The Use of Functional Near-Infrared Spectroscopy to Differentiate Alcohol-Related Neurodevelopmental Impairment.
Oxygenated (HBO) and deoxygenated hemoglobin (HBR) levels in the prefrontal cortex (PFC) were measured using functional near-infrared spectroscopy (fNIRS) to determine if PFC activity during a cognitive inhibition task distinguishes children with prenatal alcohol exposure (PAE, n = 26) from both typically developing controls (n = 19) and a contrast group of children with other neurobehavioral problems (n = 14). Despite showing evidence of increased PFC activity in the non-inhibitory condition relative to controls, children in the PAE group displayed reduced PFC HBO and increased HBR relative to both other groups in the inhibitory condition, suggesting reduced PFC activity but increased oxygen consumption without sufficient oxygen replacement.


The Pulfrich phenomenon in a large population of young healthy subjects.
To determine whether the Pulfrich phenomenon, an optical illusion occurring in many ophthalmological diseases, is perceived equally in both eyes in a large group of healthy medical students. A pendulum bob swinging perpendicular to the direction of observation was observed with either the right or the left eye covered with neutral density filters (50, 80 or 90 % absorption) and the apparent elliptical pendulum movement measured in depth. Interocular time delay was calculated from depth. Data from 65 individuals were included based on having: completed all 7 determinations of depth, a visual acuity of >/= 20/20 on both eyes and an intact stereoscopic perception (Titmus stereotest, acuity of >/= 20/25). All subjects perceived the phenomenon. Depth perception was not significantly different (p > 0.05; MANOVA) between the two eyes (depth in [mm]; mean +/- sem): OD: 8.5 +/- 0.38, 23.7 +/- 0.53, 36.3 +/- 0.81; OS 9.4 +/- 0.50, 24.1 +/- 0.69, 35.6 +/- 0.92; for 50, 80 and 90 % absorption of the filter respectively. At 0 % absorption the pendulum was seen in average at positive values (0.9 +/- 0.23 mm; p > 0.05). Calculated interocular time delay (ms) was: OD: 8.0 +/- 0.18, 5.1 +/- 0.12, 1.8 +/- 0.08; OS: 7.46 +/- 0.15, 5.0 +/- 0.11, 1.9 +/- 0.10. The average depth perceived without filter corresponded to a time delay for the right eye of 0.2 +/- 0.05 ms. Correction for the depth perception perceived without filter did not alter statistical significance. The Pulfrich phenomenon is perceived equally in both eyes. Depth perception without filters was not significantly different from zero. The illusion has clinical utility, since in normal subjects reliability of measurements is good and size of the illusion (without filters) small.


Extracellular proteolysis and cancer: meeting summary and future directions.
The contribution of extracellular proteolysis to processes of tumor invasion and metastasis has been recognized for more than 20 years. However, after millions of dollars and untold hours of investment in preclinical research and the development of broad range inhibitors of MMPs, clinical trials of late-stage tumor patients show no indication that this approach will be successful. In the basic science arena, there have been stunning advancements that illustrate novel biological activities for proteases and that suggest they are key regulators of many physiological and pathological processes. The Proteases and Cancer: Biology and Therapeutics Workshop (held in Bethesda, MD, November 20-22, 2002) was organized by the Division of Cancer Biology, National Cancer Institute (NCI) to identify research areas and directions that will accelerate understanding protease biology and enhance clinical translation. The overall consensus was that protease biology represents fertile ground for advances that will be clinically useful but perhaps not for the reasons or purpose originally thought. Protease-related technologies show particular promise for the detection, prognosis, and prevention of cancer, and for therapeutic purposes in defined situations. Promising areas for further research are identified, and specific recommendations for the development of a consortium to coordinate the efforts of the protease community are made.


Symptom management in palliative care.
Controlling patients' symptoms in palliative care requires good communication skills. Pain, vomiting and nausea are common symptoms, but anorexia and sleep disturbance are also frequently reported. Thorough evaluation and treatment of the underlying cause is imperative. Pain is different for each patient. Pain control therefore may not be achieved with analgesics alone.


Xanthogranulomatous Pyelonephritis With Extension to the Liver: A Case Report.
Xanthogranulomatous pyelonephritis (XGP) is an uncommon condition representing 1% of all renal infections. XGP due to complicated pyelonephritis associated with hepatic abscess is an extremely rare complication and has rarely been reported in the literature. We report a rare case of a 54-year-old female with a history of diabetes and recurrent urinary tract infections (UTI) who presented with acute right flank pain and fever which had been ongoing for four days. CT scan showed multiple bilateral obstructive nephrolithiasis associated with a liver abscess. Given the patient's high risk of nephron loss, a bilateral renal and liver abscess drainage followed by a two-stage flexible ureterorenoscopy (FURS) was performed. One week later, a CT scan showed a typical radiological aspect of XGP on the right kidney invading the liver. She urgently underwent a right nephrectomy with an uneventful outcome. In conclusion, the diagnosis of XGP should be considered in the presence of complicated pyelonephritis associated with hepatic abscess.


Retrieval of aerosol properties from combined multiwavelength lidar and sunphotometer measurements.
Simulation studies were carried out with regard to the feasibility of using combined observations from sunphotometer (SPM) and lidar for microphysical characterization of aerosol particles, i.e., the retrieval of effective radius, volume, and surface-area concentrations. It was shown that for single, homogeneous aerosol layers, the aerosol parameters can be retrieved with an average accuracy of 30% for a wide range of particle size distributions. Based on the simulations, an instrument combination consisting of a lidar that measures particle backscattering at 355 and 1574 nm, and a SPM that measures at three to four channels in the range from 340 to 1020 nm is a promising tool for aerosol characterization. The inversion algorithm has been tested for a set of experimental data. The comparison with the particle size distribution parameters, measured with in situ instrumentation at the lidar site, showed good agreement.


Management of Severe Dyslipidaemia: Role of PCSK9 Inhibitors.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in regulation of LDL receptors on the hepatocyte surface and therefore is essential for effective removal of LDL particles from circulation. Genetic and biochemical studies have established that altered PCSK9 functionality influences both LDL cholesterol levels and cardiovascular risk. This has prompted development of inhibitory strategies targeting PCSK9. Study of monoclonal PCSK9 antibodies has progressed to the clinic, where they have been found to lower LDL cholesterol levels and reduce cardiovascular event rates in large, clinical outcome trials. The use of PCSK9 inhibitors in the setting of dyslipidaemia is reviewed.


Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications.
Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER)-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ERα expression for effective treatment of ERα-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ERα-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ERα expression. The combination of 20 µg/mL GTPs and 5 µM SFN was found to be the optimal dose of ERα-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ERα expression was consistently correlated with ERα promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP) analysis of the ERα promoter revealed that GTPs and SFN altered the binding of ERα-transcriptional co-repressor complex thereby contributing to ERα-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens.


