Relative Abundance of apoE and Aβ1-42 Associated with Abnormal Prion Protein Differs between Creutzfeldt-Jakob Disease Subtypes.
Aggregated and protease-resistant mammalian prion protein (PrPSc) is the primary protein component of infectious prions. Enriched PrPSc preparations are often used to study the mechanisms that underly prion disease. However, most enrichment procedures are relatively nonspecific and tend to yield significant amounts of non-PrPSc components including various proteins that could confound functional and structural studies. It is thus important to identify these proteins and assess their potential relevance to prion pathogenesis. Following proteinase K treatment and phosphotungstic acid precipitation of brain homogenate, we have used mass spectrometry to analyze the protein content of PrPSc isolated from prion-infected mice, multiple cases of sporadic Creutzfeldt-Jakob disease (sCJD), and human growth hormone associated cases of iatrogenic CJD (iCJD). Creatine kinase was the primary protein contaminant in all PrPSc samples, while many of the other proteins identified were also found in non-CJD controls, which suggests that they are not CJD specific. Interestingly, the Alzheimer's disease associated peptide amyloid β 1-42 (Aβ1-42) was identified in the majority of the sCJD cases as well as non-CJD age-matched controls, while apoliprotein E was found in greater abundance in the sCJD cases. By contrast, while some of the iCJD cases showed evidence of higher molecular weight Aβ oligomers, monomeric Aβ1-42 peptide was not detected by immunoblot, and only one case had significant levels of apolipoprotein E. Our data are consistent with the age-associated deposition of Aβ1-42 in older sporadic CJD and non-CJD patients and suggest that both apolipoprotein E and Aβ1-42 abundance can differ depending upon the type of CJD.


Oxygenation of cobalt porphyrinates: coordination or oxidation?
The X-ray characterization of the five-coordinate picket-fence porphyrin complex, [Co(TpivPP)(2-MeHIm)], is reported. The complex has the displacement of cobalt from the porphyrin plane = 0.15 A, and Co-N(Im) = 2.145(3) and (Co-N(p))(av) = 1.979(3) A. This five-coordinate complex, in the presence of dioxygen and excess 2-methylimidazole, undergoes an unanticipated, photoinitiated atropisomerization of the porphyrin ligand, oxidation of cobalt(II), and the formation of the neutral cobalt(III) complex [Co(alpha,alpha,beta,beta-TpivPP)(2-MeHIm)(2-MeIm(-)]. Two distinct examples of this complex have been structurally characterized, and both have structural parameters consistent with cobalt(III). The two new Co(III) porphyrin complexes have axial Co-N(Im) distances ranging from 1.952 to 1.972 A, but which allow for the distinction between imidazole and imidazolate. An interesting intermolecular hydrogen bonding network is observed that leads to infinite helical chains. UV-vis spectroscopic study suggests that [Co(TpivPP)(2-MeHIm)(O(2))] is an intermediate state for the oxidation reaction and that the atropisomerization process is photocatalyzed. A reaction route is proposed based on the spectroscopic studies.


Implementation of biologically conformal radiation therapy (BCRT) in an algorithmic segmentation-based inverse planning approach.
The development of new biological imaging technologies offers the opportunity to further individualize radiotherapy. Biologically conformal radiation therapy (BCRT) implies the use of the spatial distribution of one or more radiobiological parameters to guide the IMRT dose prescription. Our aim was to implement BCRT in an algorithmic segmentation-based planning approach. A biology-based segmentation tool was developed to generate initial beam segments that reflect the biological signal intensity pattern. The weights and shapes of the initial segments are optimized by means of an objective function that minimizes the root mean square deviation between the actual and intended dose values within the PTV. As proof of principle, [(18)F]FDG-PET-guided BCRT plans for two different levels of dose escalation were created for an oropharyngeal cancer patient. Both plans proved to be dosimetrically feasible without violating the planning constraints for the expanded spinal cord and the contralateral parotid gland as organs at risk. The obtained biological conformity was better for the first (2.5 Gy per fraction) than for the second (3 Gy per fraction) dose escalation level.


Ligamentum Flavum Cyst: Rare Presentation Report and Literature Review.
Ligamentum flavum cysts (LFC) are uncommon and their differentiation from other Juxta-facetal cysts & epidural cystic lesions is difficult based on imaging techniques. We present one such rare case of ligamentum flavum cyst with relevant review of the literature. An eighty-eight years male presented with progressively worsening radicular symptom in the left lower limb. His neurological examination was unremarkable. Magnetic resonance imaging of lumbar spine revealed an epidural cystic lesion narrowing the left lateral recess. Intra-operatively, a mass was found originating from ventral surface of ligamentum flavum. Pathological examination was suggestive of fibro-collagenous tissue without synovial lining. The exact pathogenic mechanism for the formation of LFCs is not well understood. Association with segmental instability and degenerative conditions of spine is postulated. They are commonly seen at the mobile junctional levels of the spine. Persistent micro-traumatic events with abnormal movement maybe contributory to their origin. They present either with radiculopathy or neurogenic claudication symptoms owing to compressive effect on adjacent neural structure. LFC should be considered as a differential in patients with radicular pain or claudication symptoms with epidural cystic lesion seen on MRI. Complete excision of such lesion provides excellent pain relief in symptomatic individuals.


Cadmium and manganese hypophosphite perovskites templated by formamidinium cations: dielectric, optical and magnetic properties.
The recently discovered hypophosphite perovskites are promising functional materials. This contribution is devoted to the structural, thermal, dielectric, Raman and optical studies of a new hybrid organic-inorganic perovskite, [FA]Cd(H2POO)3 (FA = formamidinium, NH2CHNH2+). We also report the thermal, magnetic, dielectric and optical properties of the known perovskite [FA]Mn(H2POO)3. [FA]Cd(H2POO)3 crystallizes in a monoclinic structure, with the space group C2/c, and transforms at 190 K to another monoclinic structure, with the space group P21/n. For both compounds, the FA+ is disordered through the two-fold axis in the high-temperature (HT) phases. However, lowering of the temperature of [FA]Mn(H2POO)3 results in the complete ordering of FA+, while the organic cations still occupy two positions in [FA]Cd(H2POO)3. Raman data provide strong evidence that both FA+ cations have the same or a very similar structure and that the phase transition is triggered by an ordering of the FA+ cations. The dielectric studies confirm the order-disorder nature of the phase transition and reveal the presence of two dipolar relaxations observed in the 320-220 K range and near the phase transition temperature. The low-temperature (LT) process exhibits the classical Arrhenius-type behaviour, whereas the behaviour of the HT relaxation suggests glass-like behaviour. Magnetic studies show that [FA]Mn(H2POO)3 is an example of a canted antiferromagnet with a low ordering temperature of 2.4 K. Diffuse reflectance studies show that the Mn (Cd) hypophosphite is a wide bandgap material with Eg = 5.20 eV (5.42 eV). Upon ultraviolet excitation (266 nm), [FA]Mn(H2POO)3 exhibits reddish-orange emission at 656 nm associated with the 4T1g(G) →6A1g(S) transition of octahedrally coordinated Mn2+ ions. [FA]Cd(H2POO)3 shows significantly weaker purplish-blue emission at low temperatures composed of two bands at 425 and 443 nm, which are almost completely quenched at 160 K. For both compounds, CIE chromaticity coordinates show negligible change with temperature. Furthermore, the intensity of the observed emissions decreases quickly with increasing temperature, suggesting the possible application of [FA]Mn(H2POO)3 in non-contact optical thermometry.


Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.
The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period.


[Variation analysis of EPG5 gene in a Vici syndrome family].
To explore the genetic etiology of Vici syndrome in a Chinese family. Whole exome sequencing (WES) technology was used to detect gene variants in a fetus of abnormal ultrasonic structure without abnormalities in routine chromosome karyotype analysis and SNP-array. Sanger sequencing and bioinformatics prediction were performed for the suspected variants of the fetus and parents. The fetus and the elder sister have carried c. 2427delC (p.T809fs) and c.1886A>T (p.E629V) compound heterozygous variants of the EPG5 gene, which were respectively inherited from their mother and father. Neither variant was reported previously. According to ACMG guidelines, the c.2427delC variant was predicted as pathogenic, while the c.1886A>T variant was of uncertain significance. PolyPhen-2 and PROVEAN software indicated that c.1886A>T variant was probably damaging. The c.2427delC and c.1886A>T variants of the EPG5 gene probably underlie the pathogenesis of the Vici syndrome in this family. Above finding has enriched the variational spectrum of EPG5 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.


[Java's large population: two centuries of explanations].
"Explanation of demographic imbalance between Java and the socalled 'Outer-Islands' has been numerous for almost two centuries. Authors generally considered that the great density of population was a direct consequence of the high fertility of Javanese soils. Some of them, however, connected it with an early economical 'take-off'. But none of these analyses can explain why marginally suitable regions from an agricultural point of view were overcrowded especially when their economical development was low. We propose another explanation scheme on an historical basis." (SUMMARY IN ENG)


Free radicals in the neurotoxic actions of beta-amyloid.
The fragment of the beta-amyloid protein that contains the peptide sequence 25 to 35 of the parent compound, increases cytosolic calcium and is directly cytotoxic to neurons in tissue culture. The cytotoxic action of beta-amyloid has been considered to be the primary determinant of the neurodegeneration observed in Alzheimer's disease. The cytotoxic effects of beta-amyloid 25-35 or beta-amyloid 1-40 added to primary cultures of rat hippocampal or cortical neurons can be reduced or prevented by anti-oxidant lazaroid drugs such as U-74500A, U-78517F, or U-83836E. beta-amyloid 25-35 evokes an immediate increase in cytosolic calcium when added to suspensions of PC 12 cells, and is cytotoxic to PC 12 cells in tissue culture. Both the calcium-elevating and the cytotoxic actions of beta-amyloid 25-35 on PC 12 cells are reduced or prevented by lazaroid anti-oxidant drugs. Since the lazaroids have been shown to scavenge free radical species, the present results indicate that the actions of beta-amyloid 25-35 on calcium regulation and on cell survival are mediated by free radicals.


