Huaier polysaccharide inhibits the stem-like characteristics of ERα-36high triple negative breast cancer cells via inactivation of the ERα-36 signaling pathway.
Triple negative breast cancer (TNBC) is a highly aggressive cancer and lack of targeting therapies. It is believed that the breast cancer stem cells (BCSCs) are responsible for the aggressive characteristics of TNBC. Hence, developing BCSC-targeting agents may provide new therapeutic strategies for the patients. Huaier polysaccharide (HP), an active ingredient extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anti-cancer treatments in China. Here we demonstrated that HP could target BCSCs in TNBC cells, resulting in decreased mammosphere formation, downregulated expression of stem-related genes and reduced proportion of aldehyde dehydrogenase positive cells in vitro, and inhibited xenograft tumor formation in vivo. Mechanically, HP markedly reduced the expression of estrogen receptor α-36 (ERα-36), a recently identified subtype of estrogen receptor α, and attenuated ERα-36-mediated activation of AKT/β-catenin signaling in ERα-36high TNBC cells. This study provides a new insight into the mechanism of HP on BCSC-targeting therapy and new ideas for comprehensive treatment strategies for TNBC.


[Atraumatic complete esophageal rupture (Boerhave's syndrome) (author's transl)].
Two of our own patients with Boerhave's syndrome are reported. A disturbance of the vomiting process with abrupt increase of pressure in the esophageal lumen combined with a circumscribed constitutional weakness of the esophageal wall appears to be the decisive factor in the etiology of atraumatic complete esophageal rupture. The clinical picture is characterized by vomiting and painful sensations in the abdomen and thorax in addition to subsequent acute epigastric symptomatology. A water-soluble contrast medium is very useful in the radiological diagnosis. Thoracotomy with suture and drainage is recommended as the treatment of choice. Operative treatment treatment has a mortality of 38% compared with more than 60% with drainage alone.


Expectation-maximization method for reconstructing tumor phylogenies from single-cell data.
Recent studies of gene expression in cancerous tumors have revealed that cancers presenting indistinguishable symptoms in the clinic can represent substantially different entities at the molecular level. The ability to distinguish between these different cancers makes possible more accurate prognoses and more finely targeted therapeutics. Making full use of this knowledge, however, requires characterizing commonly occurring cancer sub-types and the specific molecular abnormalities that produce them. Computational approaches to this problem to date have been hindered by the fact that tumors are highly heterogeneous masses typically containing cells at multiple stages of progression from healthy to aggressively malignant. We present a computational approach for taking advantage of tumor heterogeneity when characterizing tumor progression pathways by inferring those pathways from single-cell assays. Our approach uses phylogenetic algorithms to infer likely evolutionary sequences producing cell populations in single tumors, which are in turn used to create a profile of commonly used pathways across the patient population. This approach is combined with expectation maximization to infer unknown parameters used in the phylogeny construction. We demonstrate the approach on a set of fluorescent in situ hybridization (FISH) data measuring cell-by-cell gene and chromosome copy numbers in a large sample of breast cancers. The results validate the proposed computational methods by showing consistency with several previous findings on these cancers. They also provide novel insights into the mechanisms of tumor progression in these patients.


Comparing phoneme frequency, age of acquisition, and loss in aphasia: Implications for phonological universals.
Phonological complexity may be central to the nature of human language. It may shape the distribution of phonemes and phoneme sequences within languages, but also determine age of acquisition and susceptibility to loss in aphasia. We evaluated this claim using frequency statistics derived from a corpus of phonologically transcribed Italian words (phonitalia, available at phonitalia,org), rankings of phoneme age of acquisition (AoA) and rate of phoneme errors in patients with apraxia of speech (AoS) as an indication of articulatory complexity. These measures were related to cross-linguistically derived markedness rankings. We found strong correspondences. AoA, however, was predicted by both apraxic errors and frequency, suggesting independent contributions of these variables. Our results support the reality of universal principles of complexity. In addition they suggest that these complexity principles have articulatory underpinnings since they modulate the production of patients with AoS, but not the production of patients with more central phonological difficulties.


Self-assembled nanocages for hydrophilic guest molecules.
Reverse polymeric micelles are obtained following the association of polymeric amphiphiles in apolar media. To this date, reports of pharmaceutical applications for such micelles have been scarce, mainly because these systems have been studied in solvents that are not suitable for medical use. Here, alkylated star-shaped poly(glycerol methacrylate) polymers have been proposed in the design of oil-soluble reverse polymeric micelles. Micellar behavior was studied in various apolar solvents, including ethyl oleate, a pharmaceutically acceptable vehicle. The polymers were shown to assemble into spherical nanostructures (<40 nm) as determined by cryogenic transmission electron microscopy and atomic force microscopy studies. Interestingly, the reverse micelles were able to encapsulate various peptides/proteins (vasopressin, myoglobin, and albumin) in substantial amounts and facilitate their solubilization in oil. The nature of both the polymer used in micelle formation and the guest molecules was found to influence the ability of the micelle to interact with hydrophilic compounds.


Imaging and optogenetic modulation of vascular mural cells in the live brain.
Mural cells (smooth muscle cells and pericytes) are integral components of brain blood vessels that play important roles in vascular formation, blood-brain barrier maintenance, and regulation of regional cerebral blood flow (rCBF). These cells are implicated in conditions ranging from developmental vascular disorders to age-related neurodegenerative diseases. Here we present complementary tools for cell labeling with transgenic mice and organic dyes that allow high-resolution intravital imaging of the different mural cell subtypes. We also provide detailed methodologies for imaging of spontaneous and neural activity-evoked calcium transients in mural cells. In addition, we describe strategies for single- and two-photon optogenetics that allow manipulation of the activity of individual and small clusters of mural cells. Together with measurements of diameter and flow in individual brain microvessels, calcium imaging and optogenetics allow the investigation of pericyte and smooth muscle cell physiology and their role in regulating rCBF. We also demonstrate the utility of these tools to investigate mural cells in the context of Alzheimer's disease and cerebral ischemia mouse models. Thus, these methods can be used to reveal the functional and structural heterogeneity of mural cells in vivo, and allow detailed cellular studies of the normal function and pathophysiology of mural cells in a variety of disease models. The implementation of this protocol can take from several hours to days depending on the intended applications.


Synthetic antimalarial drug therapy in lupus erythematosus and polymorphous light eruptions.
The therapeutic efficacy of the synthetic antimalarial agents in lupus erythematosus and the polymorphous light eruptions is well established. Severe toxic reactions are rare but mild disturbances are relatively common. Although gold therapy probably is as effective in discoid lupus erythematosus, the antimalarials are easier to administer and cause fewer serious side effects. The mechanism of action of these drugs is poorly understood although definite anti-inflammatory properties have been noted. Perhaps further investigations of known biological processes such as free radical formation and neutralization, redox potential alterations or enzymatic changes may shed more light on this problem.


Evaluation of the circulating CD34(+), CD309(+), and endothelial progenitor cells in patients with first attack of optic neuritis.
Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. The aim of the present study was to determine the number of circulating EPCs in patients with optic neuritis (ON). Fifty patients with ON were diagnosed by expert neurologist and optometrist at the Feiz Hospital, Isfahan, Iran (2012-2013). Blood samples were collected from ON patients in the first attack. The number of EPCs was measured by flow cytometry through the assessment of CD34(+) and CD309(+) in patients and healthy individuals. With using flow cytometry, CD34(+) and CD309(+) cells detected in peripheral blood cells of patients (n = 50) with ON, and healthy individuals (n = 30). Patients with ON had (mean = 66.71 ± 17.82) CD34(+) and CD309(+) cells compared with healthy controls (mean = 28.72 ± 22.46). In addition, there was no significant difference in CD309(+) cells in both groups. This study showed elevated CD34(+) and CD309(+) cells in the early stage of the disease. Regarded to EPC increment in neural repair, it expected the EPC level be increased in these patients, but no detectable differences were observed among both markers in healthy and patient with first attack.


ECG Findings in Active Patients: Differentiating the Benign From the Serious.
ECGs and cardiac rhythms of normal athletes can vary widely. The heightened vagal tone from athletic conditioning can result in variant ECG findings that may mimic serious disorders. ECG patterns of long-QT syndrome, arrhythmogenic right ventricular dysplasia, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy signal the need for further evaluation, therapy, and possible participation restriction. Radiofrequency ablation may be appropriate when symptomatic supraventricular arrhythmias or Wolff-Parkinson-White syndrome is present. Further research is needed to effectively distinguish normal ECG changes in the athlete from changes that underlie cardiac disease. Improvements in identifying athletes at risk of serious or life-threatening arrhythmias are also needed.


Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments.
This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1β) inhibitors by using network pharmacology, molecular docking, and cell experiments. In this study, the compounds of TFDC and the potential inflammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1β in GA. Molecular docking technology was used to analyze the optimal effective compounds from the TFDC for docking with IL-1β. 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA inflammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1β mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1β inhibitor. Our findings provide an essential role and bases for further immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1β inhibitors development in GA.


Noncontiguous finished genome sequences and descriptions of 'Paenibacillus bouchesdurhonensis,' 'Paenibacillus rubinfantis,' 'Paenibacillus senegalimassiliensis' and 'Paenibacillus tuaregi' identified by culturomics.
Microbial culturomics represents a completely new approach to investigate microbial diversity by using different optimized culture conditions, mass spectrometry, genome sequencing and annotation and phenotypic description that allow for an extensive characterization of new species and the study of the human microbiome. Here we present four new species within the genus Paenibacillus: 'Paenibacillus bouchesdurhonensis' strain Marseille-P3071T, 'Paenibacillus rubinfantis' strain MT18T, 'Paenibacillus senegalimassiliensis' strain SIT18T and 'Paenibacillus tuaregi' strain Marseille-P2472T, which are all facultatively aerobic and Gram-positive bacilli.


