SAR studies of diaryltriazoles against bacterial two-component regulatory systems and their antibacterial activities.
A series of diaryltriazole analogs was discovered to inhibit bacterial two-component regulatory systems in our primary assays, KinA/Spo0F and NRII/NRI. They also showed inhibitory activity in whole cell mechanism-based assays, and they possessed potent activities against several strains of Gram-positive pathogenic bacteria in the standard MIC broth assay.


Aptamer-antibody on-chip sandwich immunoassay for detection of CRP in spiked serum.
This study describes a RNA aptamer-based biochip with high affinity and specificity for C-reactive protein (CRP). CRP, which exists in concentrations of 1-3mg/l in the serum of healthy patients, has been identified as a reliable biomarker for inflammation and as a potential marker for sepsis and tissue necrosis. The CRP-specific aptamer was covalently immobilized with its 5'-end on ARChip Epoxy. The detection of bound CRP was carried out optically using labelled secondary antibody in a sandwich format. Assay conditions were optimized with respect to the CRP binding buffer (buffer system, pH and additives) and Ca(2+) concentration (10 mM). Moreover, two sandwich immunoassay formats were tested, the one using dye-labelled antibodies and the other with biotin-modified antibodies/Dy647-labelled streptavidin. In comparison with an antibody-based chip assay, the aptamer chip is superior in terms of CRP measuring range (10 microg/l to 100mg/l) in human serum whereas antibody-based chips result in superior data reproducibility (CV of 8-15%). In contrast to antibody chips, aptamer microarrays provide the unique potential of detecting CRP in serum samples of low risk patients (1-3mg/l) as well as high risk patients (>500 mg/l), furthermore elevated CRP levels (20-350 mg/l) with acceptable recovery (70-130%) by including only one serum sample dilution step (1:100) for the complete measuring range.


A comparison of the discriminative stimulus properties of l-5-hydroxytryptophan in the presence of either citalopram or Ro 4-4602.
The establishment of stimulus control by 5-HTP, the amino acid precursor for serotonin (5-HT), has been reported previously [1-3]. In the present investigation, two groups of rats were trained with 5-HTP versus saline in a 2-lever discrimination procedure. Prior to the administration of 5-HTP, subjects were pretreated with either Ro 4-4602, an inhibitor of peripheral decarboxylase (R-HTP), or citalopram, a specific 5-HT reuptake inhibitor (C-HTP). Neither C-HTP nor R-HTP was antagonized completely by either pirenperone or pizotyline. When C-HTP and R-HTP were tested in a third group of rats trained with LSD, complete generalization was not observed. The results of cross tests in the R-HTP and C-HTP groups with LSD, TFMPP, 8-OH-DPAT, C-HTP, and R-HTP indicate that the stimuli induced by R-HTP and C-HTP are similar but not identical. Taken together, these data suggest that 5-HTP produces a compound stimulus that is not readily explained in terms of either 5-HT1 or 5-HT2 receptors alone.


Renal single photon emission computed tomography: should we do it?
Although single photon emission computed tomography (SPECT) imaging has established a place for itself in clinical nuclear medicine for heart and brain studies, its place in renal imaging is not yet clear. Renal SPECT has been subject to limitations imposed by the efficiency of imaging equipment, and has been confined to use with static imaging agents such as technetium-99m (99mTc) dimercaptosuccinate (DMSA). SPECT has been used to investigate space-occupying lesions and anatomical abnormalities, and for quantitative studies of renal uptake and volume. In these areas, it has provided little advantage over conventional imaging, but it has been helpful in individual cases. High-resolution SPECT is a promising new development, which may have applications in detecting and classifying renal scarring. It deserves careful evaluation.


Anti-sepsis protection of Xuebijing injection is mediated by differential regulation of pro- and anti-inflammatory Th17 and T regulatory cells in a murine model of polymicrobial sepsis.
Xuebijing injection (XBJ), a Chinese herbal medicine containing extracts from 5 herbs, is frequently used as an add-on with standard therapies to treat sepsis or septic shock with fewer side effects in China. Nonetheless, its mechanism of action on septic shock remains to be unveiled. We explored the differential effects of XBJ on subtypes of CD4+ T cell differentiation and septic shock protection in a murine model to understand the contribution of XBJ to regulation of the inflammation-immune axis function. In vitro T cell differentiation assays were performed to determine the effect of XBJ on CD4+ regulatory T cell and T helper cell differentiation. Besides, 2ml/kg, 6ml/kg- and 18ml/kg of XBJ were administered to different groups of septic mice once/day for 5 days after cecal ligation and puncture (CLP) surgeries. 36h after CLP, serum levels of pro-inflammatory cytokine TNF-α and IL-6 were determined with Elisa. Frequencies of CD4+ T cells were analyzed after staining with Tregs and T helper cell lineage specific antibodies by flow cytometer. XBJ at 18ml/kg stimulated Treg differentiation and moderately inhibited Th17 differentiation in vitro. Accordingly, 18ml/kg XBJ facilitated the expansion of IL-10+ Tregs and normalized pro-inflammatory Th17 population in septic mice. This regimen also significantly reduced serum levels of inflammatory cytokines TNF-α and IL-6 in septic mice. Additionally, 18ml/kg XBJ injection effectively prevented neutrophil infiltration into the lung and kidney and improved survival in this septic shock model. In summary, XBJ improves survival in septic shock partially through preventing cytokine storm, inhibiting inflammation and regulating the balance of Tregs and Th17 cells. Thus, higher dose of XBJ is a potential regimen to benefit septic shock patients.


Multiple Breath Washout for Early Assessment of Pulmonary Complications in Patients With Primary Antibody Deficiencies: An Observational Study in Pediatric Age.
In primary antibody deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations, and respiratory physiotherapy. Current Italian recommendations for surveillance of PADs respiratory complications include an annual assessment of spirometry and execution of chest high-resolution computed tomography (HRCT) every 4 years. This study aimed to evaluate the effectiveness of the lung clearance index (LCI) as an early marker of lung damage in patients with PADs. LCI is measured by multiple breath washout (MBW), a non-invasive and highly specific test widely used in patients with cystic fibrosis (CF). Pediatric patients with PADs (n = 17, 10 male, 7 female, and age range 5-15 years) underwent baseline assessment of lung involvement with chest HRCT, spirometry, and multiple breath nitrogen washout. Among them, 13 patients were followed up to repeat HRCT after 4 years, while performing pulmonary function tests annually. Their baseline and follow-up LCI and forced expiratory volume at 1 s (FEV1) values were compared, taking HRCT as the gold standard, using logistic regression analysis. Lung clearance index [odds ratio (OR) 2.3 (confidence interval (CI) 0.1-52) at baseline, OR 3.9 (CI 0.2-191) at follow-up] has a stronger discriminating power between altered and normal HRCT rather than FEV1 [OR 0.6 (CI 0.2-2) at baseline, OR 1.6 (CI 0.1-13.6) at follow-up]. Within the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting non-uniform ventilation in the absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.


Determination of the effective dose rate for monepantel (AAD 1566) against adult gastro-intestinal nematodes in sheep.
Monepantel (AAD 1566) is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Three dose determination studies were conducted in Australia and Europe to identify the therapeutic dose of monepantel, when formulated for the oral treatment of sheep, to control adult gastro-intestinal nematodes. In each study, sheep infected with various nematode species were treated with either 1.25, 2.5 or 5.0mg monepantel/kg bodyweight. Following euthanasia and worm counting, their worm burdens were compared with those from untreated control groups. At a dose rate of 1.25mg/kg, monepantel showed efficacy above 91.9% against all major nematode species, with the exception of Chabertia ovina and Oesophagostomum venulosum. Efficacy against these two species was 93.6% and 94.0%, respectively, at a dose of 2.5mg/kg. At this dose, efficacy was above 99.2% against nine other nematode species including Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus spp. and Nematodirus spp. It was concluded that 2.5mg/kg would be a suitable dose rate for a commercial product.


Chemical interference among plants mediated by grazing insects : A reassessment.
A recent paper has proposed that frass produced by eucalypt-defoliating insects has allelopathic effects on herbaceous plants growing under the canopies of woodland eucalypts. Insect frass fall under woodland eucalypts may have been overestimated, however. Alternative estimates of frass fall are presented and it is proposed that these levels are too low to have a significant impact on the kinds of herbaceous plant species occuring under woodland eucalypts.


Venlafaxine-tramadol similarities.
Venlafaxine and tramadol are relatively new compounds indicated for the treatment of depression and pain, respectively. These agents share a number of molecular and pharmacological features that may allow for broader and overlapping therapeutic indications for both drugs. Additionally, certain patient populations with coexisting depression and pain syndromes could potentially be treated with a single agent.


Extrahepatic right portal vein ligation allows parenchyma-sparing en bloc resection of segments 7, 8 and 4a for liver tumors engaging the right and middle hepatic veins.
Right trisectionectomy for posterior liver tumors engaging the right and middle hepatic veins may lead to post-hepatectomy liver failure if the anticipated liver remnant is small. In such patients we developed a parenchyma-sparing one-step approach, that includes extrahepatic right portal vein ligation accompanied by en bloc resection only of segments 7, 8 and 4a and resection of the right and middle hepatic veins. The technique was applied in 3 patients with normal liver function, where according to the preoperative computed tomography the volume of segments 1, 2 and 3 ranged between 17% and 20% of the total liver volume. In all patients liver biochemistry improved rapidly postoperatively and a doubling of volume of segments 1, 2 and 3 was achieved by the third postoperative week, as extrahepatic right portal vein ligation ameliorated reperfusion injury of the remaining segments 5 and 6 and induced hypertrophy of segments 1, 2, 3 and 4b. There was no mortality or long-term complications. Patients are alive and free of disease 74, 50 and 17 months after the operation, respectively. We propose that the term "extended upper right sectionectomy" may be considered for the en bloc resection of segments 7, 8 and 4a, in future revisions of the Brisbane 2000 terminology of hepatic anatomy and resections.