Fatal low-dose methotrexate toxicity: A case report and literature review.
Methotrexate (MTX) is a chemotherapeutic agent that acts primarily by inhibiting the folic acid cycle. In addition to its application for treating malignancies, MTX is also used to treat chronic inflammatory diseases including psoriasis. Adverse effects have been reported even at low doses (up to 25 mg/week), and there is risk of toxicity in the form of myelosuppression, hepatotoxicity, or pulmonary fibrosis. Here, we report a case of a 67-year-old male with a past medical history of end stage renal disease on peritoneal dialysis and moderate-to-severe psoriasis with psoriatic arthritis presented with abdominal pain, diarrhea, rash, mucositis, and mucocutaneous ulcers and erosions. The patient was taking methotrexate 10 mg weekly without folic acid supplementation and was found to be pancytopenic. Despite treatment, the patient developed multiorgan failure and passed away after 16 days of hospitalization. Myelosuppression is considered the most serious side effect with the highest risk of mortality. Risk factors for toxicity include renal insufficiency, advanced age, lack of folate supplementation, drug interactions, and medication errors. Importantly, serum levels of MTX do not correlate with toxicity; therefore, folinic acid rescue therapy should be started as soon as MTX toxicity is suspected. MTX toxicity is rare with low dose, proper dose scheduling, and adherence to the recommended guidelines. It is imperative that physicians considering therapy with low dose MTX for dermatologic indications take into consideration a patient's risk factors for toxicity and monitor appropriately.


Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells.
Leukemia remains life-threatening despite remarkable advances in chemotherapy. The poor prognosis and drug resistance are challenging treatment. Novel drugs are urgently needed. Shikonin, a natural naphthoquinone, has been previously shown by us to be particularly effective towards various leukemia cell lines compared to solid tumors. However, the underlying mechanisms are still poorly understood. Here, we investigated shikonin and 14 derivatives on U937 leukemia cells. Four derivatives (isobutyrylshikonin, 2-methylbutyrylshikonin, isovalerylshikonin and β,β-dimethylacrylshikonin) were more active than shikonin. AnnexinV-PI analysis revealed that shikonins induced apoptosis. Cell cycle G1/S check point regulation and the transcription factor c-MYC, which plays a vital role in cell cycle regulation and proliferation, were identified as the most commonly down-regulated mechanisms upon treatment with shikonins in mRNA microarray hybridizations. Western blotting and DNA-binding assays confirmed the inhibition of c-MYC expression and transcriptional activity by shikonins. Reduction of c-MYC expression was closely associated with deregulated ERK, JNK MAPK and AKT activity, indicating their involvement in shikonin-triggered c-MYC inactivation. Molecular docking studies revealed that shikonin and its derivatives bind to the same DNA-binding domain of c-MYC as the known c-MYC inhibitors 10058-F4 and 10074-G5. This finding indicates that shikonins bind to c-MYC. The effect of shikonin on U937 cells was confirmed in other leukemia cell lines (Jurkat, Molt4, CCRF-CEM, and multidrug-resistant CEM/ADR5000), where shikonin also inhibited c-MYC expression and influenced phosphorylation of AKT, ERK1/2, and SAPK/JNK. In summary, inhibition of c-MYC and related pathways represents a novel mechanism of shikonin and its derivatives to explain their anti-leukemic activity.


Synthesis and cytotoxicity of a novel iridoid glucoside derived from aucubin.
The novel iridoid glycoside 2 was prepared in six steps (15% overall yield) from natural aucubin (1) and fully characterized. Compound 2, which comprises the same conjugated cyclopentenone pharmacophore as known antitumor oxylipins and prostaglandins, displayed significant antiproliferative in vitro activity towards leukemia L1210 cells. The Michael addition of nucleophilic thiols to compound 2 occurred on a different position compared to classical delta7-prostaglandin A1 methyl ester. The resulting adducts 7a and 7b were fully characterized, and their MS fragmentation patterns were elucidated.


Quantitative analysis of C bands in chromosomes 1, 9, 16 and Y in Caucasian and Japanese males.
A comparative analysis of the C bands of chromosomes 1, 9, 16 and Y of 27 Caucasian and 27 Japanese males is reported. The mean of the total centromeric heterochromatin of the three pairs (sigma h1, 9, 16) is larger in Caucasian than in Japanese subjects, but Caucasians showed a lower mean of C band size of chromosome Y. Heritability of the C band of the Y chromosome was studied in 26 families.


Peptide-treated stent graft for the treatment of saphenous vein graft lesions: first clinical results.
Percutaneous interventions of degenerated saphenous vein grafts (SVG) are associated with high rates of distal embolic events and in-stent restenosis. A novel ePTFE-covered stent graft has been developed to improve outcomes for these difficult lesions. The stent graft has been treated with a 15-amino acid, cell adhesion peptide (P-15) to promote endothelialization on the inner surface post-implantation. Patients with de novo lesions in SVGs were treated with a peptide-coated ePTFE stent graft. Follow-up data was collected at 30 days, 3 and 6 months. An angiographic core lab analyzed an angiographic follow-up at 6 months. Procedural success was achieved in all cases. No device-related major adverse cardiac events occurred in-hospital, at 30 days, or at 3 months, despite the lack of distal protection. Six-month restenosis rates were 21%, and were comparable to similar devices. The peptide-treated stent graft appears to be a safe and effective treatment for SVG lesions, and has the potential to reduce complications without the use of adjunct distal protection in this patient population.


Host Resistance and Temperature-Dependent Evolution of Aggressiveness in the Plant Pathogen Zymoseptoria tritici.
Understanding how habitat heterogeneity may affect the evolution of plant pathogens is essential to effectively predict new epidemiological landscapes and manage genetic diversity under changing global climatic conditions. In this study, we explore the effects of habitat heterogeneity, as determined by variation in host resistance and local temperature, on the evolution of Zymoseptoria tritici by comparing the aggressiveness development of five Z. tritici populations originated from different parts of the world on two wheat cultivars varying in resistance to the pathogen. Our results show that host resistance plays an important role in the evolution of Z. tritici. The pathogen was under weak, constraining selection on a host with quantitative resistance but under a stronger, directional selection on a susceptible host. This difference is consistent with theoretical expectations that suggest that quantitative resistance may slow down the evolution of pathogens and therefore be more durable. Our results also show that local temperature interacts with host resistance in influencing the evolution of the pathogen. When infecting a susceptible host, aggressiveness development of Z. tritici was negatively correlated to temperatures of the original collection sites, suggesting a trade-off between the pathogen's abilities of adapting to higher temperature and causing disease and global warming may have a negative effect on the evolution of pathogens. The finding that no such relationship was detected when the pathogen infected the partially resistant cultivars indicates the evolution of pathogens in quantitatively resistant hosts is less influenced by environments than in susceptible hosts.