Cytology and distribution in normal human cerebral cortex of neurons immunoreactive with antisera against neuropeptide Y.
The frontal, parietal, and temporal cortices in normal human brains (Brodmann areas 10, 7a, 7b, and 21) are well endowed with numerous neurons, identifiable by immunoreactivity with antisera against the 36-amino acid brain peptide neuropeptide Y (NPY). These neurons with rare exception are small, intracortical, nonspiny neurons, 12-20 microns in somatic size, with long slender dendrites and exuberant axon plexuses exhibiting finely beaded varicosities. The cells are rarest in layers I and II, are found with frequency in the lower cortical layers (IV-VI) and in significant numbers in the subcortical white matter. Within the cortex the axonal plexuses of these peptide neurons rise straight up into the upper cortical layers or descend deep into the white matter. In layers I and II, numerous other lengthy axons, some possibly of extracortical afferent origin, run along the pial surface at right angles to the axial ones running perpendicular to the cortex. This endowment of peptide neurons and their processes forms a rich network in the cerebral cortex, relating with one another in complex fashion within palisades of terminals as well as with the other cortical neurons not labeled by these methods. It remains to be shown what functions these NPY neurons have individually and in their remarkable networks, and how they are altered in neurological disease.


Molar furcation entrance and its relation to the width of curette blades used in periodontal mechanical therapy.
The purpose of this research was to evaluate molar furcation entrances and the width of periodontal curette blades used in periodontal instrumentation. One hundred extracted molars (50 upper and 50 lower) were analysed. The furcation entrances were measured using orthodontic wires of different predetermined diameters: 0.4, 0.5, 0.6, 0.7, 0.8 and 0.9 mm. McCall 17-18, Gracey 5-6 and Gracey 5-6 mini-five curette blades were measured at their anterior (AT), middle (MT) and posterior (PT) thirds by a single trained investigator, through the use of a digital caliper. The results showed significant differences (P < 0.0001) in relation to furcation entrances. The buccal upper molar furcations showed the narrowest dimensions. In relation to the blade diameter, significant differences among the instruments were found for their MT and PT (P < 0.0001), but not for the AT (P = 0.183). Significant differences were found among curette manufacturers. Nineteen per cent of evaluated furcations presented entrances <0.60 mm and 75% of the blades at their AT presented width >0.60 mm. These findings demonstrated that some molar furcation entrances could not be adequately instrumented with the tested curettes. The use of other hand instruments, such as periodontal files, rotating instruments and ultrasonic devices should be taken into consideration during periodontal therapy.


Beneficial effects of phenolic compounds: native phenolic compounds vs metabolites and catabolites.
In the human body, the positive effects of phenolic compounds are increasingly observed through their presence in tissues and organs in their native form or in the form of metabolites or catabolites formed during digestion, microbial metabolism, and host biotransformation. The full extent of these effects is still unclear. The aim of this paper is to review the current knowledge of beneficial effects of native phenolic compounds or their metabolites and catabolites focusing on their role in the health of the digestive system, including disorders of the gastrointestinal and urinary tracts and liver. Studies are mostly connecting beneficial effects in the gastrointestinal and urinary tract to the whole food rich in phenolics, or to the amount of phenolic compounds/antioxidants in food. Indeed, the bioactivity of parent phenolic compounds should not be ignored due to their presence in the digestive tract, and the impact on the gut microbiota. However, the influence of their metabolites and catabolites might be more important for the liver and urinary tract. Distinguishing between the effects of parent phenolics vs metabolites and catabolites at the site of action are important for novel areas of food industry, nutrition and medicine.


Site-specific mutagenesis of yeast 2-Cys peroxiredoxin improves heat or oxidative stress tolerance by enhancing its chaperone or peroxidase function.
Yeast peroxiredoxin II (yPrxII) is an antioxidant enzyme that plays a protective role against the damage caused by reactive oxygen species (ROS) in Saccharomyces cerevisiae. This enzyme consists of 196 amino acids containing 2-Cys Prx with highly conserved two active cysteine residues at positions 48 and 171. The yPrxII has dual enzymatic functions as a peroxidase and molecular chaperone. To understand the effect of additional cysteine residues on dual functions of yPrxII, S79C-yPrxII and S109C-yPrxII, the substitution of Ser with Cys residue at 79 and 109 positions, respectively, was generated. S109C-yPrxII and S79C-yPrxII showed 3.7- and 2.7-fold higher chaperone and peroxidase activity, respectively, than the wild type (WT). The improvement in enzyme activity was found to be closely associated with structural changes in proteins. S109C-yPrxII had increased β-sheet in its secondary structure and formed high-molecular-weight (HMW) as well as low-molecular-weight (LMW) complexes, but S79C-yPrxII formed only LMW complexes. HMW complexes predominantly exhibited a chaperone function, and LMW complexes showed a peroxidase function. In addition, transgenic yeast cells over-expressing Cys-substituted yPrxII showed greater tolerance against heat and oxidative stress compared to WT-yPrxII.


A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds.
Until recently, it has been unclear whether community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates represent the spread of hospital MRSA isolates into the community. In 2 CA-MRSA isolates, a novel genetic element, designated staphylococcal cassette chromosome mec (SCCmec) type IV, was found; it differs from SCCmec types I-III in its small size and absence of non-beta-lactam genetic-resistance determinants. To study the prevalence of type IV SCCmec, polymerase chain reaction characterization of SCCmec was performed on DNA from 12 CA-MRSA isolates. The 12 CA-MRSA isolates were from diverse genetic backgrounds, as evidenced by their stratification into 5 pulsed-field gel electrophoresis types, 4 coagulase types, and 2 ribotypes. Eleven of the 12 isolates contained the novel SCCmec type IV element. Ten were resistant only to beta-lactam antibiotics. SCCmec type IV is present on the genome of CA-MRSA isolates. Its relatively small size and presence in isolates of diverse genetic backgrounds suggest that it may spread among S. aureus isolates.


Impact of a Social Support Program Supervised by a Multidisciplinary Team on Psychosocial Distress and Knowledge About Heart Failure Among Heart Failure Patients.
Heart failure drains significant financial resources with morbidity and mortality higher than cancer. Social support is defined as the care provided by the family members, friends and health care workers to the patients. Absence of social support and poor perceived social support will create stress, anxiety, depression and anger which further deteriorate the underlying disease and worsen quality of life. Discussion in group creates better understanding of the disease which helps the patients improving their skills in managing their condition. To evaluate the impact of multidisciplinary team supervised social support program on components of psychosocial distress and knowledge about heart failure among heart failure patients. Adult patients with heart failure attending King Fahad Medical City as inpatient or outpatient were enrolled in this prospective cohort study. Patients were given questionnaire to assess their perception of social support they have at their disposal, quality of life, knowledge regarding heart failure and self-care behavior. They then had interactive education in groups supervised by multidisciplinary team members about the pathogenesis of their disease with management strategies, dietary restriction, importance of exercise and healthy life style pattern. Patients shared their experiences in the group and had opportunity to learn from each other. Patients were assessed regarding their perceived social support, quality of life, knowledge regarding heart failure and self-care behavior immediately after the session and at 1 month interval. There were total 500 patients participated in the study. Among the study participants 62% were male and majority was living with the family. Components of psychosocial distress were present in up to 40% of study participants and only 36% considered knowledgeable regarding heart failure. After the interactive social support group meeting components of psychosocial distress were significantly reduced with significant improvement in knowledge about heart failure. At 1 month follow up participants reported persistent improvement in quality of life, improvement in self-care behavior, perceived social support and wanted to continue in social group program. Social support program supervised by multidisciplinary team providing education and social support improved knowledge, self-care behavior, perceived social support and quality of life among heart failure patients.


Benzophenones from Guignardia sp. IFB-E028, an endophyte on Hopea hainanensis.
The first natural S-containing benzophenone dimer, named guignasulfide (3), was isolated from the culture of Guignardia sp. IFB-E028, an endophytic fungus residing in healthy leaves of Hopea hainanensis. Its structure was determined through correlative analyses of its MS, 1D- and 2D-NMR spectroscopic data. Two other known benzophenone derivatives, monomethylsulochrin and rhizoctonic acid (1 and 2, resp.) were also isolated. Guignasulfide (3) was more active against the human liver cancer cell line HepG2 (IC(50) value: 5.2+/-0.4 microM) than metabolites 1 and 2 (IC(50) values: 63.5+/-0.6 and 60.2+/-0.5 microM); compounds 1-3 showed also moderately inhibitory effects on the human bacterial pathogen Helicobacter pylori with MIC values of 28.9+/-0.1, 60.2+/-0.4, and 42.9+/-0.5 microM, respectively.


Artificial Oocyte: Development and Potential Application.
Millions of people around the world suffer from infertility, with the number of infertile couples and individuals increasing every year. Assisted reproductive technologies (ART) have been widely developed in recent years; however, some patients are unable to benefit from these technologies due to their lack of functional germ cells. Therefore, the development of alternative methods seems necessary. One of these methods is to create artificial oocytes. Oocytes can be generated in vitro from the ovary, fetal gonad, germline stem cells (GSCs), ovarian stem cells, or pluripotent stem cells (PSCs). This approach has raised new hopes in both basic research and medical applications. In this article, we looked at the principle of oocyte development, the landmark studies that enhanced our understanding of the cellular and molecular mechanisms that govern oogenesis in vivo, as well as the mechanisms underlying in vitro generation of functional oocytes from different sources of mouse and human stem cells. In addition, we introduced next-generation ART using somatic cells with artificial oocytes. Finally, we provided an overview of the reproductive application of in vitro oogenesis and its use in human fertility.


