Evaluation of a Neonatal Resuscitation Curriculum in Liberia.
Neonatal mortality in Africa is among the highest in the world. In Liberia, providers face significant challenges due to lack of resources, and providers in referral centers need to be prepared to appropriately provide neonatal resuscitation. A team of American Heart Association health care providers taught a two-day neonatal resuscitation curriculum designed for low-resource settings at a regional hospital in Liberia. The goal of this study was to evaluate if the curriculum improved knowledge and comfort in participation. The curriculum included simulations and was based on the Neonatal Resuscitation Protocol (NRP). Students learned newborn airway management, quality chest compression skills, and resuscitation interventions through lectures and manikin-based simulation sessions. Seventy-five participants were trained. There was a 63% increase in knowledge scores post training (p < 0.00001). Prior cardiopulmonary resuscitation (CPR) training, age, occupation, and pre-intervention test score did not have a significant effect on post-intervention knowledge test scores. The median provider comfort score improved from a 4 to 5 (p < 0.00001). Factors such as age, sex, prior NRP education, occupation, and post-intervention test scores did not have a significant effect on the post-intervention comfort level score. A modified NRP and manikin simulation-based curriculum may be an effective way of teaching health care providers in resource-limited settings. Training of providers in limited-resource settings could potentially help decrease neonatal mortality in Liberia. Modification of protocols is sometimes necessary and an important part of providing context-specific training. The results of this study have no direct relation to decreasing neonatal mortality until proven. A general resuscitation curriculum with modified NRP training may be effective, and further work should focus on the effect of such interventions on neonatal mortality rates in the region.


A new HLA-Cw*15 allele, Cw*1508, identified in the Peruvian population.
A novel HLA-Cw*15 allele , Cw*1508, has been found in the Peruvian population. This new allele, initially detected as a polymerase chain reaction with sequence-specific primers (PCR-SSP) variant, shows greatest similarity to Cw*1502. The nucleotide sequence of Cw*1508 only differs from that of Cw*1502 at position 539; this change determines the replacement of Leu by Arg 156 in Cw*1508.


Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents.
Duloxetine, a selective but balanced serotonergic and noradrenergic reuptake inhibitor, was evaluated in the acute nociceptive pain models of tail flick and hot plate in mice and in the persistent and/or inflammatory pain models of acetic acid-induced writhing in mice, carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats, and capsaicin-induced mechanical allodynia in rats. In acute pain models, duloxetine had no significant effect on response latency in the mouse tail-flick test but produced modest increases in response latencies in the mouse hot plate test. Morphine produced dose-related analgesic effects in both the mouse tail-flick and hot plate tests. In models of inflammatory and/or persistent pain, duloxetine, morphine, and ibuprofen produced dose-related decreases in acetic acid-induced writhing in mice. Duloxetine, ibuprofen, and gabapentin also produced dose-dependent reversals of both thermal hyperalgesia and mechanical allodynia produced by carrageenan in rats. In addition, both duloxetine and morphine produced a significant reduction of capsaicin-induced mechanical allodynia in rats. Duloxetine and gabapentin were without substantial effect on the Rotorod test in mice, whereas morphine and ibuprofen produced a significant impairment. Our data indicate that duloxetine may be efficacious in the treatment of persistent and/or inflammatory pain states at doses that have modest or no effect on acute nociception or motor performance.


[Successful treatment by ranimustine (MCNU) of a patient with B-cell prolymphocytic leukemia (B-PLL)].
A 66-year-old female was admitted to our hospital because of leukocytosis, anemia and splenomegaly in August 1989. The white cell count was 3.49 x 10(10)/l with 88.5% of the leukemic cells which were morphologically similar to prolymphocytes. On flowcytometric analysis, the leukemic cells were found to be positive for B-cell markers such as CD19, CD20, FMC7, Sm-IgM and Sm-IgD and negative for CD5 and CD25. The chromosome analysis demonstrated hyperdiploidy of 48, XX, (+3, +18). She was diagnosed as having B-cell prolymphocytic leukemia, and treated with alpha-interferon and VP therapy with progression. Complete remission was achieved after three courses of ranimustine (MCNU) administration. She relapsed after about one year without therapy, but when MCNU was administered again, a secondary remission followed. The prolymphocytes during the relapse stage also had the phenotypes of CD11b, CD13 and CD25. This case is considered to be rare with respect to both complete remission by MCNU and the immunophenotypic change of leukemic cells during the relapse period.


Survey on Revocation in Ciphertext-Policy Attribute-Based Encryption.
Recently, using advanced cryptographic techniques to process, store, and share datasecurely in an untrusted cloud environment has drawn widespread attention from academicresearchers. In particular, Ciphertext-Policy Attribute-Based Encryption (CP-ABE) is a promising,advanced type of encryption technique that resolves an open challenge to regulate fine-grainedaccess control of sensitive data according to attributes, particularly for Internet of Things (IoT)applications. However, although this technique provides several critical functions such as dataconfidentiality and expressiveness, it faces some hurdles including revocation issues and lack ofmanaging a wide range of attributes. These two issues have been highlighted by many existingstudies due to their complexity which is hard to address without high computational cost affectingthe resource-limited IoT devices. In this paper, unlike other survey papers, existing single andmultiauthority CP-ABE schemes are reviewed with the main focus on their ability to address therevocation issues, the techniques used to manage the revocation, and comparisons among themaccording to a number of secure cloud storage criteria. Therefore, this is the first review paperanalysing the major issues of CP-ABE in the IoT paradigm and explaining the existing approachesto addressing these issues.


Health Service Utilization Among Out-of-Pocket Payers and Fee-Wavier Users in Saesie Tsaeda-Emba District, Tigray Region, Northern Ethiopia: A Comparative Cross-Sectional Study.
Health service utilization among out-of-pocket payers and fee-wavier users and factors associated with it in Saesie Tsaeda-Emba District, Tigray Region, Northern Ethiopia. A comparative community-based cross-sectional study was conducted in Northern Ethiopia. Households with at least one person who experienced illness during the last six months were included in the study. Data were collected using a structured and interviewer-administered questionnaire. Bivariable and multivariable logistic regression analyses were used to identify factors associated with the HSU. In this study, 652 individuals (489 OOP payers and 163 fee waiver users) participated with overall response rate of 98%. The overall HSU among the participants was 44.3% (41.9 for OOP users and 51.5% for fee waiver users). The study revealed that educational status (AOR = 0.35; 95% CI: 0.21, 0.59), family size (AOR = 0.60; 95% CI: 0.37, 0.97) and income level (AOR = 2.09; 95% CI: 1.12, 3.90, and AOR = 4.12; 95% CI: 2.41, 7.53) were factors significantly associated with the HSU among OOP payers. The study also revealed that educational status (AOR = 0.65; 95% CI: 0.21, 0.59), family size (AOR = 0.4; 95% CI: 0.37, 0.97), income level (AOR = 1.12; 95% CI: 1.21, 4.87), and payment mechanism (AOR = 2.21; 95% CI = 1.34, 4.67 were significantly associated with the HSU among all study participants. This study shows that the level of the HSU is low. Educational status, family size, economic status, and payment mechanism were significantly associated with the HSU. Therefore, improving the community's educational level, promoting family planning, devising income-generating strategies, and strengthening the fee waiver mechanism may enhance the HSU.


[Xanthones from leaves of Calophyllum inophyllum Linn].
To study the xanthones from the leaves of Calophyllum inophyllum Linn., several chromatography methods were employed to isolate the constituents. Investigation on the CHCl3 extract led to the isolation of a new xanthone named inophyxanthone A (1) and four known compounds, which were pancixanthone A (2), gerontoxanthone B (3), jacareubin (4) and pyranojacareubin (5). Among them, compound 2 was obtained from this plant firstly, and compound 3 was obtained for the first time from this genus. The structure of inophyxanthone A (1) was identified as 1, 3, 5-trihydroxy-2-(1, 1-dimethylallyl)xanthone by spectral analysis.


Morphological Transition in Fatty Acid Self-Assemblies: A Process Driven by the Interplay between the Chain-Melting and Surface-Melting Process of the Hydrogen Bonds.
In surfactant systems, the major role of the nature of the counterion in the surfactant behavior is well-known. However, the effect of the molar ratio between the surfactant and its counterion is less explored in the literature. We investigated the effect of the molar ratio (R) between 12-hydroxystearic acid (12-HSA) and various alkanolamines as a function of the temperature in aqueous solution from the molecular scale to the mesoscale. By coupling microscopy techniques and small-angle neutron scattering, we showed that 12-HSA self-assembled into multilamellar tubes and transitioned into micelles at a precise temperature. This temperature transition depended on both the molar ratio and the alkyl chain length of the counterion and could be precisely tuned from 20 to 75 °C. This thermal behavior was investigated by differential scanning calorimetry and wide-angle X-ray scattering. We highlighted that the transition at the supramolecular scale between tubes and micelles came from two different mechanisms at the molecular scale as a function of the molar ratio. At low R, with an excess of counterion, the transition came from the chain-melting phenomenon. At high R, with an excess of 12-HSA, the transition came from both the chain-melting process and the surface-melting process of the hydrogen bonds. At the mesoscale, this transition of supramolecular assemblies from tubes to micelles delimited a regime of high bulk viscosity, with a regime of low viscosity.


The D10 decapping enzyme of vaccinia virus contributes to decay of cellular and viral mRNAs and to virulence in mice.
Posttranscriptional mechanisms are important for regulation of cellular and viral gene expression. The presence of the 5' cap structure m(7)G(5')ppp(5')Nm is a general feature of mRNAs that provides protection from exoribonuclease digestion and enhances translation. Vaccinia virus and other poxviruses encode enzymes for both cap synthesis and decapping. Decapping is mediated by two related enzymes, D9 and D10, which are synthesized before and after viral DNA replication, respectively. The timing of D10 synthesis correlates better with the shutdown of host gene expression, and deletion of this gene has been shown to cause persistence of host and viral mRNAs in infected cells. Here, we constructed specific mutant viruses in which translation of D10 was prevented by stop codons or activity of D10 was abrogated by catalytic site mutations, without other genomic alterations. Both mutants formed plaques of normal size and replicated to similar extents as the parental virus in monkey epithelial cells and mouse embryonic fibroblasts. The synthesis of viral proteins was slightly delayed, and cellular and viral mRNAs persisted longer in cells infected with the mutants compared to either the parental virus or clonal revertant. Despite the mild effects in vitro, both mutants were more attenuated than the revertants in intranasal and intraperitoneal mouse models, and less infectious virus was recovered from organs. In addition, there was less lung histopathology following intranasal infection with mutant viruses. These data suggest that the D10 decapping enzyme may help restrict antiviral responses by accelerating host mRNA degradation during poxvirus infection.