Adverse Health Outcomes Among Industrial and Occupational Sectors in Michigan.
We used data from the Michigan Behavioral Risk Factor Surveillance System (MIBRFSS) to estimate the prevalence of adverse health outcomes by industry and occupation and to examine the association of adverse health outcomes with industry and occupation while controlling for demographics and personal lifestyle behaviors. We calculated the prevalence of adverse health outcomes by industry by using data from the 2013-2015 MIBRFSS. Adjusted prevalence of adverse health outcomes was calculated by industry and occupation by using logistic regression for survey design, adjusting for demographics and health behaviors, and was compared with the overall prevalence in all industries and occupations. Three industries had a significantly higher prevalence of current asthma, diabetes, and depression compared with prevalence among workers employed in all industries. After controlling for confounding factors, only Health Care and Social Assistance had significantly higher prevalence of a health outcome, depression (20.1%). Three occupations had significantly higher prevalence of chronic obstructive pulmonary disease, current asthma, depression, high blood pressure, and diabetes compared with workers employed in all occupations. After adjusting for all confounding factors, only one occupation, protective service, had a significantly higher prevalence of high blood pressure (37.3%) and diabetes (12.8%). Adverse health outcomes varied significantly by industry and occupation in Michigan. Employers, policy makers, and health promotion practitioners can use results based on BRFSS to target and prioritize worksite wellness programs. MIBRFSS data also suggested the need for further research to identify why some industries had higher risks for diabetes, hypertension, and depression after controlling for covariates.


Physicians' and patients' perceptions of patients' communication competence in a primary care medical interview.
Considerable research suggests that patients and physicians often perceive aspects of the medical interview quite differently. Despite extensive research into physician-patient communication, virtually no attention has been given to assessing patients' and physicians' perceptions of communication competence during the medical interview. The purpose of this research was to determine the extent of agreement between physicians and patients on what behaviors constitute competent patient communication. The results indicate that there is considerable agreement between physicians and patients on the categories of competent patient communication. However, there is little or no evidence for agreement at the dyadic level on the occurrence of competent patient communication. Moreover, there is little evidence that physicians' and patients' perceptions of competence correlate with patients' actual discourse. These results are discussed with respect to implications for future research on patient communication skills training interventions.


The role of tetraploids in the sexual-asexual cycle in dandelions (Taraxacum).
Apomictic plants often produce pollen that can function in crosses with related sexuals. Moreover, facultative apomicts can produce some sexual offspring. In dandelions, Taraxacum, a sexual-asexual cycle between diploid sexuals and triploid apomicts, has been described, based on experimental crosses and population genetic studies. Little is known about the actual hybridization processes in nature. We therefore studied the sexual-asexual cycle in a mixed dandelion population in the Netherlands. In this population, the frequencies of sexual diploids and triploids were 0.31 and 0.68, respectively. In addition, less than 1% tetraploids were detected. Diploids were strict sexuals, triploids were obligate apomicts, but tetraploids were most often only partly apomictic, lacking certain elements of apomixis. Tetraploid seed fertility in the field was significantly lower than that of apomictic triploids. Field-pollinated sexual diploids produced on average less than 2% polyploid offspring, implying that the effect of hybridization in the 2x-3x cycle in Taraxacum will be low. Until now, 2x-3x crosses were assumed to be the main pathway of new formation of triploid apomicts in the sexual-asexual cycle in Taraxacum. However, tetraploid pollen donors produced 28 times more triploid offspring in experimental crosses with diploid sexuals than triploid pollen donors. Rare tetraploids may therefore act as an important bridge in the formation of new triploid apomicts.


YOLOv5-FPN: A Robust Framework for Multi-Sized Cell Counting in Fluorescence Images.
Cell counting in fluorescence microscopy is an essential task in biomedical research for analyzing cellular dynamics and studying disease progression. Traditional methods for cell counting involve manual counting or threshold-based segmentation, which are time-consuming and prone to human error. Recently, deep learning-based object detection methods have shown promising results in automating cell counting tasks. However, the existing methods mainly focus on segmentation-based techniques that require a large amount of labeled data and extensive computational resources. In this paper, we propose a novel approach to detect and count multiple-size cells in a fluorescence image slide using You Only Look Once version 5 (YOLOv5) with a feature pyramid network (FPN). Our proposed method can efficiently detect multiple cells with different sizes in a single image, eliminating the need for pixel-level segmentation. We show that our method outperforms state-of-the-art segmentation-based approaches in terms of accuracy and computational efficiency. The experimental results on publicly available datasets demonstrate that our proposed approach achieves an average precision of 0.8 and a processing time of 43.9 ms per image. Our approach addresses the research gap in the literature by providing a more efficient and accurate method for cell counting in fluorescence microscopy that requires less computational resources and labeled data.


Clonal differences in expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase, of 25-hydroxyvitamin D(3)-24-hydroxylase, and of the vitamin D receptor in human colon carcinoma cells: effects of epidermal growth factor and 1alpha,25-dihydroxyvitamin D(3).
Human colon carcinoma cells express 25-hydroxyvitamin D(3)-1alpha-hydroxylase (CYP27B1) and thus produce the vitamin D receptor (VDR) ligand 1alpha,25-dihydroxyvitamin D(3) (1,25-D3), which can be metabolized by 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24). Expression of VDR, CYP27B1, and CYP24 determines the efficacy of the antimitotic action of 1,25-D3 and is distinctly related to the degree of differentiation of cancerous lesions. In the present study we addressed the question of whether the effects of epidermal growth factor (EGF) and of 1,25-D3 on VDR, CYP27B1, and CYP24 gene expression in human colon carcinoma cell lines also depend on the degree of cellular differentiation. We were able to show that slowly dividing, highly differentiated Caco-2/15 cells responded in a dose-dependent manner to both EGF and 1,25-D3 by up-regulation of VDR and CYP27B1 expression, whereas in highly proliferative, less differentiated cell lines, such as Caco-2/AQ and COGA-1A and -1E, negative regulation was observed. CYP24 mRNA was inducible in all clones by 1,25-D3 but not by EGF. From the observed clonal differences in the regulatory effects of EGF and 1,25-D3 on VDR and CYP27B1 gene expression we suggest that VDR-mediated growth inhibition by 1,25-D3 would be efficient only in highly differentiated carcinomas even when under mitogenic stimulation by EGF.


Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial.
To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics. Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated. The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics. Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.