[Effect of early enteral nutrition on immune function of the patients after operation for severe abdominal trauma].
To determine the effect of early enteral nutrition (EN) on immune function of the patients after operation for severe abdominal trauma. Fourty patients who underwent operation for severe abdominal trauma were randomly divided into two groups, and received an early enteral nutrition (EN group, n=20) through jejunal nutritional tube from postoperative day 1, or parental nutrition (PN group, n=20) for 7 days. C3, IgA, IgM, IgG and CD3+, CD4+, CD8+, CD4+/CD8+ of the two groups patients were detected on the day before operation and the postoperative day 1 and 8. The infection complications were compared. After 7 days, the levels of C3+, IgA, IgG, CD3+, CD4+, CD8+, and CD4+/CD8+ in EN group increased significantly compared with those in PN group (P< 0.05). The incidence of infection was 10% in EN group, while 30% in PN group (P< 0.05). Early enteral nutrition can improve immune function and decrease postoperative infection after operation for severe abdominal trauma.


Comparative in vitro activities of temocillin and cefazolin against Klebsiella pneumoniae.
Temocillin (BRL 17421) a new penicillin, was compared with cefazolin against 20 strains of Klebsiella. The in vitro minimal bactericidal concentration of cefazolin was twice as active as that of temocillin. Serum bactericidal levels obtained in volunteers treated with temocillin were consistently higher than those levels reached after the administration of cefazolin at the 6-h sampling.


The Effectiveness of Wearable Upper Limb Assistive Devices in Degenerative Neuromuscular Diseases: A Systematic Review and Meta-Analysis.
Background: This systematic review summarizes the current evidence about the effectiveness of wearable assistive technologies for upper limbs support during activities of daily living for individuals with neuromuscular diseases. Methods: Fourteen studies have been included in the meta-analysis, involving 184 participants. All included studies compared patients ability to perform functional tasks with and without assistive devices. Results: An overall effect size of 1.06 (95% CI = 0.76-1.36, p < 0.00001) was obtained, demonstrating that upper limbs assistive devices significantly improve the performance in activities of daily living in people with neuromuscular diseases. A significant interaction between studies evaluating functional improvement with externally-assessed outcome measures or self-perceived outcome measures has been detected. In particular, the effect size of the sub-group considering self-perceived scales was 1.38 (95% CI = 1.08-1.68), while the effect size of the other group was 0.77 (95% CI = 0.41-1.11), meaning that patients' perceived functional gain is often higher than the functional gain detectable through clinical scales. Conclusion: Overall, the quality of the evidence ranged from low to moderate, due to low number of studies and participants, limitations in the selection of participants and in the blindness of outcome assessors, and risk of publication bias. Significance: A large magnitude effect and a clear dose-response gradient were found, therefore, a strong recommendation, in favor of the use of assistive devices could be suggested.


Licensed practical nurse to registered nurse transition: developing a tailored orientation.
This article depicts the journey that the clinical educators of a 296-bed community hospital pursued to develop a specific orientation pathway for the licensed practical nurse to registered nurse transition. When the orientation templates were originally developed, the new hires transitioning from LPN to RN were placed in the experienced nurse pathway without considering that they would have specific developmental needs. This journey reflects the educational challenges and subsequent revisions that were made for this specific population.


No effect of femoral canal jet-lavage on the stability of cementless stems in primary hip arthroplasty: a randomised RSA study with 6 years follow-up.
In contrast to cemented hip prostheses, the effect of washing the bone bed with jet-lavage prior to insertion of cementless stem components in primary hip arthroplasty (THA) is unclear. Jet-lavage potentially decreases the risk of fat embolisation during rasping and stem insertion and might help in avoiding bacterial contamination. An earlier animal study has shown less debris and better-organised trabecular structure of new bone when jet-lavage was used. We hypothesised that the primary stability of cementless femoral stems implanted after jet-lavage of the femoral canal prior to stem insertion would improve with earlier stabilisation, as measured with Radiostereometry (RSA), compared with insertion without prior jet-lavage. 40 patients with primary osteoarthritis operated on with a cementless titanium grit blasted stem are included in the study. The patients were randomised to either jet-lavage or control without any lavage of the femoral canal prior to insertion of the prosthesis. The stem migration pattern was measured with RSA at 0, 3, 12, 24 and 72 months. At 6 years, 19 patients remained for analysis in the jet-lavage and 18 in the control group. We found no difference in extent or pattern of migration as measured with RSA. Both groups seemed to have stabilised within 3 months after a slight subsidence and retroversion. No stem was revised or considered loose as measured with RSA. Washing the bone bed with jet-lavage prior to insertion of cementless stems does not affect the stability of cementless femoral components. No adverse effects were observed.


Spasm of the near reflex in a patient with multiple sclerosis.
A 33-year-old woman with a history of relapsing-remitting multiple sclerosis presented with complaints of episodic horizontal diplopia and blurred vision over the past two months. The patient gave a past history of similar episodes of diplopia that had occurred with previous clinical relapses of her multiple sclerosis. On eye movement examination, the patient exhibited intermittent spasms of convergence coupled with miosis. On upward gaze, the convergence and miosis became more marked. An auto-refraction revealed variable measurements in both eyes, consistent with accommodative spasms. A cycloplegic auto-refraction revealed significantly lower myopia present in both eyes than the initial pre-cycloplegic auto-refraction with minimal variability in readings. Symptomatic relief was achieved by cycloplegia and spectacle correction.


High excimer-state emission of perylene bisimides and recognition of latent fingerprints.
High excimer-state emission in the H-type aggregate of a novel asymmetric perylene bisimide derivative, 6, with triethyleneglycol chains and lactose functionalization was achieved in water. Furthermore, its application for enhancing the visualization of transfer latent fingerprints from glass slides to the poly(vinylidene fluoride) (PVDF) membrane was explored, which showed clear images of the latent fingerprint in daylight and under 365 nm ultraviolet illumination.


Predictive value of immunohistochemical thymidylate synthase expression for histological response to Tegafur/Uracil (UFT) in oral squamous cell carcinoma.
Thymidylate synthase (TS), an enzyme involved in the DNA synthesis, is a critical target for fluoropyrimidines. We investigated the relationship between the level of tumoural TS expression and response to tegafur/uracil (UFT) in 26 patients with oral squamous cell carcinoma. The patients received peroral administration of UFT alone preoperatively. In biopsy specimens, TS expression level was assessed by the immunohistochemical staining and graded as 1+, 2+ or 3+ according to the frequency of strongly-stained tumour cells. Out of 26 tumours, 10 (38.5%), 10 (38.5%) and 6 (23.1%) cases were categorized as 1+, 2+ and 3+, respectively. The response to UFT was histologically evaluated by a grading system according to the extent of degenerative or necrotic cancer cells in surgical specimens. Results showed patients with the lower TS expression had the higher response and there was a statistically significant association between TS expression and response to UFT (P=0.031). This finding suggests that TS expression is a predictor of chemosensitivity to UFT in oral squamous cell carcinomas.


Evaluation of atorvastatin for the treatment of patients with asthma: a double-blind randomized clinical trial.
Statins are known as cholesterol-lowering agents, but have been suggested for the treatment of asthma because of their anti-inflammatory effects. In this study, the potential therapeutic effects of atorvastatin were investigated in asthmatic patients. A total of 62 patients with persistent mild to moderate asthma who presented at asthma clinics of Arak University of Medical Sciences were recruited in a double-blind randomized clinical trial. The asthma clinical control score was assessed based on the standardized Asthma Control Test. Lung volume, i.e., percentage of forced expiratory volume in one second (FEV1%) and percentage of forced vital capacity (FVC%), and peripheral blood eosinophils were also measured. The intervention group was treated with atorvastatin 40 mg per day for 8 weeks, while the control group received a placebo. Asthma controller treatments were not changed. At the beginning and end of the study, serum cholesterol and triglyceride levels were measured to evaluate adherence of the patients to the treatment. The asthma control score did not significantly differ between the intervention and control groups (P=0.06). Difference in FEV1%, FVC%, and blood eosinophil count between the intervention and control groups were not statistically significant (P>0.05). The differences in post-treatment cholesterol and low-density lipoprotein cholesterol levels were significant (P<0.05). Our study shows that atorvastatin is not effective in the treatment of persistent mild to moderate asthma.


[Regulation of long non-coding RNA in signal pathways related to osteogenic differentiation].
To summarize the mechanism of long non-coding RNA (lncRNA) in signal pathways related to osteogenic differentiation. Relevant domestic and foreign researches in recent years were consulted. The characteristics and biological functions of lncRNA were introduced, and the specific mechanism of lncRNA regulating related signal pathways in osteogenic differentiation was elaborated. The exertion and maintenance of normal function of bone requires the closed coordination of transcription networks and signal pathways. However, most of these signal pathways or networks are dysregulated under pathological conditions that affect bone homeostasis. lncRNA can regulate the differentiation of various bone cells by activating or inhibiting signal pathways to achieve the balance of bone homeostasis, thereby reversing the pathological state of bones and achieving the purpose of treating bone metabolic diseases. At present, the research on the mechanism of lncRNA regulating various osteogenic differentiation pathways is still in the early stage. Its in-depth regulator mechanism, especially the cross-talk of complex signal pathways needs to be further studied. And how to apply these molecular targets to clinical treatment is also a big challenge.


The utility of competency-oriented clinical laboratory teaching combined with case-based learning (CBL).
This study aimed to evaluate the effectiveness and efficiency of competency-oriented clinical laboratory teaching combined with case-based learning (CBL) and improve the examination of students' competence of laboratory medicine. A total of 107 medical laboratory medicine interns at the Affiliated Hospital of Xuzhou Medical University from June 2017 to July 2019 volunteered to participate in the study and were randomly assigned into a control group with training of the traditional teacher-centered method, and an experimental group under a CBL teaching program. Student basic theory tests and skill assessment were designed to evaluate what the students gained from their internship when they completed their studies at the Affiliated Hospital of Xuzhou Medical University. Compared to students in the control group taught with the teacher-centered method, those in the CBL teaching program had significantly higher theory test scores and skill assessment scores on average. Competencies with particularly significant improvement included identification and processing of instrument alarm information, analysis of test results, identification and solution of the problem, as well as identification and reporting of the critical value and clinical communication. The competency-oriented teaching method combined with CBL is an effective method for improving students' professional knowledge, increasing language expression, and enhancing interpersonal relationship and teamwork, which is worthy of being promoted in laboratory medicine teaching.