The origin and nature of ramified and amoeboid microglia: a historical review and current concepts.
The origin of ramified microglia has been a longstanding controversial issue, with 4 major schools of thought, which state that they are derived (1) from invasion of mesodermal pial elements, (2) from neuroectodermal matrix cells together with the macroglia, (3) from pericytes, and (4) from invasion of monocytes in early development. This paper is in support of the last-mentioned hypothesis. It is known that ramified microglial cells do not divide under normal circumstances, and since our studies in the corpus callosum have shown that these cells do not appear until the fifth postnatal day, it is reasoned that they must be derived from some preexisting mitotically active cells. The putative precursor is the preponderant amoeboid microglia in the same region. Our experimental studies with the carbon labelling technique have demonstrated for the first time that blood monocytes invade into the early postnatal brain to become amoeboid microglia, which then differentiate into ramified microglia. Just like other tissue macrophages, the monocyte-derived amoeboid microglia exhibit features indicative of phagocytic activities. These include the content of hydrolytic enzymes, uptake of carbon, and a characteristic surface morphology, as seen by scanning electron microscopy. The transformation of amoeboid microglia into ramified microglia, which occurs between the second and third postnatal week, is considered to be a regressive phenomenon, as shown by the diminution of their content of hydrolytic enzymes and the downregulation of membrane antigen. Apart from their primary role as active phagocytes, their involvement in Alzheimer's disease (AD) is evidenced recently by the fact that the cells are specifically marked by antibodies present in the cerebrospinal fluid of AD patients. In conclusion, ramified microglial cells are derived from monocytes, but through an intermediate amoeboid microglia stage as active macrophages in the perinatal period.


[Macroglobulin alpha-2 in synovial fluid: relationship with reactants of the acute phase of rheumatoid arthritis].
Metalloproteinases (e.g. collagenase, elastase, stromelysin) are present in large amount in synovial fluid (SF) during rheumatoid arthritis (RA) and are actively involved in articular tissue damage. alpha 2-Macroglobulin (alpha 2M) functions as a "molecular trap" for proteinases and is considered the major inhibitor of metalloproteinases. We found increased concentrations of alpha 2M in SF of RA patients, significantly related to acute phase reactants, local inflammatory parameters and joint damage. The alpha 2M ratio between, RA SF and control SF, was found higher than between RA serum and control serum, indicating a selective localization and activity of alpha 2M in inflamed joint. The relationship between alpha 2M and the inflammatory parameters, including IL-6, is discussed.


Effect of timing of laparoscopic cholecystectomy on postoperative efficacy and rehabilitation of elderly patients with acute cholecystitis.
To discuss the effect of the timing of laparoscopic cholecystectomy (LC) on postoperative efficacy and rehabilitation in elderly patients with acute cholecystitis (AC). Ninety-four elderly patients with AC were retrospectively selected and assigned into a research group (n=47) and a control group (n=47). The research group was administered LC within 48 hours after the onset. The control group was administered LC 48 hours after the onset. The two groups were compared for perioperative parameters, bilirubin and immune function, concentration of inflammatory factors, stress response, energy metabolism, and complications. The research group had a shorter operation time, hospital stay, and less intraoperative blood loss than the control group (all P<0.05). No significant intergroup difference was found in the anal exhaust time (P>0.05). The levels of postoperative direct bilirubin, total bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, serum CRP, TNF-α, and IL-6 were lower than those measured preoperatively in both groups (all P<0.001), and were lower in the research group than in the control group (all P<0.05). The postoperative pulse, diastolic pressure, and systolic pressure in the two groups were higher than those measured preoperatively (all P<0.001). The levels in the research group were lower than those in the control group (all P<0.001).The levels of adenosine triphosphate and adenosine diphosphate also decreased in both groups, but they were still higher in the research group than those in the control group (all P<0.001). The incidence of complications in the research group (4.26%) was lower than that in the control group (17.02%; P<0.05). Early LC in elderly patients with AC is beneficial to postoperative functional rehabilitation, showing less impact on energy metabolism, lower stress response caused by surgery, lower bilirubin content, less inflammatory reaction, better liver function, and lower incidence of complications in patients.


Syntheses, structures and antimicrobial activities of water-soluble silver(I)-oxygen bonding complexes with chiral and racemic camphanic acid (Hca) ligands.
Water-soluble, relatively light-stable, chiral and achiral silver(I) complexes [[Ag(2)(ca)(2)]](n) and [[Ag(2)(ca)(2)(Hca)(2)]](n)(R- and S-Hca =(1R,4S)- and (1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylic acid, respectively) prepared from the reaction of Ag(2)O with chiral and racemic Hca in 1:2 and 1:4 molar ratios were characterized by elemental analysis, TG/DTA, FTIR, and solution ((1)H, (13)C and (109)Ag) and solid-state ((13)C) NMR spectroscopy. Crystallography revealed that unique 2(1) helical polymer and zigzag structures were formed on self-assembly of the dimeric units in the crystals of [[Ag(2)(S-ca)(2)]](n) and three [[Ag(2)(ca)(2)(Hca)(2)]](n). In the crystal of [[Ag(2)(S-ca)(2)]](n) two 2(1) helices and a loop were observed in the stair-like polymer structure, whereas zigzag and a loop were seen in the crystals of three [[Ag(2)(ca)(2)(Hca)(2)]](n). Carbon NMR spectra in the solid state and in D(2)O indicated that these polymeric structures were loosely bound and fast ligand-exchange reactions took place in aqueous solution. The complexes, [[Ag(2)(ca)(2)]](n) and [[Ag(2)(ca)(2)(Hca)(2)]](n), showed a wide spectrum of effective antimicrobial activity as anticipated for weak silver(i)-O bonding complexes. Similar antimicrobial activity of [[Ag(2)(ca)(2)]](n) and [[Ag(2)(ca)(2)(Hca)(2)]](n) against selected microorganisms suggested that ligand exchangeability played an important role as well as the coordination geometry of the silver(i) ion.


Violent victimization among immigrants: Using the National Violent Death Reporting System to examine foreign-born homicide victimization in the United States.
Limited research attention has focused on homicides involving foreign-born victims. Using data from the National Violent Death Reporting System, we examined 9428 homicides that occurred in 2017 in the United States across 32 states and D.C. Approximately 8% of homicide victims were foreign-born. Homicide victimization rates were substantially lower for foreign-born persons, compared to U.S.-born persons. However, foreign-born persons from Honduras, El Salvador, and Jamaica had a substantially higher risk of homicide victimization. Notably, few homicides involving foreign-born victims were gang- or drug-trade-related. With the growing number of immigrants in the United States, policy and prevention efforts should be guided by research.


Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges.
Heterozygous loss-of-function variants of the glucokinase (GCK) gene are responsible for a subtype of maturity-onset diabetes of the young (MODY). GCK-MODY is characterized by a mild hyperglycemia, mainly due to a higher blood glucose threshold for insulin secretion, and an up-regulated glucose counterregulation. GCK-MODY patients are asymptomatic, are not exposed to diabetes long-term complications, and do not require treatment. The diagnosis of GCK-MODY is made on the discovery of hyperglycemia by systematic screening, or by family screening. The situation is peculiar in GCK-MODY women during pregnancy for three reasons: 1. the degree of maternal hyperglycemia is sufficient to induce pregnancy adverse outcomes, as in pregestational or gestational diabetes; 2. the probability that a fetus inherits the maternal mutation is 50% and; 3. fetal insulin secretion is a major stimulus of fetal growth. Consequently, when the fetus has not inherited the maternal mutation, maternal hyperglycemia will trigger increased fetal insulin secretion and growth, with a high risk of macrosomia. By contrast, when the fetus has inherited the maternal mutation, its insulin secretion is set at the same threshold as the mother's, and no fetal growth excess will occur. Thus, treatment of maternal hyperglycemia is necessary only in the former situation, and will lead to a risk of fetal growth restriction in the latter. It has been recommended that the management of diabetes in GCK-MODY pregnant women should be guided by assessment of fetal growth by serial ultrasounds, and institution of insulin therapy when the abdominal circumference is ≥ 75th percentile, considered as a surrogate for the fetal genotype. This strategy has not been validated in women with in GCK-MODY. Recently, the feasibility of non-invasive fetal genotyping has been demonstrated, that will improve the care of these women. Several challenges persist, including the identification of women with GCK-MODY before or early in pregnancy, and the modalities of insulin therapy. Yet, retrospective observational studies have shown that fetal genotype, not maternal treatment with insulin, is the main determinant of fetal growth and of the risk of macrosomia. Thus, further studies are needed to specify the management of GCK-MODY pregnant women during pregnancy.


The Independent and Interactive Associations of Bilingualism and Sex on Cognitive Performance in Hispanics/Latinos of the Hispanic Community Health Study/Study of Latinos.
Sixty percent of Hispanics/Latinos are bilingual which research suggests may confer certain cognitive advantages. Female sex confers cognitive advantages in verbal learning and memory compared to male sex, regardless of race or ethnicity. Understanding the independent and interactive associations of bilingualism and sex with cognition may aid in predicting cognitive aging in Hispanics/Latinos. We examined baseline (2008-2011) data from the Hispanic Community Health Study/Study of Latinos, a multicenter, prospective community-based study. Our analyses included 6,110 males and females ≥45 years old who self-reported birth and parents' origin outside of the continental US, Spanish as their first language, and were evaluated in Spanish. Bilingualism was assessed along a Likert scale (1 = only Spanish to 4 = English>Spanish) for language proficiency (reading/spoken) and patterns of use (thinking/socializing). Cognitive testing included verbal learning, memory, fluency, and Digit Symbol Substitution (DSS). Linear regression models adjusted for relevant confounders, the complex survey design, and sampling weights. Participants' self-reported language proficiency was Spanish better than English, while patterns of use suggested more Spanish than English. Higher language proficiency was associated with higher performance on all cognitive indices while higher patterns of use associated with higher fluency and DSS scores (p-values < 0.01). Female sex was associated with higher performance on all cognitive indices (p-values < 0.05). There were no significant interactions with bilingualism (regardless of metric) by sex on cognition. For Hispanics/Latinos residing in the continental US and reporting birth and parents' origin elsewhere, bilingualism and female sex have independent cognitive benefits that are important to consider when evaluating cognitive performance.


