Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage.
Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.


Association Between Anxious Symptom Severity and Olfactory Impairment in Young Adults with Generalized Anxiety Disorder: A Case-Control Study.
The findings of olfaction are inconsistent in anxiety disorders, and few studies have reported on the olfactory performance in generalized anxiety disorder (GAD). Therefore, we aim to investigate the olfactory function of patients with GAD and the association between olfactory function and anxiety symptoms. We conducted a case-control study by selecting 107 patients with GAD and 107 healthy controls matched for sex and age, to investigate olfaction deficits in GAD and the association between anxiety severity and olfaction. All patients were treatment-naïve prior to the inclusion. Anxiety severity and olfaction were assessed by the Hamilton anxiety rating scale (HAM-A) and the Sniffin' Sticks test (SST), respectively. Partial correlations were used to analyze the relationship between olfaction and anxiety severity. False discovery rate (FDR) correction was used in multi-correlation analyses. Compared with healthy controls, patients in the GAD group demonstrated odor threshold, discrimination and identification deficits. In the moderate/severe anxiety subgroup, discrimination score was significantly and inversely correlated with the somatic anxiety score (γ=-0.44, q = 0.03), and identification score was significantly and inversely correlated with the HAM-A total score (γ=-0.42, q= 0.04). The TDI score (the sum of threshold, discrimination and identification scores) was significantly and inversely correlated with the somatic (γ=-0.44, q = 0.04) and psychic (γ=-0.45, q = 0.04) anxiety scores in the moderate/severe anxiety subgroup. This study demonstrated the olfactory impairment in patients with GAD and that poorer odor discrimination was correlated with greater severity of somatic anxiety.


Safety studies with the University of Melbourne multichannel electrotactile speech processor.
Results of safety investigations conducted as an integral part of the development of a multichannel electrotactile speech processor (Tickle Talker) are reported. Electrical parameters of the stimulus waveform, design of the electrode handset and cabling, and the electrical circuitry of the speech processor/stimulator and programming interface have been analyzed for potential risks. Constant current biphasic square pulses delivered to electrodes positioned on the skin surface over the digital nerve bundles were chosen to optimize the safety, comfort, and function of the electrotactile stimulus. The device was battery-powered, and the user circuit was isolated from earth-referenced sources. Each electrode was isolated by capacitive coupling, preventing DC leakage of current to the user circuit. Studies of finger temperature showed slight cooling of the skin on the fingers of both stimulated and unstimulated hands for individual subjects following electrotactile stimulation through the Tickle Talker. Subsequent analysis of finger and hand vascular circulation in five subjects showed slight reductions in hand blood flow in some individuals. The results did not demonstrate a significant mean decrease in hand or finger blood flow following electrotactile stimulation. No evidence of sympathetic involvement was found, nor were any changes in vascular structure of the hand such as those associated with Raynaud's disease found. Evidence suggests that the decrease in temperature found in the initial study may be due to a change in the ratio of blood flow between arteriovenous anastomoses and nutritive capillary beds. Studies of: 1) changes in mean threshold and comfortable pulse widths over time; and, 2) changes in tactual sensitivity as measured by hot/cold, sharp/dull, and two-point difference limen discrimination, did not detect any systematic change in peripheral nervous system function following electrotactile stimulation. Analysis of electroencephalogram (EEG) recordings taken during electrotactile stimulation, and after relatively long periods of experience with the device did not show any pathological changes which might be associated with epileptic foci. In summary, no contraindications to long-term use of the Tickle Talker were detected in the studies performed.


[Therapeutic prescription of antibiotics and NSAID's by dentists in the Netherlands].
Late in 2015 the Royal Dutch Dental Association (KNMT) conducted a study of the therapeutic prescription of antibiotics and NSAIDs by dentists in general practice in the Netherlands and the factors influencing their decisions. Of the 1,087 dentists contacted 367 (34%) completed the online questionnaire. In the 4 weeks preceding the study they had prescribed an antibiotic to 1.3% of their patients on average. A fifth (20%) found it difficult to decide whether an anti-inflammatory drug is indicated and/or whether this should be an antibiotic or a NSAID. Questioned about medication decisions (whether or not antibiotics are indicated) in 11 fictional cases, 11% of respondents judged every case correctly. 39% undertreated, 24% overtreated and 26% both undertreated and overtreated. In the last two categories, dentists with non-Dutch degrees are overrepresented. More than half (55%) of the respondents say they need a guideline for prescribing antibiotics in dental treatment and 28% (also) need postgraduate education on this matter.


Correlates of the Pregnancy Experience and Attitude regarding Weight Change during Pregnancy in Primigravida Women.
We aimed to examine the correlations between pregnancy experience and attitude regarding weight change during pregnancy. This correlative study was conducted from July 2017 to October 2017 by involving 156 primigravida women who were over pregnancy 20 weeks in Seoul and Gyeonggi-do province. Data were collected using a questionnaire, which included questions on demographic data, experience during pregnancy, and attitude regarding weight change during pregnancy. Descriptive statistics were calculated. Also, independent t-test, ANOVA, and Pearson's correlation coefficients were used for data analysis. The mean age of the participants was 30.62 years and their score of attitude regarding weight gain during pregnancy was low. Moreover, a significant correlation was found between the pregnancy experience and attitude regarding weight gain during pregnancy in primigravida women. As a result of analyzing the correlation between pregnancy experience and attitude towards weight gain during pregnancy, it is apparent that attitudes toward weight change are different according to experience during pregnancy in women. Based on these results, it can be concluded that nursing intervention programs are necessitated to enhance the attitude of pregnant primigravida women towards pregnancy and weight gain.


Effect of various warm-up protocols on jump performance in college football players.
The purpose of this study was to identify the effects of warm-up strategies on countermovement jump performance. Twenty-nine male college football players (age: 19.4 ± 1.1 years; body height: 179.0 ± 5.1 cm; body mass: 73.1 ± 8.0 kg; % body fat: 11.1 ± 2.7) from the Tuzla University underwent a control (no warm-up) and different warm-up conditions: 1. general warm-up; 2. general warm-up with dynamic stretching; 3. general warm-up, dynamic stretching and passive stretching; 4. passive static stretching; 5. passive static stretching and general warm-up; and, 6. passive static stretching, general warm-up and dynamic stretching. Countermovement jump performance was measured after each intervention or control. Results from one way repeated measures ANOVA revealed a significant difference on warm-up strategies at F (4.07, 113.86) = 69.56, p < 0.001, eta squared = 0.72. Bonferonni post hoc revealed that a general warm-up and a general warm-up with dynamic stretching posted the greatest gains among all interventions. On the other hand, no warm-up and passive static stretching displayed the least results in countermovement jump performance. In conclusion, countermovement jump performance preceded by a general warm-up or a general warm-up with dynamic stretching posted superior gains in countermovement jump performance.


A quantitative test of the cultural theory of risk perceptions: comparison with the psychometric paradigm.
This paper seeks to compare two frameworks which have been proposed to explain risk perceptions, namely, cultural theory and the psychometric paradigm. A structured questionnaire which incorporated elements from both approaches was administered to 129 residents of Norwich, England. The qualitative risk characteristics generated by the psychometric paradigm explained a far greater proportion of the variance in risk perceptions than cultural biases, though it should be borne in mind that the qualitative characteristics refer directly to risks whereas cultural biases are much more distant variables. Correlations between cultural biases and risk perceptions were very low, but the key point was that each cultural bias was associated with concern about distinct types of risks and that the pattern of responses was compatible with that predicted by cultural theory. The cultural approach also provided indicators for underlying beliefs regarding trust and the environment; beliefs which were consistent within each world view but divergent between them. An important drawback, however, was that the psychometric questionnaire could only allocate 32% of the respondents unequivocally to one of the four cultural types. The rest of the sample expressed several cultural biases simultaneously, or none at all. Cultural biases are therefore probably best interpreted as four extreme world views, and a mixture of qualitative and quantitative research methodologies would generate better insights into who might defend these views in what circumstances, whether there are only four mutually exclusive world views or not, and how these views are related to patterns of social solidarity, and judgments on institutional trust.


Active co-infection with HBV and/or HCV in South African HIV positive patients due for cancer therapy.
Human immunodeficiency virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) share routes of transmission. There is limited data on the incidence of active co-infection with HBV and/or HCV in cancer patients infected with HIV in Africa. This was a prospective study based on 34 patients with varied cancer diagnosis, infected with HIV and awaiting cancer therapy in South Africa. HIV viral load, CD4+ cell counts, Alanine-aminotransferase and aspartate aminotransferase levels were tested. Exposure to HBV and HCV was assessed serologically using commercial kits. Active HBV and/or HCV co-infection was detected using viral specific nested PCR assays. HCV 5'-UTR PCR products were sequenced to confirm active HCV infection. Active viral infection was detected in 64.7% of patients for HBV, 38.2% for HCV, and 29.4% for both HBV and HCV. Occult HBV infection was observed in 63.6% of the patients, while seronegative HCV infection was found in 30.8% of patients. In addition, CD4+ cell count < 350 cells/µl was not a risk factor for increased active HBV, HCV or both HBV and HCV co-infections. A total of 72.7%, 18.2% and 9.1% of the HCV sequences were assigned genotype 5, 1 and 4 respectively.The study revealed for the first time a high active HBV and/or HCV co-infection rate in cancer patients infected with HIV. The findings call for HBV and HCV testing in such patients, and where feasible, appropriate antiviral treatment be indicated, as chemotherapy or radiotherapy has been associated with reactivation of viral hepatitis and termination of cancer therapy.