Telemedicine Service Adoption During the COVID-19 Pandemic: Physicians' Experience from Nigeria.
Introduction: Telemedicine practice experiences during the COVID-19 pandemic have not been well documented in resource-constrained settings, such as Nigeria. We set out to assess knowledge, attitude, and factors associated with telemedicine practice during the COVID-19 lockdown, as well as physician experiences in Kano, Nigeria. Methods: We employed a mixed-methods approach, utilizing structured questionnaires administered to 246 physicians, followed by in-depth interviews with a purposive subsample of 20 individuals. The data were analyzed using logistic regression and the framework approach. Results: Overall, 65.0% of the respondents demonstrated moderate to good knowledge of telemedicine. Before COVID, only 47.6% (n = 117) reported practicing telemedicine, compared with 77.2% (n = 190) during the COVID lockdown (p < 0.05). Factors associated with telemedicine practice included having at least 5 years of work experience, working in pediatrics, undergoing senior residency training, receiving formal telemedicine training, possessing good knowledge of telemedicine, and having a positive attitude toward it. The odds of engaging in telemedicine practice were four times higher (adjusted odds ratio = 4.10, 95% confidence interval: 1.79-9.40) for those who practiced it before the pandemic. Challenges identified included knowledge and skill gaps, slow internet connectivity, unstable electricity, and inadequate equipment. Conclusion: To enhance telemedicine practice in resource-limited settings, it is important to focus on strengthening information and communication infrastructure, providing comprehensive clinician training, implementing careful patient selection processes, and improving practice guidelines.


Harm Reduction and Moral Desert in the Context of Drug Policy.
The target of my discussion is intuitions lay people have about justice in the context of drug policy-intuitions that take on a more or less moral-desert-based shape. I argue that even if we think desert is the right measure of how we ought to treat people, we ought still be in favour of Harm Reduction measures for people who use drugs. Harm Reduction measures are controversial with members of the public, and much of the opposition seems to come from something like an appeal to a desert conception of justice-the notion that a just state of affairs is one in which everybody gets what they deserve, no more, no less. A recent study, for example, found that 'moral outrage' predicts a preference for prevalence reduction (criminal sanction, etc.) over Harm Reduction. The thinking seems to be that, since drug use is wrong, letting people who use drugs suffer and/or die as a consequence of their use is just. Aiding their health and safety, while perhaps compassionate, is unjust. I argue that there is a bad desert fit between using drugs and suffering avoidable harm even if using drugs is morally wrong. Many of the possible harms of drug use are socially/policy driven, and much problematic drug use is context dependent, not cleanly attributable to the decisions of the person who uses drugs. This means that even if drug use is wrong, people who use drugs deserve Harm Reduction policies, at minimum.


Bidentate Phosphine-Assisted Synthesis of an All-Alkynyl-Protected Ag74 Nanocluster.
Determining the total structure of metal nanoparticles is vital to understand their properties. In this work, the first all-alkynyl-protected Ag nanocluster, Ag74(C≡CPh)44, was synthesized and structurally characterized by single crystal diffraction. Ag atoms are arranged in a Ag4@Ag22@Ag48 three shell structure and all 44 phenylethynyl ligands coordinated with Ag in a μ3 mode. In spite of being absent in nanocluster, 31P NMR study reveals that bidentate phosphine first reacts with Ag(I) to form a dinuclear complex, from which Ag atoms are then released to phenylethynyl ligands. This phosphine mediated strategy may find general application in synthesis of alkynyl-protected Ag nanoclusters.


How many species of woolly monkeys inhabit Colombian forests?
There is a controversy regarding how many species the genus Lagothrix contains, since the Lagothrix lagothricha subspecies have been recently proposed to be actual species. Clarification of species status is of particular importance in the case of L. l. lugens, because it is the most endangered and its distribution is restricted to the Colombian Andes, a highly deforested region. Using cytogenetic and molecular markers, we obtained evidence indicating that the subspecies status is appropriate for the two taxa occurring in this country. We also report high levels of intraspecific variability in the karyotype. We find evidence for a late Pleistocene separation of the subspecies, and we propose it is the limited area of contact between the taxa that allowed for them to partially differentiate.


Psychological Changes of Music and Fine Arts Students in the Education Process: A Comparative Longitudinal Study.
This study aimed to determine the changes in psychological distress, anxiety, and depressive symptoms in students from the fine arts faculty in the first 2 years of their education in Turkey, in comparison with students from other faculties, and to reveal the causes of psychological distress, anxiety, and depression in fine arts students. The General Health Questionnaire (GHQ-12), Beck Depression Inventory (BDI), and Spielberger State-Trait Anxiety Inventory (STAI) were applied to students from Faculty of Fine Arts and the Faculties of Economics and Sport Sciences (controls) in the first week of the 2017-2018 academic year. Students also completed a questionnaire measuring their possible stressful life events (at timepoint T1). The process was repeated for the same students in the second year (T2). The changes between the two time¬points were examined prospectively. A total of 96 fine arts students agreed to participate at T1 and 66 at T2 (68.8%); for the controls, it was 259 at T1 and 182 (70.3%) at T2. The fine arts students at T1 included 15 music majors, 45 cinema and television, and 36 handi¬crafts, sculpture, and painting. Their average age at T1 was 21.0 yrs (SD 5.8) and 54.2% were male; for the other students, it was 19.4 yrs (2.7) and 56.0% male. Fine arts students' GHQ-12 score averages increased significantly from T1 to T2 (11.7 to 14.3, p=0.002). Their BDI score averages increased from 10.3 to 12.3 (p=0.044). Moreover, their S-Anxiety score averages increased from 41.1 at T1 to 44.1 at T2 (p=0.008). However, the increase in T-Anxiety scores was not statistically significant. None of the control students' test scores varied between the two timepoints (p>0.05). At T2, for fine arts students, there was no significant difference between female and male students in terms of GHQ-12, BDI, and S-Anxiety scores. However, T-anxiety scores were higher in female students. By linear regression analysis, "worrying about the future (individual)" was found to be a determinant on all scale scores in fine arts students. The psychological indicators increased significantly in fine arts students during the first year of their education.


Early experience with transmyocardial laser revascularization.
Conventional treatment of coronary artery disease consists of either Coronary Artery Bypass Grafting (CABG), medical therapy or percutaneous transluminal coronary angioplasty (PTCA) or a combination. However, certain group of patients do not even qualify for CABG. Transmyocardial Laser Revascularization (TMR) is a unique new surgical modality specially for that sub group of patient population who have small and diffuse coronary artery disease not suitable for grafting. King Fahad Heart Center initiated its TMR program in February, 1994 and until February, 1996, 100 patients under went the TMR procedure. Eighty-one were males and 19 females with a mean average age of 55 years. Seventy-nine patients had 3 vessel disease (VD) and 66 patients had non-graftable small vessels. Ten patients had left ventricular ejection fraction (LVEF) less than 30%. All the patients underwent a strict protocol of follow-up. The pre and post TMR assessment at six months and 12 months follow-up showed an increase in LVEF at six and 12 months as compared to pre TMR level. The exercise time also increased from a base line level at six months and showed further improvement at 12 months which was statistically significant (p < 0.05) along-with VO2 max, which also showed improvement. Clinically, haemodynamically and symptomatically these patients showed significant improvement and use of anti-anginal drugs (87%) was reduced to minimum. Isotope myocardial perfusion scan on 15 segment viability score showed an improvement from pre TMR level of 33.8 to 45.9 at post TMR 12 months follow up. The surgical mortality in this high risk TMR population was 10%. TMR was found to be a reasonable alternative to medical treatment in patients with angina due to diffuse and or small vessel disease or occluded previous grafts not amenable to CABG.


Infant and young child feeding indicators and determinants of poor feeding practices in India: secondary data analysis of National Family Health Survey 2005-06.
In India, poor feeding practices in early childhood contribute to the burden of malnutrition and infant and child mortality. To estimate infant and young child feeding indicators and determinants of selected feeding practices in India. The sample consisted of 20,108 children aged 0 to 23 months from the National Family Health Survey India 2005-06. Selected indicators were examined against a set of variables using univariate and multivariate analyses. Only 23.5% of mothers initiated breastfeeding within the first hour after birth, 99.2% had ever breastfed their infant, 89.8% were currently breastfeeding, and 14.8% were currently bottle-feeding. Among infants under 6 months of age, 46.4% were exclusively breastfed, and 56.7% of those aged 6 to 9 months received complementary foods. The risk factors for not exclusively breastfeeding were higher household wealth index quintiles (OR for richest = 2.03), delivery in a health facility (OR = 1.35), and living in the Northern region. Higher numbers of antenatal care visits were associated with increased rates of exclusive breastfeeding (OR for 2 7 antenatal visits = 0.58). The rates of timely initiation of breastfeeding were higher among women who were better educated (OR for secondary education or above = 0.79), were working (OR = 0.79), made more antenatal clinic visits (OR for 2 7 antenatal visits = 0.48), and were exposed to the radio (OR = 0.76). The rates were lower in women who were delivered by cesarean section (OR = 2.52). The risk factors for bottle-feeding included cesarean delivery (OR = 1.44), higher household wealth index quintiles (OR = 3.06), working by the mother (OR = 1.29), higher maternal education level (OR = 1.32), urban residence (OR = 1.46), and absence of postnatal examination (OR = 1.24). The rates of timely complementary feeding were higher for mothers who had more antenatal visits (OR = 0.57), and for those who watched television (OR = 0.75). Revitalization of the Baby Friendly Hospital Initiative in health facilities is recommended. Targeted interventions may be necessary to improve infant feeding practices in mothers who reside in urban areas, are more educated, and are from wealthier households.