Compressed octahedral coordination in chain compounds containing divalent copper: structure and magnetic properties of CuFAsF6 and CsCuAlF6.
Crystal structures and magnetic investigations of CuFAsF6 and CsCuAlF6 are reported. Together with KCuAlF6, these appear to be the only examples of Jahn-Teller pure Cu(II) compounds containing only one type of ligand that exhibits a compressed octahedral coordination geometry. The Rietveld method has been used for refining the CsCuAlF6 structure based on neutron powder diffraction data at 4 K. The compound crystallizes in space group Pnma (no. 62) with a=7.055(1), b=7.112(1), c=10.153(1) A and Z=4 at 4 K. The structure is built from infinite [CuF5]n(3n-) chains of [CuF6]4- octahedra running along the [1 0 0] direction and (AlF6)3- octahedra connected by corners in the trans position, thus giving rise to chains oriented along the [0 1 0] direction. Single crystals of CuFAsF6 were prepared under solvothermal conditions in AsF5 above its critical temperature. The structure was determined from single-crystal data. CuFAsF6 crystallises in the orthorhombic space group Imma (No. 74) with a=10.732(5), b=6.941(3), c=6.814(3) A and Z=4 at 200 K. The structure can also be described in terms of one-dimensional infinite [CuF5]n(3n-) chains of tilted [CuF6](4-) octahedra linked by trans-vertices running along the b axis. The [CuF5]n(3n-) chains are connected through [AsF6]- units sharing joint vertices. The compressed octahedral coordination of CuII atoms in CuFAsF6 and CsCuAlF6 compounds at room temperature is confirmed by Cu K-edge EXAFS (extended x-ray absorption fine structure) analysis. For both compounds strong antiferromagnetic interactions within the [CuF5]n(3n-) chains were observed (theta(p)=-290+/-10 K and theta(p)=-390+/-10 K for CuFAsF6 and CsCuAlF6, respectively). The peculiar magnetic behaviour of chain compounds containing divalent copper at low temperature could be related to uncompensated magnetic moments in the one-dimensional network.


Mechanism of T cell activation. II. Antigen- and lectin-dependent acquisition of responsiveness to TCGF is a nonmitogenic, active response of resting T cells.
Small resting T cells, which do not respond to T cell growth factor (TCGF), acquire responsiveness upon a short (4-hr) pulse of specific ligands by presenting growth receptors for TCGF. The results demonstrate that the same mechanisms operate in the specific induction of primary MLR in that a 5-hr MLR is sufficient to render the responder cells reactive to TCGF. Furthermore, the results demonstrate that an active "response" by the resting T cells is required for expression of functional growth receptors, as demonstrated by the fact that: 1) a 4-hr pulse of concanavalin A (Con A) at 4 degrees C did not result in gain of reactivity to TCGF, whereas a 4-hr pulse at 37 degrees C did; 2) this metabolic requirement for acquisition of responsiveness to TCGF was not due to a secondary requirement for cap-formation of Con A-binding membrane structures, as normal responses were observed in the presence of cytochalasin B (cyt B); 3) the process of Con A-induced acquisition of susceptibility to TCGF was puromycin sensitive.


Comparison of chemical profiles, antioxidation, inhibition of skin extracellular matrix degradation, and anti-tyrosinase activity between mycelium and fruiting body of Cordyceps militaris and Isaria tenuipes.
Cordyceps militaris and Isaria tenuipes (Cordycipitaceae) are high-value fungi that are used for health-promoting food supplements. Since laboratory cultivation has begun for these fungi, increased output has been achieved. This study compared the chemical profiles, antioxidant, anti-tyrosinase, and skin extracellular matrix degradation inhibition between mycelium and fruiting body of C. militaris and I. tenuipes. The antioxidative potential of 10% v/v aqueous infused extract from each fungus was separately investigated using 2,2-azinobis(3-ethylbenzo-thiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant ability, and ferric thiocyanate methods. The inhibition against MMP-1, elastase, and hyaluronidase were determined to reveal their anti-wrinkle potential. Anti-tyrosinase activities were determined. C. militaris and I. tenuipes extracts were found to contain a wide range of bioactive compounds, including phenolics, flavonoids, and adenosine. A correlation was discovered between the chemical compositions and their biological activities. The extract from I. tenuipes fruiting body (IF) was highlighted as an extraordinary elastase inhibitor (IC50 = 0.006 ± 0.004 mg/mL), hyaluronidase inhibitor (IC50: 30.3 ± 3.2 mg/mL), and antioxidant via radical scavenging (ABTS IC50: 0.22 ± 0.02 mg/mL; DPPH IC50: 0.05 ± 0.02 mg/mL), thereby reducing ability (EC1: 95.3 ± 4.8 mM FeSO4/g extract) and lipid peroxidation prevention (IC50: 0.40 ± 0.11 mg/mL). IF had a three-times higher EC1 value than ascorbic acid and significantly higher elastase inhibition than epigallocatechin gallate. IF is proposed as a powerful natural extract with antioxidant and anti-wrinkle properties; therefore, it is suggested for further use in pharmaceutical, cosmeceutical, and nutraceutical industries.


CYP3A4 polymorphisms--potential risk factors for breast and prostate cancer: a HuGE review.
The steroid hydroxylase CYP3A4 is the most abundant P-450 enzyme in the human liver, and CYP3A enzymes metabolize more than 50% of prescription drugs. The CYP3A4 gene is expressed in the liver, gut, colon, prostate, and breast. Individual variation in CYP3A4 may play a role in breast and prostate carcinogenesis through modulation of sex hormone metabolite levels. Alternatively, CYP3A4 can metabolically activate exogenous carcinogens. CYP3A4 activity varies widely in humans, and more than 78 DNA sequence polymorphisms are known. These observations prompted the hypothesis that variant CYP3A4 may be involved in breast and prostate cancer. Two epidemiologic studies of breast cancer and five of prostate cancer examined CYP3A4 genotypes. A US study showed that inheritance of CYP3A4*1B correlates with early menarche, a breast cancer risk factor. However, an Australian breast cancer case-control study found no association with CYP3A4*1B. Two Scottish prospective studies showed CYP3A4*1B to be a risk factor for prostate cancer among men with benign prostatic hyperplasia. Three other studies were undertaken in the United States: two were case-only studies and the other was a case-sibling control study. Although results for African Americans were inconsistent, these studies suggested that CYP3A4*1B was associated with markers of advanced disease. These observations support the notion that development of robust, conventional molecular epidemiologic case-control studies to address these questions, including gene-gene and gene-environment interactions, will be timely.


Municipal records in nineteenth century Dutch emigration research.
Dutch emigrant registration records for the nineteenth century are examined in an effort to shed light on the local circumstances of the Dutch emigration movement. "Since nineteenth century emigration took place mostly through primary contacts this article will examine the newly established immigrant settlements as 'communities transplanted'...which directs our research to include local municipal records such as population censuses, population registers (which were supplemented after 1861 with registers of in- and out-migration), tax records, and records of vital events like marriage, birth and death registers. The quality and availability of these records vary from place to place, but generally speaking, in the case of the Netherlands, they are of high quality since population registration at the municipal level was required by law. The source of information for the local records are the population registers (Bevolkings Registers) which were originally constructed on the basis of information obtained from the 1850 population census...."


Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant Escherichia coli.
Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed compound diphenylmethane (DPM) for its EPI activity. The IC50 and modulation results showed that DPM has no antibacterial activity but can potentiate the activity of antibiotics against drug-resistant E. coli. Time-kill studies reported that a combination of DPM and erythromycin exhibited greater inhibitory activity against drug-resistant Escherichia coli. Dye accumulation and dye efflux studies using Hoechst 33342 and ethidium bromide showed that the addition of DPM significantly increased dye accumulation and reduced dye efflux in drug-resistant E. coli, suggesting its interference with dye translocation by an efflux pump. Using MALDI-TOF, it was observed that the addition of DPM could continuously reduce antibiotic efflux in drug-resistant E. coli. Additionally, DPM did not seem to damage the E. coli membranes, and the cell toxicity test showed that it features mild human-cell toxicity. In conclusion, these findings showed that DPM could serve as a potential EPI for drug-resistant E. coli.


Varying abilities of recombinant polypeptides from different regions of hepatitis E virus ORF2 and ORF3 to detect anti-HEV immunoglobulin M.
Following infection with hepatitis E virus (HEV), anti-HEV immunoglobulin (Ig) M is thought to develop before anti-HEV IgG and to be a better marker for differentiating between the acute and convalescent phases of infection. In order to select polypeptides for improved detection of anti-HEV IgM, six and three overlapping polypeptides from open reading frames (ORFs) 2 and 3, respectively, of HEV genotypes 1 and 4 were expressed as fusion proteins in Escherichia coli. The reactivities of the polypeptides with anti-HEV IgM were evaluated using immunoblotting and enzyme immunoassays (EIAs). The data indicated that polypeptides from the N-terminus of ORF3 and middle region of ORF2 were weakly or not reactive with anti-HEV IgM, while those from the remaining regions of ORF2 and ORF3 contained reactive epitopes. Anti-HEV IgM against the N- or C-terminus of ORF2 appeared earlier and disappeared faster than that against polypeptides from the C-terminus of ORF3, based on serum samples from rhesus monkeys infected experimentally, and from patients infected naturally, with HEV. The N- and C-terminal polypeptides from ORF2 complemented one another in detecting anti-HEV IgM and EIA sensitivity was improved significantly with a combination of these polypeptides. The reactivities of ORF2 polypeptides from genotypes 1 and 4 were similar but that of ORF3 differed with sera from monkeys infected by the two genotypes. Thus, a combination of N- and C-terminal polypeptides of ORF2 from one genotype may be effective in EIAs to detect anti-HEV IgM.