Exploring anticancer activity of structurally modified benzylphenoxyacetamide (BPA); I: Synthesis strategies and computational analyses of substituted BPA variants with high anti-glioblastoma potential.
Structural variations of the benzylphenoxyacetamide (BPA) molecular skeleton were explored as a viable starting point for designing new anti-glioblastoma drug candidates. Hand-to-hand computational evaluation, chemical modifications, and cell viability testing were performed to explore the importance of some of the structural properties in order to generate, retain, and improve desired anti-glioblastoma characteristics. It was demonstrated that several structural features are required to retain the anti-glioblastoma activity, including a carbonyl group of the benzophenone moiety, as well as 4'-chloro and 2,2-dimethy substituents. In addition, the structure of the amide moiety can be modified in such a way that desirable anti-glioblastoma and physical properties can be improved. Via these structural modifications, more than 50 compounds were prepared and tested for anti-glioblastoma activity. Four compounds were identified (HR28, HR32, HR37, and HR46) that in addition to HR40 (PP1) from our previous study, have been determined to have desirable physical and biological properties. These include high glioblastoma cytotoxicity at low μM concentrations, improved water solubility, and the ability to penetrate the blood brain barrier (BBB), which indicate a potential for becoming a new class of anti-glioblastoma drugs.


MYB30 Regulates Submergence Tolerance by Repressing Ethylene Biosynthesis via ACS7 in Arabidopsis.
Floods impose detrimental effects on natural and agro-ecosystems, leading to a significant loss of worldwide crop production. Global climate change has even worsened this situation. Flooding is a continuous process including two stages of submergence and re-oxygenation, and both are harmful to plant growth and development, resulting in a serious decline in crop yield. Therefore, the understanding of plant flooding tolerance and developing flooding-resistant crops are of great significance. Here, we report that the Arabidopsis thaliana (Arabidopsis) R2R3-MYB transcription factor MYB30 participates in plant submergence response through 1-aminocyclopropane-1-carboxylic acid synthase 7 (ACS7) by repressing ethylene (ET) biosynthesis. The MYB30 loss-of-function mutant exhibits reduced submergence tolerance with a higher level of ET production, whereas the MYB30-overexpressing plant displays enhanced submergence tolerance and repressed ET production. The coding gene of ACS7 might be a direct target of MYB30 during the submergence response. MYB30 binds to the promoter of ACS7 and represses its transcription. The ACS7 loss-of-function mutant with defect in ET biosynthesis displays enhanced submergence tolerance, whereas plants overexpressing ACS7 exhibit a submergence-sensitive phenotype. Genetic analysis shows that ACS7 functions downstream of MYB30 in both ET biosynthesis and submergence response. Taken together, our work revealed a novel transcriptional regulation that modulates submergence response in plants.


Molecular basis of EphA2 recognition by gHgL from gammaherpesviruses.
The human γ-herpesviruses Kaposi sarcoma associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are associated with many human malignancies. Viral glycoprotein H (gH) and glycoprotein L (gL) are crucial for the cell tropism by binding to specific receptors. Recently, EphA2 was identified as the specific entry receptor for both KSHV and EBV. Here, we characterized the crystal structures of KSHV gHgL or EBV gHgL in complex with the ligand binding domain (LBD) of EphA2. Both KSHV and EBV gHgL bind to the channel and peripheral regions of LBD primarily using gL. Extensive interactions with more contacts contribute to the higher affinity of KSHV gHgL to LBD than that of EBV gHgL. These binding characteristics were verified using cell-based fusion assays with mutations in key EphA2 residues. Our experiments suggest that multiple animal γ-herpesviruses could use EphA2 as an entry receptor, implying a potential threat to human health.


Acute generalized exanthematous pustulosis caused by morphine, confirmed by positive patch test and lymphocyte transformation test.
Morphine, an opium alkaloid, frequently causes side effects such as hyperhidrosis and facial flushing, but serious cutaneous adverse drug reactions are seldom observed. Best known are urticaria, erythema, and pruritus; sometimes pseudoallergic anaphylactoid reactions, and blisters are reported.


Removal of starch granule-associated proteins promotes α-amylase hydrolysis of rice starch granule.
Starch granule-surface proteins (SGSPs) and granule-channel proteins (SGCPs) are granule-associated proteins (SGAPs), which have been found to be distributed on the surface and channels of starch granules, respectively. To investigate the impacts of SGAPs on α-amylase hydrolysis of starch, SGCPs or SGAPs of waxy, low and high amylose rice starches were removed. Removal of SGAPs or SGCPs greatly increased hydrolysis rate of rice starches. Meanwhile, these granules incurred a greater number and size of pores on their surfaces during hydrolysis. Compared to low and high amylose starches, waxy starch before and after removing SGAPs exhibited a higher hydrolysis rate. Rice starch hydrolysis began with enlargement of cavity and channels both horizontally and vertically. XRD analysis revealed that removal of SGAPs decreased relative crystallinity (RC) of starch and advanced changes in RC during hydrolysis process. This study provides new information about the role of SGAPs in the mechanisms of α-amylase hydrolysis.


Analysis of miRNA expression associated with the Lr46 gene responsible for APR resistance in wheat (Triticum aestivum L.).
Lr46/Yr29/Pm39 (Lr46) is a gene for slow rusting resistance in wheat. The aim of the study was to analyze the miRNA expression in selected common wheat cultivars carrying resistance genes, Lr46 among others (HN Rod, Pavon'S', Myna'S', Frontana'S', and Sparrow'S') in response to leaf rust infection caused by Puccinia triticina Erikss. In the Pavon 'S', Myna 'S', Frontana'S', and Sparow'S' varieties a product with a length of 242 bp has been identified, which is specific to the Xwmc44 marker linked to the brown rust resistance gene Lr46. In the next step, the differences in the expression of microRNA (miR5085 and miR164) associated with the Lr46 gene, which is responsible for different resistance of selected wheat cultivars to leaf rust, were examined using emulsion PCR (ddPCR). In the experiment, biotic stress was induced in mature plants by infecting them with fungal spores under controlled conditions in a growth chamber. For analysis the plant material was collected before inoculation and 6, 12, 24, and 48 h after inoculation. The experiments also showed that plant infection with Puccinia triticina resulted in an increase in miR164 expression in cultivars carrying the Lr46 gene. The expression of miR164 remained stable in a control cultivar (HN ROD) lacking this gene. This has proved that miR164 can be involved in leaf rust resistance mechanisms.


Modeling the habitat suitability for the arbovirus vector Aedes albopictus (Diptera: Culicidae) in Germany.
Climatic changes raise the risk of re-emergence of arthropod-borne virus outbreaks globally. These viruses are transmitted by arthropod vectors, often mosquitoes. Due to increasing worldwide trade and tourism, these vector species are often accidentally introduced into many countries beyond their former distribution range. Aedes albopictus, a well-known disease vector, was detected for the first time in Germany in 2007, but seems to have failed establishment until today. However, the species is known to occur in other temperate regions and a risk for establishment in Germany remains, especially in the face of predicted climate change. Thus, the goal of the study was to estimate the potential distribution of Ae. albopictus in Germany. We used ecological niche modeling in order to estimate the potential habitat suitability for this species under current and projected future climatic conditions. According to our model, there are already two areas in western and southern Germany that appear suitable for Ae. albopictus under current climatic conditions. One of these areas lies in Baden-Wuerttemberg, the other in North-Rhine Westphalia in the Ruhr region. Furthermore, projections under future climatic conditions show an increase of the modeled habitat suitability throughout Germany. Ae. albopictus is supposed to be better acclimated to colder temperatures than other tropical vectors and thus, might become, triggered by climate change, a serious threat to public health in Germany. Our modeling results can help optimizing the design of monitoring programs currently in place in Germany.


[Employing a modified gamma nail for the treatment of proximal femoral fractures].
A modified custom-designed long gamma nail (LGN10) and the long gamma nail (LGN11) were evaluated in a prospective trial for operative treatment of proximal femoral fractures. Between May 1998 and January 2000, 50 patients (mean age 79 years) were alternately treated with LGN10 or LGN11. The femoral antecurvature varied from 6 degrees to 10 degrees, with a maximum of 14 degrees, as evidenced by lateral radiograms. The need for intramedullary reaming in LGN10 cases was significantly less ( p=0.046). Other significant differences between the two study groups were not observed. One cranial cut out of the lag screw in the LGN10 group was observed. Other complications were not recorded during hospital treatment. Follow-up results are not yet complete. Using LGN10 seems to reduce intramedullary damage to the femur and make insertion of the nail easier.


Insect Orientation: Stay on Course with the Sun.
A new study demonstrates that fruit flies can use a sun compass, which is encoded in specific neurons in the fly's brain, to maintain a fixed heading direction for up to six hours.


Substrate specificity of the 3-methylcrotonyl coenzyme A (CoA) and geranyl-CoA carboxylases from Pseudomonas aeruginosa.
Biotin-containing 3-methylcrotonyl coenzyme A (MC-CoA) carboxylase (MCCase) and geranyl-CoA (G-CoA) carboxylase (GCCase) from Pseudomonas aeruginosa were expressed as His-tagged recombinant proteins in Escherichia coli. Both native and recombinant MCCase and GCCase showed pH and temperature optima of 8.5 and 37 degrees C. The apparent K(0.5) (affinity constant for non-Michaelis-Menten kinetics behavior) values of MCCase for MC-CoA, ATP, and bicarbonate were 9.8 microM, 13 microM, and 0.8 microM, respectively. MCCase activity showed sigmoidal kinetics for all the substrates and did not carboxylate G-CoA. In contrast, GCCase catalyzed the carboxylation of both G-CoA and MC-CoA. GCCase also showed sigmoidal kinetic behavior for G-CoA and bicarbonate but showed Michaelis-Menten kinetics for MC-CoA and the cosubstrate ATP. The apparent K(0.5) values of GCCase were 8.8 microM and 1.2 microM for G-CoA and bicarbonate, respectively, and the apparent K(m) values of GCCase were 10 microM for ATP and 14 microM for MC-CoA. The catalytic efficiencies of GCCase for G-CoA and MC-CoA were 56 and 22, respectively, indicating that G-CoA is preferred over MC-CoA as a substrate. The enzymatic properties of GCCase suggest that it may substitute for MCCase in leucine catabolism and that both the MCCase and GCCase enzymes play important roles in the leucine and acyclic terpene catabolic pathways.