Comprehensive Cluster Analysis for COPD Including Systemic and Airway Inflammatory Markers.
Chronic obstructive pulmonary disease (COPD) is a complex, multidimensional and heterogeneous disease. The main purpose of the present study was to identify clinical phenotypes through cluster analysis in adults suffering from COPD. A retrospective study was conducted on 178 COPD patients in stable state recruited from ambulatory care at University hospital of Liege. All patients were above 40 years, had a smoking history of more than 20 pack years, post bronchodilator FEV1/FVC <70% and denied any history of asthma before 40 years. In this study, the patients were described by a total of 84 mixed sets of variables with some missing values. Hierarchical clustering on principal components (HCPC) was applied on multiple imputation. In the final step, patients were classified into homogeneous distinct groups by consensus clustering. Three different clusters, which shared similar smoking history were found. Cluster 1 included men with moderate airway obstruction (n = 67) while cluster 2 comprised men who were exacerbation-prone, with severe airflow limitation and intense granulocytic airway and neutrophilic systemic inflammation (n = 56). Cluster 3 essentially included women with moderate airway obstruction (n = 55). All clusters had a low rate of bacterial colonization (5%), a low median FeNO value (<20 ppb) and a very low sensitization rate toward common aeroallergens (0-5%). CAT score did not differ between clusters. Including markers of systemic airway inflammation and atopy and applying a comprehensive cluster analysis we provide here evidence for 3 clusters markedly shaped by sex, airway obstruction and neutrophilic inflammation but not by symptoms and T2 biomarkers.


Biochemical markers of recombinant human insulin-like growth factor-I (rhIGF-I)/rhIGF binding protein-3 (rhIGFBP-3) misuse in athletes.
Insulin-like growth factor-I (IGF-I) is reportedly misused by elite athletes, either alone or with growth hormone (GH). The GH-2000 and GH-2004 research groups previously developed a method for detecting GH misuse based on the GH-sensitive markers IGF-I and procollagen type III amino-terminal propeptide (P-III-NP). Both markers increase in response to rhIGF-I/rhIGF binding protein-3 (rhIGFBP-3) administration in recreational athletes. The aim of this pilot study was to assess the effect of rhIGF-I/rhIGFBP-3 administration on other serum markers of the GH-IGF axis and on other bone and collagen markers. Twenty-six female and 30 male recreational athletes were randomized to 28 days' treatment with placebo or rhIGF-I/rhIGFBP-3 complex, followed by 56 days' washout. GH-IGF axis markers (IGFBP-2, IGFBP-3, acid-labile subunit (ALS) and IGF-II) and bone and collagen markers (procollagen type I carboxy-terminal propeptide (PICP), type I collagen cross-linked carboxy-terminal telopeptide (ICTP) and osteocalcin) were measured using commercial immunoassays. In women in the high dose treatment group, mean IGF-II decreased by 53% (P=0.0028) on Day 21. Mean IGFBP-2 increased by 119% (P=0.0039) and mean ALS decreased by 40% (P=0.0022) on Day 21. There were no significant changes in IGFBP-3, osteocalcin, ICTP or PICP. In men in the high dose group, mean IGF-II decreased by 51% on Day 21 (P<0.0001). Mean IGFBP-2 increased by 125% on Day 21 (P=0.0003). There were no significant changes in IGFBP-3, ALS, osteocalcin, ICTP or PICP. Serum IGFBP-2 and IGF-II may be useful markers of rhIGF-I/rhIGFBP-3 administration in both women and men while ALS may also be a useful marker in women; these markers are now undergoing further evaluation.


Topographical variation of the human primary cortices: implications for neuroimaging, brain mapping, and neurobiology.
The relationships of the "primary" cytoarchitectonic neocortical fields, 17, 41, 3b, and 4 (Brodmann areas), to salient topographic landmarks have been reconstructed from serial histological sections in 20 human cerebral hemispheres (10 brains). Each of these architectonic fields is found to bear a characteristic relationship to a set of enframing anatomic landmarks, in particular, gyri, fissures, and sulci, that can be readily defined by MRI. Two classes of variability were found characteristic, at least to some extent, of each of the fields. Class 1 variability--variability that is not predictable from visible landmarks--was typical of the polar and for the cuneal and lingual extracalcarine distributions of field 17 and the distribution of field 4 upon the paracentral lobule. Class 2 variability--variability that is closely predictable from visible landmarks--is seen in the marked interindividual or interhemispheric variation in size or shape of a field and was found to be prominent for all four fields. Because of the prominence of class 2 variability, direct reference to the landmarks that frame these fields may be expected to be a more reliable basis for functional mapping than reference to a template or stereotactic coordinate-based system of reference to a standard or idealized brain.


Successful Treatment with Integrated Chinese and Western Medicine for Massive Colchicine Overdose: A Case Report.
A 42-year-old male was hospitalized 13.5 hours after ingestion of 50 mg (approximately 0.7 mg/kg) colchicine in a suicide attempt. The patient developed gastrointestinal dysfunction, grade IV myelosuppression, and restrictive respiratory failure without occurrences of cardiovascular collapse or fatal dysrhythmias. Emergency treatment with integrated Chinese and Western medicine was started and the patient fully recovered without long-term complications. This report describes a massive overdose of colchicine successfully treated with integrated Chinese and Western medicine. Current treatment options are reviewed.


Carvedilol stimulates nitric oxide synthesis in rat cardiac myocytes.
The purpose of this study was to investigate the effects of the beta-adrenergic blocker carvedilol on nitric oxide (NO) synthesis in cardiac myocytes. We measured the accumulation of nitrite, a stable oxidation product of NO, and the expression of inducible NO synthase (iNOS) protein in cultured neonatal rat cardiac myocytes. Incubation of the cultures with interleukin 1 beta (IL-1 beta; 10 ng/ml) caused a marked increase in nitrite production. Although carvedilol alone showed no effect on nitrite accumulation, it significantly enhanced IL-1 beta-induced nitrite production by cardiac myocytes. The effect of carvedilol was completely abolished in the presence of aminoguanidine or actinomycin D. The nitrite production enhanced by carvedilol was accompanied by increased iNOS protein expression. Unlike carvedilol, other beta-blockers, namely propranolol, atenolol and arotinolol, did not enhance IL-1 beta-induced nitrite production. Addition of isoproterenol significantly increased nitrite production by IL-1 beta-stimulated cardiac myocytes. Atenolol suppressed this isoproterenol-induced nitrite accumulation, while carvedilol further increased the nitrite accumulation. These findings indicate that carvedilol increases NO synthesis in IL-1 beta-stimulated rat cardiac myocytes by a beta-adrenoceptor-independent mechanism.


[Granulomatous amebic encephalitis caused by Balamuthia mandrillaris. First case diagnosed in Chile].
The case of a 7 month-old baby boy is presented, with a history of several weeks of evolution of personality changes, convulsions and fever. While he was hospitalized, the brain image study showed multifocal cavity lesions, which varied from millimeters to 4 cm of diameter, not producing mass effect. Their biopsy revealed necrotizing encephalitis. In spite of treatment, the lesions progressed and the boy died. The autopsy demonstrated an extensive necrotizing encephalitis with fibrinoid necrotic arteritis, signs of organization, and the presence of parasitic elements with characteristics of trophozoites and cysts of free-living amoebas belonging to the genus Acanthamoeba or Balamuthia. In addition, hypoplasia-dysplasia of the thymus and signs of shock were found. The morphologic elements correspond to the disease described as granulomatous amebic encephalitis and the agent found was identified as Balamuthia mandrillaris (Centers for Diseases Control and Prevention, Atlanta, USA ).


MDM2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Ablation and Radiotherapy in a p53-Dependent Manner.
Increased murine double minute 2 (MDM2) expression, independent of p53 status, is associated with increased cancer-specific mortality for men with prostate cancer treated with radiotherapy. We assessed MI-219, a small molecule inhibitor of MDM2 with improved pharmacokinetics over nutlin-3, for sensitization of prostate cancer cells to radiotherapy and androgen deprivation therapy, a standard treatment option for men with high-risk prostate cancer. The effect of MDM2 inhibition by MI-219 was assessed in vitro and in vivo with mouse xenograft models across multiple prostate cancer cell lines containing varying p53 functional status. MDM2 inhibition by MI-219 resulted in dose- and time-dependent p53 activation and decreased clonogenic cell survival after radiation in a p53-dependent manner. Mechanistically, radiosensitization following inhibition of MDM2 was largely the result of p53-dependent increases in apoptosis and DNA damage as evidenced by Annexin V flow cytometry and γ-H2AX foci immunofluorescence. Similarly, treatment with MI-219 enhanced response to antiandrogen therapy via a p53-dependent increase in apoptotic cell death. Lastly, triple therapy with radiation, androgen deprivation therapy, and MI-219 decreased xenograft tumor growth compared with any single- or double-agent treatment. MDM2 inhibition with MI-219 results in p53-dependent sensitization of prostate cancer cells to radiation, antiandrogen therapy, and the combination. These findings support MDM2 small molecule inhibitor therapy as a therapy intensification strategy to improve clinical outcomes in high-risk localized prostate cancer. The combination of radiotherapy and androgen deprivation therapy is a standard treatment option for men with high-risk prostate cancer. Despite improvements in outcomes when androgen deprivation therapy is added to radiation, men with high-risk prostate cancer have significant risk for disease recurrence, progression, and even death within the first 10 years following treatment. We demonstrate that treatment with MI-219 (an inhibitor of MDM2) results in prostate cancer cell sensitization to radiation and androgen deprivation therapy in vitro and in vivo. Triple therapy with MI-219, radiation, and androgen deprivation therapy dramatically decreased tumor growth compared with any single- or double-agent therapy. These findings provide evidence that inhibition of MDM2 is a viable means by which to enhance the efficacy of both radiation and androgen deprivation therapy and thereby improve outcomes in the treatment of prostate cancer. As such, further investigation is warranted to translate these findings to the clinical setting.


