligid genus Pupulina van Beneden, 1892 currently has three accepted species. Two new species, Pupulina cliffi n. sp. and P. merira n. sp., are described from Mobula kuhlii (Müller & Henle) and M. eregoodootenkee (Bleeker) (Mobulidae) caught along the east coast of South Africa. Pupulina cliffi can be distinguished from all the other species by the absence of posterolateral processes on the genital complex, whereas P. merira has very short, rounded posterolateral processes on the genital complex compared to the three previously known species. Additionally, P. merira is the only species with the abdomen only about two-thirds the length of the genital complex and the caudal rami about the same length as the abdomen. A dichotomous key to distinguish the five species of Pupulina is provided.


Dexamethasone reduces tachykinin but not ACh airway hyperreactivity after O3.
We investigated whether dexamethasone pretreatment affected the acute increase in airway reactivity produced by high-level ozone exposure. Reactivity to intravenous IV substance P (SP), IV acetylcholine (ACh), or aerosolized capsaicin (CAP) before and 1 hr after ozone exposure (3 ppm for 2 hr) was determined by measuring specific airway resistance in anesthetized, spontaneously breathing guinea pigs, half of whom had been pretreated for 2 days pre-ozone with dexamethasone (2 mg/kg intramuscularly [IM] daily). The amount of IV SP, IV ACh, or inhaled capsaicin necessary to increase baseline specific airway resistance by 100% (ED200ACh or ED200SP) or 35% (ED135CAP) was determined by interpolation from dose-response curves. Compared to their pre-ozone status on the day of exposure, we found that dexamethasone-pretreated animals manifested significantly less of an increase in airway reactivity postozone to IV SP or inhaled CAP than did untreated animals. Changes in logEDs of the pretreated group were 0.18 +/- 0.03 (mean +/- SE) for SP and 2.20 +/- 0.11 for CAP compared to 0.27 +/- 0.04 and 3.38 +/- 0.34, respectively, for the untreated groups post-ozone (p < 0.05 and n = 4 for each). In contrast, dexamethasone pretreatment had no effect on IV ACh reactivity postozone: changes in logED200ACh were 0.27 +/- 0.08 and 0.28 +/- 0.04 for the pretreated and untreated groups, respectively (n = 4). In animals pretreated with captopril to block possible dexamethasone stimulation of angiotensin-converting enzyme synthesis that could influence tachykinin reactivity, we found that the corticosteroid effect on post-ozone SP reactivity was as marked as that seen in animals without captopril (n = 4). Because these reactivity studies were consistent with the possibility that dexamethasone may ameliorate ozone-induced, tachykinin hyperreactivity by stimulating airway neutral endopeptidase (NEP), we measured NEP activity by high-performance liquid chromatography (HPLC) of each tracheal homogenate made from other groups of animals. Homogenates from ozone-exposed, dexamethasone-pretreated animals demonstrated significantly greater NEP activity (81 +/- 24%) than that from ozone-exposed, untreated animals (p < 0.05, n = 5). We conclude that corticosteroid pretreatment reduces the acute increase in airway reactivity to exogenous and endogenous tachykinins caused by ozone. This reduction may be at least partly due to stimulation of airway NEP activity, perhaps most of which is nonmucosal in that ozone acutely inactivates mucosal NEP.


Ingadosides A-C, acacic acid-type saponins from Inga sapindoides with potent inhibitory activity against downy mildew.
As part of a project aiming at the discovery of environmentally friendly alternatives to copper in organic agriculture, a 96% ethanolic extract from the leaves of Inga sapindoides showed potent inhibitory activity against grapevine downy mildew (Plasmopara viticola) in vitro (MIC100 25 μg/mL). Separation of the n-BuOH soluble fraction by silica gel column chromatography followed by a combination of RP18 and HILIC HPLC resulted in the isolation of a series of bidesmosidic saponins characterized by the presence of a monoterpenoid unit attached to a triterpenoid aglycone, a p-methoxycinnamoyl residue, and rare sugar residues such as N-acetyl-d-glucosamine, d-quinovose, and d-fucose. The isolated compounds inhibited the formation or activity of P. viticola zoospores with MIC100 values of 3 or 6 μg/mL, respectively. I. sapindoides, a tree which is often cultivated for shading coffee plantations in Central America, may represent a sustainable source of fungicidal products to be used in the replacement of copper.


Matrix-induced autologous chondrocyte implantation grafting in osteochondral lesions of the talus: Evaluation of cartilage repair using T2 mapping.
Osteochondral lesions of the talus may be treated with different autologous biological approaches. These include platelet-rich plasma, stem cells or MACI and ACI. MACI implants are used to cover cartilage lining defects in the ankle. A total of 18 patients were treated with MACI implants. NMR images were taken before and after the procedure. T2 mapping was used to quantify the changes in cartilage collagen after a 6 12-month postoperative period. Increase in collagen was recorded on all patients. Both open and arthroscopic procedures were performed depending on the technical difficulties encountered during the repair.


Improving prediction of torsadogenic risk in the CiPA in silico model by appropriately accounting for clinical exposure.
Any adverse event is reliant on three properties: the appropriate pharmacology to trigger the event, the appropriate exposure of compound, and intrinsic patient factors. Each alone is necessary but insufficient to predict the event. The Comprehensive in vitro Proarrhythmia Assessment (CiPA) initiative attempts to predict the risk of torsade de pointes (TdP) by focusing on an in-silico model with thresholds determined at modest multiples of the therapeutic exposure for the parent molecule. This emphasizes the pharmacologic properties necessary for TdP but does not account for situations where clinical exposure may be higher, or where hERG potassium channel active metabolites are involved. Could accounting for clinical worst-case scenarios and metabolites, as is already standard practice in thorough QTc studies, improve the prediction algorithm? Terfenadine, a drug classed as "Intermediate" risk by CiPA, was assessed differently in the in-silico model validation. The clinical concentration of terfenadine used for the model was the exposure in the presence of metabolic inhibition representing a 14 to 40-fold increase in exposure compared to the therapeutic plasma concentration. However, several other "Intermediate" risk compounds are also known to be sensitive to metabolic inhibition and/or to have therapeutically active major metabolites, some of which are known to block hERG. Risperidone and astemizole are relevant examples. If only parent exposure is used to calculate a therapeutic window, risperidone has a relatively large multiple between clinical exposure and the hERG potency. Using this exposure of risperidone, the drug borders the "Intermediate" and "Low/No" risk categories for the CiPA in-silico model's TdP metric. The desmethyl metabolite of astemizole likely contributes significantly to the effects on cardiac repolarization, being equipotent on hERG but circulating at much higher levels than parent. Recalculating the TdP metric and margin values for terfenadine, risperidone and astemizole using the unbound concentration normally associated with treatment and a clinical worst case changes the qNet metric to higher risk values and illustrates the potential benefit to the algorithm of consistently using a clinical high exposure scenario accounting for all "hERG-active species". This exercise suggests repeating the model qualification accounting for clinical exposures and metabolites under 'stressed' scenarios would improve prediction of the TdP risk.


An Assessment of Pediatric Primary Care Providers' and Parents' Dental Health Knowledge and Practices.
One in five children aged < 5 years has experienced caries, making it the most prevalent chronic disease in childhood. The failure to address a child's dental health can lead to short-term and long-term complications and problems with permanent dentition. Primary care pediatric providers are in the position to participate in the prevention of caries because of the frequency they see young children before establishing a dental home. A retrospective chart review and two surveys were developed to collect data from health care providers and parents of children aged < 6 years about their dental health knowledge and practices. While providers report being comfortable discussing dental health with patients, review of medical records shows inconsistent discussion and documentation of dental health. There appears to be a lack of education regarding dental health among parents and health care providers. Primary care providers are not effectively communicating the importance of childhood dental health and are not routinely documenting dental health information.