A facile alkali metal hydroxide-assisted controlled and targeted synthesis of 1T MoS2 single-crystal nanosheets for lithium ion battery anodes.
High-quality metallic 1T phase MoS2 single-crystal nanosheets were synthesized by a facile eco-friendly alkali metal hydroxide-assisted controlled and targeted approach via the calcination of lithium hydroxide and ammonium tetrathiomolybdate under argon atmosphere at 1000 °C. The 1T MoS2 single-crystal nanosheets were used as lithium-ion battery anodes, exhibiting superior electrochemical performances, including long cycle life and high capacities. The first charge and discharge capacities were up to 889.1 mA h g-1 and 892.5 mA h g-1, respectively, giving a first cycle coulombic efficiency of 98.0%, which exceeded 99.1% in the second cycle. In the 400th cycle, the charge and discharge capacities were 737.2 mA h g-1 and 738.0 mA h g-1, respectively, with 82.9% capacity retention ratio. This study not only provides a novel strategy for fabricating metallic 1T phase MoS2, which can be used as lithium ion battery anodes but also introduces a facile eco-friendly lithium hydroxide-assisted controlled and targeted approach for different phase MoS2 (1T and 2H). Moreover, it can be extended to other alkali metal hydroxide-assisted (NaOH and KOH) approaches for the MoS2 preparation.


High-speed phase imaging by parallel phase-shifting digital holography.
Parallel phase-shifting digital holography can obtain three-dimensional information of a dynamically moving object with high accuracy by using space-division multiplexing of multiple holograms required for phase-shifting interferometry. We demonstrated high-speed parallel phase-shifting digital holography and obtained images of the phase variation of air caused by a compressed gas flow sprayed from a nozzle. In particular, we found the interesting phenomenon of periodic phase distributions. Reconstructed images were obtained at frame rates of 20,000 and 180,000 frames per second.


Comparing the protective effects of three sulfur compounds against acrylonitrile-induced acute toxicity in CYP2E1-induced rats.
Cytochrome P450 2E1 (CYP2E1) can be induced by diabetes mellitus, nonalcoholic liver disease, and obesity. This study assessed the protective effects of three sulfur compounds, namely phenethyl isothiocyanate (PEITC), dimethyl trisulfide (DMTS), and sodium thiosulfate (STS), on acrylonitrile (ACN)-induced acute toxicity in rats enriched with CYP2E1. PEITC and DMTS were administered intragastrically (i.g.), whereas STS was injected intraperitoneally (i.p.) at an identical dose of 0.5 mmol/kg for 3 days in acetone-pretreated rats before ACN (90 mg/kg) injection (i.p.). Acetone-treated rats that expressed high levels of CYP2E1 were more susceptible to ACN-induced acute toxicity. The sulfur compounds reduced the rate of convulsions and loss of the righting reflex in acute ACN-exposed CYP2E1-induced rats; PEITC and DMTS also increased the survival rates. PEITC inhibited hepatic CYP2E1 activity and protected hepatic and cerebral cytochrome c oxidase (CcOx) activities in acute ACN-exposed CYP2E1-enriched rats; DMTS protected hepatic CcOx activity. DMTS attenuated ACN-induced oxidative injury by reducing malondialdehyde (MDA) levels and increasing glutathione content in the brain. STS only reduced cerebral MDA levels, whereas PEITC did not exhibit any antioxidant effects. Collectively, PEITC provided superior protective effects against ACN-induced acute toxicity in rats with increased CYP2E1 activity, followed by DMTS; STS provided limited effects. PEITC and DMTS might be considered as promising chemopreventive agents against ACN-induced acute toxicity in vulnerable subpopulations with increased CYP2E1 activity.


Cell elongation and branching are regulated by differential phosphorylation states of the nuclear Dbf2-related kinase COT1 in Neurospora crassa.
Dysfunction of the Neurospora crassa nuclear Dbf2-related kinase COT1 leads to cessation of tip extension and massive induction of new sites of growth. To determine the role phosphorylation plays in COT1 function, we mutated COT1 residues corresponding to positions of highly conserved nuclear Dbf2-related phosphorylation sites. Analyses of the point-mutation cot-1 strains (mimicking non- and constitutively phosphorylated states) indicate the involvement of COT1 phosphorylation in the regulation of hyphal elongation and branching as well as asexual development by altering cell wall integrity and actin organization. Phosphorylation of COT1's activation segment (at Ser417) is required for proper in vitro kinase activity, but has only a limited effect on hyphal growth. In marked contrast, even though phosphorylation of the C-terminal hydrophobic motif (at Thr589) is crucial for all COT1 functions in vivo, the lack of Thr589 phosphorylation did not significantly affect in vitro COT1 kinase activity. Nevertheless, its regulatory role has been made evident by the significant increase observed in COT1 kinase activity when this residue was substituted in a manner mimicking constitutive phosphorylation. We conclude that COT1 regulates elongation and branching in an independent manner, which is determined by its phosphorylation state.


Hallucinations: Clinical aspects and management.
The literature on hallucinations is reviewed, including its occurrence in different psychiatric disorders, neurological disorders and normal persons. The diagnostic significance of hallucinations is also discussed. Reports of hallucinations in normal people are reviewed. The different modes of the management of hallucinations are briefly discussed.


GFAP and astrogliosis.
One of the most remarkable characteristics of astrocytes is their vigorous response to diverse neurologic insults, a feature that is well conserved across a variety of different species. The astroglial response occurs rapidly and can be detected within one hour of a focal mechanical trauma (Mucke et al., 1991). Prominent reactive astrogliosis is seen; in AIDS dementia; a variety of other viral infections; prion associated spongiform encephalopathies; inflammatory demyelinating diseases; acute traumatic brain injury; neurodegenerative diseases such as Alzheimer's disease. The prominence of astroglial reactions in various diseases, the rapidity of the astroglial response and the evolutionary conservation of reactive astrogliosis indicate that reactive astrocytes fulfill important functions of the central nervous system (CNS). Yet, the exact role reactive astrocytes play in the injured CNS has so far remained elusive. This chapter summaries the various experimental models and diseases that exhibit astrogliosis and increase in glial fibrillary acidic protein (GFAP). Recent in vitro studies to inhibit GFAP synthesis are also presented.


Human HS1BP3 induces cell apoptosis and activates AP-1.
In the present study, we characterized the function of HS1-binding protein 3 (HS1BP3), which is mutated in essential tremor and may be involved in lymphocyte activation. We found that HS1BP3 localized to the mitochondria and endoplasmic reticulum partially. Overexpression of HS1BP3 induced apoptosis in HEK293T and HeLa cell lines. When these cell lines were transfected with HS1BP3, they exhibited nuclear DNA condensation, externalization of phosphatidylserine (PS), and cleavage of poly ADP ribose polymerase (PARP). Furthermore, suppression of HS1BP3 or HS1 expression attenuates HS1BP3 induced apoptosis. In addition, HS1BP3 enhanced activator protein 1 (AP-1)-mediated transcription in a dose-dependent manner. Therefore, we conclude that HS1BP3 regulates apoptosis via HS1 and stimulates AP-1-mediated transcription.


Hydrogels of dextran containing nonsteroidal anti-inflammatory drugs as pendant agents.
The oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal tract side effects. To reduce these effects and improve the therapeutic efficacy, NSAIDs are often formulated as controlled release systems. We have prepared a new formulation consisting of dextran hydrogels containing NSAIDs as pendant agents, through ultraviolet irradiation of solutions of dextran functionalized with methacrylic groups in the presence of the drug derivatized in the same way. Release studies of different drugs from this system, carried out in media simulating the gastrointestinal tract, have demonstrated that the amount of released drug is strictly related to the concentration of the polymer in the solution submitted to irradiation as well as to its derivatization degree. Our obtained data confirm that the system is able to realize a colon-specific drug delivery.


GRP78 regulates milk biosynthesis and the proliferation of bovinemammaryepithelial cells through the mTOR signaling pathway.
Glucose-regulated protein 78 (GRP78) is a member of the HSP70 protein family and a key endoplasmic reticulum chaperone. It has been revealed to play important roles both in the maturation, folding and transport of proteins and in cellproliferation. However, its involvement in milk biosynthesis or the proliferation of bovine primary mammary epithelial cells (BMECs) has yet to be established. The expressions of GRP78 in BMECs stimulated with methionine, leucine, estrogen and prolactin were determined using western blotting and immunofluorescence assays. To explore the function of GRP78 in BMECs, the protein was overexpressed or knocked down, respectively using an overexpression vector or an siRNA mixture transfected into cells cultured in vitro. Flow cytometry was used to analyze cell proliferation and cell activity. The contents of lactose and triglyceride (TG) secreted from the treated BMECs were measured using lactose and TG assay kits, respectively. Western blotting analysis was used to measure the β-casein content and the protein levels of the signaling molecules known to be involved in milk biosynthesis and cell proliferation. GRP78overexpression significantly stimulated milk protein and milk fat synthesis, enhanced cell proliferation, positively regulated the phosphorylation of mammalian target of rapamycin (mTOR), and increased the amount of protein of cyclinD1andsterol regulatory element-binding protein 1c (SREBP-1c). GRP78 knockdown after siRNA transfection had the opposite effects. We further found that GRP78 was located in the cytoplasm of BMECs, and that stimulating methionine, leucine, estrogen and prolactin expression led to a significant increase in the protein expression of GRP78 in BMECs. These data reveal that GRP78 is an important regulator of milk biosynthesis and the proliferation of BMECs through the mTOR signaling pathway.