A Single Flow Re-direction Endoluminal Device for the Treatment of Large and Giant Anterior Circulation Intracranial Aneurysms.
The purpose of this study was to report the author's experiences in treating large (10-25 mm) and giant (>25 mm) intracranial aneurysms (IAs) using a single Flow Re-direction Endoluminal Device (FRED) without assistant coiling, with a focus on procedure-related complications. A total of 33 patients who were treated with FRED between January 2018 and July 2020 were retrospectively reviewed. The timing of procedure-related complications was chronologically categorized as acute (within 7 days), subacute (8 to 21 days), and delayed (after 21 days) periods. Follow-up angiography was performed at 2 to 27 months (mean 9.7 months), and clinical follow-up was performed at 1 to 31 months (mean 14.1 months) in all patients. Six (18.2%) patients experienced procedure-related complications, including 2 (6.1%) in acute period, 1 (3.0%) in subacute period, and 3 (9.1%) in delayed period. Thromboembolic complications occurred in 5 (15.2%) patients and hemorrhagic complications in 1 (3.0%). Permanent morbidity and mortality rates were 3.0% each. Non-internal carotid artery (ICA) location of IAs (odds ratio 6.532; 95% confidence interval, 1.335-17.816; p=0.034) was the only independent risk factor for procedure-related complications on multivariate logistic regression analysis. The procedure-related complication rate was 18.2% in this study. Procedure-related complications might increase when treating large and giant IAs located on a non-ICA, especially on the middle cerebral artery. Therefore, it may be suggested that neurointerventionists and endovascular neurosurgeons should pay attention to the location of IAs when treating large and giant IAs with a single FRED.


Small Fiber Neuropathy in Patients with Chronic Pain and a Previous Diagnosis of Multiple Chemical Sensitivity Syndrome.
Small fiber neuropathy (SFN) is characterized by the involvement of Aδ and C fibers leading to sensory, mainly pain, and/or autonomic symptoms. Multiple chemical sensitivity syndrome (MCS) is an incompletely defined condition characterized by the onset of various symptoms in patients after exposure to several chemical substances. Pain is a common symptom in these patients. In this study, we report the histological and clinical data of a cohort of 21 patients who had been diagnosed as having MCS and who were referred to us with the suspicion of SFN because of chronic pain. All patients underwent neurological clinical examination, (including scales for pain and autonomic disorders), and a skin biopsy. Age-matched healthy subjects were used as controls for the skin biopsies. Nerve conduction studies and serum screening to exclude possible causes of peripheral neuropathy were also performed. Skin biopsies disclosed a somatic SFN in all patients. Although the majority (18 out of 21) of patients also had autonomic symptoms. we found sparing of autonomic innervation in the biopsies. These observations suggest that chronic pain in MCS could be secondary to the presence of somatic SFN, although more data are needed to confirm these observations.


Bactericidal Silver Nanoparticles by Atmospheric Pressure Solution Plasma Processing.
Silver nanoparticles have applications in plasmonics, medicine, catalysis and electronics. We report a simple, cost-effective, facile and reproducible technique to synthesise silver nanoparticles via plasma-induced non-equilibrium liquid chemistry with the absence of a chemical reducing agent. Silver nanoparticles with tuneable sizes from 5.4 to 17.8 nm are synthesised and characterised using Transmission Electron Microscopy (TEM) and other analytic techniques. A mechanism for silver nanoparticle formation is also proposed. The antibacterial activity of the silver nanoparticles was investigated with gram-positive and gram-negative bacteria. The inhibition of both bacteria types was observed. This is a promising alternative method for the instant synthesis of silver nanoparticles, instead of the conventional chemical reduction route, for numerous applications.


Quality of life following vaginal reconstructive versus obliterative surgery for treating advanced pelvic organ prolapse.
Although colpocleisis is effective in selected women, the low-morbidity obliterative procedure for treating pelvic organ prolapse (POP) and its impact on postoperative quality of life (QOL) have rarely been studied. Our aim was to assess QOL in women after colpocleisis and compare it with that of women after reconstructive vaginal surgery. This retrospective cohort study included women (aged 35-85 years) with POP who underwent obliterative or reconstructive surgical correction during 2009-2015. Patients who met the inclusion criteria underwent telephone interviews that included the validated Prolapse QOL questionnaire (P-QOL Thai). Of 295 potential participants, 197 (67%) completed the questionnaire: 93 (47%) with obliterative and 104 (53%) with reconstructive surgery. Most were Thai (95.4%), multiparous (87%), and sexually inactive (76%). Their histories included hysterectomy (12%), incontinence or prolapse surgery (11%), and POP stage 3/4 (77%). Patients undergoing obliterative surgery were significantly older than those undergoing a reconstructive procedure (69 vs 58 years, P < 0.05). The obliterative group had more children, less education, and more advanced POP. There were no significant differences in operative parameters or complications. The obliterative surgery group had a significantly shorter hospital stay: median 2 (range 1-17) days vs 3 (1-20) days (P = 0.016). P-QOL scale revealed significantly less postoperative impairment in the obliterative surgery group (1.75 vs 5.26, P = 0.023). There were no significant differences in other P-QOL domains. Colpocleisis improves condition-specific QOL in selected patients with advanced POP and remains an option for this group. Surgeons should consider counseling elderly women with advanced POP about obliterative vaginal surgery.


News at Biochemia Medica: research integrity corner, updated guidelines to authors, revised author statement form and adopted ICMJE Conflict-of-Interest Form.
From the issue 23(1) we have implemented several major changes in the editorial policies and procedures. We hope that those changes will raise awareness of our potential authors and reviewers for research and publication integrity issues as well as to improve the quality of our submissions and published articles. Among those changes is the launch of a special journal section called Research Integrity Corner. In this section we aim to publish educational articles dealing with different research and publication misconduct issues. Moreover, we have done a comprehensive revision of our Instructions to authors. Whereas our former Instructions to authors have mostly been concerned with recommendations for manuscript preparation and submission, the revised document additionally describes the editorial procedure for all submitted articles and provides exact journal policies towards research integrity, authorship, copyright and conflict of interest. By putting these Guidelines into action, we hope that our main ethical policies and requirements are now visible and available to all our potential authors. We have also revised the former Authorship and copyright form which is now called the Author statement form. This form now contains statements on the authorship, originality of work, research ethics, patient privacy and confidentiality, and copyright transfer. Finally, Journal has adopted the ICMJE Form for Disclosure of Potential Conflicts of Interest. From this issue, for each submitted article, authors are requested to fill out the "ICMJE Form for Disclosure of Potential Conflicts of Interest" as well as the Author statement form and upload those forms during the online manuscript submission process. We honestly believe that our authors and readers will appreciate such endeavors. In this Editorial article we briefly explain the background and the nature of those recent major editorial changes.