Alcohol use as a risk factor for tuberculosis - a systematic review.
It has long been evident that there is an association between alcohol use and risk of tuberculosis. It has not been established to what extent this association is confounded by social and other factors related to alcohol use. Nor has the strength of the association been established. The objective of this study was to systematically review the available evidence on the association between alcohol use and the risk of tuberculosis. Based on a systematic literature review, we identified 3 cohort and 18 case control studies. These were further categorized according to definition of exposure, type of tuberculosis used as study outcome, and confounders controlled for. Pooled effect sizes were obtained for each sub-category of studies. The pooled relative risk across all studies that used an exposure cut-off level set at 40 g alcohol per day or above, or defined exposure as a clinical diagnosis of an alcohol use disorder, was 3.50 (95% CI: 2.01-5.93). After exclusion of small studies, because of suspected publication bias, the pooled relative risk was 2.94 (95% CI: 1.89-4.59). Subgroup analyses of studies that had controlled for various sets of confounders did not give significantly different results and did not explain the significant heterogeneity that was found across the studies. The risk of active tuberculosis is substantially elevated in people who drink more than 40 g alcohol per day, and/or have an alcohol use disorder. This may be due to both increased risk of infection related to specific social mixing patterns associated with alcohol use, as well as influence on the immune system of alcohol itself and of alcohol related conditions.


Both dioscorin, the tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1), and its peptic hydrolysates exhibited angiotensin converting enzyme inhibitory activities.
Dioscorin, the tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1), was purified to homogeneity by DE-52 ion-exchange chromatography. This purified dioscorin was shown by spectrophotometric methods to inhibit angiotensin converting enzyme (ACE) in a dose-dependent manner (12.5-750 microg, respectively, 20.83-62.5% inhibitions) using N-[3-(2-furyl)acryloyl]-Phe-Gly-Gly (FAPGG) as substrates. The 50% inhibition (IC(50)) of ACE activity was 6.404 microM dioscorin (250 microg corresponding to 7.81 nmol) compared to that of 0.00781 microM (0.0095 nmol) for captopril. The commercial bovine serum albumin and casein (bovine milk) showed less ACE inhibitory activity. The use of qualitative TLC also showed dioscorin as ACE inhibitors. Dioscorin showed mixed noncompetitive inhibitions against ACE; when 31.25 microg of dioscorin (0.8 microM) was added, the apparent inhibition constant (K(i)) was 2.738 microM. Pepsin was used for dioscorin hydrolysis at 37 degrees C for different times. It was found that the ACE inhibitory activity was increased from 51.32% to about 75% during 32 h hydrolysis. The smaller peptides were increased with increasing pepsin hydrolytic times. Dioscorin and its hydrolysates might be a potential for hypertension control when people consume yam tuber.


Genetic, pathophysiological, and clinical aspects of nephrocalcinosis.
Nephrocalcinosis describes the ectopic deposition of calcium salts in the kidney parenchyma. Nephrocalcinosis can result from a number of acquired causes but also an even greater number of genetic diseases, predominantly renal but also extrarenal. Here we provide a review of the genetic causes of nephrocalcinosis, along with putative mechanisms, illustrated by human and animal data.


In vivo tissue engineering: mimicry of homing factors for self-endothelialization of blood-contacting materials.
Thrombogenicity of foreign surfaces is the major obstacle in cardiovascular interventions. Despite enormous advances in biomaterials research, the hemocompatibility of blood-contacting materials is still not satisfactory and the native endothelium still represents the ideal surface for blood contact. Circulating adult endothelial progenitor cells (EPCs) in the human blood provide an excellent source of autologous stem cells for the in vivo self-endothelialization of blood-contacting materials. For this purpose, material surfaces can be coated with capture molecules mimicking natural homing factors to attract circulating EPCs. Hitherto, several ligands, such as aptamers, monoclonal antibodies, peptides, selectins and their ligands, or magnetic molecules, are used to biofunctionalize surfaces for the capturing of EPCs directly from patient's bloodstream onto blood-contacting materials. Subsequently, attracted EPCs can differentiate into endothelial cells and generate an autologous endothelium. The in vivo self-endothelialization of blood-contacting materials prevents the recognition of them as a foreign body; this opens up revolutionary new prospects for future clinical stem-cell and tissue engineering strategies.


Adaptive mutations in the nuclear export protein of human-derived H5N1 strains facilitate a polymerase activity-enhancing conformation.
The nuclear export protein (NEP) (NS2) of the highly pathogenic human-derived H5N1 strain A/Thailand/1(KAN-1)/2004 with the adaptive mutation M16I greatly enhances the polymerase activity in human cells in a concentration-dependent manner. While low NEP levels enhance the polymerase activity, high levels are inhibitory. To gain insights into the underlying mechanism, we analyzed the effect of NEP deletion mutants on polymerase activity after reconstitution in human cells. This revealed that the polymerase-enhancing function of NEP resides in the C-terminal moiety and that removal of the last three amino acids completely abrogates this activity. Moreover, compared to full-length NEP, the C-terminal moiety alone exhibited significantly higher activity and seemed to be deregulated, since even the highest concentration did not result in an inhibition of polymerase activity. To determine transient interactions between the N- and C-terminal domains in cis, we fused both ends of NEP to a split click beetle luciferase and performed fragment complementation assays. With decreasing temperature, increased luciferase activity was observed, suggesting that intramolecular binding between the C- and N-terminal domains is preferentially stabilized at low temperatures. This stabilizing effect was significantly reduced with the adaptive mutation M16I or a combination of adaptive mutations (M16I, Y41C, and E75G), which further increased polymerase activity also at 34°C. We therefore propose a model in which the N-terminal moiety of NEP exerts an inhibitory function by back-folding to the C-terminal domain. In this model, adaptive mutations in NEP decrease binding between the C- and N-terminal domains, thereby allowing the protein to "open up" and become active already at a low temperature.


Radiosensitization of uterine cancer cell lines by cytotoxic agents.
Radiotherapy remains an integral part of uterine cancer therapy. Overcoming radioresistant tumors by sensitizers continues to be a prime objective in radiotherapy research. In this study, the effects of five cytotoxic agents on two radiosensitive and four radioresistant uterine cancer cell lines were investigated. The ATP bioluminescence was used to measure surviving fractions. Data analysis was done using the linear quadratic model and radiosensitivity index D. Both AN3 and SKUT1B were radiosensitive with Ds of 1.73 and 1.72 Gy, respectively. The resistant cell lines had the following D values: AE7, 3.50; ECC, 6.61; HEC1A, 4.59; and HEC1B, 13.49 Gy. The average radiosensitization effects for various drugs were measured by reduction of D: DXR 45 +/- 7, DDP 40 +/- 9, 5FU 55 +/- 10, MITO 59 +/- 14, and HU 1.7 +/- 7%. Except for HU, Wilcoxon analyses revealed that these sensitizing effects were significant with P < 0.02. In summary, Adriamycin, 5-fluorouracil, cisplatin, and mitomycin-C have the potential to be radiosensitizers in uterine cancer cell lines.


Quantitative magnetic resonance imaging for chronic liver disease.
Chronic liver disease (CLD) has rapidly increased in prevalence over the past two decades, resulting in significant morbidity and mortality worldwide. Historically, the clinical gold standard for diagnosis, assessment of severity, and longitudinal monitoring of CLD has been liver biopsy with histological analysis, but this approach has limitations that may make it suboptimal for clinical and research settings. Magnetic resonance (MR)-based biomarkers can overcome the limitations by allowing accurate, precise, and quantitative assessment of key components of CLD without the risk of invasive procedures. This review briefly describes the limitations associated with liver biopsy and the need for non-invasive biomarkers. It then discusses the current state-of-the-art for MRI-based biomarkers of liver iron, fat, and fibrosis, and inflammation.


Replicating an intervention: the tension between fidelity and adaptation.
Increased awareness of the importance of tailoring interventions to participants' cultures has focused attention on the limited generalizability of a single test of an intervention to determine efficacy. Adaptation is often necessary to replicate interventions across cultures. This produces a tension between fidelity to the original intervention and adaptations necessary to make the intervention relevant to the culture and circumstances of participants. This article discusses issues that arise during the course of replication, with illustrations from a replication to test the efficacy of an HIV prevention intervention for youth, using a randomized controlled design. Analysis of the issues raised leads us to suggest that a "science of replication" needs to be developed.


Correlation and agreement between eplet mismatches calculated using serological, low-intermediate and high resolution molecular human leukocyte antigen typing methods.
Structural human leukocyte antigen (HLA) matching at the eplet level can be identified by HLAMatchmaker, which requires the entry of four-digit alleles. The aim of this study was to evaluate the agreement between eplet mismatches calculated by serological and two-digit typing methods compared to high-resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the evaluation of measurement error was assessed using intra-class correlation to confirm the absolute agreement between the number of eplet mismatches at class I (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two-digit molecular typing compared to four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches between the HLA typing methods was also determined. Intra-class correlation coefficients between serological and four-digit molecular typing methods were 0.969 (95% confidence intervals [95% CI] 0.960-0.975) and 0.926 (95% CI 0.899-0.944), respectively; and 0.995 (95% CI 0.994-0.996) and 0.993 (95% CI 0.991-0.995), respectively between two-digit and four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches at class I and II loci was 4% and 16% for serological versus four-digit molecular typing methods, and 0% and 2% for two-digit versus four-digit molecular typing methods, respectively. In this small predominantly Caucasian population, compared with serology, there is a high level of agreement in the number of eplet mismatches calculated using two-compared to four-digit molecular HLA-typing methods, suggesting that two-digit typing may be sufficient in determining eplet mismatch load in kidney transplantation.


[Protective effect of losartan on insulin secretion function of RIN-m cells against angiotensin II-induced injury and the mechanism].
To investigate the protective effect of losartan against angiotensin II (AngII)-induced beta cell (RIN-m) impairment and explore its mechanism. In vitro cultured RIN-m cells were divided into control group, 100 nmol/L AngII group and losartan pretreatment group. After cell incubation with the corresponding agents for 24 h, the amount of basal (3.3 mmol/L) and glucose-stimulated (16.7 mmol/L) insulin secretion (GSIS) was detected by radioimmunoassay, and the cellular reactive oxygen species (ROS) was assayed by flow cytometry with DCFH-DA staining; the mRNA and protein expressions of uncoupling protein 2 (UCP2) were determined by RT-PCR and Western blotting, respectively. The basal insulin secretion showed no significant differences between the 3 groups (P>0.05). The GSIS in 100 nmol/L AngII group was significantly lower than that of the control group (P<0.001), but losartan pretreatment markedly restored the insulin secretion function to a level comparable to that of the control group (P<0.05). Compared with the control group, 100 nmol/L AngII significantly increased the cellular ROS level and the mRNA and protein expressions of UCP2 (P<0.05), and these changes were eliminated by losartan pretreatment. Losartan pretreatment offers protective effect against AngII-induced impairment of the GSIS of beta cells possibly by antagonizing the effects of AngII that causes increased ROS level and UCP2 expressions in beta-cells.