In vitro effects of an aromatase inhibitor on 5 alpha-reductase activity in human hypertrophic prostatic tissue.
To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT), 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstan-3 beta, 17 beta-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4-14C-T as substrate, in the presence of 4-OH-A (10(-8) to 10(-6) M); the amounts of the 5 alpha-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), a known inhibitor of the 5 alpha-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily. Both 4-OH-A and 4-MA induced significant and dose-related decreases in the formation of both DHT and the diols. The degree of inhibition induced by the different concentrations of 4-OH-A and 4-MA were 31, 41, 72% and 57, 87, 97%, respectively. The decreased formation of the diols was a consequence of the decreased availability of DHT (the immediate precursor of the diols) and was not due to direct effects of the inhibitors on the 3-hydroxysteroid dehydrogenases; both 4-OH-A and 4-MA were totally unable to modify the conversion of DHT to the diols, when 4-14C-DHT was used as substrate. Thus, 4-OH-A inhibits the process of 5 alpha-reduction of T in BPH tissue. This molecule might represent a potential new agent for the prevention and/or treatment of human BPH.


Immunological cross-reactivities of adenosine-5'-phosphosulfate reductases from sulfate-reducing and sulfide-oxidizing bacteria.
Crude extracts from 14 species of sulfate-reducing bacteria comprising the genera Desulfovibrio, Desulfotomaculum, Desulfobulbus, and Desulfosarcina and from three species of sulfide-oxidizing bacteria were tested in an enzyme-linked immunosorbent assay with polyclonal antisera to adenosine 5'-phosphosulfate reductase from Desulfovibrio desulfuricans G100A. The results showed that extracts from Desulfovibrio species were all highly cross-reactive, whereas extracts from the other sulfate-reducing genera showed significantly less cross-reaction. An exception was Desulfotomaculum orientis, which responded more like Desulfovibrio species than the other Desulfotomaculum strains tested. Extracts from colorless or photosynthetic sulfur bacteria were either unreactive or exhibited very low levels of reactivity with the antibodies to the enzyme from sulfate reducers. These results were confirmed by using partially purified enzymes from sulfate reducers and the most cross-reactive sulfide oxidizer, Thiobacillus denitrificans. Two types of monoclonal antibodies to adenosine 5'-phosphosulfate reductase were also isolated. One type reacted more variably with the enzymes of the sulfate reducers and poorly with the Thiobacillus enzyme, whereas the second reacted strongly with Desulfovibrio, Desulfotomaculum orientis, and Thiobacillus enzymes.


[What is the use of the radioimmunoassay of prostatic acid phosphatase?].
Radioimmunoassay (RIA) of prostatic acid phosphatases (PAP) using the Gammadab (R) PAP pack supplied by Clinical Assays in an effective method for determining extension of prostatic cancer. In patients with lymph node or metastatic invasion serum assay values are almost always elevated (sensitivity = 94%), especially with well differentiated cancer. Elevated levels of this variable are practically pathognomonic of external extension (specificity = 94%). This is of importance in therapy since the degree of invasion determines the choice between palliative and curative treatment. Strategy leading to this therapeutic choice can be greatly simplified and thus modified by RIA of PAP.


Cyst-forming dinoflagellates in a warming climate.
Many phytoplankton species, including many harmful algal bloom (HAB) species, survive long periods between blooms through formation of benthic resting stages. Because they are crucial to the persistence of these species and the initiation of new blooms, the physiology of benthic stages must be considered to accurately predict responses to climate warming and associated environmental changes. The benthic stages of dinoflagellates, called resting cysts, germinate in response to the combination of favorable temperature, oxygen-availability, and release from dormancy. The latter is a mechanism that prevents germination even when oxygen and temperature conditions are favorable. Here, evidence of temperature-mediated control of dormancy duration from the dinoflagellates Alexandrium catenella and Pyrodinium bahamense-two HAB species that cause paralytic shellfish poisoning (PSP)-is reviewed and presented alongside new evidence of complementary, temperature-based control of cyst quiescence (the state in which cysts germinate on exposure to favorable conditions). Interaction of the two temperature-based mechanisms with climate is explored through a simple model parameterized using results from recent experiments with A. catenella. Simulations demonstrate the importance of seasonal temperature cycles for the synchronization of cysts' release from dormancy and are consistent with biogeography-based inferences that A. catenella is more tolerant of warming in habitats that experience a larger range of seasonal temperature variation (i.e., have higher temperature seasonality). Temperature seasonality is much greater in shallow, long-residence time habitats than in deep, open-water ones. As warming shifts species' ranges, cyst beds may persist longer in more seasonally variable, shallow inshore habitats than in deep offshore ones, promoting HABs that are more localized and commence earlier each year. Recent field investigations of A. catenella also point to the importance of new cyst formation as a factor triggering bloom termination through mass sexual induction. In areas where temperature seasonality restricts the flux of new swimming cells (germlings) to narrow temporal windows, warming is unlikely to promote longer and more intense HAB impacts-even when water column conditions would otherwise promote prolonged bloom development. Many species likely have a strong drive to sexually differentiate and produce new cysts once concentrations reach levels that are conducive to new cyst formation. This phenomenon can impose a limit to bloom intensification and suggests an important role for cyst bed quiescence in determining the duration of HAB risk periods.


A domino-based approach toward stereodefined heavily functionalized cyclohexanes: synthesis of iridal's core structure.
A stereoselective synthesis of heavily functionalized six-membered ring subunits, which possess functionality at sites appropriate for further elaboration, is described. The cyclopentanone moiety of hydrindenediol is required to achieve total facial selectivity during the pre-domino installation of the second quaternary center, while oxidative cleavage is responsible for the ring-expanding rearrangement. A microwave-assisted version of the key domino transformation and a test of concept approach toward the iridal core structure are also presented.


Motilin regulates interdigestive gastric blood flow in dogs.
Gastric blood flow exhibits cyclical increases in phase with the interdigestive contractions and secretion of the stomach in dogs. The aim of this study is to clarify the regulatory role of motilin in interdigestive gastric blood flow in dogs. Blood flow of the left gastric (LGA) and superior mesenteric (SMA) arteries were measured by ultrasound transit-time blood-flow meters in 5 conscious dogs. Motilin was infused intravenously with or without Phe-cyclo[Lys-Tyr(3-tBu)-betaAla-]. trifluoroacetate (GM-109; motilin antagonist), granisetron (5-HT3 antagonist), atropine, hexamethonium (C6), phenoxybenzamine, propranolol, or cimetidine. Motilin (12.5, 25, 50, and 100 pmol x kg(-1) x h(-1)) induced LGA blood-flow responses, consisting of a sustained increase and a rapid phasic change coupled with a contraction, without affecting the blood pressure, heart rate, and SMA blood flow. GM-109 completely abolished the LGA, motility, and secretory responses to motilin (100 pmol x kg(-1) x h(-1)). Atropine abolished motilin-induced gastric contractions, secretion, and phasic changes of LGA blood flow but failed to affect the sustained flow increase. However, atropine partially inhibited the LGA responses to lower doses of motilin. The LGA flow responses to motilin were not inhibited by granisetron, C6, alpha-adrenergic, beta-adrenergic, or H2 blockers. Motilin induced significantly larger gastric vasodilatation than the equivalent doses of VIP. Motilin has a potent and selective gastric vasodilator effect, which appears to be mediated by both cholinergic and noncholinergic mechanisms. Motilin plays an important role in the regulation of interdigestive gastric blood flow in dogs.


Breeding Site Characteristics and Associated Factors of Culex pipiens Complex in Lhasa, Tibet, P. R. China.
Characterizing the breeding sites of Culex pipiens complex is of major importance for the control of West Nile disease and other related diseases. However, little information is available about the characteristics and associated factors of the breeding sites of the Cx. pipiens complex in Lhasa, a representative high-altitude region in Southwestern China. In this study, a cross-sectional study concerning the breeding site characteristics and associated factors of the Cx. pipiens complex was carried out in Lhasa, Tibet from 2013-2016. Chi-square analysis and binary logistic regression analysis were applied to identify the key factors associated with the presence of Cx. pipiens complex larvae. Using a standard dipping method, 184 water bodies were examined and Cx. pipiens complex larvae were observed in 36 (19.57%) of them. There were significant differences in the composition of Cx. pipiens complex larvae among the breeding site stability (χ2 = 19.08, p = 0.00) and presence or absence of predators (χ2 = 6.986, p = 0.008). Binary logistic regression analysis indicated that breeding site stability and presence or absence of predators were significantly associated with the presence of Cx. pipiens complex larvae in Chengguan District, Lhasa. Relatively permanent water bodies such as water bodies along river fringes, ponds and puddles, and water bodies with no predators should be paid more attention for future Cx. pipiens complex larvae abatement campaigns in Lhasa, China.


Global Cash Flows for Sustainable Development: A Case Study of Accountability and Health Systems Strengthening in Lesotho.
Despite high health expenditures, Lesotho had some of the world's worst health indicators between 2000 and 2014. Official development assistance tripled from $37 to $107 million. PEPFAR funding rose from $3.8 to $32.4 million. Yet, deaths from TB, HIV, infant mortality, and maternal mortality remained unchanged. Lesotho had declining health outcomes amidst increased disease-focused financing and several large infrastructure projects. A World Bank loan financed the state-of-the-art Mamohato Hospital, and the U.S.-supported $362.5 million Millennium Challenge Corporation Project supported primary and secondary health infrastructure. This analysis uses the WHO Health Systems Framework to explore the unintended consequences of health financing on Lesotho's health outcomes. The WHO Health Systems Framework can be used to optimize health financing through investments in health service delivery, health workforce, health information, essential medicines, leadership, and equitable financial strategies. This approach can support governments to achieve universal health coverage and develop comprehensive health systems.