Study of Karolinska Institutet and Washington University polyomaviruses in tonsil, adenoid, throat swab and middle ear fluid samples.
To study prevalence of Karolinska Institutet (KI) and Washington University (WU) polyomavirus (PyV) in 100 tonsils, 100 adenoids, 146 throat swab and 15 middle ear fluid samples collected from 146 patients (120 children and 26 adults), to analyze the sequence of noncoding control region (NCCR) and complete WUPyV genomes. Viruses were detected by quantitative real-time PCR. The NCCRs and WUPyV genomes were sequenced and analyzed. The frequency of WUPyV and KIPyV DNA was 27 and 11% in adenoids, 4 and 3% in tonsils, 4.1 and 1.4% in throat swab samples, respectively. The WUPyV DNA was detected in one middle ear fluid sample as well. The WUPyV NCCRs showed mutations which may alter the putative transcription factor binding sites. Phylogenetic analysis revealed three clades of WUPyV. Tonsils and adenoids might be site of virus replication and/or persistence, and WUPyV may invade into the middle ear.


Marangoni Convection in Evaporating Organic Liquid Droplets on a Nonwetting Substrate.
We quantitatively characterize the flow field inside organic liquid droplets evaporating on a nonwetting substrate. A mushroom-structured surface yields the desired nonwetting behavior with methanol droplets, while use of a cooled substrate (5-15 °C) slows the rate of evaporation to allow quasi-static particle image velocimetry. Visualization reveals a toroidal vortex within the droplet that is characteristic of surface tension-driven flow; we demonstrate by means of a scaling analysis that this recirculating flow is Marangoni convection. The velocities in the droplet are on the order of 10-45 mm/s. Thus, unlike in the case of evaporation on wetting substrates where Marangoni convection can be ignored for the purpose of estimating the evaporation rate, advection due to the surface tension-driven flow plays a dominant role in the heat transfer within an evaporating droplet on a nonwetting substrate because of the large height-to-radius aspect ratio of the droplet. We formulate a reduced-order model that includes advective transport within the droplet for prediction of organic liquid droplet evaporation on a nonwetting substrate and confirm that the predicted temperature differential across the height of the droplet matches experiments.


Chemotherapy-induced nausea and vomiting. Easing patients' fear and discomfort with effective antiemetic regimens.
Patients receiving chemotherapy should be given optimal antiemetic therapy to maximize their comfort initially and to prevent development of delayed and anticipatory nausea and vomiting. Understanding the mechanisms of chemotherapy-induced nausea and vomiting allows the healthcare team to design drug regimens capable of avoiding these side effects. Prevention is important, because side effects can be debilitating and sometimes dose-limiting, and up to 10% of patients refuse chemotherapy altogether to avoid them. In general, combination antiemetic therapy is preferred over single-agent therapy for chemotherapeutic regimens that produce moderate to severe adverse effects.


The direct and indirect effects of environmental toxicants on the health of bumblebees and their microbiomes.
Bumblebees (Bombus spp.) are important and widespread insect pollinators, but the act of foraging on flowers can expose them to harmful pesticides and chemicals such as oxidizers and heavy metals. How these compounds directly influence bee survival and indirectly affect bee health via the gut microbiome is largely unknown. As toxicants in floral nectar and pollen take many forms, we explored the genomes of bee-associated microbes for their potential to detoxify cadmium, copper, selenate, the neonicotinoid pesticide imidacloprid, and hydrogen peroxide-which have all been identified in floral nectar and pollen. We then exposed Bombus impatiens workers to varying concentrations of these chemicals via their diet and assayed direct effects on bee survival. Using field-realistic doses, we further explored the indirect effects on bee microbiomes. We found multiple putative genes in core gut microbes that may aid in detoxifying harmful chemicals. We also found that while the chemicals are largely toxic at levels within and above field-realistic concentrations, the field-realistic concentrations-except for imidacloprid-altered the composition of the bee microbiome, potentially causing gut dysbiosis. Overall, our study shows that chemicals found in floral nectar and pollen can cause bee mortality, and likely have indirect, deleterious effects on bee health via their influence on the bee microbiome.


Impact of Co-Administration of N-Acetylcysteine and Vitamin E on Cyclophosphamide-Induced Ovarian Toxicity in Female Rats.
Cyclophosphamide is used to treat various types of cancer. However, it can reduce ovarian function and fertility rate. The current study was done to compare the effects of N-acetylcysteine and vitamin E on cyclophosphamide-induced ovarian damage. Thirty-five rats were randomly divided into 5 groups: control (C), cyclophosphamide (CP, 200 mg/kg single dose intraperitoneally), T1 (cyclophosphamide + vitamin E at 200 mg/kg), T2 (cyclophosphamide + 200 mg/kg N-acetylcysteine), and T3 (cyclophosphamide + N-acetylcysteine and vitamin E at 200 mg/kg). The main measurements included total antioxidant capacity (TAC), glutathione peroxidase (GPx), malondialdehyde (MDA), interleukin 8 (IL-8), tumor necrosis factor-α (TNFα), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (ES). Except for the C and T3 groups, the other groups lost weight. A significantly lower concentration of MDA was observed in the T3 group. However, TAC was substantially increased compared to the other groups. The level of GPx in the S group was significantly reduced compared to all groups. Proinflammatory markers (IL-8 and TNFα) reached their lowest serum level in the T3 group, with a statistically significant difference compared to that of the S group. In addition, there were no significant differences in the means of primary, secondary, and graph and atretic follicles between the T3 and C group. On the other hand, a decrease in FSH and LH was observed while an increase in ES was seen in the T3 group compared to the S group. This study revealed that N-acetylcysteine and vitamin E coadministration could significantly decrease the side effects of cyclophosphamide, especially in ovarian tissue.


Importance of testing for usability when selecting and implementing an electronic health or medical record system.
An oncology electronic health record (EHR) was implemented without prior usability testing. Before expanding the system to new clinics, this study was initiated to examine the role of usability testing in the evaluation of an EHR product and whether novice users could identify issues with usability that resonated with more experienced users of the system. In addition, our study evaluated whether usability issues with an already implemented system affect efficiency and satisfaction of users. A general usability guide was developed by a group of five informaticists. Using this guide, four novice users evaluated an EHR product and identified issues. A panel of five experts reviewed the identified issues to determine agreement with and applicability to the already implemented system. A survey of 42 experienced users of the previously implemented EHR was also performed to assess efficiency and general satisfaction. The novice users identified 110 usability issues. Our expert panel agreed with 90% of the issues and recommendations for correction identified by the novice users. Our survey had a 54% response rate. The majority of the experienced users of the previously implemented system, which did not benefit from upfront usability testing, had a high degree of dissatisfaction with efficiency and general functionality but higher overall satisfaction than expected. In addition to reviewing features and content of an EHR system, usability testing could improve the chances that the EHR design is integrated with existing workflow and business processes in a clear and efficient way.


Transport of gibberellin a(1) in cowpea membrane vesicles.
The permeability properties of gibberellin A(1) (GA(1)) were examined in membrane vesicles isolated from cowpea hypocotyls. The rate of GA(1) uptake was progressively greater as pH decreased, indicating that the neutral molecule is more permeable than anionic GA(1). Membrane vesicles used in this study possessed a tonoplast-type H(+)-translocating ATPase as assayed by MgATP-dependent quenching of acridine orange fluorescence and methylamine uptake. However, GA(1) uptake was not stimulated by MgATP. At concentrations in excess of 1 micromolar, GA(1), GA(5), and GA, collapsed both MgATP-generated and artifically imposed pH gradients, apparently by shuttling H(+) across the membrane as neutral GA. The relatively high permeability of neutral GA and the potentially detrimental effects of GA in uncoupling pH gradients across intracellular membranes supports the view that GA(1) accumulation and compartmentation must occur by conversion of GA(1) to more polar metabolites.


Nicergoline increases serum substance P levels in patients with an ischaemic stroke.
Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted.


Pre-, post-, and longitudinal evaluation of juvenile justice education.
This article describes two stages of the Juvenile Justice Educational Enhancement Program's pre-, post-, and longitudinal evaluation research. Pilot studies were used to explore how to design statewide research of pre- and postassessment scores and community reintegration outcomes. Preliminary findings suggest that higher performing educational programs produce greater educational gains as measured by academic achievement tests, credits earned, and pupil progression rates. The findings also indicate that these programs have more students returning to school and lower recidivism rates. Building on the pilot studies, refinements were made to the research designs to enable more comprehensive statewide evaluation. Current research includes collection of pre- and postassessment scores from official sources on approximately 16,000 juvenile justice youths. In addition, a research design has been developed to examine program effectiveness by measuring community reintegration variables. Multiple data sources, including official and self-reported data on family, school, employment, and subsequent crime involvement, will be used in the longitudinal study.