The impacts of ambient temperature and ultraviolet radiation on the incidence of herpes zoster: An ecological study in Taiwan.
The aim of the study was to examine the relationship between ambient temperature, ultraviolet radiation, and the development of herpes zoster in Taiwan. An ecological study was conducted to analyse the database of the Taiwan National Health Insurance Programme. Participants aged ≥20 years with newly diagnosed herpes zoster between 2003 and 2012 were selected for analysis. The monthly incidence rate of herpes zoster was measured between 2003 and 2012. Monthly average ambient temperature in Celsius (°C) between 2003 and 2012 was measured according to the official database of the Central Weather Bureau in Taiwan. Monthly accumulated ultraviolet radiation (MJ m-2 ) between 2003 and 2012 was measured according to the official database of the Environmental Protection Administration in Taiwan. The overall incidence rates of herpes zoster ranged from 2.54 to 5.67 per 10 000 persons per month from 2003 to 2012.The monthly average ambient temperature was higher and the monthly accumulated ultraviolet radiation was stronger from May to October. The incidence rates of herpes zoster seemed to be high during the period of high ambient temperature and strong ultraviolet radiation (from May to October).Whenever ambient temperature increased 1°C per month, the incidence rate of herpes zoster increased by 0.072 per 10,000 persons per month. Whenever ultraviolet radiation increased 1 MJ m-2 per month, the incidence rate of herpes zoster increased by 0.313 per 10 000 persons per month. There is a significant association between ambient temperature, ultraviolet radiation, and the development of herpes zoster in Taiwan. The incidence rate of herpes zoster is high during the period of high ambient temperature and strong ultraviolet radiation. Low ambient temperature and weak ultraviolet radiation might be beneficial for the prevention of herpes zoster.


Modeling the XBB strain of SARS-CoV-2: Competition between variants and impact of reinfection.
XBB, an Omicron subvariant of SARS-CoV-2 that began to circulate in late 2022, has been dominant in the US since early 2023. To quantify the impact of XBB on the progression of COVID-19, we propose a new mathematical model which describes the interplay between XBB and other SARS-CoV-2 variants at the population level and which incorporates the effects of reinfection. We apply the model to COVID-19 data in the US that include surveillance data on the cases and variant proportions from the New York City, the State of New York, and the State of Washington. Our fitting and simulation results show that the transmission rate of XBB is significantly higher than that of other variants and the reinfection from XBB may play an important role in shaping the pandemic/epidemic pattern in the US.


Maternal expectations: new mothers, nurses, and breastfeeding.
By the middle of the 20th century, breastfeeding rates had fallen to less than 20% in some areas of the United States. Despite these grim statistics, many mothers continued to seek information, advice, and the experience of breastfeeding their infants. This article explores the role that nurses played in these women's struggles to breastfeed in the years between the end of World War II and the 1970s. The role of the nurse in shaping the meaning and experience of breastfeeding in America has been an important, albeit often overlooked, part of the history of infant feeding. In addition to exploring the ways in which hospital policies and structures shaped nurses' relationships with breastfeeding mothers, this article looks at how different maternal ideologies influenced the nature of these (mostly) same-sex interactions. This article argues that the ideas about, and experiences with, motherhood had important implications for how nurses and mothers approached the practice of breastfeeding in the hospital.


Sample prep for proteomics of breast cancer: proteomics and gene ontology reveal dramatic differences in protein solubilization preferences of radioimmunoprecipitation assay and urea lysis buffers.
An important step in the proteomics of solid tumors, including breast cancer, consists of efficiently extracting most of proteins in the tumor specimen. For this purpose, Radio-Immunoprecipitation Assay (RIPA) buffer is widely employed. RIPA buffer's rapid and highly efficient cell lysis and good solubilization of a wide range of proteins is further augmented by its compatibility with protease and phosphatase inhibitors, ability to minimize non-specific protein binding leading to a lower background in immunoprecipitation, and its suitability for protein quantitation. In this work, the insoluble matter left after RIPA buffer extraction of proteins from breast tumors are subjected to another extraction step, using a urea-based buffer. It is shown that RIPA and urea lysis buffers fractionate breast tissue proteins primarily on the basis of molecular weights. The average molecular weight of proteins that dissolve exclusively in urea buffer is up to 60% higher than in RIPA.Gene Ontology (GO) and Directed Acyclic Graphs (DAG) are used to map the collective biological and biophysical attributes of the RIPA and urea proteomes. The Cellular Component and Molecular Function annotations reveal protein solubilization preferences of the buffers, especially the compartmentalization and functional distributions.It is shown that nearly all extracellular matrix proteins (ECM) in the breast tumors and matched normal tissues are found, nearly exclusively, in the urea fraction, while they are mostly insoluble in RIPA buffer. Additionally, it is demonstrated that cytoskeletal and extracellular region proteins are more soluble in urea than in RIPA, whereas for nuclear, cytoplasmic and mitochondrial proteins, RIPA buffer is preferred.Extracellular matrix proteins are highly implicated in cancer, including their proteinase-mediated degradation and remodelling, tumor development, progression, adhesion and metastasis. Thus, if they are not efficiently extracted by RIPA buffer, important information may be missed in cancer research. For proteomics of solid tumors, a two-step extraction process is recommended. First, proteins in the tumor specimen should be extracted with RIPA buffer. Second, the RIPA-insoluble material should be extracted with the urea-based buffer employed in this work.


Cognitive enhancers: potential strategies and experimental results.
1. Cognitive impairments follow natural processes such as aging, diseases, exposure to neurotoxins, and traumatic injury. In all of these instances, the brain possesses some capability for recovery. 2. A cognitive enhancer is any compound that will help this recovery occur more rapidly, or increase the final level of performance. 3. This chapter describes the types of strategies that can be used to develop a cognitive enhancer with emphasis on studies of the cholinergic system.


Epigenome-wide DNA methylation in obsessive-compulsive disorder.
In adult patients with obsessive-compulsive disorder (OCD), altered DNA methylation has been discerned in several candidate genes, while DNA methylation on an epigenome-wide level has been investigated in only one Chinese study so far. Here, an epigenome-wide association study (EWAS) was performed in a sample of 76 OCD patients of European ancestry (37 women, age ± SD: 33.51 ± 10.92 years) and 76 sex- and age-matched healthy controls for the first time using the Illumina MethylationEPIC BeadChip. After quality control, nine epigenome-wide significant quantitative trait methylation sites (QTMs) and 21 suggestive hits were discerned in the final sample of 68 patients and 68 controls. The top hit (cg24159721) and four other significant QTMs (cg11894324, cg01070250, cg11330075, cg15174812) map to the region of the microRNA 12136 gene (MIR12136). Two additional significant CpG sites (cg05740793, cg20450977) are located in the flanking region of the MT-RNR2 (humanin) like 8 gene (MT-RNRL8), while two further QTMs (cg16267121, cg15890734) map to the regions of the MT-RNR2 (humanin) like 3 (MT-RNRL3) and MT-RNR2 (humanin) like 2 (MT-RNRL2) genes. Provided replication of the present findings in larger samples, the identified QTMs might provide more biological insight into the pathogenesis of OCD and thereby could in the future serve as peripheral epigenetic markers of OCD risk with the potential to inform targeted preventive and therapeutic efforts.