A case report of adult-onset multiple angiokeratomas with zosteriform distribution.
Angiokeratomas are benign vascular ectasias in the papillary dermis associated with epidermal changes in the form of hyperkeratosis and/or acanthosis. Clinically, angiokeratomas appear as solitary or multiple dark red to purple-black macules and/or papules, mostly with a verrucous surface. Five subtypes of angiokeratoma have been proposed - angiokeratoma corporis diffusum, angiokeratoma of Mibelli, angiokeratoma of Fordyce, angiokeratoma circumscriptum, and "solitary and multiple" angiokeratomas. We report an unusual case of multiple angiokeratomas in a zosteriform distribution with onset at age 74.


Sequence of a cDNA encoding mouse ribosomal protein S14.
An involution-induced clone was identified by differential screening from a cDNA library of mouse mammary gland. The clone was identified as full-length cDNA encoding the 40S subunit of ribosomal protein S14 (rps14). Comparison of the deduced amino acid sequence to sequences of rps14 from humans, hamsters, and rats showed a conservation.


Identification of Specific Variations in a Non-Motile Strain of Cyanobacterium Synechocystis sp. PCC 6803 Originated from ATCC 27184 by Whole Genome Resequencing.
Cyanobacterium Synechocystis sp. PCC 6803 is a widely used model organism in basic research and biofuel biotechnology application. Here, we report the genomic sequence of chromosome and seven plasmids of a glucose-tolerant, non-motile strain originated from ATCC 27184, GT-G, in use at Guangzhou. Through high-throughput genome re-sequencing and verification by Sanger sequencing, eight novel variants were identified in its chromosome and plasmids. The eight novel variants, especially the five non-silent mutations might have interesting effects on the phenotype of GT-G strains, for example the truncated Sll1895 and Slr0322 protein. These resequencing data provide background information for further research and application based on the GT-G strain and also provide evidence to study the evolution and divergence of Synechocystis 6803 globally.


Malignant osteoblastoma.
The clinical, radiographic and pathological features are described of eight cases of a bone tumour which we propose to classify as "malignant osteoblastoma". It presents the characteristics of genuine osteoblastoma but of an aggressive pattern, with more abundant and often plump hyperchromatic nuclei, greater nuclear atypia, and numerous giant cells of osteoclastic type. This rare tumour is regarded as the malignant counterpart of osteoblastoma and appears to be only locally aggressive. It should be separated from conventional osteosarcoma not only because of its peculiar histological pattern, but also because of its different clinical and radiological features and better prognosis. Thus seven of the eight patients were alive and free of disease from one and a half to eleven years after the initial surgical treatment, which in only two cases included amputation. Excision or block resection is the preferred method of treatment.


Development of antibodies to Plasmodium vivax as measured by two different serologic techniques.
Sera from individuals infected with Plasmodium vivax were tested for the presence of malarial antibodies using the indirect fluorescent antibody (IFA) and the indirect hemagglutination (IGA) tests. The primary infection resulted in the conversion of all sera to a positive response in the IFA test, whereas only 50% gave a positive IGA response. There was a direct relationship between the duration of the primary parasitemia and percentage giving positive IGA response. Relapse resulted in high level positive IFA and IGA responses.


Seasonal cycling of cesium-137 in a reservoir.
Studies of a reservoir in the southeastern United States show that cesium-137, introduced into the system from a leak in a nuclear fuel element, cycles between the water and sediment on a seasonal basis. The cycling, which coincides with the annual periods of thermal stratification in this monomictic lake, has been occurring for over 10 years.


Exploring the ICF-CY as a framework to inform transition programs from pediatric to adult healthcare.
To explore the utility of the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) for informing transition-related programs for youth with chronic conditions moving into adult healthcare settings, using an exemplar spina bifida program. Semi-structured in-depth interviews were conducted with 53 participants (9 youth and 11 parents who participated in a spina bifida transition program, 12 young adults who did not, 12 clinicians, and 9 key informants involved in development/implementation). Interview transcripts were thematically analyzed, and then further coded using ICF-CY domain codes. ICF-CY domains captured many key areas regarding individuals" transitions to adult care and adult functioning, but did not fully capture concepts of transition program experience, independence, and parents" role. The ICF-CY framework captures some experiences of transitions to adult care, but should be considered in conjunction with other models that address issues outside of the domains covered by the ICF-CY.


Mecobalamin and early functional outcomes of ischemic stroke patients with H-type hypertension.
To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension. From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months. After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05). Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.


Evaluation of a method for counting absolute numbers of cells with a flow cytometer.
We evaluated a method for performing absolute cell counts of lymphocyte populations with a flow cytometer. In this method, TruCount, test tubes that contain a known number of brightly fluorescent polystyrene beads are provided by the manufacturer. Whole anticoagulated blood is accurately pipetted into the tubes and mixed with fluorochrome-labeled monoclonal antibodies, the erythrocytes are lysed, and this mixture is analyzed on the flow cytometer. Absolute counts of lymphocyte subsets are calculated by determining the ratio of beads to the cell population of interest and then multiplying this ratio by the number of beads in the tube. We found this method to be reproducible. The values we obtained by the TruCount method were 5 to 10% higher than those obtained by conventional methods (flow cytometry and automated hematology) used to determine absolute numbers of cells. We believe that these differences are due to the methods of determining absolute cell counts and not to faulty identification of lymphocyte subsets.


Exploring Knowledge and Perceptions of Faculty Members about Authorship: A Study from Jordan.
Authorship has important implications and carries considerable responsibilities. The present study explored faculty members knowledge and perceptions of authorship at Jordanian universities. For this research a survey was distributed to faculty members at three major universities in Jordan. The study found that only 33% of the participants were aware about International Committee of Medical Journal Editors (ICMJE). In addition, the knowledge of the participants about basic principles of authorship was rated as medium. The number of research and level of ICMJE knowledge was found to exert a significant effect on commitment to authorship principle subscale score. Finally, the majority expressed good authorship believes that graduate students should be the lead authors on the publications that are derived from their thesis. Knowledge about authorship principles among faculty members in Jordan needs improvements.