Hormone therapy for inmates: a metonym for transgender rights.
The issue of hormone therapy for transgender inmates, while seemingly limited in importance, is one that involves issues of greater importance for the transgender community. The greatest issue at the heart of the matter is the legal argument that is traditionally used to gain access to hormone therapy: the Eighth Amendment. The Eighth Amendment prohibits deliberate indifference to the medical needs of inmates. Traditionally, transgender inmates have gained access to hormone therapy by appealing to the DSM-IV's classification of Gender Identity Disorder (GID) as a mental illness, and by establishing that prison officials' failure to provide hormone therapy constitutes deliberate indifference to a serious medical need. However, appeal to GID is a double-edged sword: while it allows access to hormone therapy, it does so by describing transgender individuals as somehow sick or infirm. This description is at odds with the transgender community's conceptualization of itself. This Note seeks to square the legal arguments for provision of hormone therapy to transgender inmates with the philosophical backdrop that shapes the transgender rights movement by using Plyler v. Doe as a model. This Note argues that access to hormone therapy by transgender inmates involves the intersection of a quasi-fundamental right with a quasi-suspect class. By utilizing such an argument, the transgender community is not bound by the negative expressive effect that the law may have in describing it as infirm or deficient.


Alternating hemiplegia of childhood: a study of 10 patients and results of flunarizine treatment.
Alternating hemiplegia of childhood is a rare syndrome characterized by onset before 18 months of age of frequent attacks of alternating paralysis, transient ocular palsies, nystagmus, choreoathetosis, and autonomic dysfunction. We describe features of 10 patients followed for up to 27 years. The mechanism of alternating hemiplegia remains unknown but an association to migraine is suspected because of the strong family history of migraine and aura symptoms in some patients. We treated nine patients with flunarizine, a calcium channel blocker, for up to 5 years; they showed a reduction in duration of the hemiplegic attacks, but the episodes ceased completely in only one patient. With long-term follow-up, the persistent motor, movement, and cognitive deficits are more apparent. It is not certain if the flunarizine alters this course.


Digital consumer behaviour: insights into the perceptions of late adolescents' consumption of digital media on cognitive health.
Digital media has become an indispensable facet of adolescents' everyday lives, playing a crucial role in their daily routines, encompassing various activities such as accessing information, accomplishing academic tasks, and facilitating interpersonal communication. Literature evidence on the effects of digital media on cognitive health is bi-directional, having both positive and negative impacts. The present research aimed to explore the perceptions of digital media consumption on cognitive health in late adolescents between the age of 17 and 21 years. A self-reported online survey was administered to 173 adolescents, and the data were analysed using statistical software (SPSS 17). The findings revealed that some late adolescents recognize the importance of cognition in their daily activities and health, particularly for activities focused on cognitive, academic, personal, and social skills. Mobile phones, laptops, and television were the most commonly preferred gadgets, while e-pads, Alexa, smartwatches, Kindle, tablets, and play stations were less preferred. Interestingly, a high proportion of participants reported neutral perceptions of digital media's influence on cognitive health, highlighting the need to create awareness and educate late adolescents on healthy digital media consumption. The findings hold significant implications for the development of comprehensive guidelines and evidence-based recommendations for digital media usage among late adolescents. Additionally, the research sheds light on the strategies adopted by adolescents to regulate and optimize their consumption of digital media, thereby providing valuable insights into effective practices and potential areas for improvement.


Cyclosporin pro-dispersion liposphere formulation.
Preparation and characterization of an oral pro-dispersion liposphere formulation for cyclosporin, a water insoluble drug with limited bioavailability. Pro-dispersion formulation consisted of a solid fat, dispersing agents and amphiphilic solvents as the major components besides cyclosporin A (CsA) were prepared in the present work. For preparation of this formulation, phospholipid was dissolved in pharmaceutically acceptable water soluble organic solvent, thereafter CsA along with other components was added and formulation optimization was carried out. After formulation preparation, particle size determination and in vitro release study was carried out. Additionally, ultracentrifugation, TEM, Cryo-TEM and DSC techniques were used for in vitro characterization of formulation. The prepared system was also compared with marketed Neoral® microemulsion formulation. Liposphere formulations were prepared and optimized as according to procedure. Though, determination of in vitro characteristics of such formulations is complex and difficult, yet selected and performed tests confirmed formation and existence of solid liposphere particles upon dispersion of formulation in water. It was also observed that particle size is influenced by the type of solid fat used and amphiphilic solvent present in the formulation. Prepared pro-dispersion was found to be stable for 2 years under normal storage conditions. Prepared pro-dispersion liposphere formulation is a homogeneous solution of a lipophilic drug such as cyclosporin in a mixture of surfactants, lipids and ethyl lactate proved to spontaneously form dispersion when added to aqueous media. This formulation concept has a potential clinical use for improved bioavailability of water insoluble drugs.


Changes in the expression of cytochrome P450s 2B1, 2B2, 2E1, and 2C11 in response to daily aromatic hydrocarbon treatment.
Treatment of rats with ethylbenzene (EB) modulates the hepatic expression of many P450s, with those induced after a single intraperitoneal hydrocarbon injection differing from those induced after more prolonged (3 day) administration. The goals of the current studies are (1) to characterize the induction response after prolonged hydrocarbon exposure, (2) to explain why the elevation of these P450s is attenuated after continued treatment, and (3) to determine how P450 2B protein remains elevated without an elevation of P450 2B1/2 RNA. P450 2C11 protein was decreased after a single EB injection and remained depressed throughout the treatment period. P450 2C11 RNA was only decreased with prolonged, but not acute treatment. P450 2E1 was induced after a single EB injection; however, the initial induction was attenuated with more prolonged treatment. P450 2B1 and P450 2B2 RNAs exhibited a similar response, being elevated after acute administration, but returned to control levels with prolonged EB administration. Interestingly, P450 2B protein levels remained elevated despite the decrease in P450 2B1 and P450 2B2 RNA to control levels. We then tested the possibility that the multiphasic induction pattern of P450 2E1 and P450 2B1/2 RNA was due to differences in the pharmacokinetics of EB. The disappearance of EB with time was measured in rats that were either (1) untreated, (2) pretreated with EB for 1 day, or (3) pretreated with EB for 3 days. These results demonstrated that prior hydrocarbon exposure caused an increase in EB clearance, which decreased the overall levels of EB in the body. Consequently, EB levels were sufficiently diminished to decrease EB's effectiveness as an inducer leading to the decrease in P450 2E1 protein and P450 2B1 and P450 2B2 RNA after continued EB administration. A further consequence of the decreased overall EB concentration is that the hydrocarbon was capable of producing only a transient elevation of P450 2B1 RNA levels. This transient elevation appears to be sufficient to maintain elevated P450 2B protein.


Thermionic emission and a novel electron collector in a liquid helium environment.
We study two techniques to create electrons in a liquid helium environment. One is thermionic emission of tungsten filaments in a low temperature cell in the vapor phase with a superfluid helium film covering all surfaces; the other is operating a glowing filament immersed in bulk liquid helium. We present both the steady state and rapid sweep I-V curves and the electron current yield. These curves, having a negative dynamic resistance region, differ remarkably from those of a vacuum tube filament. A novel low temperature vapor-phase electron collector for which the insulating helium film on the collector surface can be removed is used to measure emission current. We also discuss our achievement of producing multielectron bubbles in liquid helium by a new method.


[Necrotizing fasciitis of the breast and HIV infection. A case report].
Necrotizing fasciitis is a severe soft tissue infection caused by flesh-eating bacteria. It usually occurs on the lower limbs. The purpose of this report is to describe a case involving Streptococcus pyogenes on the breast of a 22-year-old African woman with HIV.


Deposition of beta/A4 protein along neuronal plasma membranes in diffuse senile plaques.
The origin of the extracellular beta-amyloid protein (beta/A4) found in senile plaques and the cellular mechanisms responsible for its deposition in cerebral tissues are still an unresolved issue in Alzheimer's disease. In this study we analyzed in detail the distribution of various epitopes of beta/A4 in relation to local cellular elements in diffuse plaques of the hippocampal region. We also correlated our findings with the presence and distribution of non-beta/A4 epitopes of the amyloid precursor protein (APP) and with synaptophysin immunoreactivity in the cortical neuropil. Discontinuous beta/A4-immunoreactive deposits were found along dendrites, and around the soma of neurons included in the plaques. Furthermore, increased synaptophysin reactivity with slightly dilated synaptophysin-immunolabeled presynaptic terminals were found in diffuse plaques. APP epitopes could not be found in diffuse plaques. However, some of the APP antibodies, mainly those to the C-terminal portion of APP, and antibodies to beta/A4 recognized clusters of flat vesicular profiles (0.6-1.4 micron in width and 2-3 microns in length) in the neuropil of cortical areas where plaques had developed. Our findings are compatible with a neuronal origin of beta/A4 in diffuse plaques and with a primary release of beta/A4 at synaptic sites along the immunostained neurites. They also suggest that diffuse plaques might be preceded by minute lesions of the neuropil where beta/A4 is not yet released from the precursor molecule.


Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing.
The pandemic threat of COVID-19 has severely destroyed human life as well as the economy around the world. Although, the vaccination has reduced the outspread, but people are still suffering due to the unstable RNA sequence patterns of SARS-CoV-2 which demands supplementary drugs. To explore novel drug target proteins, in this study, a transcriptomics RNA-Seq data generated from SARS-CoV-2 infection and control samples were analyzed. We identified 109 differentially expressed genes (DEGs) that were utilized to identify 10 hub-genes/proteins (TLR2, USP53, GUCY1A2, SNRPD2, NEDD9, IGF2, CXCL2, KLF6, PAG1 and ZFP36) by the protein-protein interaction (PPI) network analysis. The GO functional and KEGG pathway enrichment analyses of hub-DEGs revealed some important functions and signaling pathways that are significantly associated with SARS-CoV-2 infections. The interaction network analysis identified 5 TFs proteins and 6 miRNAs as the key regulators of hub-DEGs. Considering 10 hub-proteins and 5 key TFs-proteins as drug target receptors, we performed their docking analysis with the SARS-CoV-2 3CL protease-guided top listed 90 FDA approved drugs. We found Torin-2, Rapamycin, Radotinib, Ivermectin, Thiostrepton, Tacrolimus and Daclatasvir as the top ranked seven candidate drugs. We investigated their resistance performance against the already published COVID-19 causing top-ranked 11 independent and 8 protonated receptor proteins by molecular docking analysis and found their strong binding affinities, which indicates that the proposed drugs are effective against the state-of-the-arts alternatives independent receptor proteins also. Finally, we investigated the stability of top three drugs (Torin-2, Rapamycin and Radotinib) by using 100 ns MD-based MM-PBSA simulations with the two top-ranked proposed receptors (TLR2, USP53) and independent receptors (IRF7, STAT1), and observed their stable performance. Therefore, the proposed drugs might play a vital role for the treatment against different variants of SARS-CoV-2 infections.