A mouse model of airway disease: oncostatin M-induced pulmonary eosinophilia, goblet cell hyperplasia, and airway hyperresponsiveness are STAT6 dependent, and interstitial pulmonary fibrosis is STAT6 independent.
Oncostatin M (OSM), a pleiotropic cytokine of the gp130 cytokine family, has been implicated in chronic allergic inflammatory and fibrotic disease states associated with tissue eosinophilia. Mouse (m)OSM induces airway eosinophilic inflammation and interstitial pulmonary fibrosis in vivo and regulates STAT6 activation in vitro. To determine the requirement of STAT6 in OSM-induced effects in vivo, we examined wild-type (WT) and STAT6-knockout (STAT6(-/-)) C57BL/6 mouse lung responses to transient ectopic overexpression of mOSM using an adenoviral vector (AdmOSM). Intratracheal AdmOSM elicited persistent eosinophilic lung inflammation that was abolished in STAT6(-/-) mice. AdmOSM also induced pronounced pulmonary remodeling characterized by goblet cell hyperplasia and parenchymal interstitial fibrosis. Goblet cell hyperplasia was STAT6 dependent; however, parenchymal interstitial fibrosis was not. OSM also induced airway hyperresponsiveness in WT mice that was abolished in STAT6(-/-) mice. OSM stimulated an inflammatory signature in the lungs of WT mice that demonstrated STAT6-dependent regulation of Th2 cytokines (IL-4, IL-13), chemokines (eotaxin-1/2, MCP-1, keratinocyte chemoattractant), and extracellular matrix modulators (tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase-13), but STAT6-independent regulation of IL-4Rα, total lung collagen, collagen-1A1, -1A2 mRNA, and parenchymal collagen and α smooth muscle actin accumulation. Thus, overexpression of mOSM induces STAT6-dependent pulmonary eosinophilia, mucous/goblet cell hyperplasia, and airway hyperresponsiveness but STAT6-independent mechanisms of lung tissue extracellular matrix accumulation. These results also suggest that eosinophil or neutrophil accumulation in mouse lungs is not required for OSM-induced lung parenchymal collagen deposition and that OSM may have unique roles in the pathogenesis of allergic and fibrotic lung disease.


Multilocus microsatellite analysis of 'Candidatus Liberibacter asiaticus' associated with citrus Huanglongbing worldwide.
Huanglongbing (HLB) is one of the most destructive citrus diseases in the world. The disease is associated with the presence of a fastidious, phloem-limited α- proteobacterium, 'Candidatus Liberibacter asiaticus', 'Ca. Liberibacter africanus' or 'Ca. Liberibacter americanus'. HLB-associated Liberibacters have spread to North America and South America in recent years. While the causal agents of HLB have been putatively identified, information regarding the worldwide population structure and epidemiological relationships for 'Ca. L. asiaticus' is limited. The availability of the 'Ca. L. asiaticus' genome sequence has facilitated development of molecular markers from this bacterium. The objectives of this study were to develop microsatellite markers and conduct genetic analyses of 'Ca. L. asiaticus' from a worldwide collection. Two hundred eighty seven isolates from USA (Florida), Brazil, China, India, Cambodia, Vietnam, Taiwan, Thailand, and Japan were analyzed. A panel of seven polymorphic microsatellite markers was developed for 'Ca. L. asiaticus'. Microsatellite analyses across the samples showed that the genetic diversity of 'Ca. L. asiaticus' is higher in Asia than Americas. UPGMA and STRUCTURE analyses identified three major genetic groups worldwide. Isolates from India were genetically distinct. East-southeast Asian and Brazilian isolates were generally included in the same group; a few members of this group were found in Florida, but the majority of the isolates from Florida were clustered separately. eBURST analysis predicted three founder haplotypes, which may have given rise to three groups worldwide. Our results identified three major genetic groups of 'Ca. L. asiaticus' worldwide. Isolates from Brazil showed similar genetic makeup with east-southeast Asian dominant group, suggesting the possibility of a common origin. However, most of the isolates recovered from Florida were clustered in a separate group. While the sources of the dominant 'Ca. L. asiaticus' in Florida were not clearly understood, the less-pervasive groups may have been introduced directly from Asia or via Brazil. Notably, the recent outbreak of HLB in Florida probably occurred through multiple introductions. Microsatellite markers developed in this study provide adequate discriminatory power for the identification and differentiation of closely-related isolates, as well as for genetic studies of 'Ca. L. asiaticus'.


Genetics of the ST serotype system in Tetrahymena pyriformis, syngen 1.
Genetic analyses using lines of Tetrahymena pyroformis manifesting different serotypes indicate that the St serotypes are governed by alleles at a single genetic locus. These alleles are termed St(A) and St(C). The St locus is not closely linked to any of the other well-studied loci examined. Differentiation in St(A)/St(C) heterozygotes follows a pattern very similar to that observed with lines heterozygous at the other loci. Initially both alleles are expressed, but as the synclone divides, lines develop that manifest one allele or the other but not both. The time of differentiation is very early in the clonal life cycle, and the output ratio is eccentric. The pattern of development of the St locus places it in a category with the mating type and H serotype loci.


Carotid artery direct access for mechanical thrombectomy: the Carotid Artery Puncture Evaluation (CARE) study.
In acute ischemic stroke due to anterior large vessel occlusion (AIS-LVO), accessing the target occluded vessel for mechanical thrombectomy (MT) is sometimes impossible through the femoral approach. We aimed to evaluate the safety and efficacy of direct carotid artery puncture (DCP) for MT in patients with failed alternative vascular access. We retrospectively analyzed data from 45 stroke centers in France, Switzerland and Germany through two research networks from January 2015 to July 2019. We collected physician-centered data on DCP practices and baseline characteristics, procedural variables and clinical outcome after DCP. Uni- and multivariable models were conducted to assess risk factors for complications. From January 2015 to July 2019, 28 149 MT were performed, of which 108 (0.39%) resulted in DCP due to unsuccessful vascular access. After DCP, 77 patients (71.3%) had successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b) and 28 (25.9%) were independent (modified Rankin Scale (mRS) score 0-2) at 3 months. 20 complications (18.5%) attributed to DCP occurred, all of them during or within 1 hour of the procedure. Complications led to extension of the intubation time in the intensive care unit in 7 patients (6.4%) and resulted in death in 3 (2.8%). The absence of use of a hemostatic closure device was associated with a higher complication risk (OR 3.04, 95% CI 1.03 to 8.97; p=0043). In this large multicentric study, DCP was scantly performed for vascular access to perform MT (0.39%) in patients with AIS-LVO and had a high rate of complications (18.5%). Our results provide arguments for not closing the cervical access by manual compression after MT.


An intrahepatic cavoportal collateral pathway due to a liver hydatid cyst obstructing the inferior vena cava.
Congenital or acquired obstruction of the inferior vena cava may lead to the development of collateral pathways with tributary vein to portal system. We present a patient with intrahepatic cavoportal collateral pathway due to hepatic hydatid cyst.


Treatment results of the TPOG-NHL92 protocols for childhood non-Hodgkin's lymphomas in Taiwan: a report from the Taiwan Pediatric Oncology Group (TPOG)
A nation-wide chemotherapeutic trial for childhood non-Hodgkin's lymphoma (NHL) was conducted by the Taiwan Pediatric Oncology Group (TPOG). Four TPOG-NHL92 protocols based on stage and histology were activated in 1992: TPOG-92LD (treatment duration: 8 months) was used for localized (stages I/II) NHL with any histology, 92LB (2 years), 92SNC (5 months), and 92LC (1 year) for advanced (stages III/IV) lymphoblastic (LB), small non-cleaved cell (SNC), and large cell (LC) lymphoma, respectively. From January 1992 through June 1998, 200 children with newly diagnosed NHL from 13 member hospitals of TPOG were enrolled. There were 140 boys and 60 girls. Their ages at diagnosis ranged from 2.4 months to 18.3 years with a median of 8.2 years. There were 54 (27.3%) patients with LB, 94 (47.5%) with SNC including B-cell acute lymphoblastic leukemia (B-ALL), and 50 (25.2%) with LC. Stages I, II, III, and IV (including B-ALL) of the disease comprised 5%, 10%, 43%, and 42% of cases, respectively. There were 176 patients eligible for evaluation of treatment results. The remission rate of induction was 82.4%, induction failed in 22 (12.5%) patients, and nine patients died during induction. As of August 31, 1999, 26 patients relapsed, six died during remission, one patient developed secondary acute myelomonocytic leukemia, and 105 patients remained in continuous remission with a median remission duration of 49 months. The event-free survival (EFS) at 7 years was 63.5%, 61.5% and 65% for LB, SNC, and LC groups (P = 0.8298). The 7-year EFS for stages I/II, III, and IV of the disease was 73%, 68.9%, and 50.3% (P = 0.0212), respectively. We concluded that following the strategy of stratification of therapy, only disease stages had prognostic significance in this study. More efforts are needed to improve our treatment results.


Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae.
Exposure network analysis and molecular epidemiologic methods were used to analyze the emergence and regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae over a 1-year period. Although 40 patients and 26 health care facilities were affected, 1 long-term acute care hospital played a critical role in the convergence of patients at high risk, amplification by cross-infection, and dissemination of these multidrug-resistant bacteria. Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are an emerging antibiotic resistance threat with demonstrated epidemic potential. We conducted an outbreak investigation of KPC-producing Enterobacteriaceae among patients of acute and long-term acute care hospitals (LTACHs) in 4 adjacent counties in Indiana and Illinois from 1 January 2008 through 31 December 2008 (cases). The study used traditional and molecular epidemiologic methods and an adaptation of social network analysis ("exposure network analysis"). Clinical records for 40 (95%) of 42 patients were available. Patients were mostly older with multiple comorbid conditions. Eleven patients (27.5%) died during the index hospitalization or were discharged to hospice; 23 (57.5%) were discharged to a nursing home, and 4 (10.0%) were discharged to home. One LTACH (LTACH-A) was central to the regional outbreak: 24 (60%) of 40 cases were linked to LTACH-A, and at least 10 patients (25%) acquired KPC there. Of 16 cases not linked to LTACH-A, 12 (75%) were linked to 3 nursing homes. Only 4 patients (10%) definitely acquired KPC during an acute care hospital stay. Molecular typing revealed the 31 available KPC-positive K. pneumoniae isolates to be similar and to cluster with epidemic multilocus sequence type 258; 2 KPC-positive Escherichia coli isolates were unique. We observed extensive transfer of KPC-positive patients throughout the exposure network of 14 acute care hospitals, 2 LTACHs, and 10 nursing homes. Although few cases were identified at most institutions, many facilities were affected. Successful control of KPC-producing Enterobacteriaceae will require a coordinated, regional effort among acute and long-term health care facilities and public health departments.


Characterization of host response to Cryptococcus neoformans through quantitative proteomic analysis of cryptococcal meningitis co-infected with HIV.
Cryptococcal meningitis is the most common opportunistic fungal infection causing morbidity and mortality (>60%) in HIV-associated immunocompromised individuals caused by Cryptococcus neoformans. Molecular mechanisms of cryptococcal infection in brain have been studied using experimental animal models and cell lines. There are limited studies for the molecular understanding of cryptococcal meningitis in human brain. The proteins involved in the process of invasion and infection in human brain still remains obscure. To this end we carried out mass spectrometry-based quantitative proteomics of frontal lobe brain tissues from cryptococcal meningitis patients and controls to identify host proteins that are associated with the pathogenesis of cryptococcal meningitis. We identified 317 proteins to be differentially expressed (≥2-fold) from a total of 3423 human proteins. We found proteins involved in immune response and signal transduction to be differentially expressed in response to cryptococcal infection in human brain. Immune response proteins including complement factors, major histocompatibility proteins, proteins previously known to be involved in fungal invasion to brain such as caveolin 1 and actin were identified to be differentially expressed in cryptococcal meningitis brain tissues co-infected with HIV. We also validated the expression status of 5 proteins using immunohistochemistry. Overexpression of major histocompatibility complexes, class I, B (HLA-B), actin alpha 2 smooth muscle aorta (ACTA2) and caveolin 1 (CAV1) and downregulation of peripheral myelin protein 2 (PMP2) and alpha crystallin B chain (CRYAB) in cryptococcal meningitis were confirmed by IHC-based validation experiments. This study provides the brain proteome profile of cryptococcal meningitis co-infected with HIV for a better understanding of the host response associated with the disease.


Functional Zwitterionic Polyurethanes: State-of-the-Art Review.
Recent advancements in bioengineering and medical devices have been greatly influenced and dominated by synthetic polymers, particularly polyurethanes (PUs). PUs offer customizable mechanical properties and long-term stability, but their inherent hydrophobic nature poses challenges in practically biological application processes, such as interface high friction, strong protein adsorption, and thrombosis. To address these issues, surface modifications of PUs for generating functionally hydrophilic layers have received widespread attention, but the durability of generated surface functionality is poor due to irreversible mechanical wear or biodegradation. As a result, numerous researchers have investigated bulk modification techniques to incorporate zwitterionic polymers or groups onto the main or side chains of PUs, thereby improving their hydrophilicity and biocompatibility. This comprehensive review presents an extensive overview of notable zwitterionic PUs (ZPUs), including those based on phosphorylcholine (PC), sulfobetaine (SB), and carboxybetaine (CB). The review explores their wide range of biomedical applications, from blood-contacting devices to antibacterial coatings, fouling-resistant marine coatings, separation membranes, lubricated surfaces, and shape memory and self-healing materials. Lastly, the review summarizes the challenges and future prospects of ZPUs in biological applications. This article is protected by copyright. All rights reserved.


Bulky N(,N)-(di)alkylethane-1,2-diamineplatinum(II) compounds as precursors for generating unsymmetrically substituted platinum(IV) complexes.
Investigations of the influence of bulky groups in the equatorial ligand sphere of platinum(IV) compounds on the complexes' stability and reaction pattern were performed. Four dihydroxidoplatinum(IV) complexes were reacted with anhydrides, cinnamoyl chloride, and n-propyl isocyanate and yielded the symmetric dicarboxylated products or, if steric hindrance was observed, unsymmetrically substituted monocarboxylated analogues. With the aim of raising the steric demand, the following ligands were chosen: N-cyclohexylethane-1,2-diamine, N,N-dimethylethane-1,2-diamine, N,N-diethylethane-1,2-diamine, and N,N-diisopropylethane-1,2-diamine. All of the novel complexes were characterized by electrospray ionization mass spectrometry (ESI-MS), one- and two-dimensional NMR spectroscopy, elemental analysis, and reversed-phase HPLC; complexes B3, C3, C6, and D4 were also analyzed by X-ray diffraction. Additionally, the cytotoxicities of 10 compounds toward the cisplatin-sensitive cell line CH1 and the intrinsically cisplatin-resistant cell lines A549 and SW480 were investigated, and IC50 values down to the nanomolar range were found. To aid in the interpretation of structure-activity relationships, log k(w) values as a measure for the lipophilicity were determined for all of the new complexes, and the rates of reduction of C1, C3, and C4 relative to satraplatin were determined by means of NMR spectroscopy and ESI-MS.


Choline-mediated hepatic lipid homoeostasis in yellow catfish: unravelling choline's lipotropic and methyl donor functions and significance of ire-1α signalling pathway.
Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline's methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid β-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.


Auranofin is an apoptosis-simulating agent with in vitro and in vivo anti-leishmanial activity.
Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs worldwide. This is mainly because cutaneous leishmaniasis is frequently a disease of impoverished populations in countries where funds are limited for research and patient care. However, the health burden of individuals in endemic areas mandates readily available, effective, and safe treatments. Of the existing cutaneous leishmaniasis therapeutics, many are growth inhibitory to Leishmania parasites, potentially creating dormant parasite reservoirs that can be activated when host immunity is compromised, enabling the reemergence of cutaneous leishmaniasis lesions or worse spread of Leishmania parasites to other body sites. To accelerate the identification and development of novel cutaneous leishmaniasis therapeutics, we designed an integrated in vitro and in vivo screening platform that incorporated multiple Leishmania life cycles and species and probed a focused library of pharmaceutically active compounds. The objective of this phenotypic drug discovery platform was the identification and prioritization of bona fide cytotoxic chemotypes toward Leishmania parasites. We identified the Food and Drug Administration-approved drug auranofin, a known inhibitor of Leishmania promastigote growth, as a potent cytotoxic anti-leishmanial agent and inducer of apoptotic-like death in promastigotes. Significantly, the anti-leishmanial activity of auranofin transferred to cell-based amastigote assays as well as in vivo murine models. With appropriate future investigation, these data may provide the foundation for potential exploitation of gold(I)-based complexes as chemical tools or the basis of therapeutics for leishmaniasis. Thus, auranofin may represent a prototype drug that can be used to identify signaling pathways within the parasite and host cell critical for parasite growth and survival.


Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study.
Patients starting antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression. An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI) <16 kg/m(2) or CD4(+) lymphocyte count <50 cells/microL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP) were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43), compared to 1.06 mmol/L (IQR: 0.89, 1.27) among those who died (p<0.01). Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95). The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience. Low serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.


Genetic studies of cell fusion induced by herpes simplex virus type 1.
Eight cell fusion-causing syn mutants were isolated from the KOS strain of herpes simplex virus type 1. Unlike the wild-type virus, the mutants produced plaques containing multinucleated cells, or syncytia. Fusion kinetics curves were established with a Coulter Counter assay for the mutants and wild-type virus in single infections of human embryonic lung (HEL) cells, for the mutants and wild-type virus in mixed infections (dominance test), and for pairs of mutants in mixed infections (complementation test). In single infections, fusion began 4 to 6 h after infection and proceeded with an exponential decrease in the number of small single cells. At some later time that was characteristic of the mutant, there was a significant reduction in the rate of fusion for all but possibly one of the mutants. Although the wild-type virus did not produce syncytial plaques, it did induce a small amount of fusion that stopped abruptly about 2 h after it started. These data are consistent with the hypothesis that both mutants and wild type induce an active fusion inducer and that the activity of this inducer is subsequently inhibited. The extent of fusion is apparently determined by the length of the interval during which the fusion inducer is active. That fusion is actively inhibited in wild-type infections is indicated by the observation that syn mutant-infected cells fused more readily with uninfected cells than with wild-type infected cells. Fusion was decreased in mixed infections with the mutants and wild-type virus, but the mutants displayed a codominant fusion phenotype. Fusion was not decreased in mixed infection with pairs of mutants, indicating that the mutants, with one possible exception, are members of the same complementation group. A linkage map was established for six of the mutants by analysis of recombination frequencies.