kinDOCK: a tool for comparative docking of protein kinase ligands.
KinDOCK is a new web server for the analysis of ATP-binding sites of protein kinases. This characterization is based on the docking of ligands already co-crystallized with other protein kinases. A structural library of protein kinase-ligand complexes has been extracted from the Protein Data Bank (PDB). This library can provide both potential ligands and their putative binding orientation for a given protein kinase. After protein-protein structural superposition, the ligands are transferred from the template complexes to the target protein kinase. The resulting complexes are evaluated using the program SCORE to compute a theoretical affinity. They can be dynamically visualized to allow a rapid mapping of important steric clashes and potential substitutions relevant for specificity and affinity. These characteristics allow a quick characterization of protein kinase active sites including conformation changes potentially required to accommodate particular ligands. Additionally, promising pharmacophores can be identified in the focussed library. These features will help to rationalize or optimize virtual screening (VS) on larger chemical compound libraries. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/kindock/.


MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer.
To investigate the possible role of microRNAs in the resistance to platinum based chemotherapy in non-small cell lung cancer (NSCLC), explore their potential role and find potential biomarkers for prediction of the response to platinum. 21 miRNAs were deregulated in A549/CDDP. Increased miR-21 expression significantly increased the resistance of A549 cell to platinum, whereas reduced miR-21 decreased the resistance of A549/CDDP cell. This finding was further validated in the tissue samples of 58 patients and it was found that miR-21 expression was significantly increased in platinum based chemotherapy-resistant patients (n = 58, p = 0.000). And increased miR-21 expression was associated with the shorter DFS (p = 0.008). Among these 58 patients, 32 had the corresponding plasma samples and similar tendencies were detected in 68.75% patients. Finally, transfection of A549/CDDP with anti-miR-21 increased the expression of PTEN and decreased Bcl-2. In contrast, pre-miR-21 decreased the expression of PTEN and increased Bcl-2 in A549. Microarray was employed to compare the expression of miRNAs between A549 and A549/CDDP cells. The effect of a differently expressed miRNA (miR-21) was examined on the sensitivity of cells to platinum. MiR-21 expression in NSCLC tumor tissues and matched plasma sample was also analyzed by Real-time PCR. Our data suggests that the expression level of miR-21 in tumor tissue and plasma might be used as a biomarker to predict adjuvant platinum based chemotherapy response and disease free survival in patients with NSCLC. Thus, it may serve as a novel therapeutic target to modulate platinum-based chemotherapy.


The construction and application of physiologically based toxicokinetic models for acrylamide, glycidamide and their biomarkers in rats and humans.
Acrylamide (AA), a class 2A probable carcinogen to humans classified by the International Agency for Research on Cancer, has attracted extensive attention worldwide since it was widely used in industrial and domestic water treatment and detected in thermal processing foods. The metabolic adducts of AA and its primary metabolite glycidamide (GA) have been served as biomonitoring markers of AA intake, but the physiologically based toxicokinetics (PBTK) models to estimate internal dosimetry still remain unclear. An updated PBTK model for AA, GA and their metabolic biomarkers in rats and humans was developed and extended with time-course datasets from both literatures and our experiments. With adjustments to the model parameters, linear regression correlation coefficient (R2) between the fitting values and the validation datasets of rats and humans was greater than 0.76. The current model fits well with the experimental datasets of urinary N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and (N-(R,S)-acetyl-S-(carbamoyl-2-hydroxyethyl)-l-cysteine) (GAMA) of rats exposed to AA from 0.1 to 50 mg/kg b.w. and humans exposed to AA from 0.0005 to 0.020 mg/kg b.w., indicating the robustness of the current models. Parameters for adduct of AA with N-terminal valine of hemoglobin (AAVal) were extended to humans and validated. Kinetic parameters for rats were assessed and validated based upon fit to the experimental datasets for liver N3-(2-carbamoyl-2-hydroxyethyl)-adenine (N3-GA-Ade) and N7-(2-carbamoyl-2-hydroxyethyl)-guanine (N7-GA-Gua) adducts. Compared with the previous model, the developed model included the correlation between AA intake and its mercapturic acid adducts, AAMA and GAMA, in a larger dose range with new experimental data, and parameters for AAVal, N3-GA-Ade and N7-GA-Gua were improved and verified. The current multi-component PBTK models provide a superior foundation for the estimation of short-term to medium and long-term intake levels of human exposure to AA.


Multiparametric analysis of geometric features of fibrotic textures leading to cardiac arrhythmias.
One of the important questions in cardiac electrophysiology is to characterise the arrhythmogenic substrate; for example, from the texture of the cardiac fibrosis, which is considered one of the major arrhythmogenic conditions. In this paper, we perform an extensive in silico study of the relationships between various local geometric characteristics of fibrosis on the onset of cardiac arrhythmias. In order to define which texture characteristics have better predictive value, we induce arrhythmias by external stimulation, selecting 4363 textures in which arrhythmia can be induced and also selecting 4363 non-arrhythmogenic textures. For each texture, we determine such characteristics as cluster area, solidity, mean distance, local density and zig-zag propagation path, and compare them in arrhythmogenic and non-arrhythmogenic cases. Our study shows that geometrical characteristics, such as cluster area or solidity, turn out to be the most important for prediction of the arrhythmogenic textures. Overall, we were able to achieve an accuracy of 67% for the arrhythmogenic texture-classification problem. However, the accuracy of predictions depends on the size of the region chosen for the analysis. The optimal size for the local areas of the tissue was of the order of 0.28 of the wavelength of the arrhythmia. We discuss further developments and possible applications of this method for characterising the substrate of arrhythmias in fibrotic textures.


Lymphoreticular disorders of the gastrointestinal tract: roentgenographic features.
Recent advances have permitted close correlation of characteristic roentgen signs with the pathophysiologic alterations in lymphoreticular disorders of the gastrointestinal tract. The background of primary and secondary immunoglobin disorders with gastrointestinal manifestations is reviewed. The roentgenographic alterations in the small bowel of the enteropathic immunoglobulin deficiency syndromes and in lymphoma of the small bowel, stomach, and colon are discussed and illustrated in detail.


Progression of Alzheimer's disease: variability and consistency: ontogenic models, their applicability and relevance.
Much has been learned about the clinical symptomatology of Alzheimer's disease (AD) and ontogenic reciprocal relationships in the past few decades. It is now possible to describe and verify inexorable symptomatic sequences and corresponding temporal relationships. It is also possible to identify more variable symptoms in AD. Ontogenic models can be useful in providing a clearer understanding of the nature of AD symptomatology in terms of both consistency and variability. These models can also be informative in explicating the management needs of AD patients and the treatment possibilities of AD symptoms as well as the etiology of variability in AD symptoms.