Bacteriophages as potential new therapeutics to replace or supplement antibiotics.
Over recent decades, a growing body of literature has validated the use of bacteriophages for therapy and prophylaxis in the war against drug-resistant bacteria. Today, much more is known about bacteriophages than in the 1930s when phage therapy first appeared and began to spread to many countries. With rapid dissemination of multi-drug-resistant bacterial pathogens, the interest in alternative remedies to antibiotics, including bacteriophage treatments, is gaining new ground. Based on recent experience and current results of bacteriophage applications against bacterial infections in countries where this alternative therapy is approved, many scientists and companies have come to believe that the use of phages for treating and preventing bacterial diseases will be successful.


Image analysis cytology for DNA determination in breast and prostate cancer.
Nuclear DNA distribution in fine-needle specimens from 112 breast carcinomas and 45 prostatic tumours was studied. The distributions were described statistically with five separate descriptors, namely mean deviation from 2C, percentage of cells exceeding 2.25C and 4.5C respectively, DNA index and entropy (a mathematical measure of degree of scatter of the DNA content of the nuclei). It was shown that information about DNA index only ('diploid' versus 'aneuploid') is too limited and the term 'diploid' even incorrect and misleading for description of human cancer cell populations. Merely an addition of the percentage of cells exceeding 2.25C allowed separation of a majority of the carcinoma specimens from specimens taken from normal tissue. Moreover, in carcinoma specimens 96% of the patients had between 1 and 100% of the cancer nuclei cell population exceeding 4.5C in contrast to all normal specimens, where this percentage was 0. Entropy was clearly correlated with percentage of Ki-67-positive cells, indicating that it contains information on both scatter of nuclear DNA content and proliferation. Plotting of the scatter (entropy) versus DNA index allowed separation of greater than 97% of the carcinoma specimens from specimens taken from normal individuals. With the use of all five descriptors of DNA distribution it was possible to separate all breast cancer specimens and all moderately and poorly differentiated prostate cancer specimens from normal specimens. The discrimination between well-differentiated prostate cancer and hyperplasia constituted a special problem in that it was not possible to confirm the diagnosis well-differentiated prostate cancer by objective measurements in 8% of the patients, even when all five descriptors were used for the analysis. None of the verified carcinoma specimens had a DNA distribution that was truly 'diploid' in the sense of the distributions of cancer nuclei and normal cell nuclei from the actual organ being quite similar.


Alpha 1-adrenoceptors in neonatal rat cardiac myocytes: hypoxia alters the responsiveness of alpha 1A and alpha 1B subtypes.
We investigated the contribution of alpha 1-adrenoceptor subtypes to the chronotropic response to norepinephrine (NE) in cultured neonatal rat cardiac myocytes under normoxia and hypoxia. A dose-dependent negative chronotropic response was induced by NE in the presence of propranolol. Hypoxic exposure inverted the negative chronotropic response to NE to a positive one. All of these chronotropic responses were completely antagonized by prazosin. In normoxic conditions, the NE-induced negative chronotropic response was completely antagonized by WB4101 but only partially (55%) so by chloroethylclonidine (CEC). After hypoxic exposure, WB4101 partially antagonized the positive chronotropic response to NE (54%), while CEC completely suppressed the action of NE. Hypoxic exposure did not alter the number of alpha 1A- and alpha 1B-adrenoceptor subtypes as measured by [3H]prazosin binding following CEC treatment. These results indicate (1) that cultured neonatal rat cardiac myocytes contain both alpha 1-adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, and (2) that the predominant alpha 1-adrenoceptor subtypes mediating NE-induced chronotropy were altered by hypoxia.


Age-dependent congener profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans in the general population of Taiwan.
A congener profile of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) could provide valuable information for identifying possible sources of exposure to these compounds. The purpose of this study is to identify factors associated with PCDD/F congener profiles in the general population of Taiwan. Serum samples from 251 subjects of the general population in Taiwan were collected, and the levels of 17 2,3,7,8-chlorinated substituted PCDD/Fs were measured. The relationships between PCDD/F congener profiles and demographic parameters were evaluated using a multivariate analysis of variance method (MANOVA). Of the five demographic factors investigated, age was found to have the greatest impact on PCDD/F congener profiles. The PCDD/F congener pattern for the group I subjects (aged 18-29) was significantly different from those for the other three older age groups (p<0.001), and 12 congeners contributed to the effects (difference index: 71%). In addition, the group I subjects did not exhibit trends parallel to those of the other groups in the relationship between age and PCDD/F levels. Age was associated with PCDD/F levels and congener profiles in the general population of Taiwan and the young subjects (aged 18-29) was quite different from the other older subjects that could be influenced by the individual differences in pharmacokinetics and/or background exposure from dietary sources. We conclude that investigators must consider subjects' age and other underlying factors that could influence PCDD/F congener profiles in humans when identifying exposure sources.


The benzamide derivative metoclopramide causes DNA damage and inhibition of DNA repair in human peripheral mononuclear leukocytes at clinically relevant doses.
The polysubstituted benzamide derivative metoclopramide (MCA) has previously been shown to enhance the effect of cisplatin and ionizing radiation treatment of xenografted human squamous cell carcinomas from the head and neck region. In the present work we show that MCA decreases the nucleoid sedimentation rate, indicating that MCA causes strand breaks in the DNA of human peripheral mononuclear leukocytes treated in vitro. This effect is seen with MCA in the dose range from 100 nM to 1 mM. MCA also stimulated the activity of the enzyme adenosine-diphospho-ribosyl transferase both in cells treated with MCA alone, and in combination with 15 Gy. This was taken as additional evidence that MCA causes DNA strand breaks. The DNA damage induced by MCA was poorly repaired when assessed by nucleoid sedimentation analysis, and this effect on repair was confirmed by showing that MCA also inhibits N-acetoxy-2-acetylaminofluorene-induced unscheduled DNA synthesis. The effect of MCA on DNA damage measured by nucleoid sedimentation has also been demonstrated in permeabilized cells. These data indicate that the DNA-damaging effect of MCA is not dependent on surface receptors or cytoplasmic processes.


Vibronic Coupling in Spherically Encapsulated, Diatomic Molecules: Prediction of a Renner-Teller-like Effect for Endofullerenes.
In the year 1933, Herzberg and Teller realized that the potential energy surface of a triatomic, linear molecule splits into two as soon as the molecule is bent. The phenomenon, later dubbed the Renner-Teller effect due to the detailed follow-up work of Renner on the subject, describes the coupling of a symmetry-reducing molecular vibration with degenerate electronic states. In this article, we show that a very similar type of nonadiabatic coupling can occur for certain translational degrees of freedom of diatomic, electronically degenerate molecules when trapped in a nearly spherical or cylindrical quantum confinement, e.g., realized through electromagnetic fields or molecular encapsulation. We illustrate this on the example of fullerene-encapsulated nitric oxide, and provide a prediction of its interesting, perturbed vibronic spectrum.


Parenting Stress in Mothers of Children and Adolescents with Down Syndrome.
Parenting stress has deleterious effects on parents, children, and overall family functioning. Parents of children with intellectual disability, including Down Syndrome (DS), show higher levels of parenting stress than parents of typically developing children. This research aimed to (i) evaluate parenting stress levels in a group of mothers of youths with DS using a parent-report questionnaire, (ii) identify children's individual and clinical features associated with maternal stress, and (iii) identify specific situational life/demographics factors related to maternal stress. Seventy-eight youths with DS underwent a neuropsychological evaluation, whereas mothers completed questionnaires for the assessment of parenting stress and of the child's emotional and behavioral problems. We found that Parent-Child Difficult Interaction was the domain with the highest percentage of clinical scores (39.7%). Both internalizing and externalizing problems correlated with maternal stress, as well as autistic symptoms. The levels of maternal stress were not associated with any socio-demographic variable. After controlling for child-related correlates of maternal stress and for mothers' age and education level, unemployed mothers exhibited higher levels of parental distress than employed mothers. The present study highlights that unemployment is related with parenting stress and potentially amenable to policy interventions supporting parents in combining work and family care.


Increased incidence of euthyroid and hyperthyroid goiters independently of thyrotropin in patients with acromegaly.
The incidence of palpable goiters, the thyroid functional state and thyroid radioisotope uptake was analyzed retrospectively in 80 patients with acromegaly and 80 patients with prolactinomas. 71% of all patients with acromegaly had an enlargement of the thyroid (goiter); 49% of them had diffuse and 39% nodular goiters. The incidence of goiters in patients with prolactinomas from the same iodine deficient geographic region was only 35% (82% diffuse and 18% nodular). 17.5% of acromegalic patients underwent thyroid surgery before diagnosis of growth hormone excess. 17.5% of acromegalic patients with goiters had autonomous areas in their thyroids and 5% were clearly hyperthyroid. Goiters developed slightly more often in females (74%) than in males (67%). The mean preoperative growth hormone level was higher in acromegalic patients with goiter. The incidence of goiters was positively correlated with the documented time of elevated growth hormone concentration in serum. Two patients with exaggerated response of thyrotropin (TSH) (delta TSH greater than 20 mU/l) to the application of thyrotropin-releasing hormone (TRH) had no goiters. On the other hand most patients (61%) with goiters had a low TSH-response to TRH (delta TSH less than 10 mU/l) representing in part occult autonomy of thyroid function. No patient with prolactinoma has had previous thyroid surgery nor thyroid autonomy. One patient with prolactinoma suffered from Graves' disease and none of the acromegalic patients had this disease. We finally conclude that the elevation of growth hormone leads to increased incidence of euthyroid and hyperthyroid (autonomous) goiters independently of the influence of TSH.