"The Duty of Their Elders" - Doctors, Coaches, and the Framing of Youth Football's Health Risks, 1950s-1960s.
After World War II, organized tackle football programs for boys younger than high school age grew enormously in popularity in the United States, prompting concerns from pediatricians and educators about the sport's physical and emotional health effects. At the same time, sports medicine was emerging as a sub-specialty. Examining how American sports medicine doctors and football coaches established their professional authority on youth football safety in the 1950s and 1960s reveals how their justifications for this collision sport were connected to broader cultural trends. Doctors and coaches, who were virtually all men, emphasized their firsthand knowledge of an all-male sport that was widely promoted as a means of teaching boys to become men. They insisted that proper supervision and equipment were sufficient to protect young athletes. Their arguments for youth football's benefits were based on the belief that men best knew how to impart desired values such as loyalty, patriotism and discipline to boys. In framing football's health risks as manageable with adult supervision, coaches and sports medicine doctors played a crucial role in promoting the vision of American manhood associated with tackle football.


The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association.
Loss-of-function mutations in the gene encoding FAM161A were recently discovered as the cause for RP28, an autosomal recessive form of retinitis pigmentosa. To initiate the characterization of the cellular role of FAM161A in the retina, we focused on its subcellular localization and conducted in vitro studies to identify FAM161A-interacting proteins and associated cellular structures. Immunohistochemistry revealed the presence of mouse FAM161A in the photoreceptor inner segments, the synaptic regions of the outer and inner plexiform layers and the ganglion cells. In mouse and human retinal sections from unfixed eyes, FAM161A localized to the ciliary region linking photoreceptor outer and inner segments. High-resolution immunofluorescence and immunoelectron microscopy mapped FAM161A to the connecting cilium, the basal body region and the adjacent centriole. Ectopic FAM161A was found in the centrosome and concentrated at the base of primary cilia in cultured cells. In addition, overexpressed FAM161A was clearly associated with microtubules during interphase and mitosis. The presence of FAM161A increased microtubule acetylation and stabilization. We further show that the evolutionarily conserved UPF0564 domain of FAM161A is crucial for its binding to microtubules and mediates homo- and heterotypic FAM161A and FAM161B interaction. In conclusion, our study shows that FAM161A is a microtubule-associated ciliary protein presumably involved in microtubule stabilization to maintain the microtubule tracks and/or in transport processes along microtubules in photoreceptors and other retinal cell types.


Age and Ageing During the COVID-19 Pandemic; Challenges to Public Health and to the Health of the Public.
The distribution of the SARS-CoV-2 virus has reached pandemic proportions. While COVID-19 can affect anyone, it is particularly hazardous for those with "co-morbidities." Older age is an especially strong and independent risk factor for hospital and ICU admission, mechanical ventilation and death. Health systems must protect persons at any age while paying particular attention to those with risk factors. However, essential freedoms must be respected and social/psychological needs met for those shielded. The example of the older population in Israel may provide interesting public health lessons. Relatively speaking, Israel is a demographically young country, with only 11.5% of its population 65 years and older as compared with the OECD average of >17%. As well, a lower proportion of older persons is in long-term institutions in Israel than in most other OECD countries. The initiation of a national program to protect older residents of nursing homes and more latterly, a successful vaccine program has resulted in relatively low rates of serious COVID-19 related disease and mortality in Israel. However, the global situation remains unstable and the older population remains at risk. The rollout of efficacious vaccines is in progress but it will probably take years to cover the world's population, especially those living in low- and middle-income countries. Every effort must be made not to leave these poorer countries behind. Marrying the principles of public health (care of the population) with those of geriatric medicine (care of the older individual) offers the best way forward.


A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus.
Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.


Support to family carers of patients with frontotemporal dementia.
To examine the provision of support to patients with frontotemporal dementia (FTD) and their family carers compared with patients with early onset Alzheimer's dementia (AD) and their carers, and the carers' satisfaction with the support. Data came from 60 dyads of patients with dementia and their principal family carers, 23 subjects with frontotemporal dementia and their 23 carers, and 37 subjects with early onset Alzheimer's disease and their 37 carers. Patients with a frontotemporal dementia diagnosis were significantly more frequently offered stays in nursing homes (p = 0.04). Carers of patients with frontotemporal dementia were significantly less satisfied with the provision of information about the disease compared with carers of early onset Alzheimer's disease patients (p = 0.05) and were significantly less satisfied with counseling and follow-up advice (p = 0.05). Changes of personality in patients with frontotemporal dementia may be the major reason why they were offered more stays in institutions. These family carers tend to be less satisfied with the provision of support they received from the specialist health service compared to carers of Alzheimer's disease patients, and are in need of more, and other forms of support.


Venus upper atmosphere neutral gas composition: first observations of the diurnal variations.
Measurements of the composition, temperature, and diurnal variations of the major neutral constituents in the thermosphere of Venus are being made with a quadrupole mass spectrometer on the Pioneer Venus orbiter. Concentrations of carbon dioxide, carbon monoxide, molecular nitrogen, atomic oxygen, and helium are presented, in addition to an empirical model of the data. The concentrations of the heavy gases, carbon dioxide, carbon monoxide, and molecular nitrogen, rapidly decrease from the evening terminator toward the nightside; the concentration of atomic oxygen remains nearly constant and the helium concentration increases, an indication of a nightside bulge. The kinetic temperature inferred from scale heights drops rapidly from 230 K at the terminator to 130 K at a solar zenith angle of 120 degrees , and to 112 K at the antisolar point.


A quantum theoretical explanation for probability judgment errors.
A quantum probability model is introduced and used to explain human probability judgment errors including the conjunction and disjunction fallacies, averaging effects, unpacking effects, and order effects on inference. On the one hand, quantum theory is similar to other categorization and memory models of cognition in that it relies on vector spaces defined by features and similarities between vectors to determine probability judgments. On the other hand, quantum probability theory is a generalization of Bayesian probability theory because it is based on a set of (von Neumann) axioms that relax some of the classic (Kolmogorov) axioms. The quantum model is compared and contrasted with other competing explanations for these judgment errors, including the anchoring and adjustment model for probability judgments. In the quantum model, a new fundamental concept in cognition is advanced--the compatibility versus incompatibility of questions and the effect this can have on the sequential order of judgments. We conclude that quantum information-processing principles provide a viable and promising new way to understand human judgment and reasoning.


A plant-based chemical genomics screen for the identification of flowering inducers.
Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study. Here we describe the set-up of the screening platform and various issues and pitfalls that need to be addressed in order to perform a chemical genomics screening on Arabidopsis plantlets. We describe the choice for a molecular marker, in combination with a sensitive reporter that's active in plants and is sufficiently sensitive for detection. In this particular screen, the firefly Luciferase marker was used, fused to the regulatory sequences of the floral meristem identity gene APETALA1 (AP1), which is an early marker for flowering. Using this screening platform almost 9000 compounds were screened, in triplicate, in 96-well plates at a concentration of 25 µM. One of the identified potential flowering inducing compounds was studied in more detail and named Flowering1 (F1). F1 turned out to be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more potent than SA in the induction of flowering. The effect could be confirmed by watering Arabidopsis plants with SA or F1, in which F1 gave a significant reduction in time to flowering in comparison to SA treatment or the control. In this study a chemical genomics screening platform was developed to discover compounds that can induce flowering in Arabidopsis. This platform was used successfully, to identify a compound that can speed-up flowering in Arabidopsis.


Revision of the family Acidopsidae Števčić, 2005, and the systematic position of Typhlocarcinodes Alcock, 1900, Caecopilumnus Borradaile, 1902, and Raoulia Ng, 1987, with descriptions of two new genera and five new species (Crustacea: Brachyura: Goneplacoidea).
The family Acidopsidae Števčić, 2005, is revised; and two subfamilies are recognised. The Acidopsinae Števčić, 2005, is characterised by the coxal male opening, a quadrate basal antennal article and vulvae arranged near the median longitudinal thoracic sternal groove. Three genera are included in the Acidopsinae: Acidops Stimpson, 1871 (with two species), Parapilumnus Kossmann, 1877 (with two species) and Crinitocinus gen. nov. (monotypic for Pilumnus alcocki Borradaile, 1902). The Raouliinae Števčić, 2005 (= Typhlocarcinodidae Števčić, 2005; Caecopilumnidae Števčić, 2011), is characterised by its coxo-sternal male opening, a short basal antennal article which is distinctly wider than long and vulvae arranged submedially on thoracic sternite 6. Four genera are included in the Raouliinae: Raoulia Ng, 1987 (with five species, three of which are described as new), Caecopilumnus Borradaile, 1902 (with three species of which one is described as new), Typhlocarcinodes Alcock, 1900 (monotypic) and Thecaplax gen. nov. (for one new species).