Rapid development of severe osteoarthritis associated with osteoid osteoma in a young girl.
In a 14-year-old girl with a 5 month history of left sided thigh pain, X-rays demonstrating osteoarthritis and a bone scintigraphy showing increased focal uptake in the femoral neck led to the diagnosis of an osteoid osteoma. The protuberant bone at the femoral neck was removed en-bloc and the diagnosis histologically confirmed. The synovium was extensively infiltrated with lymphocytes. Postoperatively the girl experienced neither the expected pain relief nor improvement of her hip function over the next 4 months. MRI and CT results indicated development of a severe osteoarthritis even though no residual lesion could be found.


Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania.
The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly lower (p<0.001) in T. solium infected (4.7±3.0pg/mg) compared to control pigs (9.0±3.7pg/mg) prior to arrival at the research facility, however no significant difference was observed between the two groups at arrival and after approximately two weeks. Similar patterns were also observed for DHEA concentrations (infected pigs 253.9±82.3pg/mg, control pigs 387.7±116.4pg/mg) (p<0.001). Results showed that lean animals had significantly higher cortisol concentrations in both groups, infected and controls pigs, while DHEA was not significantly different between lean and normal animals. Results of this study have shown that an environmental change could have an effect on pigs' hormonal levels suggesting an undergoing adaptation process. After the pigs were kept under the same conditions, fed and watered ad libitum, no significant differences were observed between the groups, but a drop in DHEA concentrations was observed in all the pigs. Weight however had an effect on cortisol levels as lean animals had significantly higher cortisol concentrations in both groups, compared to normal pigs.


Evidence of Toscana virus circulation in Umbria: first report.
To evaluate, for the first time, circulation and clinical expression of Toscana virus (ToSv) in Umbria region we studied: (1) 93 cases of aseptic meningitis and meningoencephalitis admitted to our Department from 1989 to 2001 with negative results for common neurotropic virus; (2) 50 healthy subjects. Specific antibodies (IgM and IgG) anti-TOSv were found in 36.6% of aseptic meningitis, in 6.06% of meningoencephalitis and (IgG) in 16% of healthy subjects.


Epigenetics in the wild.
Studies of wild populations of the model plant Arabidopsis thaliana have started to reveal how patterns of DNA methylation change in response to the local environment.


Fracture healing with osteopathy in traditional Mongolian medicine.
To explore the concept and norm of fracture healing with osteopathy in traditional Mongolian medicine (TMM). Based on the correspondence between man and the universe (including psychosomatic integration) in fracture healing with osteopathy in TMM, we used modern physio-psychological and biomechanical principles and methods to probe the integrated, dynamic and functional characteristics of fracture healing. Based on the integration of limbs and the body, unification of the body and function and harmony of man and nature (including psychosomatic integration), fracture healing with osteopathy in TMM comprises the concept of natural functional healing of fractures, and follows the norm of considering physiological healing and psychological function as well as limb healing and motor function. Fracture healing with osteopathy in TMM is characterized by a lack of trauma without future complications. This therapy makes the concept of fracture healing develop in the direction of humanity, behaviorism and integration.


Stroke in Asia.
The epidemic of cardiovascular disease across most of Asia is at a different stage from that in the West; the incidence and prevalence of stroke are increasing steadily, associated with nutritional changes and aging of the population. Epidemiologic data, crucial in combating stroke, have been relatively sparse in Asian populations, but a few international collaborative studies on stroke have been in progress for several years. Through these, we now know that ischemic stroke is actually the most frequent type of cerebrovascular accident in Asia, although hemorrhagic stroke remains more common in Asia than in the West. Also, the percentage of ischemic stroke attributable to intracranial vascular disease is much higher than in the West. In Japan and a few other countries, stroke rates are declining; however, increasing rates in most other countries make primary prevention of critical importance in minimizing the severe impact of this epidemic in Asia.


The Long Lost Speech: Letter Offers Glimpse Into 19th Century Surgery.
The fifth floor of the Texas Medical Association building in Austin houses an archival collection of thousands of books, photographs, and artifacts documenting the rich history of Texas medicine. And there's always room for more. That's what unexpectedly happened in October, when TMA staff found an 1892 hand-written letter tucked away in the pages of an old medical journal. The speech gives modern-day physicians a look at the tools and techniques surgeons used more than 100 years ago.


Stimuli-Responsive Non-viral Nanoparticles for Gene Delivery.
Considering nucleic acids as the language of life and the genome as the instruction manual of cells, their targeted modulation promises great opportunities in treating and healing diseases. In addition to viral gene transfer, the overwhelming power of non-viral mRNA-based vaccines is driving the development of novel gene transporters. Thereby, various nucleic acids such as DNA (pDNA) or RNA (mRNA, siRNA, miRNA, gRNA, or ASOs) need to be delivered, requiring a transporter due to their high molar mass and negative charge in contrast to classical agents. This chapter presents the specific biological hurdles for using nucleic acids and shows how new materials can overcome these.


Effect of head position on cochlear implant MRI artifact.
A new generation of cochlear implant (CI) magnets and specific surgical techniques (e.g., implant positioning) has changed the relationship between a CI and magnet resonance imaging (MRI). MRI allows a pain free in vivo evaluation of the inner ear fluid state and internal auditory canal after the insertion of an electrode. The aim of this study is to evaluate how the patient's head position in the MRI scanner influences the CI magnet-related artefact. We performed in vivo measurement of MRI artefacts at 3 T with a CI system containing a bipolar diametrical magnet. The implant magnet was positioned with a head bandage at different positions from the nasion and external auditory canal in three volunteers. We used a turbo spin echo (TSE) T2w sequence on the axial and coronal planes and observed three positions: (1) regular position, (2) chin to chest (anteflexion), and (3) hyperextension (retroflexion). By comparing the positions, anteflexion of the cervical spine in a chin-to-chest position allowed us to place the artefact in a more apical position from the IAC in the coronal plane. The hyperextension of the cervical spine position shifts the artefact father towards the cochlea's direction. The head's position can influence the location of MRI artefacts. In cases where the artefact diminished the IAC or cochlea, anteflexion of the cervical spine in the chin-to-chest position of the head in the MRI scanner should be attempted to allow a visualization of the IAC.


A repertoire of cytokines in human seminal plasma.
The pathophysiological significance of seminal cytokines in sperm function is still controversial. We determined the repertoire of cytokines in seminal plasma obtained from men with or without abnormalities in semen and assessed the pathophysiological significance of seminal cytokines. After conventional analysis of semen samples obtained from 86 men, levels of seminal cytokines (interleukin [IL]-1alpha, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma, granulocyte colony-stimulating factor [G-CSF], macrophage CFS [M-CSF]) and granulocyte elastase were measured by an enzyme-linked immunosorbent assay. Leukocytospermia was defined as seminal plasma, which has > or =1000 ng/ml granulocyte elastase. Leukocytospermia was found in nine of 62 of the subjects in the normozoospermic group but in none of the 24 subjects showing abnormal sperm parameters (azoospermia, n=5; oligozoospermia, n=4; asthenozoospermia, n=15). The IL-8 level in the leukocytospermic group was significantly higher than those in the normal and oligozoospermic groups. IL-1alpha and TNF-alpha levels in the leukocytospermic group were significantly higher than those in the normal and asthenozoospermic groups. Although the G-CSF level in the leukocytospermic group was significantly higher than that in the normal group, high levels of M-CSF were detected in all groups. The IL-8 level was strongly correlated with IL-1alpha (r=0.935, P<0.0001) and G-CSF (r=0.916, P<0.0001) levels. Cytokines detected in seminal plasma are associated with the pathogenesis of leukocytospermia but not with the pathogenesis of asthenozoospermia and oligozoospermia.


Synaptic development in the rabbit superior colliculus and visual cortex.
The development of synapses in the visual cortex (VC) and superior colliculus (SC) of the rabbit has been examined with the electron microscope. In both areas, the number of synapses reaches adult levels by 20--25 days of postnatal age, but the development in the visual cortex is delayed in comparison to that in the superior colliculus. When S synapses (spheroidal vesicles, asymmetric thickening) are compared with F synapses (flattened vesicles, symmetric thickening), even greater differences are seen. In both the VC and SC, S synapses develop earlier than F synapses, though there is considerable overlap. Of interest is that fact that synapses in the visual cortex seem to overshoot their adult levels late in development, suggesting that an excess of synapses may be formed in this system. Multiple synapses, probably of retinal origin, increase in the first 3 weeks of synaptic development in the SC, but never are present in significant proportions in the VC. Synapse formation most often is characterized by formation of a junction and a postsynaptic thickening, followed by acquisition of synaptic vesicles. After 15 days, there is only a small number of such "non-vesicle synapses" in either the SC or VC.


Trends in child and adolescent mental health in Catalonia in the context of the COVID-19 pandemic during the 2020-2021 school year.
The SARS-CoV-2 pandemic has had a great impact on the physical and psychological health of the population. The aim of this study was to evaluate child and adolescent mental health in a population cohort along the 2020-2021 school year. This was a prospective longitudinal study of a cohort of children from 5-14 years of age in Catalonia, Spain, performed from September 2020 to July 2021. The participants were randomly selected and accompanied by their primary care paediatrician. Evaluation of risk of psychopathology was performed using the Strengths and Difficulties Questionnaire (SDQ) carried out by one of the legal guardians of the child. We also collected sociodemographic and health variables of the participants and their nuclear family. Data were collected by an online survey through the RedCap platform at the beginning of the academic year and at the end of each trimester (4 cuts). At the beginning of the school year, 9.8% of the patients were probable cases of psychopathology compared to 6.2% at the end of the year. The perception of the level of preoccupation of the children for their health and that of their family was related to presenting psychopathology, especially at the beginning of the year, with the perception of a good family atmosphere being always related to lower risk. No variable related to COVID-19 was associated with an altered SDQ result. Along the 2020-2021 school year, the percentage of children with a probability of presenting psychopathology decreased from 9.8% to 6.2%.


The first chemoselective tandem acylation of the Blaise reaction intermediate: a novel method for the synthesis of alpha-acyl-beta-enamino esters, key intermediate for pyrazoles.
The Blaise reaction intermediate, a zinc bromide complex of beta-enamino ester, could be activated in situ by addition of a stoichiometric or catalytic amount of n-BuLi to allow chemoselective tandem C2-acylation providing alpha-acyl-beta-enamino esters, which are valuable intermediates for the syntheses of tri- and tetrasubstituted pyrazoles.