A novel HURRAH protocol reveals high numbers of monomorphic MHC class II loci and two asymmetric multi-locus haplotypes in the Père David's deer.
The Père David's deer is a highly inbred, but recovered, species, making it interesting to consider their adaptive molecular evolution from an immunological perspective. Prior to this study, genomic sequencing was the only method for isolating all functional MHC genes within a certain species. Here, we report a novel protocol for isolating MHC class II loci from a species, and its use to investigate the adaptive evolution of this endangered deer at the level of multi-locus haplotypes. This protocol was designated "HURRAH" based on its various steps and used to estimate the total number of MHC class II loci. We confirmed the validity of this novel protocol in the giant panda and then used it to examine the Père David's deer. Our results revealed that the Père David's deer possesses nine MHC class II loci and therefore has more functional MHC class II loci than the eight genome-sequenced mammals for which full MHC data are currently available. This could potentially account at least in part for the strong survival ability of this species in the face of severe bottlenecking. The results from the HURRAH protocol also revealed that: (1) All of the identified MHC class II loci were monomorphic at their antigen-binding regions, although DRA was dimorphic at its cytoplasmic tail; and (2) these genes constituted two asymmetric functional MHC class II multi-locus haplotypes: DRA1*01 ∼ DRB1 ∼ DRB3 ∼ DQA1 ∼ DQB2 (H1) and DRA1*02 ∼ DRB2 ∼ DRB4 ∼ DQA2 ∼ DQB1 (H2). The latter finding indicates that the current members of the deer species have lost the powerful ancestral MHC class II haplotypes of nine or more loci, and have instead fixed two relatively weak haplotypes containing five genes. As a result, the Père David's deer are currently at risk for increased susceptibility to infectious pathogens.


Anchoring of Formamidinium Lead Bromide Quantum Dots on Ti3C2 Nanosheets for Efficient Photocatalytic Reduction of CO2.
Metal halide perovskite with a suitable energy band structure and excellent visible-light response is a prospective photocatalyst for CO2 reduction. However, the reported inorganic halide perovskites have undesirable catalytic performances due to phase-sensitive and severe charge carrier recombination. Herein, we anchor the FAPbBr3 quantum dots (QDs) on Ti3C2 nanosheets to form a FAPbBr3/Ti3C2 composite within a Schottky heterojunction for photocatalytic CO2 reduction. Upon visible-light illumination, the FAPbBr3/Ti3C2 composite photocatalyst exhibits an appealing photocatalytic performance in the presence of deionized water. The Ti3C2 nanosheet acts as an electron acceptor to promote the rapid separation of excitons and supply specific catalytic sites. An optimal electron consumption rate of 717.18 μmol/g·h is obtained by the FAPbBr3/0.2-Ti3C2 composite, which has a 2.08-fold improvement over the pristine FAPbBr3 QDs (343.90 μmol/g·h). Meanwhile, the FAPbBr3/Ti3C2 photocatalyst also displays a superior stability during photocatalytic reaction. This work expands a new insight and platform for designing superb perovskite/MXene-based photocatalysts for CO2 reduction.


Smad3 Sensitizes Hepatocelluar Carcinoma Cells to Cisplatin by Repressing Phosphorylation of AKT.
Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC remains elusive. The role of smad3 in chemosensitivity of HCC was measured by cell viability, apoptosis, plate colony formation assays and xenograft tumor models. Non-smad signaling was detected by Western blotting to search for the underlying mechanisms. Smad3 enhanced the chemosensitivity of HCC cells to cisplatin. Smad3 upregulated p21(Waf1/Cip1) and downregulated c-myc and bcl2 with the treatment of cisplatin. Moreover, overexpression of smad3 repressed the phosphorylation of AKT, and vice versa. Inhibition of PI3K/AKT pathway by LY294002 restored chemosensitivity of smad3-deficiency cells to cisplatin in HCC. Smad3 sensitizes HCC cells to the effects of cisplatin by repressing phosphorylation of AKT and combination of inhibitor of AKT pathway and conventional chemotherapy may be a potential way to solve drug resistance in HCC.


Temperature does not influence functional response of amphipods consuming different trematode prey.
Direct consumption on free-living cercariae stages of trematodes by non-host organisms interferes with trematode transmission and leads to reduced infections in the next suitable hosts. Consumer functional responses provide a useful tool to examine relationships between consumption rates and ecologically relevant prey densities, whilst also accounting for abiotic factors that likely influence consumption rates. We investigated how temperature influences the consumer functional response of the amphipod Gammarus lacustris towards the cercariae of three freshwater trematodes (Diplostomum, Apatemon and Trichobilharzia). Amphipods displayed different functional responses towards the parasites, with Type II responses for Diplostomum and Type I responses for Apatemon prey. Temperature did not alter the consumption rate of the amphipod predator. Trichobilharzia was likely consumed at similar proportions as Diplostomum; however, this could not be fully evaluated due to low replication. Whilst Type II responses of invertebrate predators are common to various invertebrate prey types, this is the first time a non-filter feeding predator has been shown to exhibit Type I response towards cercarial prey. The prey-specific consumption patterns of amphipods were related to cercarial distribution in the water column rather than to the size of cercariae or temperature influence. The substantial energy flow into food webs by non-host consumer organisms highlights the importance of understanding the mechanisms that modulate functional responses and direct predation in the context of parasitic organisms.


Cutaneous manifestations of systemic mycoses.
Systemic fungal diseases are primary pulmonary diseases caused by the dimorphic fungal pathogens, Blastomyces dermatitides, Coccidioides immitis. Histoplasma capsulatum, or Paracoccidioides brasiliensis. Infection occurs after inhalation of the infectious form of the fungus and may be acute, self-limited, or subclinical. Primary cutaneous infection occurs only after traumatic implantation of the fungus and is unusual. Erythema nodosum or erythema multiforme may accompany the acute form of the disease. Other cutaneous manifestations represent disseminated disease and, as such, require systemic antifungal therapy. Because cutaneous lesions have occurred coincidentally with other cutaneous pathologies, emphasis should be placed on a complete clinical history, physical examination, and diagnosis by histopathology and culture.


Foamy Virus Protein-Nucleic Acid Interactions during Particle Morphogenesis.
Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches.


Utilisation of the falciform ligament pedicle flap as an alternative approach for the repair of a perforated gastric ulcer.
An 83-year-old woman presented to the emergency department with sudden onset of severe abdominal pain. She had a background of ulcerative colitis managed surgically at the age of 18 years with panproctocolectomy and permanent ileostomy. On admission, clinical assessment suggested a visceral perforation and an urgent CT scan demonstrated a perforated prepyloric ulcer. Emergency laparotomy was performed and confirmed a 3 cm perforated pre-pyloric ulcer. Repair of the defect was challenging due to the absence of omental fat to patch the perforation. A modification to the standard technique was therefore performed: the falciform ligament was mobilised and its free end used as a patch to repair the defect. The patient made a good postoperative recovery. This case report highlights an alternative operative technique for the treatment of perforated gastric/duodenal ulcers in patients who lack omentum, or when omentum cannot be used to cover perforated gastroduodenal ulcers.


Patent Foramen Ovale and Hypoxemia.
Patent foramen ovale (PFO), an embryonic remnant of the fetal circulation, is present in 20-25% of adults. Although recent observational studies and clinical trials have established the link between PFO-mediated right-to-left shunting with cryptogenic stroke and migraine with aura, the role of a PFO in exacerbating hypoxemic medical conditions (ie, sleep apnea, chronic obstructive pulmonary disease, pulmonary hypertension, platypnea-orthodeoxia, pulmonary arteriovenous malformation, high-altitude pulmonary edema, and exercise desaturation) remains less understood. PFO-mediated hypoxemia occurs when deoxygenated venous blood from the right atrium enters and mixes with oxygenated arterial blood in the left atrium. Patients with an intracardiac right-to-left shunt may have profound hypoxemia out of proportion to underlying primary lung disease, even in the presence of normal right-sided pressures. The presence of right-to-left cardiac shunting can exacerbate the degree of hypoxemia in patients with underlying pulmonary disorders. In a subset of these patients, percutaneous PFO closure may result in marked improvement in dyspnea and hypoxemia. This review discusses the association between PFO-mediated right-to-left shunting with medical conditions associated with hypoxemia and explores the role of percutaneous PFO closure in alleviating the hypoxemia.


Application of hydrolysis probe analysis to identify clade types of the malaria vector mosquito Anopheles funestus sensu stricto from Muheza, northeastern Tanzania.
A hydrolysis probe analysis (TaqMan assay) was used to study clade types in Anopheles funestus sensu stricto Giles, a major malaria vector in sub-Saharan Africa, with specimens collected from Muheza in Tanga, northeastern Tanzania. A total of 186 An. funestus specimens were analysed, revealing that 176 (94.6%) were of clade I and 10 (5.4%) of clade II. These findings extend the distribution of clade type II from southern Mozambique and northern Zambia to northeastern Tanzania. The technique used can also be of great value in assessing the role and contribution of these clade types in malaria transmission and insecticide resistance frequencies for An. funestus s.s.


Differential expression of the three Alcanivorax borkumensis SK2 genes coding for the P450 cytochromes involved in the assimilation of hydrocarbons.
Alcanivorax borkumensis, a marine bacterium highly specialized in degrading linear and branched alkanes, plays a key ecological role in the removal of marine oil spills. It contains several alternative enzyme systems for terminal hydroxylation of alkanes, including three P450 cytochromes (P450-1, P450-2 and P450-3). The present work shows cytochrome P450-1 to be expressed from the promoter of the upstream gene fdx. Promoter Pfdx was more active when C8 -C18 n-alkanes or pristane were assimilated than when pyruvate was available. The product of ABO_0199 (named CypR) was identified as a transcriptional activator of Pfdx . The inactivation of cypR impaired growth on tetradecane, showing the importance of the fdx-P450-1 and/or cypR genes. P450-2 expression was low-level and constitutive under all conditions tested, while that of P450-3 from promoter P450-3 was much higher when cells assimilated pristane than when n-alkanes or pyruvate were available. However, the inactivation of P450-3 had no visible impact on pristane assimilation. Cyo terminal oxidase, a component of the electron transport chain, was found to stimulate promoter PP450-3 activity, but it did not affect promoters Pfdx or PP450-2 . A. borkumensis, therefore, appears to carefully coordinate the expression of its multiple hydrocarbon degradation genes using both specific and global regulatory systems.


An automated Internet application to help patients with bipolar disorder track social rhythm stabilization.
This column describes a pilot study of a fully automated, Internet-based program that provides a key element of interpersonal and social rhythm therapy, a form of psychotherapy shown to be effective in the treatment of bipolar disorder when combined with mood-stabilizing medication. Participants (N=64) recorded the time they completed activities of daily living and their mood at the time of each entry. After 90 days they demonstrated a 31% increase in social rhythm stability and a small, though statistically significant, decrease in symptoms of abnormal mood. Internet-based programs can enhance access to a best practice in the management of bipolar disorder.