Carbon dioxide in the critically ill: too much or too little of a good thing?
Hypercapnia and hypocapnia commonly complicate conditions that are present in critically ill patients. Both conditions have important physiologic effects that may impact the clinical management of these patients. For instance, hypercapnia results in bronchodilation and enhanced hypoxic vasoconstriction, leading to improved ventilation/perfusion matching. Hypocapnia reduces cerebral blood volume through arterial vasoconstriction. These effects have also been exploited for therapeutic aims. In patients with traumatic brain injury (TBI), hypocapnia is often utilized to control intracranial pressure. However, this effect is not sustained, and prolonged hypocapnia increases the risk of mortality and severe disability in patients with TBI. Hypercapnia and hypercapnic acidosis are common consequences of lung-protective ventilation in ARDS. Hypercapnic acidosis reduces ischemic lung injury and preserves lung compliance, but concern has arisen over hypercapnia-induced immunosuppression and the potential for bacterial proliferation in sepsis. Experimental studies suggest that buffering hypercapnic acidosis attenuates these effects, whereas hypocapnia appears to potentiate lung injury through increased capillary permeability and decreased lung compliance. Several areas of uncertainty surround the role of hypercapnia/hypocapnia in treating TBI and ARDS. Current data support recommendations to avoid hypocapnia in treating TBI, with the exception of emergent treatment of elevated intracranial pressure, while awaiting definitive management. Permissive hypercapnia is commonly accepted as a consequence of lung-protective ventilation in ARDS, but there is insufficient evidence to support the induction of hypercapnic acidosis in clinical practice. Buffering hypercapnic acidosis should be considered only for a specific clinical indication (eg, hemodynamic instability). For clinicians choosing to buffer hypercapnic acidosis, tris-hydroxymethyl aminomethane is recommended over sodium bicarbonate, as it is more effective in correcting pH and is not associated with increased carbon dioxide production. Future studies should aim to address these areas of uncertainty to help guide clinicians in the therapeutic use and management of hypercapnia/hypocapnia in critically ill patients.


Peripheral control and lateralization of birdsong.
Recent studies on several species of oscine songbirds show that they achieve their varied vocal performances through coordinated activity of respiratory, syringeal, and other vocal tract muscles in ways that take maximum advantage of the acoustic flexibility made possible by the presence of two independently controlled sound sources in their bipartite syrinx (vocal organ). During song, special motor programs to respiratory muscles alter the pattern of ventilation to maintain the supply of respiratory air and oxygen to permit songs of long duration, high syllable repetition rates, or maximum spectral complexity. Each side of the syrinx receives its own motor program that, together with that sent to respiratory muscles, determines the acoustic properties of the ipsilaterally produced sound. The acoustic expression of these bilaterally distinct, phonetic motor patterns depends on the action of dorsal syringeal adductor muscles that, by opening or closing the ipsilateral side of the syrinx to airflow, determine the amount each side contributes to song. The syringeally generated sound is further modified by muscles that control the shape of the vocal tract. Different species have adopted different motor strategies that use the left and right sides of the syrinx in patterns of unilateral, bilateral, alternating, or sequential phonation to achieve the differing temporal and spectral characteristics of their songs. As a result, the degree of song lateralization probably varies between species to form a continuum from unilateral dominance to bilateral equality.


Comparison of marginal fit of 3 different metal-ceramic systems: an in vitro study.
The aim of this study was to compare the marginal adaptation of metal-ceramic crowns made with 3 different metal substructures. Seventy-five gypsum dies were fabricated from a master steel die. They were randomly divided into 3 groups of 25 dies each. A metal coping was prepared on each die using a different technique for each group: composite alloy, electroforming, and cast high-noble alloy. Ceramic was baked on all of the samples following the same protocol and simulating the shape and size of a maxillary central incisor. All specimens were evaluated under a stereomicroscope at 200x magnification. The marginal gap was measured at 8 different points on each specimen before and after ceramic application and also on the master steel die. A total of 3,600 measurements was evaluated. The results were statistically elaborated by means of a t test and one-way analysis of variance (ANOVA). The ANOVA revealed a significant difference in mean marginal gap before and after ceramic application within each group. Electroforming (mean 32 microns) and high-noble alloy (mean 31 microns) showed better marginal fit after ceramic application and on the master steel die compared to composite alloy (mean 68 microns; P < 0.0001). Marginal gaps are influenced by the application of ceramic and by the alloy used for the substructure, and the values obtained were within the limits of clinical acceptability (70 microns).


Rapid determination of transferrin isoforms by immunoaffinity liquid chromatography and electrospray mass spectrometry.
Congenital disorders of glycosylation (CDG) are autosomal recessive disorders that produce increased serum carbohydrate-deficient transferrin (CDT) isoforms. Methods to resolve CDT from fully glycosylated transferrin (Trf) have been based on a neutral shift in the isoelectric focusing (IEF) pattern or on a reduction in the negative charge, allowing resolution by anion-exchange chromatography. Our purpose was to develop a method of resolution and relative quantification of Trf isoforms using online immunoaffinity liquid chromatography-mass spectrometry (LC-MS). Serum (25 microL) was diluted with 100 microL of water before application to an immunoaffinity column that sequestered Trf isoforms. Trf isoforms were eluted from the immunoaffinity column, concentrated on a C4 column, eluted from the C4 column, and introduced into the mass spectrometer. Analysis of the Trf isoforms was entirely automated and completed in <10 min per sample. The LC-MS method demonstrated that the major abnormal Trf isoforms in CDG lack one complete oligosaccharide structure (mono-oligosaccharide) or both oligosaccharide structures (a-oligosaccharide), but not the sialic acids, as presumed on the basis of IEF methods. Calculation of relative ratios among three possible species (mono-/di-oligosaccharide and a-/di-oligosaccharide) is reproducible [mean intra- and interassay CVs were 9.3% (n = 10) and 10% (n = 5), respectively]. A reference range for patients <18 years was determined by analysis of 209 samples (for mono-/di-oligosaccharide, the median was 0.041 and the range was 0.018-0.083; for a-/di-oligosaccharide, the median was 0.007 and the range was 0.002-0.036). Comparison of data obtained with an affinity chromatography-IEF method and the LC-MS method demonstrated equivalence in the interpreted results (n = 170). Advantages of the LC-MS method include improved sensitivity, minimal sample preparation, and an analysis time of <10 min. The method was automated, which allowed high throughput, with >100 samples analyzed in a single day. Moreover, the nature of the oligosaccharide defect in CDG is accurately reflected by mass resolution, and subtle oligosaccharide truncations may also be detected by this method.


Visible-Light-Sensitive Triazine-Coated Silica Nanoparticles: A Dual Role Approach to Polymer Nanocomposite Materials with Enhanced Properties.
Nanocomposite materials are of great interest because of their superior properties. Besides the traditional synthesis methods that require high temperatures or toxic solvents, photopolymerization technology provides a simple, low-cost, and environmentally friendly route in preparing nanocomposites. In this research, the preparation of blue-light-sensitive triazine derivative-coated silica nanoparticles is presented. The resulting triazine-coated silica nanoparticles can play a dual role, i.e., acting as both photoinitiators to trigger photopolymerization reactions under the irradiation of LED@410 nm and fillers to endow the produced photopolymer nanocomposite materials with enhanced properties. Specifically, the triazine-coated silica nanoparticles can successfully induce free radical polymerization of trimethylolpropane triacrylate efficiently under the irradiation of LED@410 nm and demonstrate comparable photoinitiation ability to the triazine derivative-based photoinitiator. The effects of different loading amounts of triazine-coated silica nanoparticles toward the photopolymerization kinetics are also evaluated. By coating with the triazine derivative, the nanoparticles show good dispersion in the polymer matrix and significantly reduce the shrinkage of the samples during the photopolymerization. Moreover, the photocured nanocomposites exhibit enhanced migration stability and mechanical properties when an optimal amount of triazine-coated silica nanoparticles is added in the formulation.


Evidence for the Rhythmic Perceptual Sampling of Auditory Scenes.
Converging results suggest that perception is controlled by rhythmic processes in the brain. In the auditory domain, neuroimaging studies show that the perception of sounds is shaped by rhythmic activity prior to the stimulus, and electrophysiological recordings have linked delta and theta band activity to the functioning of individual neurons. These results have promoted theories of rhythmic modes of listening and generally suggest that the perceptually relevant encoding of acoustic information is structured by rhythmic processes along auditory pathways. A prediction from this perspective-which so far has not been tested-is that such rhythmic processes also shape how acoustic information is combined over time to judge extended soundscapes. The present study was designed to directly test this prediction. Human participants judged the overall change in perceived frequency content in temporally extended (1.2-1.8 s) soundscapes, while the perceptual use of the available sensory evidence was quantified using psychophysical reverse correlation. Model-based analysis of individual participant's perceptual weights revealed a rich temporal structure, including linear trends, a U-shaped profile tied to the overall stimulus duration, and importantly, rhythmic components at the time scale of 1-2 Hz. The collective evidence found here across four versions of the experiment supports the notion that rhythmic processes operating on the delta time scale structure how perception samples temporally extended acoustic scenes.


Predictors of low back pain disability.
Low back pain has major socioeconomic implications; much of the costs relate to disability and compensation. Theoretically, the early identification of patients at risk to become disabled from a low back episode would lead to more aggressive intervention and reduction of subsequent disability. Low back disability is related to occupational, psychosocial, diagnostic, demographic, anthropometric, health behavior, and injury factors that have been reported in the literature. The multiattribute utility model is a new experimental approach to prediction of disability. The relative weights of the various factors that might be predictive of low back disability are determined by a panel of experts. Although this model is not yet scientifically proven, it offers a promising method of answering the question, "Can low back disability be predicted?"