A multi-residue method for pesticide residue analysis in rice grains using matrix solid-phase dispersion extraction and high-performance liquid chromatography-diode array detection.
Pesticides are widely used in rice cultivation, often resulting in detection of their residues in rice grains. So far, no analytical method has been available for the simultaneous determination of most rice pesticides in rice grains. This paper reports the development and validation of such a method for the determination of eight rice pesticides (penoxsulam tricyclazole, propanil, azoxystrobin, molinate, profoxydim, cyhalofop-butyl, deltamethrin) and 3,4-dichloroaniline, the main metabolite of propanil. Pesticide extraction and clean-up was performed by an optimized matrix solid-phase dispersion (MSPD) protocol on neutral alumina (5 g) using acetonitrile as the elution solvent. Samples were analyzed in a high-performance liquid chromatography-diode array detection (HPLC-DAD) system. Pesticide separation was achieved with a mobile phase of acetonitrile/water in a linear elution gradient from 30:70% (v/v) to 100:0% (v/v) in 14 min at a flow rate of 0.8 mL min(-1). Method validation was performed by means of linearity, intra-day accuracy, inter-day precision and sensitivity. Linear regression coefficients (R(2)) were always above 0.9948. Limits of detection (LOD) and quantification (LOQ) varied from 0.002 to 0.200 mg kg(-1) and 0.006 to 0.600 mg kg(-1), respectively. Recoveries were investigated at three fortification levels and were found to be acceptable (74-127%) with relative standard deviations (RSD) below 12%. Application of the method for the analysis of five commercial rice grain samples showed that the pesticide levels were below the LOD. Overall, the method developed is suitable for the determination of residues of most rice pesticides in rice grains at levels below the established MRLs.


Direct oral anticoagulants: an alternative treatment for thrombotic antiphospholipid syndrome?
Background Direct oral anticoagulants (DOACs) demonstrate a lower risk-benefit ratio than vitamin K antagonists (VKAs) for secondary thromboprophylaxis of thrombotic events. But there are no data on the efficacy of DOACs for the prevention of thrombotic recurrence in patients with antiphospholipid syndrome (APS). In this study, we evaluated the efficacy of DOACs to prevent recurrences of thrombotic events in patients with APS. Methods This was a single-center pilot, using a multi-step Fleming design. If seven or fewer patients presented treatment failure with rivaroxaban, the study could conclude efficacy. Results A total of 23 patients were included. APS involved the veins only ( n = 19), arteries only ( n = 2) or both ( n = 1) and 1 patient exhibited catastrophic antiphospholipid syndrome (CAPS). Overall, two patients were positive for lupus anticoagulant, anti-beta-2 glycoprotein I antibodies and anticardiolipid antibodies (triple positivity). The mean duration of follow up was 35.6 (range, 29-40) months. A total of six treatment failures were reported: one patient, with triple positivity, developed bilateral distal pulmonary embolism (PE) after 20 months of treatment with rivaroxaban, two patients refused to take rivaroxaban, the treatment was stopped in three other patients: two with adverse effects and one with chronic iron-deficiency anemia. Conclusions Rivaroxaban may represent an alternative for secondary thromboprophylaxis for thrombo-embolism in patients with APS, in particular, those with poor international normalized ratio (INR) control and those who are not at the highest risk of recurrent thrombosis, such as those with triple positivity.


Histamine release from blood of asthmatics.
A group of forty-two steroid-dependent perennial asthmatics was studied over a 13-week period incuding the 8 weeks of a double-blind controlled trial of oral sodium cromoglycate. Given at a dose of 200 mg four times per day the drug provided no significant benefit to the patients when compared with results for those on placebo. Blood from eleven patients consistently failed to release more than 25% of the total cellular histamine when challenged with a range of concentrations of antibody to IgE. All six of the cryptogenic (intrinsic) asthmatics in the trial fell within this group, together with 2/12 asthmatics with negative skin tests but suggestive clinical histories implicating common alergens, and 3/24 extrinsic asthmastics with positive skin prick tests. There was no correlation between drug usage and histamine release in response to challenge with antibody to IgE.


Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data.
Cortical surface-based analysis of fMRI data has proven to be a useful method with several advantages over 3-dimensional volumetric analyses. Many of the statistical methods used in 3D analyses can be adapted for use with surface-based analyses. Operating within the framework of the FreeSurfer software package, we have implemented a surface-based version of the cluster size exclusion method used for multiple comparisons correction. Furthermore, we have a developed a new method for generating regions of interest on the cortical surface using a sliding threshold of cluster exclusion followed by cluster growth. Cluster size limits for multiple probability thresholds were estimated using random field theory and validated with Monte Carlo simulation. A prerequisite of RFT or cluster size simulation is an estimate of the smoothness of the data. In order to estimate the intrinsic smoothness of group analysis statistics, independent of true activations, we conducted a group analysis of simulated noise data sets. Because smoothing on a cortical surface mesh is typically implemented using an iterative method, rather than directly applying a Gaussian blurring kernel, it is also necessary to determine the width of the equivalent Gaussian blurring kernel as a function of smoothing steps. Iterative smoothing has previously been modeled as continuous heat diffusion, providing a theoretical basis for predicting the equivalent kernel width, but the predictions of the model were not empirically tested. We generated an empirical heat diffusion kernel width function by performing surface-based smoothing simulations and found a large disparity between the expected and actual kernel widths.


Re-entrant transitions of locally stiff RNA chains in the presence of polycations leads to gelated architectures.
The liquid-liquid phase separation of protein and nucleic acid mixtures drives the formation of numerous membraneless compartments in cells. Temperature variation is commonly used for mapping condensate phase diagrams, which often display unique upper critical temperatures. Recent report on peptide-RNA mixtures has shown the existence of lower and upper critical solution temperatures, highlighting the importance of temperature-dependent solvent and ion-mediated forces. In the present work, we employ residue-level coarse-grained models of RNA and polycation peptide chains for simulating temperature-induced re-entrant transitions and shedding light on the role played by mobile ions, temperature-dependent dielectric permittivity, and local chain stiffness. We show that differences in bending rigidity can significantly modulate condensate topology leading to the formation of gelated or fibril like architectures. The study also finds that temperature dependence of water permittivity is generally sufficient for recapitulating experimentally observed closed loop and LCST phase diagrams of highly charged protein-RNA mixtures. However, we find that similar-looking closed-loop phase diagrams can correspond to vastly different condensate topologies.


Hepatocyte selection medium-enriched hepatocellular carcinoma cells are positive for α-fetoprotein and CD44.
Tissues surrounding hepatocellular carcinomas (HCCs) lack glucose. Hepatocyte selection medium (HSM) is deficient in glucose and is supplemented with galactose. HCC cells were cultured in HSM to investigate the stem cell markers α-fetoprotein (AFP) and cluster of differentiation 44 (CD44). HCC cells (HLF and PLC/PRF/5 cells) were cultured in HSM. Viable cell numbers were determined on days 0 and 7 following culture in HSM. RNA was isolated and subjected to reverse transcription-quantitative PCR (RT-qPCR) to analyze the mRNA expression levels of AFP and CD44. Immunostaining was performed to analyze the protein levels of AFP and CD44. The number of viable cells was significantly decreased on day 7 following culture in HSM. The expression levels of AFP and CD44 increased on day 7 as assessed using RT-qPCR. Immunostaining confirmed the results of RT-qPCR analysis. The number of viable HCC cells was decreased in HSM, whereas the expression levels of AFP and CD44 increased. Therefore, HSM is potentially useful for the enrichment of HCC cells with cancer stem cell characteristics.