Monocyte aggregation and multinucleated giant-cell formation in vitro in Crohn's disease. The effect of cell adhesion molecules.
Multinucleated giant-cell (MGC) formation is a common histopathologic feature of various granulomatous diseases, including Crohn's disease (CD). We have investigated monocyte aggregation and subsequent MGC formation by in vitro culturing peripheral monocytes from 25 CD patients, 15 ulcerative colitis (UC) patients, and 10 healthy controls. The effect of cell adhesion molecules on the monocyte aggregation and MGC formation in CD patients was investigated by using anti-beta 2 integrin and anti-ICAM-1 antibodies. The monocyte aggregation and MGC formation were significantly higher in CD than those seen in UC and controls (p < 0.05). In CD, antibody to beta 2 integrin could inhibit not only the monocyte aggregation but also the subsequent MGC formation. In contrast, the antibody to ICAM-1 could inhibit the monocyte aggregation; however, it could not inhibit the MGC formation. Monocyte aggregation and MGC formation are increased in CD. beta 2 Integrin may play an important role in the monocyte aggregation and MGC formation of CD patients.


Preparation of Fluoroalkyl End-Capped Vinyltrimethoxysilane Oligomeric Silica Nanocomposites Containing Gluconamide Units Possessing Highly Oleophobic/Superhydrophobic, Highly Oleophobic/Superhydrophilic, and Superoleophilic/Superhydrophobic Characteristics on the Modified Surfaces.
Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH₂-CHSi(OMe)₃)n-RF (RF-(VM)n-RF)] undergoes the sol-gel reaction in the presence of N-(3-triethoxysilylpropyl)gluconamide [Glu-Si(OEt)₃] under alkaline conditions to afford the corresponding fluorinated oligomeric silica nanocomposites containing gluconamide units [RF-(VM-SiO3/2)n-RF/Glu-SiO3/2]. These obtained nanocomposites were applied to the surface modification of glass to provide the unique wettability characteristics such as highly oleophobic/superhydrophobic and highly oleophobic/superhydrophilic on the modified surfaces under a variety of conditions. Such a highly oleophobic/superhydrophobic characteristic was also observed on the modified PET (polyethylene terephthalate) fabric swatch, which was prepared under similar conditions, and this modified PET fabric swatch was applied to the separation membrane for the separation of the mixture of fluorocarbon oil and hydrocarbon oil. The RF-(VM-SiO3/2)n-RF/Glu-SiO3/2 nanocomposites, which were prepared under lower feed amounts of basic catalyst (ammonia), were found to cause gelation in water. Interestingly, it was demonstrated that these gelling nanocomposites are also applied to the surface modification of the PET fabric swatch to give a highly oleophobic/superhydrophobic characteristic on the surface. On the other hand, the modified glass surfaces treated with the corresponding nanocomposite possessing no gelling ability were found to supply the usual hydrophobic characteristic with a highly oleophobic property. More interestingly, the wettability change on the modified PET fabric swatch from highly oleophobic to superoleophilic was observed, and remained superhydrophobic after immersing the modified PET fabric swatch into water.


Qualitative effect on mRNAs of injury-associated proteins by cell phone like radiation in rat facial nerves.
Rats were exposed to cell phone radiation for 6 hours per day for 18 weeks. The buccal and mandibular branches of the facial nerve were evaluated for this study. The mRNA levels of four proteins that are usually up regulated when an injury has occurred were investigated; included were Calcium ATP-ase, Endothelin, Neural Cell Adhesion Molecule, and Neural Growth Factor. These isolated mRNAs were subjected to RT-PCR and all four were up regulated. The mandibular nerve showed a higher and broader level of up regulation than the buccal nerve. All four mRNA up regulations for the mandibular nerve and two for the buccal nerve were also statistically significant. These specific injury-related findings were mild. As the use of these cell phones continues, there most likely will be permanent damage to these tissues over the years and the likelihood of tumors, cancers, and system failures will potentially increase.


Histopathological patterns and biological characteristics of ameloblastoma: A retrospective cross-sectional study.
This study aims to determine the histopathological patterns and biological characteristics of ameloblastoma. This was a cross-sectional retrospective laboratory-based study using 82 formalin-fixed paraffin-embedded tissue blocks from patients diagnosed histologically with ameloblastoma. Information regarding age, sex, anatomical location of the lesion, histopathologic type, and biological behaviour or characteristics of the types of ameloblastoma was obtained from laboratory request forms. Categorical and continuous variables were summarized in percentage and mean ± standard deviation, respectively. The cohort was conducted on Ugandan patients diagnosed between 2016 and 2019. Most patients (66.3%) were clinically presenting a painless jaw swelling, and a follicular pattern was common (39%) followed by the plexiform pattern (12.2%). All the ameloblastoma cases (100%) were benign, with the majority (76.8%) cases being non-recurrent while the remaining (23.2%) were recurrent, and the plexiform pattern was the commonest recurrent histopathological pattern. This study reports a relatively significant rate of recurrence in almost a quarter of the study population. The plexiform histopathologic type was the dominant type in recurrence cases. Therefore, this finding provides insightful information to clinicians to ensure close follow-up for patients diagnosed with such a variant to prevent possible relapse of the disease.


Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.
To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass index 24.8 ± 3.1 kg m-2 [mean ± standard deviation]) received ≥1 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF-05190457 and/or placebo in the SAD. In the MAD study, 35 healthy men (age 39.7 ± 10.1 years; body mass index 25.9 ± 3.3 kg m-2 ) received ≥1 dose (2, 10, 40 and 100 mg twice daily) of PF-05190457 and/or placebo daily for 2 weeks. PF-05190457 absorption was rapid with a Tmax of 0.5-3 hours and a half-life between 8.2-9.8 hours. PF-05190457 dose-dependently blocked ghrelin (1 pmol kg-1 min-1 )-induced growth hormone (GH) release with (mean [90% confidence interval]) 77% [63-85%] inhibition at 100 mg. PF-05190457 (150 mg) delayed gastric emptying lag time by 30% [7-58%] and half emptying time by 20% [7-35%] with a corresponding decrease in postprandial glucose by 9 mg dL-1 . The most frequent adverse event reported by 30 subjects at doses ≥50 mg was somnolence. PF-05190457 plasma concentrations also increased heart rate up to 13.4 [4.8-58.2] beats min-1 and, similar to the effect on glucose and ghrelin-induced GH, was lost within 2 weeks. PF-05190457 is a well-tolerated first-in-class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing. Blocking ghrelin receptors inhibits ghrelin-induced GH, and increases heart rate, effects that underwent tachyphylaxis with chronic dosing. PF-051940457 has the potential to treat centrally-acting disorders such as insomnia.


Correlation between Visual Acuity, Inner Segment/Outer Segment Junction, and Cone Outer Segment Tips Line Integrity in Uveitic Macular Edema.
To investigate the correlation between best-corrected visual acuity (BCVA), the foveal inner segment/outer segment (IS/OS) junction or ellipsoid portion of inner segment (EPIS/ellipsoid zone), and the cone outer segment tips (COST) line or interdigitation zone integrity in eyes with uveitic macular edema (ME). A retrospective observational study involving all patients from January 2012 to December 2013 with uveitic ME was performed. All patients underwent BCVA using Snellen charts spectral-domain optical coherence tomography (SD-OCT) examination using Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). Fifty-two eyes from 45 patients were included in this study. Multivariate analysis showed a negative correlation between BCVA and the central retinal subfield thickness (CST), the cystoid pattern of edema, and the interdigitation zone interruption. Univariate logistic analysis showed a strong correlation between the ellipsoid zone and the interdigitation zone integrity. The ellipsoid zone defect, the interdigitation zone interruption, and the CST are correlated with poor vision. Visual acuity is also strongly affected by the cystoid pattern. The interdigitation zone integrity appears to be the most important factor in the visual prognosis of uveitic ME.


[Cervical chemodectoma disclosed by coma. Pathogenic hypotheses].
The authors reported a case of cervical paraganglioma. Patient had a coma suggesting secretary activity of the lesion or cerebral venous thrombosis. Angiography showed an hypervascular lesion characterized by venous reflux into the contro-lateral sinus. After neurological stabilization by tumor embolization, the tumor was surgically removed.


Lung cancer histologic type and family history of cancer.
The authors studied 300 patients with pathologically confirmed cancer of the trachea, bronchus, or lung in a 16-parish (county) area of southern Louisiana. Squamous-cell carcinoma was observed most frequently among these patients (39.3%), with nearly equal numbers of adenocarcinoma (25.0%) and small cell varieties (25.5%). Patients with large cell cancer, the least frequent type (10.3%), were 4.6 years younger on average than those with small cell (P less than 0.05) or squamous cell (P less than 0.05) neoplasias. Squamous cell neoplasia was more frequent among men (45.5%) than women (22.0%) (P less than 0.05). To assess whether family history differed according to the histologic cell type of the index family member, 248 patients were interviewed with regard to a family history of neoplasia. Those with small cell cancer had the highest family-size adjusted mean number of lung cancers per family (0.28). This was 2.2 times greater than the mean number of affected persons among relatives of patients with adenocarcinoma and 1.5 times greater than the mean for the families of patients with large or squamous cell types. However, none of these differences was statistically significant. Similar results were obtained when the total number of cancers at all sites was tabulated. Probands with small cell neoplasia were again most likely to have a positive family history, but the differences between histologic types were small. Although these data suggest an association, a larger study sample is required to determine conclusively whether or not a family history of lung cancer differs according to histologic type.