Best-worst scaling methodology to evaluate constructs of the Consolidated Framework for Implementation Research: application to the implementation of pharmacogenetic testing for antidepressant therapy.
Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best-worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use. We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites. Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions. This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.


Effect of Delta9-tetrahydrocannabinol on sucrose palatability as measured by the taste reactivity test.
The taste reactivity test was employed to determine the effect of pre-treatment with Delta9-Tetrahyrdrocannabinol THC on sucrose palatability. In Experiment 1, on each of 9 trials, rats were injected with THC or Vehicle prior to receiving a 5 min intraoral infusion of sucrose solution. The concentration of sucrose (2%, 10% or 32%) and the interval between the injection and the sucrose infusion (30, 60 or 120 min) were varied in a within-subjects design. THC enhanced the frequency of ingestion reactions only when administered 120 min prior to the taste reactivity test, regardless of sucrose concentration. In Experiment 2, the CB1 antagonist, SR141716, reversed the enhanced sucrose palatability produced by THC. These results suggest that the increased intake of palatable food 2 h, but not earlier, following administration of a low dose of THC may be the result of enhanced palatability and that this effect is the result of action of THC at the CB1 receptor.


A review of the quality assurance processes for the Australasian Triage Scale (ATS) and implications for future practice.
Triage is a critical component in the delivery of time-sensitive emergency care. Decision-making and the activity of the triage nurse affect patient access to care and allocation of emergency department (ED) resources. It is important to be able to evaluate decision-making at triage to ensure patient safety, and to identify opportunities for professional and service development. At present, there is no standard approach to retrospective examination of triage decisions using the Australasian Triage Scale. The aim of this literature review is to identify the quality control strategies used in triage and the factors that appear to influence triage decisions in relation to the Australasian Triage Scale.


Effect of energy dependence of primary beam divergence on the X-ray standing wave characterization of layered materials.
Incident primary beam divergence is a source of systematic error in X-ray standing wave (XSW) characterization of single and multilayer thin films. Primary beam divergence significantly alters the XSW profile of a layered material and can lead to large errors when used with higher excitation energies. The present study suggests that when one uses Mo-Kalpha excitation, the primary beam divergence should be in range of 0.005(0). On the other hand, in the case of Cu-Kalpha excitation, primary beam divergence can be relaxed up to 0.01(0).


Reductions in neural activity underlie behavioral components of repetition priming.
Repetition priming is a nonconscious form of memory that is accompanied by reductions in neural activity when an experience is repeated. To date, however, there is no direct evidence that these neural reductions underlie the behavioral advantage afforded to repeated material. Here we demonstrate a causal linkage between neural and behavioral priming in humans. fMRI (functional magnetic resonance imaging) was used in combination with transcranial magnetic stimulation (TMS) to target and disrupt activity in the left frontal cortex during repeated classification of objects. Left-frontal TMS disrupted both the neural and behavioral markers of priming. Neural priming in early sensory regions was unaffected by left-frontal TMS--a finding that provides evidence for separable conceptual and perceptual components of priming.


Multidrug resistance gene cfr in methicillin-resistant coagulase-negative staphylococci from chickens, ducks, and pigs in China.
The multidrug-resistance gene cfr was detected in coagulase-negative staphylococci from 3/401 pigs, 15/305 chickens, and 3/78 ducks from 31 different farms and one slaughterhouse in 2 provinces of China. Twenty of the 21 cfr-positive isolates were methicillin-resistant. Various SmaI-PFGE patterns were observed among the isolates of the same staphylococcal species and suggested horizontal transfer of cfr rather than clonal expansion. The detection of cfr on plasmids in the majority of the isolates supported this assumption. Analysis of the drug usage records of the farms strongly correlated with the resistance patterns of the cfr-positive isolates and suggested that antimicrobial use on farms supports the spread of the cfr gene.


Physiological characteristics of free-living and parasitic stages of strains of Haemonchus contortus, susceptible or resistant to benzimidazole anthelmintics.
The effect of changes in genetic constitution (associated with developing benzimidazole resistance) on the physiological characteristics of Haemonchus contortus was investigated. Benzimidazole resistant H contortus were significantly more infective for sheep (20 per cent) than benzimidazole susceptible strains. Pathological changes were more severe in sheep infected with resistant H contortus as measured by packed cell volume, plasma protein concentration and haemoglobin levels. Faecal egg output was significantly higher for resistant strains as was the development and survival of eggs and free-living stages on pasture. Infective third stage larvae of benzimidazole resistant H contortus had a significantly faster exsheathment rate in rumenal fluid than did susceptible strains. These adaptive changes in response to continuing anthelmintic selection of resistant worm populations are discussed and the implications of these findings for worm control programmes indicated.


Measurement of immunosuppression in chickens caused by infectious bursal disease vaccines using Brucella abortus strain 19.
The serological response of chicks to Brucella abortus strain 19 was monitored over a period of seven weeks to assess the degree of immunosuppression caused by vaccination at one day of age with two infectious bursal disease vaccines. One of the vacy. This vaccine caused severe immunosuppression judged by the minimal serological response following B abortus inoculation. The test also detected a significant delay caused by the other vaccine in the development of the serological response but the maximum titre was not significantly different from that in chicks which had received no infectious bursal disease vaccine.


Assessment of requirements for selenium and adequacy of selenium status: a review.
The intent of this review is to evaluate the scientific evidence for the assessment of adequacy of selenium status and of the requirements for selenium. From this evidence, attempts have been made to define levels of plasma selenium and dietary selenium intake, which could be used for the assessment of deficiency or adequacy of selenium status. The first section briefly reviews the methods for assessment of selenium status. The second section outlines the requirements for selenium based on a number of criteria, and how these have been translated into recommended intakes of selenium. In the final section, levels of plasma selenium and dietary intake based on different criteria of adequacy have been proposed. The minimum requirement for selenium is that which prevents the deficiency disease, Keshan disease. The recommended intakes of selenium have been calculated from the requirement for optimum plasma glutathione peroxidase (GPx) activity that must, because of the hierarchy of selenoproteins, also take account of the amounts needed for normal levels of other biologically necessary selenium compounds. Whether optimal health depends upon maximization of GPx or other selenoproteins, however, has yet to be resolved, and the consequences of less-than-maximal GPx activities or mRNA levels need investigation. Intakes, higher than recommended intakes, and plasma selenium concentrations that might be protective for cancer or result in other additional health benefits have been proposed. There is an urgent need for more large-scale trials to assess any such beneficial effects and to provide further data on which to base more reliable estimates for intakes and plasma selenium levels that are protective.


Role of homeobox genes in the patterning, specification, and differentiation of ectodermal appendages in mammals.
Homeobox genes are an evolutionarily conserved class of transcription factors that are key regulators during developmental processes such as regional specification, patterning, and differentiation. In this review, we summarize the expression pattern, loss- and/or gain-of-function mouse models, and naturally occurring mouse and human mutations of known homeobox genes required for the development of ectodermal appendages.


Quality of life assessment among patients suffering from different dermatological diseases.
To assess the quality of life (QoL) of patients with different dermatological diseases. Multiple international studies have evaluated the QoL among patients with different dermatological diseases; however, few studies of this kind have been conducted in Saudi Arabia. This quantitative, observational, cross-sectional study was carried out in the dermatology outpatient clinics of King Saud University Medical City, Riyadh, Saudi Arabia, from September 2019 until February 2020. Data was collected using the validated Arabic version of the Dermatology of Life Quality Index (DLQI). A total of 391 patients ≥18 years participated in the study. The mean age of participants was 33 years (18-75 years). Most participants in this study reported that their dermatological disease had a small or no effect on their QoL (62.5%). The majority of patients who had acne vulgaris (79.7%), vitiligo (79.3%), hair disorders (76.9%), or rosacea (71.5%) reported a small to no effects on their QoL. However, diseases that reflected the largest percentages of a large to extremely large effect on QoL were urticaria (37.1%), eczema (26.6%), and psoriasis (24%). A total of 42.9% of the participants suffered from lichen planus and 66.7% of participants suffered from cutaneous neoplasms reported a moderate effect on their QoL. Understanding the impact of different dermatological diseases on QoL can help dermatologists to improve thier patients' QoL. Therefore, we recommend that further studies on this topic be conducted in multiple health centers.


The effect of direction and reaction on the neuromuscular and biomechanical characteristics of the knee during tasks that simulate the noncontact anterior cruciate ligament injury mechanism.
Jumping and landing tasks that have a change in direction have been implicated as a mechanism of noncontact anterior cruciate ligament injury. Yet, to date, neuromuscular and biomechanical research has focused primarily on straight landing tasks during planned jumps. Lateral and reactive jumps increase the neuromuscular and biomechanical demands placed on the anterior cruciate ligament, and women perform these tasks differently from men. Controlled laboratory study. A total of 18 male and 17 female healthy high school basketball players underwent an analysis of the knee during planned and reactive 2-legged stop-jump tasks in 3 different directions that included novel methodology to incorporate a reactive component. Ground-reaction forces, joint kinematics, joint kinetics, and electromyographic activity were assessed during the tasks. Jump direction and task (planned or reactive) significantly affected joint angles, ground-reaction forces, knee joint moments, and proximal anterior tibia shear forces; female players demonstrated different kinematic, kinetic, and electromyographic characteristics during these tasks. Jump direction significantly influenced knee biomechanics, suggesting that lateral jumps are the most dangerous of the stop-jumps. Reactive jumps were also significantly different, suggesting differences between planned laboratory experiments and actual athletic competition. The results of this study indicate that directional and reactive jumps should be included in research methodology and injury-prevention programs.