Synthesis and characterization of stable and biological active chitin-based polyurethane elastomers.
In this work, the preparation of novel biocompatible polyurethane (PU) elastomers were carried out using curcumin and 1,4-butanediol (1,4-BDO) via step growth polymerization reaction of hydroxyl terminated polybutadiene (HTPB), toluene diisocyanate (TDI) and chitin to improve the biocompatibility, antibacterial and antioxidant properties of PU elastomers. Five samples were synthesized by varying moles ratio of curcumin and 1,4-BDO. The structural study of blends was done by FTIR spectroscopy which confirmed the incorporation of curcumin and 1,4-BDO into the polyurethane matrix. TGA analysis of polyurethane (PU) blends showed good thermal stability with 0.25 M curcumin and 1.75 M 1,4-BDO. Measurements of antibacterial properties were done via agar diffusion method which showed outstanding potential against selected strains of bacteria. The results revealed that biocompatibility, antibacterial and antioxidant potential of purposed polyurethanes elastomers were improved by the incorporation of curcumin which might be the precursor of biomedical applications. Collectively, this work is a footstep towards the synthesis of innovative biocompatible materials which made it suitable for biological applications.


The selective cytotoxic activity in breast cancer cells by an anthranilic alcohol-derived acyclic 5-fluorouracil O,N-acetal is mediated by endoplasmic reticulum stress-induced apoptosis.
Advance in the knowledge of molecular biology has thrown light on many aspects of apoptosis regulation mechanisms. This has allowed a change in anti-cancer therapy trends, from classic cytotoxic strategies to the development of new non-harmful therapies which target the apoptosis response selectively only in tumour cells. We have selected an anthranilic alcohol-derived acyclic 5-fluorouracil O,N-acetal (5) to carry out the anti-cancer studies. This compound shows activity as a potent growth inhibitor of the tumour cell line MCF-7 at a very low concentration. Moreover, when this compound was administered to the non-neoplastic cell line, MCF-10A displayed less toxicity resulting in lower rates of apoptosis. Further studies by microarray hybridization, real-time PCR and western blot showed that when administered to human breast cancer cells, MCF-7, 5 had no activity against classic pro-apoptotic genes such as p53, and even induced the down-regulation of anti-apoptotic genes such as Bcl-2. In contrast, several pro-apoptotic genes related with the endoplasmic reticulum (ER)-stress-induced apoptosis, such as BBC3 and Noxa, appeared up-regulated. These results seem to show that the mechanism of action and selectivity of 5 was via the activation of the ER stress-induced apoptosis. The selective activity of this compound against tumour cells via the ER stress-induced apoptosis supposes a great advantage for future therapeutic use.


TPMG Northern California appointments and advice call center.
Kaiser Permanente (KP) has been developing its use of call centers as a way to provide an expansive set of healthcare services to KP members efficiently and cost effectively. Since 1995, when The Permanente Medical Group (TPMG) began to consolidate primary care phone services into three physical call centers, the TPMG Appointments and Advice Call Center (AACC) has become the "front office" for primary care services across approximately 89% of Northern California. The AACC provides primary care phone service for approximately 3 million Kaiser Foundation Health Plan members in Northern California and responds to approximately 1 million calls per month across the three AACC sites. A database records each caller's identity as well as the day, time, and duration of each call; reason for calling; services provided to callers as a result of calls; and clinical outcomes of calls. We here summarize this information for the period 2000 through 2003.


Regulating Cation Interactions for Zero-Strain and High-Voltage P2-type Na2/3 Li1/6 Co1/6 Mn2/3 O2 Layered Oxide Cathodes of Sodium-Ion Batteries.
Deep sodium extraction/insertion of sodium cathodes usually causes undesired Jahn-Teller distortion and phase transition, both of which will reduce structural stability and lead to poor long-cycle reliability. Here we report a zero-strain P2- Na2/3 Li1/6 Co1/6 Mn2/3 O2 cathode, in which the lithium/cobalt substitution contributes to reinforcing the host structure by reducing the Mn3+ /Mn4+ redox, mitigating the Jahn-Teller distortion, and minimizing the lattice change. 94.5 % of Na+ in the unit structure can be reversibly cycled with a charge cut-off voltage of 4.5 V (vs. Na+ /Na). Impressively, a solid-solution reaction without phase transitions is realized upon deep sodium (de)intercalation, which poses a minimal volume deviation of 0.53 %. It attains a high discharge capacity of 178 mAh g-1 , a high energy density of 534 Wh kg-1 , and excellent capacity retention of 95.8 % at 1 C after 250 cycles.


tRNA-derived fragments: mechanism of gene regulation and clinical application in lung cancer.
Lung cancer, being the most widespread and lethal form of cancer globally, has a high incidence and mortality rate primarily attributed to challenges associated with early detection, extensive metastasis, and frequent recurrence. In the context of lung cancer development, noncoding RNA molecules have a crucial role in governing gene expression and protein synthesis. Specifically, tRNA-derived fragments (tRFs), a subset of noncoding RNAs, exert significant biological influences on cancer progression, encompassing transcription and translation processes as well as epigenetic regulation. This article primarily examines the mechanisms by which tRFs modulate gene expression and contribute to tumorigenesis in lung cancer. Furthermore, we provide a comprehensive overview of the current bioinformatics analysis of tRFs in lung cancer, with the objective of offering a systematic and efficient approach for studying the expression profiling, functional enrichment, and molecular mechanisms of tRFs in this disease. Finally, we discuss the clinical significance and potential avenues for future research on tRFs in lung cancer. This paper presents a comprehensive systematic review of the existing research findings on tRFs in lung cancer, aiming to offer improved biomarkers and drug targets for clinical management of lung cancer.


Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts.
Yersinia pestis causes human plague and colonizes both a mammalian host and a flea vector during its transmission cycle. A key barrier to bacterial infection is the host's ability to actively sequester key biometals (e.g., iron, zinc, and manganese) required for bacterial growth. This is referred to as nutritional immunity. Mechanisms to overcome nutritional immunity are essential virulence factors for bacterial pathogens. Y. pestis produces an iron-scavenging siderophore called yersiniabactin (Ybt) that is required to overcome iron-mediated nutritional immunity and cause lethal infection. Recently, Ybt has been shown to bind to zinc, and in the absence of the zinc transporter ZnuABC, Ybt improves Y. pestis growth in zinc-limited medium. These data suggest that, in addition to iron acquisition, Ybt may also contribute to overcoming zinc-mediated nutritional immunity. To test this hypothesis, we used a mouse model defective in iron-mediated nutritional immunity to demonstrate that Ybt contributes to virulence in an iron-independent manner. Furthermore, using a combination of bacterial mutants and mice defective in zinc-mediated nutritional immunity, we identified calprotectin as the primary barrier for Y. pestis to acquire zinc during infection and that Y. pestis uses Ybt to compete with calprotectin for zinc. Finally, we discovered that Y. pestis encounters zinc limitation within the flea midgut, and Ybt contributes to overcoming this limitation. Together, these results demonstrate that Ybt is a bona fide zinc acquisition mechanism used by Y. pestis to surmount zinc limitation during the infection of both the mammalian and insect hosts.


Current status and future prospects of membrane separation processes for value recovery from wastewater.
Resource constraints and deteriorating environment have made it necessary to look for intensification of the industrial processes, to recover value from spent streams for reuse. The development of reverse osmosis has already established that water can be recovered from aqueous streams in a cost-effective and beneficial manner to the industries. With the development of several membrane processes and membrane materials, the possibility of recovering value from the effluents looks like a workable proposition. In this context, the potentialities of the different membrane processes in value recovery are presented. Among the pressure-driven processes, reverse osmosis can be used for the recovery of water as value. Nanofiltration has been used for the recovery of several dyes including crystal violet, congo red, methyl blue, etc., while ultrafiltration has been used in the fractionation of different solute species using membranes of different pore-size characteristics. Diffusion dialysis is found useful in the separation of acids from its salt solutions. Bipolar membrane electrodialysis has the potential to regenerate acid and base from salt solutions. Thermally driven membrane distillation can provide desalinated water, besides reducing the temperature of hot discharge streams. Passive membrane processes such as supported liquid membranes and membrane-assisted solvent extraction have been found useful in separating minor components from the wastewater streams. The details are discussed to drive home that membrane processes can be useful to achieve the objectives of value recovery, in a cost-effective manner through process intensification, as they are more compact and individual streams can be treated and value used seamlessly.