Histiocytic medullary reticulosis: a report of four cases from India.
Four cases of histiocytic medullary reticulosis encountered between 1968 and 1972 at the All-India Institute of Medical Sciences Hospital, New Delhi, are reported. One of the cases was diagnosed during life and the other three postmortem. A complete remission was achieved in the former following prednisolone and cyclophosphamide therapy. The histological changes consisted of malignant histiocytosis with erythrophagocytosis in the organs of the reticuloendothelial system. The lymph nodes and the bone marrow were involved in all the cases. The importance of biopsy examination of these organs in making an early diagnosis is emphasised.


Clinical and molecular assessment of regorafenib monotherapy.
Regorafenib has shown survival benefits in metastatic colorectal cancer patients who were exacerbated after all standard therapies. Some patients, however, exhibit severe adverse events (AEs) resulting in treatment discontinuation. Therefore, the selection of patients likely to benefit from regorafenib is crucial. Twenty patients were treated with regorafenib for metastatic colorectal cancer; 122 plasma samples were taken from 16 of these patients for monitoring of circulating tumor DNA (ctDNA) in the blood. The treatment response, AEs, overall survival (OS), progression-free survival (PFS) and tumor morphologic changes on CT images were evaluated. KRAS mutant ctDNA was determined using digital PCR. Median PFS and OS were 2.5 and 5.9 months, respectively. Treatment was discontinued because of disease progression (PD) in 10 patients, and AEs in another 10 patients. AEs included hyperbilirubinemia, severe fatigue and skin rash. Hyperbilirubinemia was seen in two patients with multiple bilateral liver metastases, and severe fatigue in another 2 patients with poor performance status (PS). These severe AEs resulted in treatment discontinuation. Ten patients had a median PFS of 2.1 months with AE related discontinuation; PD occurred at 3.5 months (p=0.00334). Four patients exhibited a morphologic response, achieving better PFS times of 3.5, 5.3, 5.6 and 14.2 months. Emergence of the KRAS mutation in ctDNA was observed during anti-EGFR antibody treatment in 3 patients among 11 with KRAS wild-type tumors; it was detectable in the blood prior to radiographic detection of PD. Moreover, the KRAS mutation declined in two patients during regorafenib monotherapy. These patients were re-challenged with anti-EGFR antibody. Patients with extensive multiple liver metastases or poor PS are unlikely to benefit from regorafenib. Patients with a morphologic response will probably benefit from regorafenib with adequate management of other AEs. KRAS monitoring in ctDNA could be useful regarding treatment response and in determining treatment strategy.


The interaction between plant viroid-induced symptoms and RNA silencing.
A large body of evidence has lead to the suggestive proposal of a potential interplay between viroid-induced pathogenesis and RNA silencing regulatory mechanisms. A variety of techniques have been used to examine this interaction. This chapter outlines the use of a green fluorescent protein (GFP) sensor, containing viroid-specific sequence targets to study this phenomenon. In addition, a symptomatic transgenic line of Nicotiana benthamiana that expresses and processes Hop stunt viroid (HSVd) is used as stocks in grafting assays with the rdr6i-Nb lines, in which the RNA-dependent RNA polymerase 6 (NbRDR6) is constitutively silenced. The combination of the use of a viroid-specific GFP-sensor, the grafting assays with plants silenced for the RDR6 and the analysis of siRNAs allows to address how to monitor viroid-specific RNA silencing and how to associate this regulatory pathway with symptom expression.


Molecular typing of Shigella sonnei isolates circulating in Nanjing, China, 2007-2011.
Shigellosis is a major public health concern worldwide. This study intended to assess the baseline genotyping data among local Shigella sonnei strains spanning over five years. Fifty non-repeat clinical strains of S. sonnei isolated from stools of patients in different hospitals in Nanjing, China, were studied. Three subtyping tools, pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and multi-locus variable-number tandem-repeat (VNTR) analysis (MLVA), were used for routinely subtyping local S. sonnei. DNA sequencing only identified two sequence types (STs) among the 50 isolates in the MLST profiles, whereas PFGE and MLVA both showed suitable discriminatory power and yielded 19 and 30 different patterns, respectively. The major PFGE pattern comprised 21 strains isolated from different years. A total of four complexes were identified by MLVA, with the isolates differing by a single locus (single-locus variants). The S. sonnei strains circulating in Nanjing, China, in 2007-2011 originated from different clones with a degree of diversity. Most of the clones were closely related to each other. Overall, the strains were distinguishable by PFGE and MLVA. MLVA based on eight selected VNTR loci represented a more favorable degree of discrimination than did PFGE and may be a reliable complement for PFGE for routine subtyping of S. sonnei. The problems of MLST in subtyping regarding S. sonnei were also demonstrated.


Host defense against bacterial keratitis.
To define factors that protect the eye from Staphylococcus aureus keratitis and limit tissue damage once keratitis occurs. Rabbit tears were analyzed for bactericidal and phospholipase A(2) (PLA(2)) activities on S. aureus. Inhibition by spermidine of PLA(2) anti-staphylococcal activity in tears was tested in vitro and in vivo. Rabbits immunized with heat-inactivated alpha-toxin were challenged with intrastromal injection of S. aureus. Arachidonic acid was cleaved from S. aureus by purified PLA( 2) or rabbit tears. Spermidine inhibited these reactions in vitro and facilitated keratitis in vivo. PLA(2) activity decreased with advanced age and shortly following sleep, but increased with keratitis. Antibody to alpha-toxin significantly reduced corneal damage and epithelial cell sloughing during keratitis. PLA(2) is a major host-defense component of rabbit tears. Alpha-toxin is a major mediator of corneal damage, and antibody to alpha-toxin reduces pathologic changes during keratitis.


[HPA-5b neonatal allo-immune thrombocytopenia: two cases described in Tunisia].
Alloimmune thrombocytopenia is due to feto-maternal incompatibility in the HPA systems and is usually considered in the diagnosis of neonatal thrombocytopenia after other causes have been excluded. We report on two Tunisian observations of alloimmune neonatal thrombocytopenia due to anti-HPA-5b (Bra) antibodies. Two neonates presented at birth with a thrombocytopenic purpura unexplained by usual causes of neonatal thrombocytopenia. Alloimmune neonatal thrombocytopenia was diagnosed by the determination of parental and neonatal platelets antigens phenotypes and by the presence of HPA-5b (antiBra) antibodies in maternal sera. A favourable evolution was obtained after maternal platelet transfusions. Alloimmune neonatal thrombocytopenia is a serious affection, which exposes to intracranial haemorrhage. These observations of HPA-5 neonatal alloimmunisation in Tunisia provide additional information on the geographic distribution of the disease and its prognosis.