The Relationship Between Prescribed, Perceived, and Actual Delivery Intensity in Cricket Pace Bowling.
To investigate the relationship between prescribed (preDI), perceived (perDI), and actual delivery intensity (actDI) in cricket pace bowling. Fourteen male club-standard pace bowlers (mean [SD]: age 24.2 [3.2] y) completed 1 bowling session comprising 45 deliveries. The first 15 deliveries composed the warm-up, where participants bowled 3 deliveries each at a preDI of 60%, 70%, 80%, 90%, and 95%. Bowlers reported the perDI after each delivery. The fastest delivery in the session was used as a reference to calculate relative ball-release speed for the warm-up deliveries, with this measure representing the actDI. Ball-release speed was captured by a radar gun. For perDI, there was a very large relationship with preDI (rs = .90, P < .001). Similarly, for actDI, there was a large relationship with preDI (rs = .52, P < .001). Higher concordance was observed between perDI and preDI from 60% to 80% preDI. A plateau was observed for actDI from 70% to 95% preDI. The relationship between perDI and actDI was very large and large with respect to preDI, indicating that both variables can be used to monitor delivery intensity against the planned intensity and thus ensure healthy training adaptation. The optimal preDI that allowed pace bowlers to operate at submaximal perDI but still achieve close to maximal ball-release speeds was 70%. Bowling at the optimal preDI may significantly reduce the psychophysiological load per delivery in exchange for a trivial loss in ball-release speed.


Revision posterior cruciate ligament reconstruction using a modified tibial-inlay double-bundle technique.
Revision of an unsuccessful posterior cruciate ligament (PCL) reconstruction is a complicated clinical procedure with an outcome that may be less satisfactory than that after a typical primary PCL reconstruction. The purpose of this study was to evaluate the reasons for failure of primary PCL reconstructions and to determine the clinical outcomes of revision PCL reconstruction after a minimum of two years of follow-up. Twenty-eight revision PCL reconstructions were performed by a single surgeon. Four cases that involved diverse operative procedures and two cases with a duration of follow-up of less than twenty-four months were excluded; the outcomes of the remaining twenty-two reconstructions were analyzed at the time of the latest follow-up (at least twenty-four months postoperatively). A technique involving a double femoral tunnel, a modified tibial inlay, and Achilles tendon allograft was used in all twenty-two of these revision reconstructions. Seventeen patients (77%) underwent concomitant reconstruction of posterolateral corner structures. Knee stability was measured with use of posterior stress radiography as well as with a maximum manual displacement test utilizing a KT1000 arthrometer. The subjective International Knee Documentation Committee (IKDC) and objective Orthopädische Arbeitsgruppe Knie (OAK) scoring systems were used to evaluate the clinical outcome. Nine (41%) of the primary PCL reconstructions most likely failed because of a single factor and thirteen (59%) most likely failed because of multiple factors. The most common probable causes of failure were posterolateral rotatory instability (seventeen knees, 77%) and improper graft tunnel placement (nine knees, 41%). Side-to-side differences during posterior stress radiography improved from 9.9 ± 2.8 mm preoperatively to 2.8 ± 1.8 mm at the time of the latest follow-up (p < 0.001). The subjective and objective clinical scores at the latest follow-up evaluation were significantly better than the preoperative scores (p < 0.001). Arthroscopic revision PCL reconstruction with use of the modified tibial-inlay double-bundle technique improved knee stability, as measured with posterior stress radiography and clinically, and outcomes. Associated posterolateral rotatory instability should be surgically corrected during PCL reconstruction to prevent graft failure resulting from abnormal opening of the lateral aspect of the tibiofemoral joint.


[Acute closure-angle glaucoma after treatment with ipratropium bromide and salbutamol aerosols].
We report a case of acute angle-closure glaucoma in a patient treated with bronchodilator nebulization. An 82-year-old man with chronic obstructive bronchopathy was treated for acute respiratory decompensation with salbutamol and ipratropium bromide aerosols. Twenty-four hours after beginning the treatment, the patient developed acute angle-closure glaucoma which resolved rapidly with appropriate treatment. The case emphasizes the importance of precautionary measures (waterproof glasses and inhalation masks). In addition patients with a high risk of angle-closure glaucoma should be detected prior to prescribing bronchodilating aerosols.


Peritonsillar abscess in early childhood. Presentation and management.
To highlight the modes of presentation and management of a peritonsillar abscess in children younger than 5 years. Retrospective case series. Tertiary referral pediatric otolaryngology practice. Seven children younger than 5 years. The mean age of the children studied was 27 months (age range, 7-41 months). Five (71%) of the 7 patients underwent computed tomographic scanning to confirm the diagnosis. Pus was cultured at surgery in every case. The most common organism detected was Streptococcus viridans. The average hospital stay was 72 hours (range, 22 hours to 12 days). After diagnosis of an abscess, all patients underwent an electrocautery tonsillectomy and had an uneventful recovery. Children younger than 5 years who present with poor oral intake, high fever, drooling, and trismus should be suspected of having a peritonsillar abscess. A computed tomographic scan of the neck is usually required to confirm a suspected diagnosis. Prompt diagnosis and treatment will lead to a considerable decrease in morbidity. Immediate tonsillectomy is a safe and effective means of abscess drainage.


The degradation of platelet-activating factor in the plasma of a patient with familial high density lipoprotein deficiency (Tangier disease).
Platelet Activating Factor (PAF) (1-O-alkyl-2-acetyl sn-glycerol 3-phosphocholine) has been characterized by its ability to aggregate platelets at low concentrations and its profound hypotensive effects. There is evidence that the rate of catabolism of this compound in the plasma regulates its concentration. In humans, we and others have shown that a PAF acetylhydrolase is associated with low density lipoprotein (LDL). The LDL particle in the plasma of patients with Tangier disease is quite different from normal as its lipid core appears to be enriched with triacylglycerol. Thus, we have studied the potential of this abnormal lipoprotein to degrade PAF. The assay for PAF acetylhydrolase was based on the release of 3H from PAF that was labelled in the acetate moiety of the sn-2 position. Tangier disease plasma had approximately 3.3-fold higher PAF acetylhydrolase activity (208 +/- 9 nmol/min/mL) than controls (63 +/- 18 nmol/min/mL). This increase was brought about by an increase in the Vmax (400 +/- 40, Tangier disease; 54 +/- 5, controls) and Km for PAF (120 +/- 20 mumol/L, Tangier disease; 28 +/- 4 mumol/L, controls). The activity appears to be a specific acetylhydrolase rather than a phospholipase A2 as preincubation of the substrate with 0 to 100 mumol/L phosphatidylcholine did not affect the amount of [3H] acetate released. The role of PAF, and its degradation by LDL-bound PAF acetylhydrolase in the phenotypic expression of this patient with Tangier disease, is not known. However, this is the first patient so far described who has an increased ability to degrade PAF in the plasma.


Genome organization and three kinds of heritable changes: general description and stochastic factors (a review).
Due to the increased knowledge of genome architecture, topology, and the mechanisms of hereditary variability, the list of genetic components has grown. This review outlines the general features and principles of genome organization in diverse organisms. The genome codes, stores, and transfers information in both structurally and dynamically. The genome includes two subsystems of genetic elements: obligatory (genes and gene families) and various types of facultative elements which are predominant the content of the human genome. The features of three kinds of heritable changes: mutations, variations (changes in the number or topography of facultative elements), and epigenetic alterations are described. Facultative elements are the first to react to environmental challenges. Together with epigenetic changes, they implement the operational genomic memory. This review discusses both the role of stochastic factors and the transient features of DNA components.


Human cytomegalovirus protein US11 provokes an unfolded protein response that may facilitate the degradation of class I major histocompatibility complex products.
The human cytomegalovirus (HCMV) glycoprotein US11 diverts class I major histocompatibility complex (MHC) heavy chains (HC) from the endoplasmic reticulum (ER) to the cytosol, where HC are subjected to proteasome-mediated degradation. In mouse embryonic fibroblasts that are deficient for X-box binding protein 1 (XBP-1), a key transcription factor in the unfolded protein response (UPR) pathway, we show that degradation of endogenous mouse HC is impaired. Moreover, the rate of US11-mediated degradation of ectopically expressed HLA-A2 is reduced when XBP-1 is absent. In the human astrocytoma cell line U373, turning on expression of US11, but not US2, is sufficient to induce a UPR, as manifested by upregulation of the ER chaperone Bip and by splicing of XBP-1 mRNA. In the presence of dominant-negative versions of XBP-1 and activating transcription factor 6, the kinetics of class I MHC HC degradation were delayed when expression of US11 was turned on. The magnitude of these effects, while reproducible, was modest. Conversely, in cells that stably express high levels of US11, the degradation of HC is not affected by the presence of the dominant negative effectors of the UPR. An infection of human foreskin fibroblasts with human cytomegalovirus induced XBP-1 splicing in a manner that coincides with US11 expression. We conclude that the contribution of the UPR is more pronounced on HC degradation shortly after induction of US11 expression and that US11 is sufficient to induce such a response.