Acute coronary syndrome: role of the nurse in patient assessment and management.
Coronary heart disease is a leading cause of mortality, morbidity and hospitalisation in the UK and worldwide. Acute coronary syndrome (ACS) is a serious manifestation of coronary heart disease. ACS encompasses several conditions that represent acute injury or damage to the myocardium, including ST-elevation myocardial infarction (STEMI), unstable angina and non-ST elevation myocardial infarction (NSTEMI). Management may differ depending on the diagnosis, so prompt and accurate assessment is crucial to establish the patient's condition and ensure timely initiation of the appropriate treatment. This article explains how ACS develops and what characterises its different types. It also outlines the assessment and management of patients with ACS, and explains the nurse's role in these processes.


Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis.
Rhabdomyolysis is a life-threatening condition caused by skeletal muscle damage with acute kidney injury being the main complication dramatically worsening the prognosis. Specific treatment for rhabdomyolysis-induced acute kidney injury is lacking and the mechanisms of the injury are unclear. To clarify this, we studied intra-kidney complement activation (C3d and C5b-9 deposits) in tubules and vessels of patients and mice with rhabdomyolysis-induced acute kidney injury. The lectin complement pathway was found to be activated in the kidney, likely via an abnormal pattern of Fut2-dependent cell fucosylation, recognized by the pattern recognition molecule collectin-11 and this proceeded in a C4-independent, bypass manner. Concomitantly, myoglobin-derived heme activated the alternative pathway. Complement deposition and acute kidney injury were attenuated by pre-treatment with the heme scavenger hemopexin. This indicates that complement was activated in a unique double-trigger mechanism, via the alternative and lectin pathways. The direct pathological role of complement was demonstrated by the preservation of kidney function in C3 knockout mice after the induction of rhabdomyolysis. The transcriptomic signature for rhabdomyolysis-induced acute kidney injury included a strong inflammatory and apoptotic component, which were C3/complement-dependent, as they were normalized in C3 knockout mice. The intra-kidney macrophage population expressed a complement-sensitive phenotype, overexpressing CD11b and C5aR1. Thus, our results demonstrate a direct pathological role of heme and complement in rhabdomyolysis-induced acute kidney injury. Hence, heme scavenging and complement inhibition represent promising therapeutic strategies.


[Radical pleurectomy and hyperthermic intrathoracic chemotherapy for treatment of thymoma with pleural spread].
Patients with pleural thymoma spread (Masaoka stage IV a) should be treated within a multimodal treatment regime. However, the extent of local surgical resection to achieve optimal tumour control remains controversial. Prospective analysis between September 2008 and April 2013 of all patients with a Masaoka stage IV a thymoma, who underwent radical pleurectomy/decortication (P/D) followed by hyperthermic intrathoracic chemotherapy (HITHOC). A total of 11 patients (male n = 7; mean age 46.5 ± 11.4 years) with a primary stage IV a thymoma (n = 3) or thymoma with pleural relapse (n = 8) were included after successful transsternal thymoma resection. WHO histological classification was: B1 n = 1, B2 n = 6, B3 n = 3 and C n = 1. A radical P/D (5/11; 45 %) was extended with resection of the pericardium and diaphragm in 6/11 (55 %) patients. After surgical resection (91 % complete macroscopic R0/R1-resection) the HITHOC with cisplatin (100 mg/m2 body surface area (BSA) n = 7; 150 mg/m2 BSA n = 4) was performed for one hour at 42 °C. Operative revision was necessary in two patients (chylo- and hematothorax) with one patient also requiring temporary renal replacement therapy due acute renal failure (cisplatin 150 mg/m2 BSA). 30-day mortality was 0 %. Local recurrence (pulmonary n = 1, paravertebral n = 2) was documented in 3/10 (30 %) patients after R0/R1 resection. After a mean follow-up of 23 months the overall median survival was 27 months and 82 % (9/11) patients are still alive at the end of the study period. Masaoka stage IV a thymoma could be safely treated with lung-sparing radical P/D and HITHOC with cisplatin in a multimodality treatment regime. Early results with respect to recurrence and survival are encouraging, but further studies are warranted and we have to await long-term results.


Chromosomal aberrations induced by (12)C6+ ions and 60Co gamma-rays in mouse immature oocytes.
The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of (12)C6+ ion or (60)Co gamma-ray. Chromosomal aberrations were analyzed in metaphase II oocytes at 7 weeks after irradiation. The relative biological effectiveness (RBE) of (12)C6+ ion was calculated with respect to 60Co gamma-ray for the induction of chromosomal aberrations. The (12)C6+ ion and 60Co gamma-ray dose-response relationships for chromosomal aberrations were plotted by linear quadratic models. The data showed that there was a dose-related increase in frequency of chromosomal aberrations in all the treated groups compared to controls. The RBE values for (12)C6+ ions relative to 60Co gamma-rays were 2.49, 2.29, 1.57, 1.42 or 1.32 for the doses of 0.5, 1.0, 2.0, 4.0 or 6.0 Gy, respectively. Moreover, a different distribution of the various types of aberrations has been found for (12)C6+ ion and 60Co gamma-ray irradiations. The dose-response relationships for (12)C6+ ion and 60Co gamma-ray exhibited positive correlations. The results from the present study may be helpful for assessing genetic damage following exposure of immature oocytes to ionizing radiation.


Importance of gut microbiome regulation for the prevention and recovery process after SARS-CoV-2 respiratory viral infection (Review).
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported to affect organs other than the lungs, including the liver, brain, kidneys and intestine, and gastrointestinal symptoms, such as nausea, vomiting, diarrhea and abdominal discomfort, have also been reported. Thus, SARS-CoV-2 could potentially directly or indirectly regulate the gut microbiome profile and its homeostasis. The abundance of Coprobacillus, Clostridium ramosum and Clostridium are associated with the severity of COVID-19, and Firmicutes, Bacteriodetes, Proteobacteria and Actinobacteria are also related to COVID-19 infection. The four phyla are correlated with the severity of COVID-19 infection in patients. The modulation of factors that control the physiological growth of the gut microbiome will determine the proportionate ratio of microbiome types (profile). Taken together, gut microbiome profile alterations in COVID-19 patients may have a cross effect with the modulation of cytokine levels in COVID-19 infection. With these findings, several factors that regulate gut microbiome homeostasis may support the degree of the clinical symptoms and hasten the recovery process after COVID-19 infection.


DNA binding and bending to initiate packaging of phage lambda DNA.
Physical and genetic studies verify that the DNA binding domain of protein gpNu1 (which initiates packaging of phage lambda DNA) is a winged helix-turn-helix (w HTH) and that gpNu1 dimers bind sites that are brought close through DNA bending.


Removal of cyanide from dilute solution using a cell with three-phase three-dimensional electrode.
The removal of cyanide from dilute solutions containing free cyanide or cuprocyanide was experimentally investigated using a new electrochemical reactor, three-phase three-dimensional electrode cell. The experimental results were assessed in term of removal efficiency of cyanide. The results showed that the reactor could efficiently remove cyanide from the two solutions. The removal efficiency reached as high as about 93% for the two solutions by electrolysis for 10 min at 20 V cell voltage and 0.16 m3/h airflow. It was also observed that the removal efficiency depended on the applied cell voltage, airflow, interelectrode and initial pH value of the containing-cyanide solution. The former two factors have a positive effect while the latter two have a negative effect on cyanide removal in the experimental range.


The ozone stress transcriptome of pepper (Capsicum annuum L.).
We used cDNA microarrays to monitor the transcriptome of ozone stress-regulated genes (ORGs) in two pepper cultivars [Capsicum annuum cv. Dabotop (ozone-sensitive) and Capsicum annuum cv. Buchon (ozone-tolerant)]. Ozone stress up- or down-regulated 180 genes more than three-fold. Transcripts of 84 of these ORGs increased, transcripts of 88 others diminished, and those of eight either accumulated or diminished at different time points in the two cultivars or changed in only one of the cultivars. 67% (120) of the ORGs were regulated differently in ozone-sensitive and ozone-tolerant peppers, most being specifically up-regulated in the ozone-sensitive cultivar. Many were also represented in the plant defense transcriptome against non-host pathogen infection, and some in the transcriptomes for cold, drought, and salinity stresses.