Production mechanisms of NH and NH2 radicals in N2-H2 plasmas.
We measured the densities of NH and NH(2) radicals by cavity ring-down spectroscopy in N(2)-H(2) plasmas expanding from a remote thermal plasma source and in N(2) plasmas to which H(2) was added in the background. The NH radical was observed via transitions in the (0,0), (1,1), and (2,2) vibrational bands of the A(3)Pi <-- X(3)Sigma- electronic transition and the NH(2) radical via transitions in the (0,9,0) <-- (0,0,0) band of the A(2)A(1) <-- X(2)B(1) electronic transition. The measurements revealed typical densities of 5 x 10(18) m(-3) for the NH radical in both plasmas and up to 7 x 10(18) m(-3) for the NH(2) radical when N(2) and H(2) are both fed through the plasma source. In N(2) plasma with H(2) injected in the background, no NH(2) was detected, indicating that the density is below our detection limit of 3 x 1016 m-3. The error in the measured densities is estimated to be around 20%. From the trends of the NH(x) radicals as a function of the relative H(2) flow to the total N(2) and H(2) flow at several positions in the expanding plasma beam, the key reactions for the formation of NH and NH(2) have been determined. The NH radicals are mainly produced via the reaction of N atoms emitted by the plasma source with H(2) molecules with a minor contribution from the reaction of N+ with H(2). The NH(2) radicals are formed by reactions of NH(3) molecules, produced at the walls of the plasma reactor, and H atoms emitted by the plasma source. The NH radicals can also be produced by H abstraction of NH(2) radicals. The flux densities of the NH(x) radicals with respect to the atomic radicals are appreciable in the first part of the expansion. Further downstream the NH(x) radicals are dissociated, and their densities become smaller than those of the atomic radicals. It is concluded that the NH(x) radicals play an important role as precursors for the N and H atoms, which are key to the surface production of N(2), H(2), and NH(3) molecules.


High burden of breast cancer in Belgium: recent trends in incidence (1999-2006) and historical trends in mortality (1954-2006).
In Belgium, breast cancer mortality has been monitored since 1954, whereas cancer incidence data have only been made available for a few years. In this article we update historical trends of breast cancer mortality and describe the recent breast cancer incidence. Incidence data were extracted from the Belgium Cancer Registry from 2004 to 2006 for the Walloon and Brussels Regions and Belgium, and from 1999 to 2006 for the Flemish Region. The Directorate-general Statistics and Economic information provided the mortality data for the years 1954-1999 and 2004. The regional authorities of the Flemish and Brussels Regions provided the mortality data for the years 2000-2003 and 2005-2006. In 2004, the World age-standardised breast cancer incidence for the whole of Belgium was 110 per 100, 000 person-years for all ages; and 172, 390 and 345 per 100, 000 person-years for the 35-49, 50-69, and 70+ age groups, respectively. The incidence rate was slightly higher in each age group in the Brussels Region. In Flanders, where the incidence could be observed during a longer period, an increase was observed until 2003 in the 50-69 age group, followed by a decrease. To the contrary, in the oldest age group, incidence continued to rise over the whole period, whereas no change in incidence was observed between 1999 and 2006 in the 35-49 age group.Mortality increased until the late 1980s and afterwards decreased in all regions and in age groups younger than 70. In women of 70 years and older, the decline began later. The burden of breast cancer in Belgium is very high. In 2004, Belgium ranked first for the age-standardised incidence rate in Europe for all ages combined and in the 35-49 and 50-69 age groups. The impact of the known risk factors and of mammographic screening should be further studied. The mortality rate in Belgium ranked lower than incidence, suggesting favourable survival. Plausible explanations for the discrepancy between incidence and mortality are discussed.


Strategies in probabilistic feedback learning in Parkinson patients OFF medication.
Studies on classification learning suggested that altered dopamine function in Parkinson's Disease (PD) specifically affects learning from feedback. In patients OFF medication, enhanced learning from negative feedback has been described. This learning bias was not seen in observational learning from feedback, indicating different neural mechanisms for this type of learning. The present study aimed to compare the acquisition of stimulus-response-outcome associations in PD patients OFF medication and healthy control subjects in active and observational learning. 16 PD patients OFF medication and 16 controls were examined with three parallel learning tasks each, two feedback-based (active and observational) and one non-feedback-based paired associates task. No acquisition deficit was seen in the patients for any of the tasks. More detailed analyses on the learning strategies did, however, reveal that the patients showed more lose-shift responses during active feedback learning than controls, and that lose-shift and win-stay responses more strongly determined performance accuracy in patients than controls. For observational feedback learning, the performance of both groups correlated similarly with the performance in non-feedback-based paired associates learning and with the accuracy of observed performance. Also, patients and controls showed comparable evidence of feedback processing in observational learning. In active feedback learning, PD patients use alternative learning strategies than healthy controls. Analyses on observational learning did not yield differences between patients and controls, adding to recent evidence of a differential role of the human striatum in active and observational learning from feedback.


Variation in communicative complexity in relation to social structure and organization in non-human primates.
Communicative complexity relates to social complexity, as individuals in more complex social systems either use more signals or more complex signals than individuals living in less complex ones. Taking the individual group member's perspective, here we examine communicative complexity in relation to social complexity, which arises from two components of social systems: social structure and social organization. We review the concepts of social relationships and social complexity and evaluate their implications for communicative and cognitive complexity using examples from primate species. We focus on spider monkeys (Ateles geoffroyi), as their social organization is characterized by flexibility in grouping dynamics and they use a variety of communicative signals. We conclude that no simple relationship exists among social complexity, communicative complexity and cognitive complexity, with social complexity not necessarily implying cognitive complexity, and communicative and cognitive complexity being independently linked to social complexity. To better understand the commonly implied link between social complexity and cognitive complexity it is crucial to recognize the complementary role of communicative complexity. A more elaborated communicative toolkit provides the needed flexibility to deal with dynamic and multifaceted social relationships and high variation in fission-fusion dynamics. This article is part of the theme issue 'Cognition, communication and social bonds in primates'.


Self-Reported Computer Vision Syndrome among Thai University Students in Virtual Classrooms during the COVID-19 Pandemic: Prevalence and Associated Factors.
During the COVID-19 pandemic, computer vision syndrome (CVS) related to online classrooms were unavoidable. This cross-sectional study aimed to explore the prevalence, characteristics and associated factors of CVS. A total of 527 students who were currently studying in a virtual classroom (70.40% female, mean (standard deviation; SD) age of 20.04 (2.17) years) were included. The prevalence of CVS assessed by an online CVS-Questionnaire was 81.0% (427/527). Comparing with those in the period before the online study, an increase in screen time (interquartile range) in students with and without CVS was 3 (0−3) and 2 (1−5) h, respectively. Overall, 516 students (97.9%) experienced at least one symptom. The most frequent symptom in CVS subjects was eye pain (96.5%). The most intense symptoms were the feeling of worsening eyesight (15.9%). The factors associated with CVS were female (p < 0.001), age (p = 0.010), atopic diseases (p = 0.020), prior ocular symptoms (p < 0.001), astigmatism (p = 0.033), distance from display <20 cm (p = 0.023), presence of glare or reflection on screen (p < 0.001), low screen brightness (p = 0.045), sleep duration (p = 0.030), inadequate break time between classes (p < 0.001) and increased screen time usage during online study (p < 0.001). Recommendations to prevent CVS based on the adjustable factors might reduce the burden of online study.


Metabolism of meperidine in several animal species.
Four new meperidine metabolites were identified by GC-MS in the urine of rats, guinea pigs, rabbits, cats, and dogs. In addition to known meperidine metabolites, 4-ethoxycarbonyl-4-phenyl-1,2,3,4-tetrapyridine (dehydronormeperidine; IV, the N-hydroxydehydro derivative of normeperidine (X), the dihydroxy derivative of meperidine (XII), and the dihydroxy derivative of normeperidine (XIII) were identified. The possible role of the N-hydroxy derivative of normeperidine (IX) in the pharmacological interaction of meperidine (I) with MAO inhibitors, seen selectively in the rabbit (and humans), is discussed. Following the administration of the p-hydroxy derivative of meperidine (VII), the major metabolite was conjugated VII. Trace amounts of the p-hydroxy derivative of normeperidine (VIII), the methoxy hydroxy derivative of meperidine (XI), XII, and XIII also were detected as metabolites of VII. The degree of N-demethylation of VII, both in vitro and in vivo, was small.


Temporal transcriptomic analysis of metabolic genes in maternal organs and placenta during murine pregnancy.
Maternal pregnancy adaptation is crucial for fetal development and long-term health. Complex interactions occur between maternal digestive and excretory systems as they interface with the developing fetus through the placenta, and transcriptomic regulation in these organs throughout pregnancy is poorly understood. Our objective is to characterize transcriptomic changes across gestation in maternal organs and placenta. Gene expression was quantified in the kidney, liver, and small intestine harvested from nonpregnant and pregnant FVB mice at four time points and placenta at three time points (N = 5/time point) using Affymetrix Mouse Gene 1.0 ST arrays. In maternal organs, we identified 476 genes in the liver, 207 genes in the kidney, and 27 genes in the small intestine that were differentially expressed across gestation (False Discovery Rate [FDR] adjusted q < 0.05). The placenta had a total of 1576 differentially expressed genes between the placenta at either/gd15 or gd19 compared to gd10. We identified a number of pathways enriched for genes differentially expressed across gestation, including 5 pathways in the placenta, 9 pathways in the kidney, and 28 pathways in the liver, including the citrate cycle, retinol metabolism, bile acid synthesis, and steroid bile synthesis, which play functional roles in fetal development and pregnancy maintenance. Characterization of normal longitudinal changes that occur in pregnancy provides context to understand how perturbations in these biochemical pathways and perturbations in nutrient signaling may impact pregnancy.


Selective separation and simultaneous determination of trace levels of five types of fluorinated quinolone drugs by thin-layer chromatography/fluorescence densitometry.
This paper reports the determination of trace levels of 5 types of fluorinated quinolone drugs, i.e., ciprofloxacin, norfloxacin, enoxacin, pefloxacin, and ofloxacin, by thin-layer chromatography (TLC)/fluorescence densitometry. The new analytical method uses 2-step TLC development, selective separation, and simultaneous determination of the 5 drugs. The method was also applied to the determination of recoveries of standards of the 5 drugs in plasma and urine samples. The results show that the method has a wide linear range, high repeatability, and good stability.