Vitamin D levels and oxidative stress markers in patients hospitalized with COVID-19.
COVID-19 is characterized by the presence of oxidative stress. Vitamin D status has been reviewed as one of the factors that may affect disease severity. The aim of this study was to assess the relationship between serum vitamin D levels, oxidative stress markers and disease severity in hospitalized COVID-19 patients. Vitamin D levels were measured in 33 patients with COVID-19. The total antioxidant power and plasma peroxides were determined in serum. Severe COVID-19 patients have lower vitamin D levels (18.39 ± 2.29 ng/mL vs. 28.47 ± 3.05 ng/mL, p < .05) and higher oxidative stress compared to the moderate group. When divided according to serum vitamin D levels, significantly higher values of LDH (604.8 ± 76.98 IU/mL vs. 261.57 ± 47.33 IU/mL) and D-dimer (5978 ± 2028ng/mL vs. 977.7 ± 172 ng/mL) were obtained in the group with vitamin D below 30 ng/mL, followed with significantly higher levels of plasma peroxides (d-ROMs: 414.9 ± 15.82 U.Carr vs. 352.4 ± 18.77 U.Carr; p < .05) and oxidative stress index (OSI: 92.25 ± 6.60 vs. 51.89 ± 6.45; p < .001). The presented data provide a justification to consider vitamin D as an important factor that could ameliorate disease severity through its anti-inflammatory and antioxidant effects.


Biphasic nature of the binding of cationic amphipaths with artificial and biological membranes.
We have studied the interaction with liposomes and red cell membrane of various cationic amphipaths, chlorpromazine, methochlorpromazine, imipramine and propranolol. At low concentrations the interaction is a partition of the molecule between the lipid hydrophobic phase and the aqueous medium. The extent of the partition is dependent on the membrane composition or physical properties, on the incubation conditions (pH, ions) and on the amphipath used. After a given amount of amphipath has entered in the membrane, a new type of interaction appears which leads to an apparent saturable association. This association, which probably involves the anionic groups of the membrane components, might result from structural or/and electrical membrane perturbations induced by the presence of drug molecules between the phospholipids. Thus the interaction of a molecule of cationic amphipath with a membrane varies according to the amount of drug present.


Endovascular treatment of pediatric basilar artery aneurysms: case series and literature review.
Pediatric basilar artery aneurysms are rare and challenging to treat. Microsurgical options and standard endovascular coiling are often undesirable choices for treatment of this pathology. Additional endovascular strategies are needed. Presentation, diagnosis, and management of pediatric basilar aneurysms were reviewed, with an emphasis on endovascular treatment strategies. Our case series of 2 patients was presented in detail, one treated with flow diversion and vessel sacrifice and one treated with stent-assisted coiling. An extensive review of the literation was performed to find other examples of pediatric basilar artery aneurysms treated with endovascular techniques. Twenty-nine studies met inclusion criteria. Fifty-nine aneurysms in 58 patients were treated using endovascular techniques. Mortality rate was 10.3% (6/58) and a poor outcome (GOS 1-3) occurred in 15.5% (9/58). There were 4 reported recurrences requiring retreatment; however, only 46.5% of patients had reported follow-up of at least 1 year. 71.1% (42/59) were dissecting aneurysms. Basilar artery aneurysms in the pediatric population are rare, commonly giant and fusiform, and often not amenable to microsurgical or coiling techniques. The surrounding vasculature, location, size, and morphology of the aneurysm along with the durability of treatment must be considered in treatment decisions. With proper patient selection, stent-assisted coiling and flow diversion may increase the durability and safety of endovascular treatment in this population.


Sustained esophageal contraction: a marker of esophageal chest pain identified by intraluminal ultrasonography.
Intraluminal pressure recording systems have not demonstrated predictable esophageal motor correlates of unexplained chest pain. This study used continuous high-frequency intraluminal ultrasonography to characterize esophageal contraction at the time of spontaneous and provoked chest pain. Intraluminal pressure, pH, and ultrasound images of the esophagus were recorded for a maximum of 24 hours in 10 subjects with unexplained chest pain. Changes in esophageal muscle thickness were measured as a marker of muscle contraction. Ten additional subjects with suspected esophageal chest pain were studied after edrophonium chloride injection to provoke symptoms. Ten healthy subjects were studied as controls. Eighteen of 24 spontaneous chest pain episodes were preceded by a sustained esophageal contraction (SEC) detected on ultrasonography (mean duration, 68.0 seconds). This motor pattern was not accompanied by changes in intraluminal pressure. Four of 24 asymptomatic control periods were accompanied by SEC, although these contractions were of shorter mean duration (29.0 seconds; P < 0.001). SEC was observed in 5 subjects with a positive chest pain response to edrophonium and in none of the 5 subjects with a negative response. SEC was not detected in normal subjects. There is a strong temporal correlation between a previously unrecognized esophageal motor event, SEC, and both spontaneous and provoked esophageal chest pain.


Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals.
Cigarette smoking is associated with increased insulin resistance and other metabolic abnormalities. Here, we investigate the prevalence of metabolic syndrome (MetS) in cigarette smokers and people who never smoked by analyzing cross-sectional data of 5033 subjects aged between 35 and 65 years who underwent general health screening. Both former and current smoking was associated with an increased incidence of metabolic syndrome defined by modified-National Cholesterol Education Program (NCEP) criteria with odds ratios of 1.77 (95% CI 1.42-2.22, P < 0.0001) and 2.38 (95% CI 1.95-2.91, P < 0.0001), respectively. In both former and current smokers, prevalence of metabolic syndrome increased when the duration of cigarette smoking was > or = 10 years. The positive association between metabolic syndrome and smoking was only partially reversed even 5 years after quitting. Multivariate logistic regression analysis showed that metabolic syndrome was an independent risk factor for carotid plaque with an odds ratio of 1.72 (95% CI 1.43-2.08, P < 0.0001). On the other hand, when limited to individuals without metabolic syndrome, former and current smoking was still found to be associated with carotid plaque with odds ratios of 1.49 (95% CI 1.15-1.92, P = 0.0023) and 1.57 (95% CI 1.22-2.03, P = 0.0005), respectively, in men. Collectively, these data suggest that the atherogenic consequences of smoking may, at least in part, be explained by its association with metabolic syndrome.


Schistosomal myelopathy mimicking spinal cord neoplasm.
We describe a 48-y-old male with chronic progressive myelopathy suggesting thoracic intramedullary neoplasm but in whom laboratory workup disclosed Schistosoma mansoni myelopathy. The case illustrates the need for careful investigation of schistosomiasis in patients from endemic regions with myeloradiculopathy signs.


Cognitive control in childhood-onset obsessive-compulsive disorder: a functional MRI study.
Failure to resist chronic obsessive-compulsive symptoms may denote an altered state of cognitive control. We searched for the cerebral regions engaged in this dysfunction. Differences in brain regional activity were examined by event-related functional magnetic regional imaging (fMRI) in a group of adolescents or young adults (n = 12) with childhood-onset obsessive-compulsive disorder (OCD), relative to healthy subjects. Subjects performed a conflict task involving the presentation of two consecutive and possibly conflicting prime and target numbers. Patients' image dataset was further analysed according to resistance or non-resistance to symptoms during the scans. Using volume correction based on a priori hypotheses, an exploratory analysis revealed that, within the prime-target repetition condition, the OCD subjects activated more than healthy subjects a subregion of the anterior cingulate gyrus and the left parietal lobe. Furthermore, compared with 'resistant' patients, the 'non-resistant' OCD subjects activated a bilateral network including the precuneus, pulvinar and paracentral lobules. Higher regional activations suggest an abnormal amplification process in OCD subjects during the discrimination of repetitive visual stimuli. The regional distribution of functional changes may vary with the patients' ability to resist obsessions.


Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone.
Pelvic lymph node metastasis carries the highest impact on decreased survival among surgical-pathological risk factors for early-stage cervical cancer. Although concurrent administration of chemotherapy during postoperative radiotherapy is the current standard treatment for surgically treated high-risk early-stage cervical cancer, its effectiveness specific to node-positive disease has not been completely studied. To examine the association between the use of concurrent chemotherapy and survival in women with early-stage cervical cancer and nodal metastasis receiving adjuvant radiotherapy. This is a population-based cohort study using the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Women with stage T1-2 cervical cancer with pelvic lymph node metastasis who underwent hysterectomy and received postoperative radiotherapy were examined. Trends, characteristics, and overall survival were compared between women who received postoperative radiotherapy alone (n = 729) or in combination with concurrent chemo-radiotherapy (n = 1809). Propensity score-based inverse probability of treatment weighting was used to account for the effect of measured covariates on treatment selection. Among 2538 women, there was a marked increase in the use of concurrent chemotherapy from 1997 to 2000 (20.7% to 78.5%, P = .052), followed by a more gradual rise through 2016 (88.3%, P < .001). In a multivariable model, women with non-squamous cell carcinomas and those diagnosed more recently were more likely to receive concurrent chemo-radiotherapy, whereas older women were less likely to receive concurrent chemo-radiotherapy (all, P < .05). At the population level, the 5-year overall survival rates remained unchanged (annual percent change for 1997-2012: -0.1; 95% confidence interval, -1.2 to 1.0; P = .776). In a propensity score weighted cohort, women who received concurrent chemo-radiotherapy had a 5-year overall survival rate similar to women treated with radiotherapy alone (73.1% vs 73.6%; hazard ratio, 1.004; 95% confidence interval, 0.887-1.136; P = .955). Significant differences were also not seen in older women, nonsquamous types, stage T2 disease, and multiple node metastases (all, P > .05). Despite the marked increase in the use of concurrent chemo-radiotherapy for women with early-stage cervical cancer and nodal metastases, there was no association between use of concurrent chemotherapy during postoperative radiotherapy and improved survival.


Lectin activity of chromatin non-histone proteins.
Non-histone proteins from chromatin of sea urchin embryos were found to possess the ability to agglutinate erythrocytes.


Involvement of LMA1 and GATE-16 family members in intracellular membrane dynamics.
Intracellular membrane fusion is conserved from yeast to man as well as among different intracellular trafficking pathways. This process can be generally divided into several well-defined biochemical reactions. First, an early recognition (or tethering) takes place between donor and acceptor membranes, mediated by ypt/rab GTPases and complexes of tethering factors. Subsequently, a closer association between the two membranes is achieved by a docking process, which involves tight association between membrane proteins termed SNAREs. The formation of such a trans-SNARE complex leads to the final membrane fusion, resulting in an accumulation of cis-SNARE complexes on the acceptor membrane. Thus, multiple rounds of transport and delivery of the donor SNARE back to its original membrane require dissociation of the SNARE complexes. SNARE dissociation, termed priming, is mediated by the AAA ATPase, N-ethylmaleimide-sensitive factor (NSF) and its partner, soluble NSF attachment protein (SNAP), in a reaction that requires ATP hydrolysis. In the present review we focus on LMA1 and GATE-16, two low-molecular-weight proteins, which assist in priming SNARE molecules in the vacuole in yeast and the Golgi complex in mammals, respectively. LMA1 and GATE-16 are suggested to keep the dissociated cis-SNAREs apart from each other, allowing multiple fusion processes to take place. GATE-16 belongs to a novel family of ubiquitin-like proteins conserved from yeast to man. We discuss here the involvement of this family in multiple intracellular trafficking pathways.