Participation in Online Research Examining End-of-Life Experiences: Is It Beneficial, Burdensome, or Both for Parents Bereaved by Childhood Cancer?
It is important for the health care community to understand the impact of a child's death on parent functioning. Yet involving bereaved parents in research that enquires about such a stressful time in their life can potentially bring harm to them. The current study examines the perceived benefit and burden of parents participating in a survey exploring their perceptions of their child's end-of-life (EoL) and bereavement experiences. Parents whose child died from cancer or complications of cancer treatment were invited to complete a survey developed by pediatric psychosocial oncology professionals with input from bereaved parent advocates through a closed social media (Facebook) group. One hundred seventy-eight parents of children aged 0 to 37 years at death (median age 12 years) participated. More than three quarters of parents reported at least "a little benefit" and half reported at least "a little burden" associated with participation. Less burden was perceived by younger and female parents, parents of younger children, those who had felt prepared to meet their children's emotional needs at EoL, and those not using bereavement services at the time of the survey. With the increasing use of social media as a source for bereaved parents to receive and provide emotional support, it is important for clinicians and researchers to understand the perceived benefits and risks of participating in research about EoL experiences via online recruitment. Our findings suggest that the benefit and burden of online research participation may vary for bereaved parents, but further research is necessary to replicate the findings and explore ways to optimize the use of this approach.


The lonepair triloop: a new motif in RNA structure.
The lonepair triloop (LPTL) is an RNA structural motif that contains a single ("lone") base-pair capped by a hairpin loop containing three nucleotides. The two nucleotides immediately outside of this motif (5' and 3' to the lonepair) are not base-paired to one another, restricting the length of this helix to a single base-pair. Four examples of this motif, along with three tentative examples, were initially identified in the 16S and 23S rRNAs with covariation analysis. An evaluation of the recently determined crystal structures of the Thermus thermophilus 30S and Haloarcula marismortui 50S ribosomal subunits revealed the authenticity for all of these proposed interactions and identified 16 more LPTLs in the 5S, 16S and 23S rRNAs. This motif is found in the T loop in the tRNA crystal structures. The lonepairs are positioned, in nearly all examples, immediately 3' to a regular secondary structure helix and are stabilized by coaxial stacking onto this flanking helix. In all but two cases, the nucleotides in the triloop are involved in a tertiary interaction with another section of the rRNA, establishing an overall three-dimensional function for this motif. Of these 24 examples, 14 occur in multi-stem loops, seven in hairpin loops and three in internal loops. While the most common lonepair, U:A, occurs in ten of the 24 LPTLs, the remaining 14 LPTLs contain seven different base-pair types. Only a few of these lonepairs adopt the standard Watson-Crick base-pair conformations, while the majority of the base-pairs have non-standard conformations. While the general three-dimensional conformation is similar for all examples of this motif, characteristic differences lead to several subtypes present in different structural environments. At least one triloop nucleotide in 22 of the 24 LPTLs in the rRNAs and tRNAs forms a tertiary interaction with another part of the RNA. When a LPTL containing the GNR or UYR triloop sequence forms a tertiary interaction with the first (and second) triloop nucleotide, it recruits a fourth nucleotide to mediate stacking and mimic the tetraloop conformation. Approximately half of the LPTL motifs are in close association with proteins. The majority of these LPTLs are positioned at sites in rRNAs that are conserved in the three phylogenetic domains; a few of these occur in regions of the rRNA associated with ribosomal function, including the presumed site of peptidyl transferase activity in the 23S rRNA.


The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas-mediated apoptosis.
The chemopreventive properties of the isothiocyanates have been attributed to their ability to inhibit phase I enzymes that activate procarcinogens, induce phase II protective enzymes and trigger apoptosis in transformed cells. In this study we provide evidence for a new mechanism of chemoprevention, wherein sublethal doses of phenethyl isothiocyanate (PEITC) sensitize cells to Fas-mediated apoptosis. The phenomenon was observed in the Fas-resistant T24 bladder carcinoma cell line and in Jurkat T cells overexpressing the anti-apoptotic protein Bcl-2. Caspase-3-like activity was increased up to 20-fold of that observed with either PEITC or anti-Fas antibody alone. While PEITC activated ERK, JNK and p38, inhibitors of these MAP kinases did not block apoptosis. PEITC transiently depleted cellular glutathione, providing a putative mechanism for sensitizing the cells to apoptosis. However, lowering glutathione with buthionine sulfoximine did not mimic the effect of PEITC. Instead, we propose that PEITC promotes apoptosis by directly modifying intracellular thiol proteins. The ability of PEITC to sensitize cells to receptor-mediated apoptosis provides an additional mechanism to explain its chemopreventive properties.


Successful aging: analysis of the components of a gerontological paradigm.
Since the mid-20th century, scientist has been searching the components of successful or active aging. At the beginning of the 21st century, demographic aging is now a global issue and successful aging has emerged as a gerontological paradigm through nation and international policies. Conducting a comprehensive review of scientific literature on this paradigm offers the opportunity to identify the key components of successful aging. Based on the results of this approach, we show that the components are not limited to the functional and cognitive health of individuals. Multidimensionality of successful aging highlights the complexity of factors influencing the experiences of aging, and the variety of dimensions involved: functional, psychological, social, spiritual or environmental. Representations and aspirations of what would be successful aging differ from one society to another, from culture to another. The article proposes a framework for an exploratory analysis of the vulnerabilities of elderly not to assess the success of aging, but to capture the components of the well-being of people in old age.


Tibet as a potential domestication center of cultivated barley of China.
The importance of wild barley from Qinghai-Tibet Plateau in the origin and domestication of cultivated barley has long been underestimated. Population-based phylogenetic analyses were performed to study the origin and genetic diversity of Chinese domesticated barley, and address the possibility that the Tibetan region in China was an independent center of barley domestication. Wild barley (Hordeum vulgare ssp. spontaneum) populations from Southwest Asia, Central Asia, and Tibet along with domesticated barley from China were analyzed using two nuclear genes. Our results showed that Tibetan wild barley distinctly diverged from Southwest Asian (Near East) wild barley, that Central Asian wild barley is related to Southwest Asian wild barley, and that Chinese domesticated barley shares the same haplotypes with Tibetan wild barley. Phylogenetic analysis showed a close relationship between Chinese domesticated barley and the Tibetan wild barley, suggesting that Tibetan wild barley was the ancestor of Chinese domesticated barley. Our results favor the polyphyletic origin for cultivated barley.


ARF mutation accelerates pituitary tumor development in Rb+/- mice.
Mice heterozygous for the retinoblastoma (Rb) tumor suppressor gene develop pituitary and thyroid tumors with high penetrance. We demonstrate here that loss of the ARF tumor suppressor strongly accelerates intermediate lobe pituitary tumorigenesis in Rb heterozygous mice. These effects in the pituitary are greater than those conferred by p53 loss in that Rb+-;ARF-- mice display significantly more early atypical lesions than Rb+-; p53-- mice. Also, Rb+-;ARF-- compound mutants do not develop many of the novel tumors or precancerous lesions seen in Rb+-;p53-- compound mutants. Although complete loss of ARF expression is not obligatory for pituitary tumorigenesis in Rb+- mice, alterations of the ARF locus are observed in tumors from Rb+-;ARF+- mice, consistent with a selective advantage of ARF inactivation in this context. We conclude that inactivation of ARF acts more broadly than that of p53 in connecting abrogation of the Rb pathway to tumorigenesis.


Single risk factor interventions to promote physical activity among patients with chronic diseases: systematic review.
To provide a summary of evidence on the effectiveness of interventions to promote physical activity among patients affected by at least 1 chronic disease. The interventions studied were each targeted at a single risk factor. MEDLINE, CINAHL, and EMBASE were searched from 1966 to 2006 using 2 sets of search terms. First we searched using physical activity or physical fitness or exercise and health care or primary care or primary health care or family practice or medical office or physician's office and health promotion or health education or counselling. Then we used physical activity or exercise and diabetes or hyperlipidemia or hypertension or obesity or cardiovascular disease or pulmonary disease or risk factor or comorbidity and health promotion or health education or counselling or prescription. We chose randomized controlled trials or trials with a controlled quasi-experimental design that evaluated single risk factor interventions to promote physical activity among adult patients in primary care settings who were affected by at least 1 chronic disease, that reported participation in physical activity as a primary outcome, and that were published in English or French. Of the 4858 articles found, 62 were assessed, and 3 were selected. Two studies concluded that the interventions evaluated had no effect on level of physical activity. The other reported a positive short-term effect with use of an intensive intervention that was based on the theory of planned behaviour and integrated nurses into the general practitioner counseling process. There is insufficient evidence to assess the effectiveness of single risk factor interventions to promote physical activity among patients affected by at least 1 chronic disease in primary care settings. Of 3 studies, only 1 reported a short-term positive effect.


Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA.
Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for in vivo use; however, issues regarding their efficacy, toxicity and stability continue to drive further research. Thus, the aim of this study was to evaluate the potential use of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) as a strategy to formulate stable cationic lipopolymers in the delivery and protection of plasmid DNA. Cationic lipopolymers were prepared following two different methodologies by using DC8,9PC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and the cationic lipids (CL) 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), stearylamine (SA), and myristoylcholine chloride (MCL), in a molar ratio of 1:1:0.2 (DMPC:DC8,9PC:CL). The copolymerization methodology allowed obtaining cationic lipopolymers which were smaller in size than those obtained by the cationic addition methodology although both techniques presented high size stability over a 166-day incubation period at 4°C. Cationic lipopolymers containing DOTAP or MCL were more efficient in complexing DNA than those containing SA. Moreover, lipopolymers containing DOTAP were found to form highly stable complexes with DNA, able to resist serum DNAses degradation. Furthermore, neither of the cationic lipopolymers (with or without DNA) induced red blood cell hemolysis, although metabolic activity determined on the L-929 and Vero cell lines was found to be dependent on the cell line, the formulation and the presence of DNA. The high stability and DNA protection capacity as well as the reduced toxicity determined for the cationic lipopolymer containing DOTAP highlight the potential advantage of using lipopolymers when designing novel non-viral carrier systems for use in in vivo gene therapy. Thus, this work represents the first steps toward developing a cationic lipopolymer-based gene delivery system using polymerizable and cationic lipids.