Cell factory engineering for improved production of natural products.
Natural product biosynthesis is inherently linked with the primary metabolism in terms of providing precursors and co-factors. Thus, even though it is important to improve the performance of natural product biosynthetic enzymes in building efficient cell factories, it is equally important to engineer the central carbon metabolism, such that this is adjusted to meet the biosynthetic demand of the desired product.


Identification of stage I/II melanoma patients at high risk for recurrence using a model combining clinicopathologic factors with gene expression profiling (CP-GEP).
Patients with cutaneous melanoma stage I/IIA disease are currently not eligible for adjuvant therapy, despite their risk for relapses and death. This study validates the ability of a model combining clinicopathologic factors with gene expression profiling (CP-GEP) to identify patients at high risk for disease recurrence in stage I/II and subgroup stage I/IIA. 543 patients with stage I/II primary cutaneous melanoma from the University of Tuebingen diagnosed between 2000 and 2017 were analysed. All patients received sentinel lymph node biopsy (SLNB). Analysis was conducted for a separate group of 80 patients who did not undergo SLNB. CP-GEP stratified 424 stage I/IIA patients (78% of the cohort) according to their risk for recurrence, with five-year relapse-free survival (RFS) rates of 77.8% and 93% for CP-GEP high risk (195 patients) and low risk (229 patients), respectively, and hazard ratio of 3.53 (p-value <0.001). In patients who did not receive SLNB biopsy, CP-GEP captured 6 out of 7 relapses. CP-GEP can be used to identify primary cutaneous melanoma patients with a high risk for disease recurrence - especially for stage I/IIA, who are considered low risk by AJCC 8th. These patients may benefit from adjuvant therapy. Also, in the future, when SLNB may become irrelevant, CP-GEP may serve as a risk stratification tool.


Helical sorbent microtrap for continuous sampling by a membrane and trap interface for on-line gas chromatographic monitoring of volatile organic compounds.
A helical sorbent microtrap consisting of a helical sorbent fixed inside a silicosteel capillary tube is presented. The main parameters that affect the safe sampling time of the helical sorbent microtrap in continuous sampling by a membrane and trap interface for on-line gas chromatographic monitoring of organic volatiles in gaseous samples are examined, taking into account the helical configuration of the sorbent, the presence of the membrane in system, and the properties of the analytes. Thermal desorption of analytes from the helical sorbent trap was also examined having regard to the influence of the turbulent flow generated by the helical sorbent in the heat transfer and the effect of thermal backward flow on the peak shape. The practical application of the helical sorbent microtrap in a membrane and trap interface was demonstrated by on-line gas chromatographic monitoring of four volatile organic compounds in the fume hood air and of volatile organic compounds from a diesel engine exhaust. The limit of detection was in the picogram per milliliter range, depending on the time of trapping and the parameters that affect the permeation through the membrane.


O-antigen diversity among Acinetobacter baumannii strains from the Czech Republic and Northwestern Europe, as determined by lipopolysaccharide-specific monoclonal antibodies.
O-antigen-specific monoclonal antibodies (MAbs) are currently being generated to develop an O-serotyping scheme for the genus Acinetobacter and to provide potent tools to study the diversity of O-antigens among Acinetobacter strains. In this report, Acinetobacter baumannii strains from the Czech Republic and from two clonal groups identified in Northwestern Europe (termed clones I and II) were investigated for their reactivity with a panel of O-antigen-specific MAbs generated against Acinetobacter strains from various species. The bacteria were characterized for their ribotype, biotype, and antibiotic susceptibility and the presence of the 8.7-kb plasmid pAN1. By using the combination of these typing profiles, the Czech strains could be classified into four previously defined groups (A. Nemec, L. Janda, O. Melter, and L. Dijkshoorn, J. Med. Microbiol. 48:287-296, 1999): two relatively homogeneous groups of multiresistant strains (termed groups A and B), a heterogeneous group of other multiresistant strains, and a group of susceptible strains. O-antigen reactivity was observed primarily with MAbs generated against Acinetobacter calcoaceticus and Acinetobacter baumannii strains. A comparison of reaction patterns confirmed the previously hypothesized clonal relationship between group A and clone I strains, which are also similar in other properties. The results show that there is limited O-antigen variability among strains with similar geno- and phenotypic characteristics and are suggestive of a high prevalence of certain A. baumannii serotypes in the clinical environment. It is also shown that O-antigen-specific MAbs are useful for the follow-up of strains causing outbreaks in hospitals.


Phase-locked responses to tones of chinchilla auditory nerve fibers: implications for apical cochlear mechanics.
Responses to tones with frequency < or = 5 kHz were recorded from auditory nerve fibers (ANFs) of anesthetized chinchillas. With increasing stimulus level, discharge rate-frequency functions shift toward higher and lower frequencies, respectively, for ANFs with characteristic frequencies (CFs) lower and higher than approximately 0.9 kHz. With increasing frequency separation from CF, rate-level functions are less steep and/or saturate at lower rates than at CF, indicating a CF-specific nonlinearity. The strength of phase locking has lower high-frequency cutoffs for CFs >4 kHz than for CFs < 3 kHz. Phase-frequency functions of ANFs with CFs lower and higher than approximately 0.9 kHz have inflections, respectively, at frequencies higher and lower than CF. For CFs >2 kHz, the inflections coincide with the tip-tail transitions of threshold tuning curves. ANF responses to CF tones exhibit cumulative phase lags of 1.5 periods for CFs 0.7-3 kHz and lesser amounts for lower CFs. With increases of stimulus level, responses increasingly lag (lead) lower-level responses at frequencies lower (higher) than CF, so that group delays are maximal at, or slightly above, CF. The CF-specific magnitude and phase nonlinearities of ANFs with CFs < 2.5 kHz span their entire response bandwidths. Several properties of ANFs undergo sharp transitions in the cochlear region with CFs 2-5 kHz. Overall, the responses of chinchilla ANFs resemble those in other mammalian species but contrast with available measurements of apical cochlear vibrations in chinchilla, implying that either the latter are flawed or that a nonlinear "second filter" is interposed between vibrations and ANF excitation.


Not All Street Food Is Bad: Low Prevalence of Antibiotic-Resistant Salmonella enterica in Ready-to-Eat (RTE) Meats in Ghana Is Associated with Good Vendors' Knowledge of Meat Safety.
Foodborne infections due to the consumption of meat is a significant threat to public health. However, good vendor and consumer knowledge of meat safety could prevent meat contamination with and transmission of foodborne pathogens like Salmonella. Thus, this study investigated the vendor and consumer perception, knowledge, and practices of meat safety regarding ready-to-eat (RTE) meat and how this affected the prevalence and antibiotic susceptibility of Salmonella enterica in RTE meats in the streets of Ghana. A semi-structured questionnaire was used to obtain the demographics, knowledge, and practices of meat safety data from RTE meat vendors (n = 300) and consumers (n = 382). Salmonella enterica detection was done according to the United State of America (USA)-Food and Drugs Administration (FDA) Bacteriological Analytical Manual. The disk diffusion method was used for antibiotic resistance testing. The results revealed that most of the respondents had heard of meat safety (98.3% vendors, 91.8% consumers) and knew that meat could be contaminated by poor handling (100.0% vendors, 88.9% consumers). The respondents knew that regular hand washing reduced the risk of meat contamination (100.0% vendors, 94.0% consumers). Responses to the practices of meat safety by vendors were generally better. A very low Salmonella enterica prevalence was observed in the samples, ranging between 0.0 and 4.0% for guinea fowl and beef, respectively. However, the six isolates obtained were resistant to five of the nine antibiotics tested, with all isolates displaying different resistance profiles. Overall, the good knowledge and practice of meat safety demonstrated by the respondents corroborated the negligible prevalence of Salmonella in this study, reiterating the importance of vendor meat safety knowledge. However, the presence of resistant Salmonella enterica in some of the meat samples, albeit in a very low prevalence, warrants stricter sanitary measures and greater meat safety awareness in the general population to prevent meat-borne infections and potential transmission of drug-resistant bacteria to humans.


Ferroelastic switching in a layered-perovskite thin film.
A controllable ferroelastic switching in ferroelectric/multiferroic oxides is highly desirable due to the non-volatile strain and possible coupling between lattice and other order parameter in heterostructures. However, a substrate clamping usually inhibits their elastic deformation in thin films without micro/nano-patterned structure so that the integration of the non-volatile strain with thin film devices is challenging. Here, we report that reversible in-plane elastic switching with a non-volatile strain of approximately 0.4% can be achieved in layered-perovskite Bi2WO6 thin films, where the ferroelectric polarization rotates by 90° within four in-plane preferred orientations. Phase-field simulation indicates that the energy barrier of ferroelastic switching in orthorhombic Bi2WO6 film is ten times lower than the one in PbTiO3 films, revealing the origin of the switching with negligible substrate constraint. The reversible control of the in-plane strain in this layered-perovskite thin film demonstrates a new pathway to integrate mechanical deformation with nanoscale electronic and/or magnetoelectronic applications.


Comparison of tissular disposition of pentamidine mesylate in the rat after aerosol or parenteral administration.
The tissular distribution of pentamidine mesylate (4 mg/kg as free base) after intravenous, intramuscular, and aerosol administration in healthy rats was examined. Pentamidine levels in the plasma, lungs, liver, kidneys, and other organs were determined by high-performance liquid chromatography. Pentamidine was undetectable in the plasma after day 5. At day 1, the injected groups had high concentrations of the drug in the kidneys (32-34 micrograms/g) and spleen with much lower concentrations in the lungs and the liver (3.12-5.70 micrograms/g and 1.64-2.19 micrograms/g, respectively). Aerosol delivery of pentamidine produced negligible extrapulmonary drug levels (3.29 micrograms/g in kidneys at day 1) and high sustained pulmonary levels throughout the 60 d of the study (range 5.42-19.62 micrograms/g). The half-time of elimination was longer in the lungs and kidneys (29-45 d) than in the liver (1.4-7.0 d) regardless of the mode of administration.