Localization of the human tripeptidyl peptidase II gene (TPP2) to 13q32-q33 by nonradioactive in situ hybridization and somatic cell hybrids.
We have assigned the human tripeptidyl peptidase II (TPP2) gene to chromosome region 13q32-q33 using two different methods. First, a full-length TPP2 cDNA was used as a probe on Southern blots of DNA from a panel of human/rodent somatic cell hybrids. The TPP2 sequences were found to segregate with the human chromosome 13. Second, fluorescence in situ hybridization analysis was performed with the same probe. This analysis supported the chromosome 13 localization and further refined it to region 13q32-q33.


c-erbB-3: a nuclear protein in mammary epithelial cells.
c-erbB receptors are usually located in cell membranes and are activated by extracellular binding of EGF-like growth factors. Unexpectedly, using immunofluorescence we found high levels of c-erbB-3 within the nuclei of MTSV1-7 immortalized nonmalignant human mammary epithelial cells. Nuclear localization was mediated by the COOH terminus of c-erbB-3, and a nuclear localization signal was identified by site-directed mutagenesis and by transfer of the signal to chicken pyruvate kinase. A nuclear export inhibitor caused accumulation of c-erbB-3 in the nuclei of other mammary epithelial cell lines as demonstrated by immunofluorescence and biochemical cell fractionation, suggesting that c-erbB-3 shuttles between nuclear and nonnuclear compartments in these cells. Growth of MTSV1-7 on permeable filters induced epithelial polarity and concentration of c-erbB-3 within the nucleoli. However, the c-erbB-3 ligand heregulin beta1 shifted c-erbB-3 from the nucleolus into the nucleoplasm and then into the cytoplasm. The subcellular localization of c-erbB-3 obviously depends on exogenous stimuli and on the stage of epithelial polarity and challenges the specific function of c-erbB-3 as a transmembrane receptor protein arguing for additional, as yet unidentified, roles of c-erbB-3 within the nucle(ol)us of mammary epithelial cells.


Simple acoustic grating modulators.
Simple low-cost modulators based on the Raman-Nath regime of acoustooptic diffraction have been demonstrated. Experimental results on internal laser modulators constructed from some dense flint glasses and fused quartz are presented. 100% modulation of He-Ne lasers with rise times on the order of 1 musec are obtained with 10-MHz modulator drive powers of 100 mW. The theory necessary for the design of this class of modulators is reviewed and compared with the experiments.


Demographic, clinical, and functional factors associated with antidepressant use in the home healthcare elderly.
Determine rates and demographic, clinical, and functional correlates of antidepressants (ADs) in home healthcare patients. Year 2007 cross-sectional National Home Health and Hospice Care Survey (N = 3,226) of patients 65 years or older (mean 80.11, confidence interval [CI] = 79.65-80.57). Overall 33.50% used ADs. Among the 6.76% with depression, 70.84% used ADs compared with 29.15% who used ADs without a documented depression diagnosis. In a regression, controlling for depression, blacks used less ADs than whites (odds ratio [OR] = 0.41, CI = 0.24-0.70). Younger age (OR = 0.96, CI = 0.94-0.98), activities of daily living impairments (OR = 1.15, CI = 1.05-1.26), benzodiazepines (OR = 2.63, CI = 1.88-3.69), antipsychotics (OR = 2.08, CI = 1.29-3.36), and nonpsychotropics (OR = 1.07, CI = 1.04-1.10) were related to AD use. Among home healthcare patients, more than one-third took ADs including patients without depression. Blacks used fewer ADs than whites. Increased use was associated with younger age, disability, and nonpsychotropics.


[Localization and extent of tissue damage caused by extracorporeal lithotripsy (ESWL)].
Extracorporeal shock wave lithotripsy (ESWL) causes proteinuria. In our study we investigated the protein fractions and the electrolyte composition of the urine in patients who had been treated with ESWL. The aim was to obtain information on the degree and the localisation of the glomerular, tubular or vascular destruction caused by ESWL in humans. A total of 34 patients with stones had been treated with ESWL. As parameters we used: urine output, creatinine clearance, total protein, albumin, immunoglobulin G, N-acetyl-beta-D-glucosaminidase (beta-NAG), alpha-1-microglobulin, the fractional excretion of Na+ and apolipoprotein-A-1. After ESWL treatment proteinuria and albuminuria are found. Our parameters show no deterioration of the glomerula or the tubulus. The increase in apolipoprotein-A-1, a postglomerular parameter, however, is interpreted as a manifestation of vascular destruction after ESWL; this is normally temporary, leaving no permanent damage.


Sustained manual abdominal compression during cardiopulmonary resuscitation in a pig model: a preliminary investigation.
The present study was undertaken to determine whether sustained manual abdominal compression (SMAC) using left paramedian compression technique can improve coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) and resuscitation outcomes without causing liver laceration. Ventricular fibrillation was induced in 14 pigs, and circulatory arrest was maintained for 6 min. Animals were resuscitated either by standard CPR (control group) or by standard CPR with SMAC (SMAC-CPR group). Mean blood pressure, aortic diastolic pressure and right atrial diastolic pressure in the SMAC-CPR group were significantly greater than in the control group throughout simulated basic life support. However, since the increases in aortic and right atrial diastolic pressures were similar, no significant intergroup difference was found in terms of CPP. Return of spontaneous circulation (ROSC) was attained in four of seven animals in the control group and in six of seven animals in the SMAC-CPR group (p = 0.55). Three animals in the control group and four in the SMAC-CPR group survived 24 h after ROSC (p = 1.00). Two of the seven animals in the SMAC-CPR group had a ruptured liver, but no such injury occurred in the control group. SMAC using left paramedian compression technique failed to improve CPP during CPR and resuscitation outcomes. Furthermore, this method could not avoid liver laceration.


Effects of material hydrophobicity on physical properties of polymeric microspheres formed by double emulsion process.
Human serum albumin (HSA) was encapsulated as a model protein in microspheres of biodegradable and biocompatible polymers by the water-in-oil-in-water (w/o/w) emulsion solvent extraction/evaporation (double emulsion) technique for purpose of controlled release. To improve the properties and control the rate of drug release of the delivery vehicle, materials with different hydrophobicity from that of their conventional counterparts, such as poly(lactide-co-ethylene glycol) (PELA) in place of poly(lactide-co-glycolide) (PLGA) as the polymer matrix, ethyl acetate/acetone in place of dichloride methane (DCM) as the (co)solvent and d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as the additive, were used to prepare the microspheres. It has been found that PELA microspheres, compared with PLGA ones, were slightly smaller in size if prepared at identical emulsification strength. They had more porous surface and internal structure, higher encapsulation efficiency (EE) and more rapid in vitro release rate. Furthermore, the physical properties of the microspheres were also affected by the presence of solvents and additives and their properties. Our results suggest that these materials could have interesting potential applications in preparation of polymeric microspheres for controlled protein release.


Tumor vascularization: assessment with duplex sonography.
In this prospective study, the authors examined 123 patients with benign or malignant neoplasms (breast cancer, n = 44; liver neoplasms, n = 43; and tumors affecting other organs, n = 36) to establish general criteria for evaluation of neoplastic lesions by means of duplex sonography. The frequency shifts determined by means of different Doppler frequencies (2.31 or 3.75 MHz) were converted into flow velocities. Only the highest systolic peak flow velocity obtained from a lesion was used for statistical evaluation. Receiver operating characteristic curves showed that a flow velocity of 0.4 m/sec is the optimal threshold value with which to differentiate benign from malignant tumors. The data obtained in all lesions indicated that only positive findings are potentially reliable. It is concluded that negative results of sonography should not be used to diagnose the presence of a benign lesion. The resistive index of the tumors was of negligible importance.


The brain in the 18q-syndrome.
The authors describe the cerebral neuropathological findings of a 25 1/2-year-old male with 18q-syndrome. An abnormal gyral pattern, atrophy of the olfactory and optic nerves and small neocerebellar hemispheres with hemispheral lobular sclerosis were noted. Microscopically there were pial glioneuronal heterotopias; misplacement of neurons in the molecular layer of the cortex, as well as in deep white matter; not readily identifiable Betz cells; gliosis of olfactory and optic tracts and elsewhere; and loss of Purkinje cells. Further detailed studies of other cases are needed to determine whether these abnormalities are characteristic of the 18q-syndrome.


[Small intestinal plasmacytoid lymphoma. Clinical presentation with acute abdominal pain].
Primary tumors of the small intestine are rare; 15-20% of the cases are extranodal lymphomas from B or T cells. Higher Incidence occurs in patients between 21 and 50 years. The clinical symptoms are pain, intestinal obstruction, diarrhea, bleeding or perforated peritonitis. In high-grade lymphomas, the cells are large and pleomorphic, with immunoblastic and plasmacytoid features, and immunopositive for alpha chain immunoglobulins. We reported the case of a 56-year-old patient presented with abdominal pain associated with intestinal perforation. Resections of a 9-centimetres-long segment in the small intestine was performed, which was covered by purulent plaques, with a perforation of 5 mm, surrounded by a greyish-white thick intestinal wall. It can be observed in the microscopy a proliferation of neoplastic cells arranged diffusely and with frequent mitosis. Large areas of immunoblastic and plasmacytoid configuration were evident. The immunomarcation was consistent with a lymphoma of large cells, immunophenotype B, with plasmacytoid development. We highlighted the clinical presentation like acute abdominal pain and its clinical and pathological characteristics, especially in the plasmacytoid development that should differ of the true plasmocytoma.


Can a virtual patient trainer teach student nurses how to save lives--teaching nursing students about pediatric respiratory diseases.
Virtual environments offer a variety of benefits and may be a powerful medium with which to provide nursing education. The objective of this study was to compare the achievement of learning outcomes of undergraduate nursing students when a virtual patient trainer or a traditional lecture was used to teach pediatric respiratory content. This was a randomized, controlled, posttest design. A virtual pediatric hospital unit was populated with four virtual pediatric patients having different respiratory diseases that were designed to meet the same learning objectives as a traditional lecture. The study began in Spring 2010 with 93 Senior I, baccalaureate nursing students. Students were randomized to receive either a traditional lecture or an experience with a virtual patient trainer. Students' knowledge acquisition was evaluated using multiple-choice questions, and knowledge application was measured as timeliness of care in two simulated clinical scenarios using high-fidelity mannequins and standardized patients. Ninety-three students participated in the study, of which 46 were in the experimental group that received content using the virtual patient trainer. After the intervention, students in the experimental group had significantly higher knowledge acquisition (P = 0.004) and better knowledge application (P = 0.001) for each of the two scenarios than students in the control group. The purpose of this project was to compare a virtual patient trainer to a traditional lecture for the achievement of learning outcomes for pediatric respiratory content. Although the virtual patient trainer experience produced statistically better outcomes, the differences may not be clinically significant. The results suggest that a virtual patient trainer may be an effective substitute for the achievement of learning outcomes that are typically met using a traditional lecture format. Further research is needed to understand how best to integrate a virtual patient trainer into undergraduate nursing education.