Investigating sonic injustice: A review of published research.
Sound has been researched as either an environmental pollutant (noise) with detrimental health effects or an environmental resource with beneficial outcomes for well-being. We define sonic injustice as unjust inequalities in both noise exposure and access to high-quality, beneficial sound environments. We performed a comparative analysis of 34 peer-reviewed studies on sonic injustice. These studies were from Europe, North America, Accra and Hong Kong. We found suggestive evidence of a social inequality in noise exposure, particularly for low income and racial/ethnic groups. In contrast, children were often associated with an underexposure to noise. We did not find any studies on inequalities in access to beneficial sound environments, except for one study on quiet areas. As well, this review identifies trends in European and North American studies; discusses causal mechanisms for sonic inequalities; and presents avenues for future investigations into sonic injustice.


Binge toluene exposure in pregnancy and pre-weaning developmental consequences in rats.
Binge Toluene Exposure in Pregnancy and Pre-weaning Developmental Consequences in Rats. Bowen, S.E. and Hannigan, J.H. The persistent rate of abuse of inhaled organic solvents, especially among women of child-bearing age, raises the risk for teratogenic effects of maternal toluene abuse. In this study, timed-pregnant Sprague Dawley rats were exposed from Gestation Day (GD) 8 to GD20 to 12,000 or 8000 parts per million (ppm) toluene, or 0ppm (controls) for 30min twice daily, 60min total daily exposure. Pups were assessed from postnatal day (PN) 4 to PN21 using a developmental battery measuring growth (i.e., body weight), maturational milestones (e.g., eye opening & incisor eruption), and biobehavioral development (e.g., negative geotaxis & surface righting). Pups exposed in utero to 12,000ppm or 8000ppm toluene weighed significantly less than the non-exposed control pups beginning at PN4 and PN12 (respectively) until PN21. Toluene resulted in significant increases in an index of poor perinatal outcome, specifically a composite of malformations, defined "runting" and neonatal death. No significant delays were observed in reaching maturational milestones. The results reveal that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth retardation and malformations in rats. A comparison of the present, conservative results with findings in previous studies implies that binge patterns of toluene exposure in pregnant rats modeling human solvent abuse can result in developmental and morphological deficits in offspring. These results do not exclude the possibility that maternal toxicity as well as teratogenic effects of toluene may contribute to outcomes. The results suggest that abuse of inhaled organic solvents like toluene may result in similar early developmental outcomes in humans.


Frey syndrome. A proposal for evaluating severity.
We aimed to establish the incidence of Frey's syndrome in patients that have been submitted to partial and total parotidectomy at a cancer-treating hospital in Mexico City and to propose a grading system to determine its severity. The incidence of Frey's syndrome in 77 patients (25 male and 52 female) under oncological follow-up due to parotid tumors was subjectively evaluated through clinical findings and objectively diagnosed through Minor's test. The positive hyperhydrotic areas were recorded and measured on transparent acetates. Numeric values were assigned according to clinical perception of symptomatology by the patients (0 for no perception and 1 for clinical recognition), extent of the affected area (1 if less than 2 cm; 2 if between 2.1 and 4 cm, and 3 if more than 4 cm), intensity and smell of sweat (3 if it was excessive or of unpleasant odor). Results were expressed as mild (if less than 4 points) or severe grades (if 4 or more points). Frey syndrome was objectively diagnosed in 28 patients (36%), although only 17 (22%) recognized to have clinical manifestations of this condition. There were 22 women (79%) and six men (21%). Of these, seventeen (61%) had been subjected to partial and eleven (39%) to total parotidectomy. Adjuvant radiotherapy had been employed in nine cases (32%). The cutaneous affected area in the whole group ranged from 0.7 to 29.8 cm(2) (mean 8.9 cm(2)), with a mean affected surface of 8.7+/-10.8 cm(2) for women and 9.0+/-8.8 cm(2) for men ( p > 0.05). Twelve cases were classified as mild and sixteen as severe. No significant differences were found between patients treated with partial vs. total parotidectomy or between patients treated with or without adjuvant radiotherapy. The incidence of Frey's syndrome in Mexican patients seems to be similar to those reported in other countries; however, the extent of hyperhydrosis is lower when compared to some European studies. Our proposal for evaluating this condition may be a helpful tool in assessing the incidence and severity among the diverse populations and it may be a useful tool to define more precisely the indications for treatment and to evaluate the available therapeutic methods according to the severity of the condition.


Diurnal nonstress test variations in the human fetus at risk.
To compare the results of the nonstress test (NST) performed at 9:00 PM and 9:00 AM on women with high-risk pregnancies. The NST was performed 2 h after a meal, at 9:00 AM and 9:00 PM, in a quiet room exposed to daylight, on 80 women with high-risk singleton pregnancies. Each session lasted 20 min. If the NST was nonreactive, the entire biophysical profile was immediately performed. The women's blood pressure was measured before, 10 min within, and at the end of the NST. Women who smoked or had uterine contractions were excluded from the study. Diurnal nonstress test variations were manifested by a higher incidence of reactive NSTs and an increased number of fetal heart accelerations after 9:00 PM (82.5%) than at 9:00 AM (68.8%) (p<0.027 P<0.001). Evening appointments for fetal assessments, except in emergency conditions, may eliminate the need for additional tests such as the entire biophysical profile because of the decreased incidence of nonreactive NSTs. Evening NSTs would save time and decrease maternal anxiety.


Use of calcium-channel blocking drugs in hypertrophic cardiomyopathy.
Verapamil exerts a wide spectrum of hemodynamic effects in patients with hypertrophic cardiomyopathy (HC), and its administration offers an important alternative to beta-receptor blocker therapy in such patients. The intravenous administration of verapamil to 62 patients in the catheterization laboratory decreased systolic blood pressure from 118 +/- 17 to 102 +/- 17 mm Hg (p less than 0.001). It had no significant effect on heart rate, mean pulmonary artery wedge pressure, left ventricular (LV) end-diastolic pressure or cardiac output; however, LV outflow gradient in the basal state decreased from 62 +/- 34 to 29 +/- 34 mm Hg (p less than 0.05). These findings demonstrate a decrease in LV outflow tract obstruction. Radionuclide angiography indicated the major action responsible for the reduction in obstruction appears to be an improvement in LV diastolic function. Short-term nifedipine administration to patients with HC produced no significant effect on LV outflow tract gradients and early diastolic filling. Short-term double-blind studies showed that verapamil improved exercise time by 26 +/- 35% (p less than 0.005) compared with placebo, whereas propranolol improved it by 21 +/- 35% (p less than 0.025). In a separate study, verapamil improved exercise duration by 38 +/- 58% (p = 0.02) compared with placebo, whereas nifedipine improved it by 20 +/- 47% (difference is not significant). Verapamil resulted in a more beneficial subjective symptomatic response than propranolol or nifedipine when compared with placebo. Long-term verapamil therapy was instituted in 227 patients; 133 of these patients have continued taking the medication for an average of 25 +/- 13 months because their quality of life improved compared with what they experienced with their former therapy (usually beta blocker). Improved exercise capacity of 40% has been maintained in 32 patients for 2 years. A decrease in ventricular septal thickness of 1.5 +/- 2.6 mm was also found in 32 patients studied after 39 +/- 8 months of verapamil therapy. Nine patients died during follow-up study, but it is unclear whether the drug increased survival or, conversely, whether any of the deaths could be attributed to verapamil administration. Significant adverse electrophysiologic and hemodynamic effects were seen in 59 instances. The electrophysiologic events, atrioventricular block and sinus arrest, were definitely verapamil-related, but it is uncertain how many of the hemodynamic problems of hypotension and pulmonary congestion were drug-related.(ABSTRACT TRUNCATED AT 400 WORDS)


Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies.
Researches have shown the relevance of antioxidants in the management of several diseases. In the present study, the effects of quercetin and vitamin E were investigated on the mitochondrial functions in vivo and in silico. Structures of quercetin and vitamin E were docked against mitochondrial Adenosine triphosphatase (mATPase), and cytochrome c cavity. Activity of liver mATPase and mitochondrial permeability transition pore opening were determined by spectrophotometry and activation of cytochrome c was examined by immunohistochemistry. The binding energy of vitamin E (-9 Kcal/mol) in mATPase cavity compares well with glibenclamide (-9.4 Kcal/mol), while quercetin had a binding energy of -7.1 Kcal/mol. Similarly, vitamin E, quercetin were bound to cytochrome c by -6.4 and - 5.5 Kcal/mol energy, while glibenclamide had -7.0 Kcal/mol binding energy. The results showed that vitamin E was more accessible to the protoporphyrin prosthetic group in cytochrome c than quercetin. In the experimental studies, it was validated that vitamin E inhibited the uncontrolled activity of mATPase in diabetic rat liver. This was also proven and tested on the liver mitochondrial permeability transition pore opening observed in diabetic rats. Further experimental assessment of these on activation of cytochrome c showed that vitamin E reduced the extent of the activation more than quercetin and glibenclamide. There is a favorable protein-ligand interaction between quercetin and vitamin E in certain apoptotic proteins implicated in diabetes complications.


Synthesis of DNA analogues with novel carboxamidomethyl phosphonamide and glycinamide internucleoside linkages.
Thymidine oligonucleotide analogues with phosphodiester bonds fully substituted by carboxamidomethyl phosphonamide, or glycinamide linkages were synthesized on a solid support, and their hybridization properties toward DNA and RNA targets were determined by Tm analysis.


Transformation of barley (Hordeum vulgare L.) by Agrobacterium tumefaciens infection of in vitro cultured ovules.
We report on a novel transformation procedure for barley by Agrobacterium infection of in vitro cultured ovules. Ovules of the cultivar Golden Promise were isolated a few hours after pollination and infected with the Agrobacterium tumefaciens strain AGL0 carrying the binary vector pVec8-GFP. The vector harboured a hygromycin resistance gene and the green fluorescence protein (GFP) gene. GFP-expressing embryos were isolated from the ovules, regenerated to plants and investigated by Southern blot analysis. Transformation frequencies amounted to 3.1% with hygromycin selection and 0.8% without selection. Mendelian inheritance and stable expression of the GFP gene was confirmed in 18 independent lines over two generations. We conclude that the described technique allows for the rapid and direct generation of high quality transgenic plants.


Pravastatin attenuates noise-induced cochlear injury in mice.
Noise-induced hearing loss (NIHL) is one of the most common forms of sensorineural hearing loss and a well-known contributor to presbycusis. Based on the generation of reactive oxygen species (ROS) in the pathogenesis of NIHL, augmentation of the antioxidative defense system is a major target for pharmacological prevention. In this study, we assessed whether administration of pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, which is a rate-limiting enzyme of cholesterol synthesis, before noise exposure protects against cochlear injury in BALB/c mice. Noise exposure produced both compound threshold shift (CTS) and permanent threshold shift (PTS) over 40 dB at 16 and 32 kHz. Pretreatment with pravastatin (25 mg/kg) for 5 days significantly decreased both CTS and PTS. Pravastatin also reduced hair cell death after noise exposure in the cochlea, which was identified by surface preparation and scanning electron microscopy (SEM). It also reduced the formation of noise-induced 4-hydroxynonenal (4-HNE), a byproduct of lipid peroxidation. Activation of Rac1, one of the subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which is a major superoxide generator in the cell membrane, was inhibited by the administration of pravastatin. These findings suggest that pravastatin can protect against cochlear acoustic injury by lowering ROS generation via inhibition of the formation of the NADPH oxidase complex. This study will be helpful for the development of new therapeutic strategies for NIHL and other hearing loss-related diseases caused by ROS overproduction.


Giant solitary fibrous tumor of the pelvis successfully treated with preoperative embolization and surgical resection: a case report.
Solitary fibrous tumors (SFTs) rarely develop in the pelvis. When they do arise, they are usually treated using surgery, although SFTs are often very large by the time of diagnosis, which makes surgical excision difficult. We report a case of a 63-year-old man who was referred to our hospital for the treatment of a giant tumor of the pelvis. Computed tomography (CT) revealed a 30 × 25 × 19 cm sized hypervascular tumor that almost completely filled the pelvic cavity. The diagnosis of SFT was made by CT-assisted needle biopsy. The feeding arteries of the tumor were embolized twice. The first embolization aimed to reduce the tumor volume, while the second one was planned a day prior to the surgery to obtain hematostasis during the operation. Tumor resection was then performed. The blood loss during the operation was 440 ml, and there was no uncontrollable bleeding. The postoperative course was uneventful. No recurrence of SFT was observed during a 2-year follow-up.


The structural elements of hirudin which bind to the fibrinogen recognition site of thrombin are exclusively located within its acidic C-terminal tail.
Six lysyl residues of human thrombin (LysB21, LysB52, LysB65, LysB106, LysB107 and LysB154) have been previously shown to participate in the binding site of hirudin, a thrombin-specific inhibitor [(1989) J. Biol. Chem. 264, 7141-7146]. In this report, we attempted to delineate the region of hirudin which binds to these basic amino acids of thrombin. Using the N-terminal core domains (r-Hir1-43 and r-Hir1-52) derived from recombinant hirudins and synthetic C-terminal peptides (Hir40-65 and Hir52-65)--all fragments form complexes with thrombin--we are able to demonstrate that the structural elements of hirudin which account for the shielding of these 6 lysyl residues are exclusively located within the acidic C-terminal region. Since hirudin C-terminal peptides were shown to bind to a non-catalytic site of thrombin and inhibit its interaction with fibrinogen [(1987) FEBS Lett. 211, 10-16], our data consequently imply that these 6 lysyl residues are constituents of the fibrinogen recognition site of thrombin.


Occurrence ofAlternaria andFusarium mycotoxins in winter wheat from domestic crop in year 2003.
The aim of this study was a monitoring of the occurrence ofAlternaria andFusarium mycotoxins in winter wheat from domestic crop in the year 2003. Altenuene was determined in 56 (100%) samples of winter wheat, range 14.5-41 μg/kg, mean 25 μg/kg. Alternariol was determined in 16 (28.6%) samples of winter wheat, range 6.3-22.1 μg/kg, mean 5.7 μ/kg. DON was determined in 42 (100%) samples of winter wheat, range 250-3500 μg/kg, mean 330 μg/kg. T2-toxin was determined in 42 (100%) samples of winter wheat, range 25-337 μg/kg, mean 99 μg/kg. ZEA was not determined in samples of winter wheat.