Risk-reductive dental strategies for medication related osteonecrosis of the jaw among cancer patients: A systematic review with meta-analyses.
The purpose of this systematic review with meta-analysis was to assess the effectiveness of dental interventions in preventing or reducing the incidence of medication-related osteonecrosis of the jaw (MRONJ) in cancer patients receiving antiresorptive therapy, compared to similar control groups receiving no intervention. Randomized controlled trials (RCT), case-controls and cohorts on cancer patients with primary outcome being the prevalence of MRONJ were included. Four electronic databases were searched (Cochrane Library, PubMed, EMBASE and Web of Science) up to February 12, 2018. A total of 409 abstracts were assessed and one case-control, one RCT and four cohort studies with 2332 cancer patients met our inclusion criteria. Risk of bias analysis followed Cochrane's handbook. Risk of bias was unclear for the case-control study and high risk for the RCT and all cohort studies. Five studies utilized preventive measures consisting of an initial examination and performing all necessary dental treatment before patients initiated antiresorptive therapy; one study used specialized post-extraction protocols utilizing plasma-rich in growth factors (PRGF) on cancer patients receiving antiresorptive therapy. Though dental preventive measures decreased MRONJ incidence by 77.3% in six studies with 2332 cancer patients (95% CI = 47.4-90.2%; p = .001) compared to control groups, quality of the evidence was low due to high or unclear risk of bias and the observational nature of five of the included studies. In conclusion, high-quality long-term prospective large sample size studies are needed to confirm these results due to high risk of bias and heterogeneous interventions. No funding.


Exercise dependence and orthorexia nervosa in Crossfit: exploring the role of perfectionism.
Physical exercise and healthy diet have a positive effect on health. However, the pathological dimension of both behaviors, namely exercise dependence and orthorexia nervosa, can lead to negative results. So far, literature on these behaviors in the context of high-intensity sports is limited. The present study aims for investigating exercise dependence and orthorexia nervosa in a sample of Crossfit athletes, as well as examining the mediating role of perfectionism in their manifestation.The sample consisted of 110 people who attended Crossfit programs and 131 active gym members. The Exercise Dependence Scale was used to assess exercise dependence, the ORTO-15 to assess orthorexic behavior and the Almost Perfect Scale to evaluate perfectionism.19.8% of crossfitters and 3.8% of gym members were at risk for exercise dependence. 11.7% of participants in the Crossfit group and 10% of participants in the control group had orthorexic symptoms. An association was found between the scores on the two behaviors. In addition, the dimension of perfectionism high standards predicted obligatory exercise and orthorexia nervosa, while the dimension of discrepancy predicted only exercise dependence.The study suggests that exercise dependence is more evident in Crossfit compared to gym athletes and may be accompanied by orthorexic symptoms. Orthorexia nervosa is a noticeable phenomenon in the population of active exercisers. Perfectionism is a risk factor for obligatory exercise and orthorexia. A more demanding selection of target populations is encouraged in order to better understand exercise dependence, orthorexia nervosa and their personality background.


The effect of forced running on heat production in brown adipose tissue in rats.
The effect of running on heat production in brown adipose tissue (BAT) was compared between trained and untrained rats. Rats were forced to run a treadmill while temperatures of colon (T col) and interscapular BAT (T bat) were measured. The daily running for 5 weeks neither changed the size of interscapular BAT nor the norepinephrine-induced thermogenesis (8 micrograms/kg X min). During running, both T bat and T col increased. In rats trained for 2 weeks, the increases in T bat were similar to those in T col. In untrained rats, however, the increases in T bat were larger than those in T col. It is suggested that exercise increases heat production in BAT in untrained rats, but such heat production in BAT is abolished by daily exercise. Exercise suppresses cold-induced heat production in BAT of trained rats.


[The Impact of Supra- and Infracolic Reconstruction on Delayed Gastric Emptying Following Pancreatoduodenectomy].
Delayed gastric emptying (DGE) is the most frequent complication following pancreatoduodenectomy. While antecolic and retrocolic reconstruction does not influence the occurrence of DGE, infracolic reconstruction might alleviate DGE due to the vertical position of the distal stomach compared to supracolic reconstruction. Supra- and infracolic reconstruction have not yet been compared. 138 patients underwent pylorus-preserving pancreatoduodenectomy with retrocolic reconstruction at our department between 2011 and 2017. Of these, 105 were reconstructed with supracolic duodenoenterostomy and 33 with infracolic duodenoenterostomy. Patients were analysed with respect to demographic factors, diagnosis, pre-existing conditions, intraoperative characteristics, hospital stay and morbidity and mortality with special emphasis on DGE. All complications were classified according to the definitions of the International Study Group on Pancreatic Surgery. The two groups were comparable with respect to diagnosis, medical history, intraoperative characteristics, morbidity and mortality. DGE was equally distributed between supra- and infracolic reconstruction (DGE stage A/B/C25/14/10 vs. 12/5/2, p = 0.274). With DGE, intensive care unit stay (p = 0.007) and hospital stay (p = 0.001) are significantly delayed. Risk factor analysis showed that pre-existing diabetes (p = 0.047) and major complications (Clavien stage III - V, p = 0.048) are risk factors for DGE, while the use of somatostain-analogues seems to have a protective effect (p = 0.021). Supra- or infracolic reconstruction does not influence the frequency of DGE following pancreatoduodenectomy. When DGE occurs, hospital stay is delayed. Somatostatin analogues may act prophylactically on DGE.


Effect of Rare-Earth Doping on Free-Volume Nanostructure of Ga-Codoped Glassy (As/Sb)2Se3.
Subsequent stages of atomic-deficient nanostructurization finalizing rare-earth functionality under Pr3+-doping in Ga2(As0.28Sb0.12Se0.60)98 glass are studied employing method of positron annihilation lifetime spectroscopy. Genesis of free-volume positron trapping sites, composed of atomic-accessible geometrical holes (void cores) arrested by surrounding atomic-inaccessible Se-based bond-free solid angles (void shells), are disclosed for parent As2Se3, Ga-codoped Ga2(As0.40Se0.60)98, as well as Ga-codoped and Sb-modified Ga2(As0.28Sb0.12Se0.60)98 glasses. The finalizing nanostructurization due to Pr3+-doping (500 wppm) in glassy Ga2(As0.28Sb0.12Se0.60)98 is explained in terms of competitive contribution of changed occupancy sites available for both rare-earth ions and positrons.


ELISA for herpes simplex virus (HSV) type-specific antibodies in human sera using HSV type 1 and type 2 polyspecific antigens blocked with type-heterologous rabbit antibodies.
Crude antigenic preparations made from rabbit cornea cells infected with either HSV type 1 or type 2 could be used in ELISA for titration of HSV type-specific antibodies in human sera. After immunochemical binding of the crude HSV antigens in microtitre wells by use of type-homologous rabbit antibodies, type-common antigenic sties were blocked with type-heterologous rabbit antibodies. Titration of human sera in this system showed that high concentrations of type heterologous rabbit antibodies were capable of completely blocking type-common antigenic sites, while leaving type-specific antigenic sites unblocked and capable of reacting with human antibodies. Thus HSV type-specific antibodies in human sera could be measured in ELISA without the use of purified typespecific antigens.


Family Economic Stress, Quality of Paternal Relationship, and Depressive Symptoms among African American Adolescent Fathers.
This study examined the association between perceived family economic stress, quality of father-son relationships, and depressive symptoms among African American adolescent fathers. Data were collected during pregnancy from 65 African American adolescents who were first-time fathers, ages 14-19. Results from multiple regression analyses indicated that higher paternal relationship satisfaction was associated with fewer depressive symptoms among adolescent fathers. Additionally, depressive symptoms were higher among adolescent fathers who reported experiencing higher levels of conflict with their fathers. Further, paternal conflict moderated the effect of perceived family economic stress on depressive symptoms. That is, among adolescent fathers experiencing low levels of conflict with their fathers, high perceived family economic stress was associated with more depressive symptoms. Study findings suggest that the risk for depressive symptoms is highest among adolescent fathers experiencing low family economic stress and highly conflictual relations with their fathers. These results highlight the complexities of paternal relationships and perceived economic stressors on depressive symptoms during pregnancy for African American adolescent fathers. The importance of expanding research on influential familial relationships and economic stressors on adolescent African American fathers is discussed.


Purification and biochemical characterization of Hel a 6, a cross-reactive pectate lyase allergen from Sunflower (Helianthus annuus L.) pollen.
Sunflower pollen was reported to contain respiratory allergens responsible for occupational allergy and pollinosis. The present study describes the comprehensive characterization of a major sunflower allergen Hel a 6. Natural Hel a 6 was purified from sunflower pollen by anion exchange and gel filtration chromatography. Hel a 6 reacted with IgE-antibodies from 57% of 39 sunflower-sensitized patient sera suggesting it to be a major allergen. The patients were of Indian origin and suffering from pollinosis and allergic rhinitis. Hel a 6 exhibited allergenic activity by stimulating mediator release from basophils. Monomeric Hel a 6 displayed pectate lyase activity. The effect of various physicochemical parameters such as temperature, pH, and calcium ion on the functional activity of Hel a 6 revealed a stable nature of the protein. Hel a 6 was folded, and its melting curve showed reversible denaturation in which it refolded back to its native conformation from a denatured state. Hel a 6 displayed a high degree of sequence conservation with the pectate lyase allergens from related taxonomic families such as Amb a 1 (67%) and Art v 6 (57%). The IgE-cross reactivity was observed between Hel a 6 and its ragweed and mugwort homologs. The cross-reactivity was further substantiated by the mediator release when Hel a 6-sensitized effector cells were cross-stimulated with Art v 6 and Amb a 1. Several putative B cell epitopes were predicted and mapped on these 3 allergens. Two antigenic regions were found to be commonly shared by these 3 allergens, which could be crucial for cross-reactivity. In conclusion, Hel a 6 serves as a candidate molecule for diagnosis and immunotherapy for weed allergy.