An evaluation of the predictive performance of distributional models for flora and fauna in north-east New South Wales.
To use models of species distributions effectively in conservation planning, it is important to determine the predictive accuracy of such models. Extensive modelling of the distribution of vascular plant and vertebrate fauna species within north-east New South Wales has been undertaken by linking field survey data to environmental and geographical predictors using logistic regression. These models have been used in the development of a comprehensive and adequate reserve system within the region. We evaluate the predictive accuracy of models for 153 small reptile, arboreal marsupial, diurnal bird and vascular plant species for which independent evaluation data were available. The predictive performance of each model was evaluated using the relative operating characteristic curve to measure discrimination capacity. Good discrimination ability implies that a model's predictions provide an acceptable index of species occurrence. The discrimination capacity of 89% of the models was significantly better than random, with 70% of the models providing high levels of discrimination. Predictions generated by this type of modelling therefore provide a reasonably sound basis for regional conservation planning. The discrimination ability of models was highest for the less mobile biological groups, particularly the vascular plants and small reptiles. In the case of diurnal birds, poor performing models tended to be for species which occur mainly within specific habitats not well sampled by either the model development or evaluation data, highly mobile species, species that are locally nomadic or those that display very broad habitat requirements. Particular care needs to be exercised when employing models for these types of species in conservation planning.


Neuropsychiatric effects of Parkinson's disease treatment.
Advances in the treatment of Parkinson's disease have led to significant improvement in many of the disabling motor symptoms of the disease, but often at the cost of neuropsychiatric side-effects. These include psychosis, dopamine dysregulation syndrome, impulse control disorders, mood disorders and Parkinson's disease drug withdrawal syndromes. Such side-effects can be as disabling and have as much impact on activities of daily living, quality of life, relationships and caregiver burden as motor symptoms. Awareness of these potential side-effects is important both in terms of obtaining informed consent, and to aid early identification and intervention, as patients may not spontaneously report side-effects because of lack of insight, or deny them out of shame or embarrassment. The challenge of treatment can be a trade off between the emergence of such side-effects and the amelioration of parkinsonism, best mastered with an informed dialogue between clinician and patient.


A century of Hereditas: from local publication to international journal.
The Mendelian Society of Lund launched Hereditas in 1920. The purpose of this article is to give an overview of Hereditas's hundred-year existence, focusing on the conditions for a learned society to publish a scientific journal, and the journal's importance for the publication and dissemination of genetic research. The article focuses on the historical development of the journal and analyses how the content and orientation of research published in Hereditas have changed over the years. The historical study is based on the collation and interpretation of archival material, mainly held in the Mendelian Society's archive, which includes the Hereditas archive. The bibliometric analyses are based on bibliographic metadata from Web of Science (WoS). Together with descriptive statistics, co-citation analyses were performed by using BibExcel, in combination with the clustering and visualisation tool VOSviewer. Journals with articles citing Hereditas articles were identified as a complement to the co-citation analyses. The history of the journal falls into three main periods: a local period, 1920-1959, when Hereditas was primarily intended for Swedish geneticists; a Scandinavian period, 1960-1988, when Hereditas was the official journal of the Scandinavian Association of Geneticists; and an international period from 1989 onwards. The original decision that Hereditas should cover genetic research with no particular specialisation was retained throughout. Its publications demonstrate the continuing presence of genetic research on plants and animals, albeit with a shifting focus, while human genetics emerged slowly and reached its peak in the period 1960-1988. In the hundred years of Hereditas's existence, the publishing landscape has changed dramatically, including a far greater number of specialist journals, changes to the academic merit system, new commercial models for publishing, and digitalisation. Over the years, the journal's survival has therefore been dependent on the strong commitment of its owners and an ability to adapt to changing conditions.


Improved survival in simulated surgical infection with combined cytokine, antibiotic and immunostimulant therapy.
A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.


First case report of nematode parasitic myelopathy in a wild feline in Brazil.
Parasitic myelopathy caused by Gurltia paralysans in domestic cats is a disease commonly reported in several South American countries. The adult parasite is lodged in the meningeal veins and spinal cord, often causing clinical manifestations of vascular proliferation, thrombophlebitis, and medullary compression. Wild felines are believed to be the definitive hosts of this parasite. The infection occurs through the ingestion of paratenic hosts, but the life cycle of G. paralysans is not yet clearly understood. In this paper, we discuss a case of parasitic myelopathy in a margay (Leopardus wiedii) that died during post-surgical care. Necropsy revealed focal hemorrhages in the thoracolumbar spinal cord. A microscopic examination revealed adult nematodes and eggs inside the veins of subarachnoid space in spinal cord, suggesting G. paralysans infection. This is first description of parasitic myelopathy in a margay in Brazil.


Emotional face recognition in male adolescents with autism spectrum disorder or disruptive behavior disorder: an eye-tracking study.
Autism Spectrum Disorder (ASD), Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) are often associated with emotion recognition difficulties. This is the first eye-tracking study to examine emotional face recognition (i.e., gazing behavior) in a direct comparison of male adolescents with Autism Spectrum Disorder or Oppositional Defiant Disorder/Conduct Disorder, and typically developing (TD) individuals. We also investigate the role of psychopathic traits, callous-unemotional (CU) traits, and subtypes of aggressive behavior in emotional face recognition. A total of 122 male adolescents (N = 50 ASD, N = 44 ODD/CD, and N = 28 TD) aged 12-19 years (M = 15.4 years, SD= 1.9) were included in the current study for the eye-tracking experiment. Participants were presented with neutral and emotional faces using a Tobii 1750 eye-tracking monitor to record gaze behavior. Our main dependent eye-tracking variables were: (1) fixation duration to the eyes of a face and (2) time to the first fixation to the eyes. Since distributions of eye-tracking variables were not completely Gaussian, non-parametric tests were chosen to investigate gaze behavior across the diagnostic groups with Autism Spectrum Disorder, Oppositional Defiant Disorder/Conduct Disorder, and Typically Developing individuals. Furthermore, we used Spearman correlations to investigate the links with psychopathy, callous, and unemotional traits and subtypes of aggression as assessed by questionnaires. The relative total fixation duration to the eyes was decreased in both the Autism Spectrum Disorder group and the Oppositional Defiant Disorder/Conduct Disorder group for several emotional expressions. In both the Autism Spectrum Disorder and the Oppositional Defiant Disorder/Conduct Disorder group, increased time to first fixation on the eyes of fearful faces only was nominally significant. The time to first fixation on the eyes was nominally correlated with psychopathic traits and proactive aggression. The current findings do not support strong claims for differential cross-disorder eye-gazing deficits and for a role of shared underlying psychopathic traits, callous-unemotional traits, and aggression subtypes. Our data provide valuable and novel insights into gaze timing distributions when looking at the eyes of a fearful face.


Components explain, but do eddy fluxes constrain? Carbon budget of a nitrogen-fertilized boreal Scots pine forest.
Nitrogen (N) fertilization increases biomass and soil organic carbon (SOC) accumulation in boreal pine forests, but the underlying mechanisms remain uncertain. At two Scots pine sites, one undergoing annual N fertilization and the other a reference, we sought to explain these responses. We measured component fluxes, including biomass production, SOC accumulation, and respiration, and summed them into carbon budgets. We compared the resulting summations to ecosystem fluxes measured by eddy covariance. N fertilization increased most component fluxes (P < 0.05), especially SOC accumulation (20×). Only fine-root, mycorrhiza, and exudate production decreased, by 237 (SD = 28) g C m-2 yr-1 . Stemwood production increases were ascribed to this partitioning shift, gross primary production (GPP), and carbon-use efficiency, in that order. The methods agreed in their estimates of GPP in both stands (P > 0.05), but the components detected an increase in net ecosystem production (NEP) (190 (54) g C m-2 yr-1 ; P < 0.01) that eddy covariance did not (19 (62) g C m-2 yr-1 ; ns). The pairing of plots, the simplicity of the sites, and the strength of response provide a compelling description of N effects on the C budget. However, the disagreement between methods calls for further paired tests of N fertilization effects in simple forest ecosystems.


Follow-up study of the arrhythmic graduates from the schools under the heart disease program for students in Osaka.
A long term follow-up study of arrhythmic graduates from junior or senior high schools under the Heart Disease Program in Osaka was performed by mailing questionnaires. The age of the total 515 subjects ranged from 20 to 38 years, 26.9 years on an average. From 397 graduates (77%), answers to questionnaires were obtained. We could confirm 92 graduates were alive (18% of total subjects) among the 118 graduates who did not return their answers to the questionnaires. The following is what we could confirm through the present study: The prognoses of simple premature beats, Wenckebach type heart block and complete right bundle branch block are good in young adults. The prognosis of sick sinus syndrome does not warrant an optimistic prognosis even in young adults. The prognosis of WPW syndrome in young adults is not always fair if they have a history of paroxysmal tachycardia. From 95 to 97% of the graduates with arrhythmia as a whole answered that their daily lives are quite similar to those of healthy people. Attitudes toward daily life and medical checks were also studied.


Irreversible topological transition of a stretched superhelix: the interplay of chiralities.
Helical complexes with certain intramolecular constraints on their topological state, exhibit nontrivial conformational changes in response to an external tension. We consider a generic right-handed helix and construct identical right and left-handed superhelixes. By using molecular dynamics simulations, we discover that under an external tension, the interplay between the helix chirality and the chirality of the superhelix leads to a fundamental topology transition of the stretched right-handed superhelix to its left-handed counterpart. We characterize and rationalize this irreversible phenomenon for a wide range of intramolecular angular stiffnesses and determine the associated phase diagram at different external loadings.