Tissue reactions to a new mineral trioxide aggregate-containing endodontic sealer.
The purpose of this study was to analyze the connective tissue reactions to MTA Fillapex (Ângelus Indústria de Produtos Odontlógicos Ltda, Londrina, Brazil) compared with a zinc oxide-based sealer (EndoFill; Dentsply Indústria e Comérico Ltda, Petrópolis, Brazil) and an epoxy resin-based material (AH Plus; Dentsply DeTrey GmbH, Konstanz, Germany) in Wistar rats. Polyethylene tubes containing the test materials and empty polyethylene tubes (control) were implanted in the subcutaneous tissue of 12 rats. Empty tubes were used as a negative control. After 7 and 60 days (n = 6 per period), observations were made for cellular inflammatory components, fibrous condensation, and abscess formation. Comparisons among the groups and between the experimental periods were made using 2-way analysis of variance and the Bonferroni post hoc test (P < .05). At the end of the 7-day experimental period, all sealers scored higher than the control group for the variable lymphocytes, and MTA Fillapex presented lower fiber condensation compared with empty tubes. After 60 days, macrophages and lymphocytes scored significantly higher for MTA Fillapex and EndoFill compared with the negative control, and AH Plus showed similar results related to the empty tubes. Comparing the materials' responses at the end of the 2 evaluated periods, for EndoFill samples the variable neutrophils was detected less after 60 days. Both EndoFill and MTA Fillapex presented increased fiber condensation after 60 days. Although none of the sealers promoted ideal tissue responses, AH Plus presented the best outcomes. Although MTA Fillapex contains MTA powder, it presented no biocompatibility advantages when compared with AH Plus and EndoFill.


Cardiovascular safety of noninsulin antidiabetic drugs: facts and promises.
Non insulin antidiabetic drugs are widely used in patients with type 2 diabetes. However, the drugs' effect in terms of reducing cardiovascular risk has been the subject of controversy. In 2008, based on the evidence of cardiovascular risk resulting from the use of a number of non insulin antidiabetic drugs, the US Food and Drug Administration published directives on the need to perform cardiovascular safety studies. These directives have helped obtain more evidence, such that at present there are 2 families of drugs that can reduce cardiovascular risk. These recent data have helped us add the reduction of cardiovascular morbidity and mortality to the objective of controlling blood glucose. Nevertheless, research continues with the development of new long-term studies.


Factors affecting the programme completion of pre-registration nursing students through a three year course: A retrospective cohort study.
Students who leave pre-registration nurse education having failed to complete remain a concern for higher education institutions. This study identifed factors influencing completion using a retrospective cohort analysis to map student characteristics at entry against Year 3 completion data. The study was set in a nursing faculty in a higher education institution in northern England. Data were collected between 2009 and 2014 with five cohorts of students participating (n = 807). Multinomial logistic regression was used to model the dependent variable Progression Outcome with categories of; completion and non-completion (academic and non-academic reasons). Predictors included cohort, programme, branch, gender, age on entry, ethnic group, disability status, domicile, change of home postcode, change of term-time postcode, entry qualifications, previous experience of caring, and dependents. Age on Entry and Domicile or alternatively Dependents and Domicile emerged as statistically significant (p < 0.05) in the multivariable analysis. Older students were less likely to be lost from the programme, as were students who lived locally at all times and those with dependents. There is currently little reliable, consistent information on nursing student attrition, progression and completion. This study contributes to the evidence base by identifying some of the factors that may contribute to successful programme completion.


Research note: Effects of deoxynivalenol on immunohistological parameters in pigs.
TheFusarium toxin deoxynivalenol (DON) is known to exert immunomodulatory effects. Numerous studies in mice demonstrated that dietary exposure leads to an upregulation of polymeric serum immunoglobulin A (IgA) suggesting the mucosal immune system as a primary target while at the cellular level T cells and macrophages are involved in this process.The present study aimed to verify these effects in pigs. A total of 24 male pigs were subjected to four treatments, a control group fed a diet devoid of DON, a chronically exposed group receiving a diet containing contaminated wheat (5.7 mg DON/kg diet), an acute orally exposed group receiving only one meal (550 g) of the contaminated feed and an acute intravenous exposed group receiving 53 μg DON/kg body weight. Cryosections of the spleen and the jejunum of the pigs were immunohistologically stained for IgA+, CD3+, CD4+ and CD8+ cells. The number of positive stained cells did not differ significantly between the treatment groups and the control group of any of the specimen.


Physics-informed machine learning with differentiable programming for heterogeneous underground reservoir pressure management.
Avoiding over-pressurization in subsurface reservoirs is critical for applications like CO[Formula: see text] sequestration and wastewater injection. Managing the pressures by controlling injection/extraction are challenging because of complex heterogeneity in the subsurface. The heterogeneity typically requires high-fidelity physics-based models to make predictions on CO[Formula: see text] fate. Furthermore, characterizing the heterogeneity accurately is fraught with parametric uncertainty. Accounting for both, heterogeneity and uncertainty, makes this a computationally-intensive problem challenging for current reservoir simulators. To tackle this, we use differentiable programming with a full-physics model and machine learning to determine the fluid extraction rates that prevent over-pressurization at critical reservoir locations. We use DPFEHM framework, which has trustworthy physics based on the standard two-point flux finite volume discretization and is also automatically differentiable like machine learning models. Our physics-informed machine learning framework uses convolutional neural networks to learn an appropriate extraction rate based on the permeability field. We also perform a hyperparameter search to improve the model's accuracy. Training and testing scenarios are executed to evaluate the feasibility of using physics-informed machine learning to manage reservoir pressures. We constructed and tested a sufficiently accurate simulator that is 400 000 times faster than the underlying physics-based simulator, allowing for near real-time analysis and robust uncertainty quantification.


Human corneal endothelial wound repair. In vitro and in vivo.
Endothelial wound repair was studied in 85 organ-cultured human corneas classed in Groups I--IV by means of a combined silver stain, nuclear stain, and autoradiography after denuding the endothelium from a circular area in the center of the cornea. Endothelial migration into the defect occurred first, but by 48 hours (before the wound was completely covered), incorporation of tritiated thymidine showed synthesis of DNA had occurred. Cell division, shown by the presence of mitotic figures, was greatest at 72 hours. In Group V, the endothelial wound repair was studied in vivo in two patients (a 65-year-old and a 67-year-old). The wound was created by a central transcorneal freeze. After removing the cornea from the enucleated eye, the wound was exposed for one hour to tritiated thymidine at 37 C in vitro. The results of Group V were similar to those of Groups I--IV. Both migration and proliferation were found.


Extraadrenal pheochromocytoma: dynamic demonstration at 0.5 tesla.
We report a case of extraadrenal pheochromocytoma of Zuckerkandl imaged by dynamic magnetic resonance imaging (dynamic MRI) with a 0.5 tesla (T) machine. The dynamic MRI proved useful in disclosing the tumor clearly because of strong enhancement in its early phase. This case has the advantages of dynamic computed tomography (dynamic CT) as well as of T2-weighted spin-echo (SE) MR images.