Loss of the diurnal variation of pyridostigmine-induced growth hormone responses in depression: the effect of cortisol.
Growth hormone (GH) plasma concentrations reflect a balance between stimulation via GH-releasing hormone and inhibition by somatostatin. Cholinergic agonists enhance GH release by inhibiting somatostatin secretion and in health, stimulated GH release undergoes diurnal variation. We investigated the influence of cortisol on pyridostigmine-induced GH responses by testing six patients with DSM-III-R major depression at 09.00 and 14.00 h. There were no differences in GH responses to pyridostigmine between 09.00 and 14.00 h despite a preservation of the circadian variation of cortisol levels. If cortisol plays an important role in regulating cholinergic activity one would expect the diurnal variation of pyridostigmine-induced GH release to be preserved. As it is not, a reasonable assumption to make is that the muscarinic supersensitivity observed in depression may be independent of the prevailing steroid milieu.


Splenic torsion presenting as a twisted hemorrhagic ovarian cyst.
Torsion of a wandering spleen is rare, usually presenting as an acute abdomen and commonly misdiagnosed. In our case, a 14-year-old girl was diagnosed preoperatively as having a twisted hemorrhagic ovarian cyst. On laparotomy, an infarcted spleen that was twisted on its pedicle was found in the lower abdomen. The patient recovered uneventfully. The clinical spectrum of wandering spleen is discussed briefly.


The effect of finasteride on prostate-specific antigen in men with benign prostatic hyperplasia.
Finasteride is a specific 5-alpha-reductase inhibitor that has been shown to reduce prostate size and decrease serum levels of prostate specific antigen (PSA). Among men who received finasteride (5 mg/day) for 12 months in North American clinical trials and in whom prostate cancer was not diagnosed the median percentage change in PSA was -50% (5-95% range: -81% to +20%). At baseline 72% had PSA < or = 4.0 ng/ml and 93% had PSA < or = 10.0 ng/ml. After 12 months on finasteride, 75% had PSA < or = 2.0 ng/ml and 95% had PSA < or = 5.0 ng/ml. Thus, the proportion of BPH patients with PSA levels of 2.0 ng/ml and 5.0 ng/ml after 12 months of treatment was comparable to the proportion with pretreatment PSA levels of 4.0 ng/ml and 10.0 ng/ml. Among the 10 men in these trials subsequently diagnosed with prostate cancer while on long-term finasteride therapy (5 mg/day), the median percentage change in PSA was -26% (range: -48% to +12%). Limited experience with finasteride in men with prostate cancer suggests that the reduction in PSA of malignant origin appears to be no greater than the percentage reduction in PSA of benign origin. These effects on PSA have not been shown to confer any therapeutic benefit. Physicians using finasteride should be aware of its effect on PSA levels.


Heparan structure and the modulation of angiogenesis.
It is postulated that the angiogenic potential of tissues is influenced by the fine structure of heparan glycosaminoglycans present in the tissues. Possible mechanisms involved are discussed. It is suggested that compounds chemically related to heparans might usefully act as inhibitors of pathological angiogenesis.


Transformations of griseofulvin in strong acidic conditions--crystal structures of 2'-demethylgriseofulvin and dimerized griseofulvin.
The structure of griseofulvic acid, C16H15ClO6, at 100 K has orthorhombic (P2(1)2(1)2) symmetry. It is of interest with respect to biological activity. The structure displays intermolecular O-H...O, C-H...O hydrogen bonding as well as week C-H...pi and pi...pi interactions. In strong acidic conditions the griseofulvin undergoes dimerization. The structure of dimerized griseofulvin, C34H32C12O12 x C2H6O x H2O, at 100 K has monoclinic (P2(1)) symmetry. The molecule crystallized as a solvate with one ethanol and one water molecule. The dimeric molecules form intermolecular O-H...O hydrogen bonds to solvents molecules only but they interact via week C-H...O, C-H...pi, C-Cl...pi and pi...pi interactions with other dimerized molecules.


Religious perspectives on the use of psychopharmaceuticals as an enhancement technology.
The use of psychopharmaceuticals as an enhancement technology has been the focus of attention in the bioethics literature. However, there has been little examination of the challenges that this practice creates for religious traditions that place importance on questions of being, authenticity, and identity. We asked expert commentators from six major world religions to consider the issues raised by psychopharmaceuticals as an enhancement technology. These commentaries reveal that in assessing the appropriate place of medical therapies, religious traditions, like secular perspectives, rely upon ideas about health and disease and about normal human behavior. But unlike secular perspectives, faith traditions explicitly concern themselves with ways in which medicine should or should not be used to live a "good life".


Cohort profile: Scotland's record-linkage e-cohorts of people with intellectual disabilities, and autistic people (SCIDA).
To investigate health, mortality and healthcare inequalities experienced by people with intellectual disabilities, and autistic people, and their determinants; an important step towards identifying and implementing solutions to reduce inequalities. This paper describes the cohorts, record-linkages and variables that will be used. Scotland's Census, 2011 was used to identify Scotland's citizens with intellectual disabilities, and autistic citizens, and representative general population samples with neither. Using Scotland's community health index, the Census data (demography, household, employment, long-term conditions) were linked with routinely collected health, death and healthcare data: Scotland's register of deaths, Scottish morbidity data 06 (SMR06: cancer incidence, mortality, treatments), Prescribing Information System (identifying asthma/chronic obstructive pulmonary disease; angina/congestive heart failure/hypertension; peptic ulcer/reflux; constipation; diabetes; thyroid disorder; depression; bipolar disorders; anxiety/sleep; psychosis; attention deficit hyperactivity disorder; epilepsy; glaucoma), SMR01 (general/acute hospital admissions and causes, ambulatory care sensitive admissions), SMR04 (mental health admissions and causes), Scottish Care Information-Diabetes Collaboration (diabetic care quality, diabetic outcomes), national bowel screening programme and cervical screening. Of the whole population, 0.5% had intellectual disabilities, and 0.6% were autistic. Linkage was successful for >92%. The resultant e-cohorts include: (1) 22 538 people with intellectual disabilities (12 837 men and 9701 women), 4509 of whom are children <16 years, (2) 27 741 autistic people (21 390 men and 6351 women), 15 387 of whom are children <16 years and (3) representative general population samples with neither condition. Very good general health was reported for only 3389 (15.0%) people with intellectual disabilities, 10 510 (38.0%) autistic people, compared with 52.4% general population. Mental health conditions were reported for 4755 (21.1%) people with intellectual disabilities, 3998 (14.4%) autistic people, compared with 4.2% general population. Analyses will determine the extent of premature mortality, causes of death, and avoidable deaths, profile of health conditions and cancers, healthcare quality and screening and determinants of mortality and healthcare.


Factorial validity of the EE scales.
High 'expressed emotion' (EE) has been held to be predictive of a poor course in patients with schizophrenia, a finding that has emphasized the predictive validity of the EE measure. We review appropriate research examining properties of the EE measure to suggest that, in particular, little is known about the construct validity of the EE measure. We report a longitudinal study examining three measures of parental style (EE; Parental Bonding Instrument or PBI; and interviewer ratings). By comparing EE scale scores with ratings derived by an interviewer we find support for the accuracy of the process generating EE scale scores, and by factor analytic techniques we examine the factorial (construct) validity of the EE scales. A principal components analysis suggested two other dimensions of relevance in parents involved with a schizophrenic member (vigilance, and acceptance of illness in their child) which may be of value in predictive studies. We examined the capacity of interviewer-generated scores (as a simple clinical rating) and factor scores (as central constructs) to predict the course, and were unable to discriminate 'relapsers' and 'non-relapsers' with either predictor.


Hemodynamic and hemorheological profiles in women with proteinuric hypertension of pregnancy and in pregnant controls.
We obtained blood samples from 52 patients with pre-eclampsia and from 40 pregnant controls for measurement of plasma urate levels, hematocrit, white cell count and various hemorheological parameters. We also used impedance cardiography to measure cardiac output in both groups and from the results derived values for total peripheral resistance and oxygen transport. Central venous pressure was measured with a superior vena cava catheter in patients with pre-eclampsia but not in controls. Women with pre-eclampsia had significantly lower cardiac output and central venous pressure when compared with a control group. A modest correlation was observed between central venous pressure and cardiac output. The majority of pre-eclamptic patients had significantly raised hematocrit, leucocyte count, uric acid and red cell aggregation. Red cell deformability was significantly decreased in patients with pre-eclampsia. Most patients with severe pre-eclampsia (BP diast. greater than 100 mmHg) had a low Antithrombin III and colloid osmotic pressure level. The leucocyte count was raised when compared with the women with moderate pre-eclampsia. Oxygen delivery was reduced in patients with pre-eclampsia because of impaired rheological properties of their blood.


Ingestion of deoxynivalenol (DON) contaminated feed alters the pig vaccinal immune responses.
Deoxynivalenol (DON), a mycotoxin produced by some Fusarium species, is a frequent contaminant of cereals. This toxin is known to modulate the immune function but only few studies have investigated the effect of DON on the vaccinal immune response. In the present experiment, 24 pigs received for 9 weeks either control feed or feed naturally contaminated with 2.2-2.5 mgDON/kg feed. At days 4 and 15 of the experiment, the animals were subcutaneously immunized with ovalbumin. Consumption of DON-contaminated diet does not have a major effect on the hematological and biochemical blood parameters. By contrast, ingestion of DON significantly affects the global and the specific immune response of the pigs. In the serum, DON increases the concentration of total IgA and, in vaccinated animals, DON also increases the concentration of ovalbumin-specific IgA and IgG. DON does not modulate lymphocytes proliferation after mitogenic stimulation but the toxin had a biphasic effect on lymphocyte proliferation after antigenic stimulation (up-regulation at day 21 and down-regulation at day 35-49). Because cytokines play a key role in immunity, the expression levels of TGF-beta, IFN-gamma, IL-4 and IL-6 were measured, by RT-PCR in the spleen, the ileum and the mesenteric lymph node of the animals at the end of the experiment. In the mesenteric lymph node, a significantly lower expression of both TGF-beta and IFN-gamma mRNA expression levels is observed in animals feed with DON when compared with control piglets. Taken together, our data indicate that DON alters the vaccinal immune response. These results may have implications for humans and animals consuming DON-contaminated food or feed as breakdown in vaccinal immunity may lead to the occurrence of disease even in properly vaccinated populations.