[The analysis of formant characteristics of vowels in the speech of patient with cleft palate].
To analyze the formant frequency of vowels in the sequence therapy of patient with cleft palate. The formant frequency of vowels [a], [e], [i], [u] of normal children and postoperative patients with and without speech therapy was measured and analyzed by VS-99. 1. The mean value of F1, F2, F3 of [a] did not show significant difference among the three groups (P > 0.05). 2. The difference of mean value of [e] was significant between control group and pre-speech-therapy group, and between pre-speech-therapy and post-speech-therapy group (P < 0.05), but no significant difference was found between post-speech-therapy and control group(P > 0.05). The mean value of the formant in post-speech-therapy was higher than that of pre-speech-therapy. 3. The difference of mean value of [i] was significant between pre-speech-therapy and post-speech-therapy (P < 0.05), the mean value of F2, F3 in post-speech-therapy group decreased significantly compared with control (P < 0.05). 4. The difference of mean value of [u] showed significance between pre-speech-therapy and post-speech-therapy (P < 0.05), while the differences among other groups were insignificant (P > 0.05). Surgical repair of cleft palate cannot make all patients obtain perfect Velopharyngeal competence (VPC), while speech therapy can improve patient's pronunciation. Speech spectrum analysis can judge the effect of cleft palate therapy objectively.


Evaluation of Quality of Obturation Using Two Different Rotary Files and Hand Files in Primary Teeth: A Randomized Controlled Trial.
To estimate the obturation quality and instrumentation time on comparing traditional hand files and two rotary file types during root canal instrumentation in deciduous molars. Forty-five deciduous mandibular molars were taken and randomly allotted to three groups (n = 15). Group I: K-hand files, group II: ProTaper Gold rotary file, and group III: Kedo-SG Blue rotary files. Before and after root canal instrumentation, standardized digital radiography was taken and the instrumentation time was also noted. The recorded data were then subjected to statistical analysis utilizing SPSS Software version 22.0. To compare the instrumentation time and quality of obturation between the groups, a Chi-square test and ANOVA with the level of significance at 0.05 were employed. There was no significant difference recorded with reference to the quality of obturation (p > 0.05). However, the difference was noticed to be statistically significant when the instrumentation time between the two rotary groups and the manual instrumentation groups was taken into account (p < 0.05). The rotary systems ProTaper Gold and Kedo-SG Blue exhibited a significantly less instrumentation time on comparing with that of the hand files. Concerning the quality of obturation, all three file groups demonstrated almost a similar performance. However, there was a significant difference noticed in the instrumentation time with the use of manual instrumentation in comparison to rotary instrumentation in deciduous teeth. Preethy NA, Jeevanandan G, Mathew MG, et al. Evaluation of Quality of Obturation Using Two Different Rotary Files and Hand Files in Primary Teeth: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2021;14(4):471-474.


Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer.
This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials. The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling. Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER-/HER2- disease had worse OS than patients with ER+/HER2- disease, for both patients treated with SRS and for patients treated with WBRT. Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.


[Characterization of SH groups in the membrane proteins of human spermatozoa].
Membrane proteins rich in SH- groups were identified in human ejaculated spermatozoon, using the alkylation reaction with radioactive iodoacetic acid with a subsequent determination of the electrophoretic characterization of the proteins, as well as their comparison with the proteins in seminal plasma and blood serum of the same individuals. The determination of the incorporated radioactivity shows that out of 20 proteic bands identified by staining with Coomassie Blue, only 9 were alkylated with the iodoacetate. Among these 9 proteic bands, 4 are glycoproteins since they give a PAS positive reaction. All the proteins which incorporated the marked iodoacetate had a molecular weight below 67,000 daltons with a predominance of molecular weight below 25,000 daltons. A comparison of the electrophoresis obtained from the spermatozoon's plasmatic membrane, seminal plasma and blood serum, one finds that among the 9 proteins which were alkylated with the iodoacetate in the plasmatic membranes, two, bands I and IV are also found in the seminal plasma and blood serum, two more, bands VII and IX are found in the membranes and seminal plasma, but not in blood serum, while the rest are only found in the spermatozoon.


Work and health: A comparison between Norwegian onshore and offshore employees.
The effect of work-related variables on self reported health complaints were examined among Norwegian onshore and offshore oil workers. Differences in work and health perceptions were also examined as part of the paper. Employees working onshore and offshore in the maintenance and modification division of a large contractor company took part in the study (N=414, response rate 47.1%). The design of the study was a cross-sectional survey. A questionnaire was distributed to onshore personnel while at work - in cooperation with the personnel safety representative - and sent to the home addresses of the offshore personnel. Offshore workers perceived significantly more hazards associated with the work and experienced less control over the work pace compared to onshore workers. Onshore workers experienced significantly more pressure at work and their work tasks as more repetitive. Differences in health perceptions were identified in terms of job type in the onshore and offshore groups respectively. Different work-related factors influenced the self-reported health complaints among onshore and offshore workers. Workers in different work environments and in different job types encounter different type of threats to employee health, indicating that job type must be taken into account when studying the relationship between work-related factors and employee health.


Servant Leadership, Organisational Citizenship Behavior and Creativity: The Mediating Role of Team-Member Exchange.
Using a multi-source field study design with 184 unique triads of employees-supervisor dyads, this paper examines whether servant leaders install a serving attitude among employees. That is, servant leaders aim to encourage employees to take responsibility, to cooperate and to create high quality interactions with each other (team-member exchange; TMX). We hypothesise that servant leadership will have an influence on Organisational Citizenship Behavior (OCB) and creativity through team-member exchange. Two facets of OCB are distinguished: organisational citizenship behaviour towards individuals (OCBI), on the one hand, and taking up extra tasks that benefit the organisation (OCBO), on the other hand. The results show that servant leadership is positively related to team-member exchange, and that team-member exchange is positively related to OCBI, OCBO and creativity. The bootstrapping estimates indicated significant indirect effects of servant leadership on the three target variables through team-member exchange. The study's findings add to the body of literature on servant leadership, OCB and creativity at the workplace, and underline the importance of creating favourable working conditions that foster positive and high quality team-member exchange. This study also broadens our understanding on the importance of co-workers on the relation between servant leadership and organizational citizenship behavior (OCB) and creativity.


Incomplete contact investigation and risk of developing TB among healthcare professionals.
BACKGROUND: Data on the impact of incomplete contact investigation on TB incidence among healthcare professionals (HCPs) after TB exposure are limited.METHODS: This was a prospective cohort study with 2-year follow-up among Thai HCPs exposed to TB to determine TB incidences and factors associated with TB development.RESULTS: Of the 398 HCPs with TB exposure, 367 (92%) participated in the study; 342 HCPs were included in the final analysis; 311 participated in contact investigations; 303 underwent chest X-ray; 252 completed baseline TB and latent TB infection screening using tuberculin skin test (TST); 210 had negative baseline TST; and 45 completed follow-up tests at 3 months. Altogether, 20 HCPs developed TB (2.92/100 person-years). TB incidences in HCPs not participating in or not completing the investigation at any step were higher than in those who completed the evaluation (11.29 and 2.90, respectively, vs. 0/100 person-years; P < 0.05). No participation in contact investigation and no baseline chest X-ray were independent factors associated with TB development (adjusted odds ratio [aOR] 6.7; P < 0.001 and aOR 8.9; P = 0.01, respectively).CONCLUSION: Study findings indicate increased risks of TB development among HCPs not undergoing or not completing contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.


Hemogram study of an artificially feeding tree shrew (Tupaia belangeri chinensis).
Systematic classification and determination of various cells in normal peripheral blood of artificially feeding Tupaia belangeri chinensis of different ages and genders and evaluation of the effectiveness of an automatic blood cell classification counter for measuring tree shrew blood cells. Child, young and adult tree shrews (forty for each group) were randomly selected, half male and half female. After the animals were stable, the peripheral blood of each group was collected through the femoral vein, and the morphology of various blood cells of the tree shrew was observed and classified by the manual microscopic counting method and by an automatic blood cell classification counter. The Reference intervals of the normal peripheral blood cell absolute count, cell diameter and white blood cell percentage in tree shrews of different ages and genders has been calculated. White blood cell count and neutrophil relative count increased with age, while lymphocyte relative count decreased. The white blood cell count, neutrophil relative count, and lymphocyte relative count in the child group, as well as lymphocyte relative count in the young group, significantly differed according to gender (P<0.05), and the differences in other indicators were not significant. The Bland-Altman plot and the Passing-Bablok scattergram showed that the change trend of each indicator was consistent but exhibited large systematic differences between methods. Differences in peripheral blood cells exist among different age groups and different genders. An automatic blood cell classification counter is not suitable for the absolute count of blood cells in the tree shrew.


Bifunctional acid-base ionic liquid organocatalysts with a controlled distance between acid and base sites.
Bifunctional acid-base ionic liquid organocatalysts with different distances between the two sites have been synthesised, and their activity for the Knoevenagel condensation has been tested. As has been found to be the case with enzymes, the distance between the acidic and basic sites determines the activity of the bifunctional organocatalyst, and at the optimal distance the reaction rate increases by two orders of magnitude with respect to the purely acidic or basic counterpart organocatalysts. The experimental results have been rationalised through the study of the reaction mechanism of the Knoevenagel condensation between malononitrile and benzaldehyde by means of DFT calculations. It has been found that it consists of two consecutive steps. First, deprotonation of malononitrile on the basic site to obtain a methylene carbanion intermediate takes place, and second, co-adsorption and activation of benzaldehyde on the acid centre of this intermediate followed by the C-C bond-formation reaction. The calculations and the kinetic study indicate that there is an inversion of the rate-controlling step when the distance between the acidic and the basic sites is modified, with a direct implication on the reaction rate.