Protein content of polyhedral organelles involved in coenzyme B12-dependent degradation of 1,2-propanediol in Salmonella enterica serovar Typhimurium LT2.
Salmonella enterica forms polyhedral organelles during coenzyme B(12)-dependent growth on 1,2-propanediol (1,2-PD). Previously, these organelles were shown to consist of a protein shell partly composed of the PduA protein, the majority of the cell's B(12)-dependent diol dehydratase, and additional unidentified proteins. In this report, the polyhedral organelles involved in B(12)-dependent 1,2-PD degradation by S. enterica were purified by a combination of detergent extraction and differential and density gradient centrifugation. The course of the purification was monitored by electron microscopy and gel electrophoresis, as well as enzymatic assay of B(12)-dependent diol dehydratase. Following one- and two-dimensional gel electrophoresis of purified organelles, the identities and relative abundance of their constituent proteins were determined by N-terminal sequencing, protein mass fingerprinting, Western blotting, and densitometry. These analyses indicated that the organelles consisted of at least 15 proteins, including PduABB'CDEGHJKOPTU and one unidentified protein. Seven of the proteins identified (PduABB'JKTU) have some sequence similarity to the shell proteins of carboxysomes (a polyhedral organelle involved in autotrophic CO(2) fixation), suggesting that the S. enterica organelles and carboxysomes have a related multiprotein shell. In addition, S. enterica organelles contained four enzymes: B(12)-dependent diol dehydratase, its putative reactivating factor, aldehyde dehydrogenase, and ATP cob(I)alamin adenosyltransferase. This complement of enzymes indicates that the primary catalytic function of the S. enterica organelles is the conversion of 1,2-PD to propionyl coenzyme A (which is consistent with our prior proposal that the S. enterica organelles function to minimize aldehyde toxicity during growth on 1,2-PD). The possibility that similar protein-bound organelles may be more widespread in nature than currently recognized is discussed.


Growth Factor Gene-Modified Mesenchymal Stem Cells in Tissue Regeneration.
There have been marked changes in the field of stem cell therapeutics in recent years, with many clinical trials having been conducted to date in an effort to treat myriad diseases. Mesenchymal stem cells (MSCs) are the cell type most frequently utilized in stem cell therapeutic and tissue regenerative strategies, and have been used with excellent safety to date. Unfortunately, these MSCs have limited ability to engraft and survive, reducing their clinical utility. MSCs are able to secrete growth factors that can support the regeneration of tissues, and engineering MSCs to express such growth factors can improve their survival, proliferation, differentiation, and tissue reconstructing abilities. As such, it is likely that such genetically modified MSCs may represent the next stage of regenerative therapy. Indeed, increasing volumes of preclinical research suggests that such modified MSCs expressing growth factors can effectively treat many forms of tissue damage. In the present review, we survey recent approaches to producing and utilizing growth factor gene-modified MSCs in the context of tissue repair and discuss its prospects for clinical application.


Screening for extensor tendon rupture in rheumatoid arthritis.
Surgery can prevent extensor tendon rupture in the rheumatoid wrist but it is difficult to identify patients at risk. Extensor digiti minimi (EDM) usually ruptures first, but rupture may pass unnoticed because extensor digitorum communis (EDC) extends all four fingers simultaneously. We assessed the value of screening for EDM rupture by examining for absent independent extension of the little finger in a hospital rheumatoid arthritis population. The EDM test was performed in 550 previously unoperated wrists. Disease activity, joint damage, wrist swelling, tenderness and crepitus were recorded. Unsuspected EDM loss was found in nine of the 550 wrists (1.6%); dorsal synovitis was absent or minimal in eight and ulnar tenderness was absent in six. EDM loss was not associated with activity, severity or duration of disease. The EDM test is simple and cheap. It may identify patients at risk and permit prophylactic surgery before hand function is lost.


Human natural yeast killer toxin-like candidacidal antibodies.
A murine mAb (mAbKT4, IgG1) that neutralized in vitro the anti-Candida activity of a killer toxic (KT) from the yeast Pichia anomala acted as an idiotypic (Id) vaccine in eliciting anti-Id Abs with toxin-like activity (KT-IdAb) in a rat vaginitis model. In this study, we demonstrate that intravaginal or intragastric inoculations of Candida albicans bearing a receptor for the toxin was able to recall KT-IdAb production in the vagina of the animals primarily immunized with mAbKT4 and also to elicit by themselves an Ab that functionally mimicked the KT (KTAb). Anti-Id-like, KT-like Abs were also consistently found in the vaginal fluid of human vaginitis patients who were infected by Candida but who had never been exposed to the Id vaccine. These Abs were as candidacidal in vitro as those raised in rat vagina by the Id vaccination, and, likewise, their cytocidal effect was totally neutralized by previous reaction with mAbKT4. Importantly, they were also able to confer a significant anticandidal protection in the rat vaginitis model, comparable to that achievable by KT-IdAb passively transferred to naive rats from Id-vaccinated animals. Thus, candidacidal Abs representing the internal image of a yeast KT are part of the Ab repertoire that follows infection or immunization with Candida. It is speculated that the host's immune system response may exploit the KT receptor of microbial pathogens to produce microbicidal Abs, possibly mirroring competition events among microorganisms in natural habitats.


Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals.
In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references).


Transdermal administration of bromocriptine.
Bromocriptine (BRC) has been mainly used for the inhibition of lactation, treatment of menstrual disorders, Parkinson disease, breast tumours, infertility and brain tumours as a dopamine agonist in clinics. But current BRC formulations have some side effects and bioavailability problems because of hepatic first pass effect. Transdermal application could be an alternative route to overcome all these problem and penetration properties of BRC has not been studied yet. Therefore, it was aimed to investigate the effectiveness of transdermal formulation of BRC which is applicable to the skin. For this purpose, a number of BRC gel formulations (Carbopol-934 (C-934), chitosan (CH) and Gantrez-SP215 (G-SP215) were developed and the effectiveness and bioavailability of the formulations were compared in rabbits. Commercial BRC tablets (Parlodel) were also given to rabbits orally and plasma levels were compared. The effects of two different penetration enhancers, sodium taurocholate (ST) and ethoxydiglycol-Transcutol) (TR) on the BRC penetration were also investigated. The skin samples from the dorsal part of the rabbit were removed after CH gel application and investigated under electron microscope to understand the effects of the gel on the penetration and the possible penetration mechanisms through skin were also discussed. In conclusion, CH gel formulation was found to be the best formulation and comparable blood BRC concentrations were obtained when applied to the rabbit skin. Higher blood levels were obtained with the use of CH. The main penetration process was found to be through transcellular route but some other mechanisms were also found to be incorporated, after microscopic investigation. CH gel was found to be a useful carrier for BRC administration through dermal route and the penetration enhancing effect and the mechanism of CH gel were first established in this study. It was concluded that transdermal delivery of BRC may be a very promising alternative route to the oral route for the treatment.


The effects of diet on growth and reproduction in gray short-tailed opossums (Monodelphis domestica).
In order to develop standard conditions for rearing the gray short-tailed opossum, Monodelphis domestica, as a potentially useful experimental laboratory animal, the effects of four different diets on growth and reproduction were assessed. One diet was a meat-based diet prepared in the laboratory. The other three diets were commercially produced fox foods designated Reproduction diet, Lactation diet, and Growing and Furring diet. All pairs of M. domestica fed the Reproduction diet produced at least one litter, but only two-thirds or fewer of the pairs fed any of the other three diets reproduced. There were no significant differences in the number of young born per litter or the number of young weaned per litter among the diets. Weight at weaning was significantly lower for individuals on the meat-based diet compared to those on the fox food diets. Young on the meat-based diet suffered 50% mortality within 6 weeks after weaning, whereas none of the animals fed the fox food diets died within the same 6-week period. Age-weight data were described using the Bertalanffy growth function. In terms of growth and overall reproductive performance, the fox food diets were clearly superior to the meat-based diet, and the Reproduction diet was judged to be the best of the fox food diets tested. Growth curves, from birth to 550 days of age, of individuals fed the Reproduction diet were developed and can be used as standards for the species under laboratory conditions. The maximal weights attained by animals fed the fox food diets were similar to the weights of the wild-caught founders of the laboratory population, indicating that the fox food diets provide adequate nutrition for normal growth. An additional observation was that females housed singly past the normal age of sexual maturity attained significantly lower adult weights than did females that were paired with males at 6 months of age.


'His brain is totally different': an analysis of care-staff explanations of aggressive challenging behaviour and the impact of gendered discourses.
Using a discourse analysis on the texts of 10 interviews with care staff, this research explored the discourses used by care staff in constructing the aggressive challenging behaviours of men and women with learning disabilities. The research also explored discourses used differentially to understand the aggressive challenging behaviour of one gender. The analysis demonstrated the use of two main discourses, an individual pathology discourse which constructed the behaviour as originating in factors stable and internal to the client, and a context discourse which constructed the behaviour as a response to the client's circumstances. Participants used these accounts flexibly within their talk, and also used a mixed discourse which constructed the behaviour as due to both individual pathology and context. Despite the staff presenting their understandings as not being affected by the client's gender, the presence of two gendered individualizing discourses within the interviews was also demonstrated. Women's behaviour, unlike men's, was constructed with the use of discourses about their menstrual cycle or character flaws. The consequences of the use of these different discourses are discussed, as are the subject positions which they afford for both staff and clients. It is argued that clients are disempowered by the individual pathology discourse; that consideration of the broad contexts within which care-staff actions are situated may allow them to manage blame whilst reflecting on their practice, and that the impact of gender stereotypes on the understandings staff have of a client's behaviour should be a legitimate area for consideration in clinical practice.