Targeting lncRNAs in programmed cell death as a therapeutic strategy for non-small cell lung cancer.
Lung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the most common histological type. Owing to the limited therapeutic efficacy and side effects of currently available therapies for NSCLC, it is necessary to identify novel therapeutic targets for NSCLC. Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs with a transcript length of more than 200 nucleotides, which play a vital role in the tumorigenesis and progression of multiple cancers, including NSCLC. Induction of programmed cell death (PCD) is the main mechanism leading to tumour cell death in most cancer treatments. Recent studies have demonstrated that lncRNAs are closely correlated with PCD including apoptosis, pyroptosis, autophagy and ferroptosis, which can regulate PCD and relevant death pathways to affect NSCLC progression and the efficacy of clinical therapy. Therefore, in this review, we focused on the function of lncRNAs in PCD of NSCLC and summarized the therapeutic role of targeting lncRNAs in PCD for NSCLC treatment, aiming to provide new sights into the underlying pathogenic mechanisms and propose a potential new strategy for NSCLC therapy so as to improve therapeutic outcomes with the ultimate goal to benefit the patients.


Assessing knowledge of Saudi mothers with regard to parenting and child developmental milestones.
Knowledge about childrearing and development of children greatly impacts on how parents can adequately and safely raise and interact with a child. This study aimed to assess Saudi mothers' level of knowledge of parenting and developmental milestones and describe the associated factors that affect their knowledge. This cross-sectional study was conducted in the Eastern Province of Saudi Arabia from January to February 2020. Four hundred Saudi mothers with children up to 6 years of age were included in the study from 20 randomly selected primary healthcare centers. The Knowledge of Infant Developmental Inventory Tool (KIDI-P) was used. Relevant demographic data were collected. Data were analyzed using the Statistical Package for the Social Sciences software version 21 (SPSS). One-way ANOVA and t-test were used to detect any significant differences in mother's knowledge about developmental milestones related to the research variables. The majority of mothers (42.2%) were between 28 and 35 years of age. Knowledge about parentaging scored on the average 53.3%, health and safety scored 63.4%, general principles 55.9%, and developmental milestones 51.8%. Data showed a statistically significant relation between mothers' age and parenting subscale (mean = 0.54, standard deviation [SD] = 0.18, P = 0.001), and mothers' education and parenting (mean = 0.52, SD = 0.18, P = 0.015). Significant differences were found between planned pregnancy and parenting (mean = 0.53, SD = 0.178, P = 0.044) and between planned pregnancy and child developmental milestones (mean = 0.51, SD = 0.12, P = 0.042). Saudi mothers have limited overall knowledge of childrearing and developmental milestones of their children. Mothers' age, parental education, parity, and planned pregnancies had a positive effect on mother's knowledge of parenting and milestones parameters.


How mothers of a child with type 1 diabetes cope with the burden of care: a qualitative study.
Caregiver burden is a complex construct that depends heavily on the context and culture of the community in which care takes place. This study aimed to explore the lived experience of being mothers of a child with type 1 diabetes aged 6 to 18 years. We used a qualitative methodology utilizing conventional content analysis. We conducted 24 interviews with 20 mothers who had a child with type 1 diabetes aged 6 to 17 years. The mean age of mothers and children were 36.3 and 12.3 years, respectively. The mean of years with the disease was 4.3 years. Thirteen children were girls. The essential theme was coping with the burden of care through personalized coping and active acquisition of social support. The main theme consists of four sub-themes including Crisis in the family and burden of care, Losing the family equilibrium, Personalized coping strategies, and Active acquisition of social support. Mothers used personalized strategies and every support they could get to reach their aim. Families of children with type 1 diabetes need extensive and personalized care plans.


The economic impacts of traffic consumption during the COVID-19 pandemic in China: A CGE analysis.
The transportation sector has played an important role during the COVID-19 pandemic. Like many industries, it experienced a sharp decline during the pandemic. The reduced traffic consumption has been caused by objective conditions, such as traffic control measures, and subjective factors, such as the perception of the COVID-19 pandemic. This study uses the computable general equilibrium (CGE) model to examine the economic impacts of traffic consumption during the COVID-19 pandemic in China. Moreover, to evaluate the impact of the government's economic stimulus policy related to transportation, this study examines the policy effects of transportation investment. This study suggests that, first, China's macroeconomy has been severely affected by reduced traffic consumption. The period when the pandemic was most severe had the largest GDP decrease (0.49%). Second, transportation consumption is closely associated with the output of all industries. As the pandemic worsens, the output of all sectors declines more. Of the transport sectors, road transport has the largest output decrease (10.17%), followed by railway (1.76%) and air sectors (1.53%). The service industry is the most negatively affected among the non-transportation sectors. Finally, transportation infrastructure investment can effectively promote the economy and create jobs. In addition, railway investment plays a more positive role in the economy than road and air transports. The findings provide a detailed understanding of the economic impact of the significantly reduced traffic consumption at different stages of the pandemic.


Four stroke diesel engine performance and emission studies of ethanol recovered from Kappaphycus alvarezii reject -solid food waste mixed substrates and its blends.
Bioethanol is an eco-friendly green fuel, owing to its production from sustainable bio-based sources. In this study, bioethanol (BE) is produced from Kappaphycus alverezii reject (KR) blended with Solid Food Waste (SFW). This bioethanol is blended with petroleum-based diesel (PBD) in the following proportions: 15%, 20% and 25% for further studies. Performance characteristics, specifically Brake Specific Fuel Consumption (BSFC), Brake Thermal Efficiency (BTE), Brake Power (BP) and exhaust emissions, mainly Carbon monoxide (CO), Carbon dioxide (CO2), Smoke Opacity (SO), hydrocarbons (HC) and oxides of Nitrogen (NOX) have been investigated. The blended test fuels show better results, which is confirmed by the performance characteristics of BTE being lower than PBD. The emission report shows lesser CO (0.12%) and SO (59.6%) compared to PBD (0.14% and 67.2%), signifying the clean-burning tendency of BE blends. From the findings, PBD75: BE25 is an excellent fuel blend for improving flow properties, engine performance, and emission characteristics.


Mapping of cerebral metabolites in rats by 1H magnetic resonance spectroscopic imaging. Distribution of metabolites in normal brain and postmortem changes.
The goal of this study was to examine metabolic differences between cortex and basal ganglia in normal rat brain and to determine postmortem changes using in vivo 1H magnetic resonance spectroscopic imaging at 300 MHz. The resonances observed were: choline, creatine + phosphocreatine, N-acetyl aspartate (NAA), lactate (Lac), and three small resonances in the amino acid region which included resonances from aspartate + NAA (Asp), glutamine + NAA (Gln), and glutamate + GABA (Glu). A previously unassigned resonance was observed at 1.13 ppm in brain of rats anesthetized with pentobarbital. Spectroscopic images in normal brain demonstrated increased NAA and Gln and decreased Glu in cortex compared to basal ganglia. The major postmortem changes were an increase of Lac, Glu and Cho and a decrease of NAA and Asp. The rise in Lac was significantly higher in cortex than in basal ganglia.


Acute spinal cord injury patients--who cares?
Pertinent aspects of the remarkable advances instituted and developed for the management of patients who have sustained serious spinal injuries are discussed in this communication, and the responsibilities of medical doctors and others who care for such patients is taken up in relation to some of the recent advances in our knowledge, both experimental, and clinical. There are new challenges in investigations and therapy to be considered, some of which are being somewhat precipitiously put into practice. In particular, early spinal operations, where certain closed or open reduction procedures are followed by some of the newer forms of vertebral column fixation, may cause complications. Also the apparent benefits from such techniques may not be achieved and a plea is made for careful well documented accounts to be assembled and where possible set out, using modern statistical methods, to be made by doctors treating such patients. The significance of a full understanding of the importance of modern rehabilitation techniques for spinal cord injury patients is stressed; and finally, the practical realisation of insurance claims and of possible medical litigation is mentioned.


Distinguishing post-treatment changes from recurrent disease in cholangiocarcinoma: a case report.
Three-dimensional techniques for radiotherapy have expanded possibilities for partial volume liver radiotherapy. Characteristic, transient radiographic changes can occur in the absence of clinical radiation-induced liver disease after hepatic radiotherapy and must be distinguished from local recurrence. In this report, we describe computed tomography changes after chemoradiotherapy for cholangiocarcinoma as an example of collaboration to determine the clinical significance of the radiographic finding. Because of improved three-dimensional, conformal radiotherapy techniques, consultation across disciplines may be necessary to interpret post-treatment imaging findings.


Incontinentia Pigmenti Associated with Aplasia Cutis Congenita in a Newborn Male with Klinefelter Syndrome: Is the Severity of Neurological Involvement Linked to Skin Manifestations?
We report a rare case of a newborn male affected by incontinentia pigmenti, Klinefelter syndrome, and aplasia cutis congenita, who developed severe cutaneous, neurological, and ophthalmological manifestations. Genetic analysis showed the presence of the common mutation of NEMO (exon 4-10 deletion), Klinefelter syndrome karyotype (47 XXY), and random X inactivation. This is in accordance with the severity of involvement of the affected tissues (skin, central nervous system, and retina). Indeed, the patient developed typical skin lesions all over the body, except the head. Equally, multiple lesions diffusely involving both the cortical grey matter and subcortical white matter of the cerebellum and cerebral hemispheres were observed. Discussing current knowledge about the etiopathogenesis of skin and brain lesions in incontinentia pigmenti, our case seems to support the proapoptotic origin of central nervous system involvement. Possibly, incontinentia pigmenti patients suffer an impaired protection against apoptosis at the level of cerebral endothelial cells of small vessels, leading to vascular damage and subsequent ischemic brain lesions.