Stability of root coverage outcomes at single maxillary gingival recession with loss of interdental attachment: 3-year extension results from a randomized, controlled, clinical trial.
The aim of this study was to assess the stability of root coverage outcomes 3 years after Connective Tissue Graft (CTG) plus Coronally Advanced Flap (CAF) or CAF alone at single maxillary gingival recession with minimal inter-dental clinical attachment loss. Twenty-four of the original 29 patients, 13 treated with CAF + CTG and 11 with CAF, were available for the 3-year follow-up. Measurements were performed by a blind and calibrated examiner. Outcome measures included complete root coverage (CRC), recession reduction (RecRed), Root coverage Esthetic Score (RES) and Keratinized Tissue (KT) Gain. Visual Analogue Scale (VAS) was used to evaluate patient satisfaction. After 3 years, CAF + CTG resulted in better outcomes in terms of CRC (p = 0.0054) than CAF alone. No difference was detected in terms of RecRed, RES score and VAS values. Furthermore, CAF + CTG was associated with higher KT gain than CAF at the last follow-up (p < 0.0001). Root coverage outcomes in single gingival recession with inter-dental CAL loss are stable after 3 years. The application of CTG under CAF was associated with increased probability to obtain CRC than CAF alone at the final follow-up.


Effects of damage to median raphe nucleus on ingestive behavior and wheel running activity.
The effects of damage to the median raphe nucleus on the ingestive behavior and wheel running activity of rats were studied. This nucleus was damaged by the placement of either electrolytic or chemical (5,7-dihydroxytryptamine) lesions. After the placement of either type of lesion, wheel running activity was significantly decreased for the duration of the 8 week post-operative period. Although there were transient decreases in both food and water intakes after damage to the median raphe nucleus, these decreases did not appear to result from impairments in neuro-regulatory mechanisms. Rather, the decrease in food intake seemed to be related to the decrease in locomotor activity, and the decrease in water intake appeared to be linked to the decrease in food intake. In some rats with electrolytic lesions in the median raphe nucleus, the decrease in water intake was followed by a transient period of hyperdipsia.


Influence of participatory monitoring and evaluation on decision-making in maternal and newborn health programs in Mombasa County, Kenya.
The study assessed the utilization of participatory monitoring and evaluation approaches (PM&E) and their influence on decision-making in maternal and newborn health programs (MNH) in Mombasa County, Kenya. We conducted a cross-sectional study with a sample of 390 participants and used a structured questionnaire, modified Quality of Decision-Making Orientation Scheme, and an interview guide to collect data. We analyzed quantitative responses using descriptive statistics and binary logistic regression (at significance level of 0.05) and qualitative responses using content analysis. The study established that quality decision-making was more likely to occur in MNH programs in Mombasa County that used PM&E approaches at the initiation (OR 1.728, p < 0.05), design and planning (OR 2.977, p < 0.05), and implementation (OR 5.665, p < 0.05) phases of MNH programs than in those that did not use the PM&E approaches. This study shapes a persuasive case for improving the provision of maternal and newborn health services.


Expanding the β-substitution reactions of serine synthase through mutagenesis of aromatic active site residues.
The Gram-negative bacterium, Fusobacterium nucleatum, possesses a fold II type pyridoxal 5'-phosphate-dependent enzyme that catalyzes the reversible β-replacement of l-cysteine and l-serine, generating H2S and H2O, respectively. This enzyme, termed serine synthase (FN1055), contains an active site Asp232 that serves as a general base in the activation of a water molecule for nucleophilic attack of the ⍺-aminoacrylate intermediate. A network of hydrophobic residues surrounding Asp232 are key to catalysis as they increase the basicity of the side chain. However, these residues severely restrict the range of nucleophilic substrates that can react with the ⍺-aminoacrylate, making the enzyme an ineffective biocatalyst for noncanonical amino acid biosynthesis. Herein, we systematically substituted four aromatic active residues (Trp99, Phe125, Phe148 and Phe234) to an alanine to determine their catalytic importance in serine/cysteine synthase reactions and if their substitution could broaden the scope of nucleophiles that could react with the ⍺-aminoacrylate intermediate. All four single site mutants W99A, F125A, F148A, and F234A could form the ⍺-aminoacrylate intermediate upon reaction with either l-cysteine or l-serine; however, the rate constant associated with the elimination of the β-hydroxyl group from l-serine was 150 to 200-fold lower in the F125A and F148A variants. Substitution of Phe125 and Phe148, situated ∼3-4 Å from the general base, also abolished the serine synthase reaction due to their inability to activate a water molecule for nucleophilic attack of the ⍺-aminoacrylate. Overall, the mutational studies indicate that the clustering of aromatic residues disproportionately benefits the serine synthase reaction as they increase the binding affinity for l-cysteine, decrease the binding of the product, l-serine, and promote the activation of a water molecule. Notably, the aminoacrylate species present in F125A and F148A was able to react with thiophenol, signifying that serine synthase has biocatalytic potential in the synthesis of noncanonical amino acids.


Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro.
Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy.


Serum and tissue proteinase-like peptidase activities in women undergoing total mastectomy for breast cancer.
Serum proteinase-like peptidases and proteinase inhibitor activities have been determined in 40 women with breast cancer at presentation and following total mastectomy. Activities of these enzymes have also been determined in homogenates of malignant (n = 13) and non-malignant (n = 11) breast tissue and benign breast lesions (n = 10). Following surgical treatment, the serum collagenase-like, cathepsin B-like and cathepsin H-like peptidase activities were significantly reduced. In addition, the activities of collagenase-like, cathepsin B-like and elastase-like peptidases were significantly higher in malignant breast tissue than in either non-malignant tissue from the same breast, or benign breast lesions. These findings are consistent with the suggestion that proteinases may have a role in tumour invasion.


Premigration social adversity and autism spectrum disorder.
Several studies suggest significant relationships between migration and autism spectrum disorder (ASD) but there are discrepant results. Given that no studies to date have included a pathological control group, the specificity of the results in ASD can be questioned. To compare the migration experience (premigration, migratory trip, postmigration) in ASD and non-ASD pathological control groups, and study the relationships between migration and autism severity. Parents' and grandparents' migrant status was compared in 30 prepubertal boys with ASD and 30 prepubertal boys without ASD but with language disorders, using a questionnaire including Human Development Index (HDI)/Inequality-adjusted Human Development Index (IHDI) of native countries. Autism severity was assessed using the Child Autism Rating Scale, Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised scales. The parents' and grandparents' migrant status frequency did not differ between ASD and control groups and was not associated with autism severity. The HDI/IHDI values of native countries were significantly lower for parents and grandparents of children with ASD compared with the controls, especially for paternal grandparents. Furthermore, HDI/IDHI levels from the paternal line (father and especially paternal grandparents) were significantly negatively correlated with autism severity, particularly for social interaction impairments. In this study, parents' and/or grandparents' migrant status did not discriminate ASD and pathological control groups and did not contribute either to autism severity. However, the HDI/IHDI results suggest that social adversity-related stress experienced in native countries, especially by paternal grandparents, is potentially a traumatic experience that may play a role in ASD development. A 'premigration theory of autism' is then proposed.


The construction of DNAzyme-based logic gates for amplified microRNA detection and cancer recognition.
Benefiting from the simple DNAzyme and a duplex-specific nuclease, a series of microRNA-stimulated DNAzyme logic gates were rationally assembled for the highly accurate detection of multiple low-abundant microRNA biomarkers that correspond to the specific aberrant microRNA expression patterns of cancer tissues, thus showing a great potential in early diagnosis.