Elevated 3,4-dihydroxyphenylethyleneglycol (DHPG) excretion in dexamethasone resistant depressed patients.
Urinary and plasma DHPG and MHPG were estimated in patients with MADD and showing DST non-suppression as compared to those with normal suppression. Day and night 12h urine collections and morning plasma samples were analyzed by GC-MS for total MHPG and DHPG and free MHPG levels. Urinary DHPG excretion was significantly elevated in DST non-suppressors compared to suppressors, but no differences were found in urinary MHPG or plasma glycol levels. Elevated DHPG excretion in DST non-suppressors suggests that increased peripheral sympathetic NE activity occurs in association with dexamethasone resistance in MADD.


Preventing potentially inappropriate medication use in hospitalized older patients with a computerized provider order entry warning system.
Potentially inappropriate medication (PIM) use in hospitalized older patients is common. Our objective was to determine whether a computerized provider order entry (CPOE) drug warning system can decrease orders for PIMs in hospitalized older patients. We used a prospective before-and-after design among patients 65 years or older admitted to a large, urban academic medical center in Boston, Massachusetts, from June 1, 2004, through November 29, 2004 (for patients admitted before the warning system was added), and from March 17, 2005, through August 30, 2008 (patients admitted after the warning system was added). We instituted a medication-specific warning system within CPOE that alerted ordering providers at the point of care when ordering a PIM and that advised alternative medication or dose reduction. The main outcome measure was the rate of orders for PIMs before and after the warning system was deployed. The mean (SE) rate of ordering medications that were not recommended dropped from 11.56 (0.36) to 9.94 (0.12) orders per day after the implementation of a CPOE warning system (difference, 1.62 [0.33]; P<.001), with no evidence that the effect waned over time. There were no appreciable changes in the rate of ordering medications for which only dose reduction was recommended or that were not targeted after CPOE implementation. These effects persisted in autoregressive models that accounted for secular trends and season (P<.001). Specific alerts embedded into a CPOE system, used in patients 65 years or older, can decrease the number of orders of PIMs quickly and specifically.


The effect of hole diameter on the torsional mechanical properties of the equine third metacarpal bone.
The torsional monotonic structural material properties of equine metacarpi with or without, either a 5/16 inch or 3/8 inch diameter bicortical lateromedial middiaphyseal hole were assessed to determine the effect of a hole on metacarpal strength. Torsional stiffness was not significantly effected by the presence of a bicortical hole, whereas yield and failure angles, torques and energies of metacarpi with a hole were 51% to 97% of those of intact bones. Significant differences were not apparent for yield and failure mechanical properties between metacarpi with a 5/16 inch diameter hole and metacarpi with a 3/8 inch diameter hole; however, postyield mechanical properties were lower for metacarpi with a 3/8 inch hole. Whereas some metacarpi with a 5/16 inch hole were capable of plastic deformation before failure, metacarpi with a 3/8 inch diameter hole appeared to have sufficient stress concentration to propagate complete fracture on structural yield.


Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa.
Apoptosis after ischemia-reperfusion (I/R) was characterized in rat small intestine. Under halothane anesthesia, the superior mesenteric artery in the rat was occluded for 15 or 60 min, followed by reperfusion. Ratios of fragmented DNA to total DNA, electrophoresis, and immunohistochemical staining were examined after I/R. Some rats were pretreated with alpha-difluoromethylornithine (DFMO) to examine the relationship between intestinal apoptosis and ornithine decarboxylase (ODC) activity. The percentage of fragmented DNA significantly increased just after ischemia and peaked at 1 h after reperfusion in the jejunum and ileum. These increases were significantly higher in the 60-min ischemia group compared with the 15-min ischemia group. This increase decreased 6 h after reperfusion. The results were corroborated by histological evaluations of the intestine under the same conditions. DFMO completely abolished elevation of ODC activity 6 h after reperfusion but did not change the percentage of fragmented DNA. Apoptosis in rat small intestine was induced by ischemia of the gut, and this process was exacerbated by reperfusion. The changes in apoptosis were independent of ODC activity.


A radially controlled ZnS interlayer on ultra-long ZnO-Gd2S3 core-shell nanorod arrays for promoting the visible photocatalytic degradation of antibiotics.
Nanorod (NR) arrays offer commendable visible-light-driven photocatalytic performances. Herein, we describe the construction of a ternary ZnO-ZnS-Gd2S3 nanostructural array in which a sulfidation process is used to decorate a Gd2S3 shell layer with a ZnS interface over vapor-phase-grown vertically-aligned ZnO. With control over the shell-wall thickness, the shell layer of ∼25 nm wall thickness on the ultra-long ZnO NR arrays exhibited a higher catalytic efficiency close to 3.3, 2.0, 1.2, and 1.8 times those of the bare ZnO, the ZnO-ZnS, the Gd2S3-decorated (∼10 nm) and Gd2S3 shell-layered (∼40 nm) ZnO-ZnS core-shell structures, respectively. The core-shell geometry and the shell-wall thickness with maximized contact interface afforded increased light absorption in the visible region and effectively retarded the recombination rate of the photoinduced charge carriers by confining electrons and holes separately, thus providing advantages in terms of the degradation of the pharmaceutical residue tetracycline and the industrial pollutant 4-nitrophenol in wastewater.


Pegylated-interferon plus ribavirin therapy in the treatment of CHC: individualization of treatment duration according to on-treatment virologic response.
Standard treatment of chronic hepatitis C (CHC) is peginterferon alfa (PEG-IFN alfa) plus ribavirin (RBV) for 48 weeks in patients infected with genotype 1, and 24 weeks for those infected with genotype 2 or 3. However, recent studies have shown that on-treatment markers of virologic response can be used to tailor treatment duration according to each patient's response to therapy. To discuss the rationale for assessing on-treatment markers of virologic response to PEG-IFN alfa plus RBV. A literature search was conducted using MEDLINE and conference proceedings for clinical studies of reduced and extended treatment durations in the treatment of CHC. Patients infected with genotype 1 and low baseline viral load who have undetectable HCV RNA by week 4 can be effectively treated for 24 weeks without any decline in efficacy. Extended treatment duration of 72 weeks has been studied in various selected patient groups with genotype 1 infection who are slow to respond to treatment; however, data are conflicting regarding the patient subgroup that may benefit most from this strategy. Finally, selected HCV genotype 2 or 3 patients with undetectable HCV RNA at week 4 and other favorable prognostic features may be effectively managed with shorter (12 to 16 weeks) treatment duration. Further work is required to determine how the findings of this review relate to patients who do not fit with the enrollment criteria of randomized clinical trials or who require dose adjustment based on adverse tolerability. Care should also be exercised when comparing data between studies because of differences in design and patient populations. Evaluation of on-treatment markers of virologic response has revolutionized the treatment of CHC: implementation of these assessments in clinical practice is strongly supported by data from recent clinical studies, even in advance of formal recognition in treatment guidelines.


A systematic review of microfinance and women's health literature: Directions for future research.
While growing evidence suggests that microfinance is an effective approach for improved women's health, a significant gap remains in our understanding. The objective of this review is to synthesise the findings from published literature focused on microfinance and health issues particularly affecting women, including HIV/AIDS, reproductive health, mental health, and violence. Forty-one articles that examine the impact of microfinance participation on women's health were identified through a systematic search of electronic databases, coded using a structured abstraction form, and synthesised. Review results indicate that the impact of microfinance on women's health is an area in great need of research and publication attention. Varied quality and reporting in the identified articles restricted the ability to draw concrete conclusions regarding the relationship between microfinance participation and women's health, but led to the identification of current gaps in existing published research. Future research should work to address the recommendations provided in order to offer additional evidence to better understand the use of microfinance programming as a structural intervention to improve women's health.


[Nitric oxide production in pregnancy and experimental acute kidney insufficiency].
Nitric oxide production in organs of pregnant mice (liver, kidney, placenta) was measured using specifical NO traps, Fe-dithiocarbamate complexes (Fe-DETC) forming with NO paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC), detected by EPR method (-196 degrees C). The amount of NO formed increased in dependence of the pregnancy period (from the first to the third trimesters). Addition of NO-synthase substrate, L-arginine, insignificantly influenced endogenous NO production. However, endogenous NO amount sharply decreased at experimental acute renal failure.


Modulation of Mitochondrial Membrane Potential and ROS Generation by Nicotinamide in a Manner Independent of SIRT1 and Mitophagy.
Nicotinamide (NAM) plays essential roles in physiology through facilitating NAD+ redox homeostasis. Importantly, at high doses, it protects cells under oxidative stresses, and has shown therapeutic effectiveness in a variety of disease conditions. In our previous studies, NAM lowered reactive oxygen species (ROS) levels and extended cellular life span in primary human cells. In the treated cells, levels of NAD+/NADH and SIRT1 activity increased, while mitochondrial content decreased through autophagy activation. The remaining mitochondria were marked with low superoxide levels and high membrane potentials (Δψm); we posited that the treatment of NAM induced an activation of mitophagy that is selective for depolarized mitochondria, which produce high levels of ROS. However, evidence for the selective mitophagy that is mediated by SIRT1 has never been provided. This study sought to explain the mechanisms by which NAM lowers ROS levels and increases Δψm. Our results showed that NAM and SIRT1 activation exert quite different effects on mitochondrial physiology. Furthermore, the changes in ROS and Δψm were not found to be mediated through autophagy or SIRT activation. Rather, NAM suppressed superoxide generation via a direct reduction of electron transport, and increased Δψm via suppression of mitochondrial permeability transition pore formation. Our results dissected the effects of cellular NAD+ redox modulation, and emphasized the importance of the NAD+/NADH ratio in the mitochondria as well as the cytosol in maintaining mitochondrial quality.