The allometry of cellular DNA and ribosomal gene content among microbes and its use for the assessment of microbiome community structure.
The determination of taxon-specific composition of microbiomes by combining high-throughput sequencing of ribosomal genes with phyloinformatic analyses has become routine in microbiology and allied sciences. Systematic biases to this approach based on the demonstrable variability of ribosomal operon copy number per genome were recognized early. The more recent realization that polyploidy is probably the norm, rather than the exception, among microbes from all domains of life, points to an even larger source bias. We found that the number of 16S or 18S RNA genes per cell, a combined result of the number of RNA gene loci per genome and ploidy level, follows an allometric power law of cell volume with an exponent of 2/3 across 6 orders of magnitude in small subunit copy number per cell and 9 orders of magnitude in cell size. This stands in contrast to cell DNA content, which follows a power law with an exponent of ¾. In practical terms, that relationship allows for a single, simple correction for variations in both copy number per genome and ploidy level in ribosomal gene analyses of taxa-specific abundance. In biological terms, it points to the uniqueness of ribosomal gene content among microbial properties that scale with size. Video Abstract.


Course of employment in adults with cerebral palsy over a 14-year period.
To explore the course of employment in adults with cerebral palsy (CP) over 14 years, and to identify subgroups at risk for unemployment. Sixty-five adults with CP (33 males, 32 females; baseline age 25y 8mo, standard deviation [SD] 3y 2mo; intellectual impairment 25%; bilateral CP 65%) participated in a prospective cohort study. Self-reports of employment and work hours per week in 1996, 2000, and 2010 were documented. The course of employment (including sheltered work) and work hours per week were analysed, using generalized estimating equations (GEE). Overall, employment rate was stable over time (38-45%, p=0.413), but lower than in the general population (75-86%, p<0.001). Employment rates were specifically low in adults with intellectual impairment, bilateral CP, and in adults with Gross Motor Function Classification System (GMFCS) levels IV and V. Work hours per week declined (35.0 [SD 7.9] to 31.2 [SD 10.3], p=0.033), especially among females (32.3 [SD 6.4] to 23.4 [SD 7.4], p<0.001). Similar to the general population, females often worked part-time. Employment was low compared with the general population, but remained stable in the long term; however, work hours per week decreased. Adults with intellectual impairment, bilateral CP, and GMFCS levels IV and V are subgroups at risk for unemployment.


NMC consultation on proficiencies to be met for registration.
Emeritus Professor Alan Glasper, from the University of Southampton, discusses the Nursing and Midwifery Council's public consultation on the efficacy of its new draft standards for pre-registration nursing education.


[How to distinguish science from non science].
The questions discussed in this article concern the demarcation between scientific theories and non scientific theories. The problem is not only an epistemological one, but it implies also ethical and social consequences. For example, is it acceptable for an European country to allow the practice of non-traditional medicines which are not yet considered officially as scientific? According to Karl Popper, the author discusses the following points: 1. Is there a logical asymmetry between the verification and the falsification of a theory? 2. The criterion of falsifiability demarcates science from non-science. 3. There is no automatic method to find new theories. 4. The facts of science are discovered by scientists through theories. 5. The scientific method is only one and it consists of these three steps: problems-theories-refutations. The article's core is that the rational physician is the one who kills (falsifies) his own diagnosis instead of his own patients.


Mevalonic acid kinase in Euglena gracilis.
The isolation and partial purification of mevalonic acid kinase from Euglena gracilis is described. The product of the reaction MVA-5-P has been characterized by paper chromatography. The apparent Km values for l-mevalonic acid, ATP, and Mg(2+) are 3 x 10(-5)m, 6 x 10(-3)m, and 9 x 10(-3)m, respectively. A concentration of 1 x 10(-3)mp-hydroxymercuribenzoate completely inactivates the enzyme. A distribution study has shown that mevalonic acid kinase is present in most higher plants and the algae Euglena gracilis and Chlamydomonas. No enzymatic activity could be detected in several species of photosynthetic bacteria or blue-green algae.


Contributions of social influences and psychopathological factors to cannabis use and dependence in high-school students.
To evaluate the relative contributions of peers cannabis use or non use, parental approval of such use, adolescents' own beliefs about use, self-esteem, and depressive and symptoms of borderline personality disorder, in the prediction of cannabis use and dependence. Participants were 257 high-school students who completed questionnaires assessing cannabis use frequency, cannabis dependence, the number of peers using cannabis, the number of peers opposed to cannabis use, parental attitude toward cannabis use, participants' attitude toward use, self-esteem, depressive and borderline symptomatology. Logistic regression analyses were conducted to predict cannabis use, daily use and dependence. The number of peers using cannabis, participants' approval of cannabis use, and the intensity of symptoms of borderline personality disorder were risk factors for use whereas the number of peers opposed to cannabis use was a protective factor. Parental attitudes toward use and participants' depressive symptomatology were not significant independent predictors of use. There were no significant predictors of probable cannabis dependence. To inform adolescents that a significant proportion of them disapprove of cannabis use may be an effective component of prevention of use. Symptoms of borderline personality disorder may account for the association between depression and cannabis use. The social influences and psychopathological factors evaluated in this study did not appear to play a major role in the development of cannabis dependence.


Does vaginal pH affect the efficacy of dinoprostone in cervical ripening/labor duration?
Prostaglandins are effective in the ripening of the cervix and facilitating labor induction. Vaginal pH is probably an important factor in the effectiveness of vaginal prostaglandins. The aim of this study was to evaluate the effect of vaginal pH on the function of prostaglandin vaginal tablet during labor. This is a double-blinded clinical trial study of 147 pregnant primigravid trated in the Yahyanejad Hospital of Babol (Iran) from January 2006 to December 2007. Initial pH was measured during vaginal examination with nitrazin paper and the Bishop score was determined. All women received vaginal dinoprostone inserted in the posterior fornix of the vagina for cervical ripening and the second dose was administered if the uterine contractions were inadequate. Reassessment of the Bishop score after 12 hours, duration of latent and active phases, and also the duration of the second stage of labor were compared between the two groups with low or high vaginal pH. The incidence of Cesarean section was lower in women with high vaginal pH but was not statistically significant. The Bishop score after 12 hours, latent phase, and second stage durations were not different in the two groups of high or low vaginal pH, but active phase duration in patients with high pH was significantly shorter than those with low pH (p = 0.019). High vaginal pH influences the function of prostaglandin tablet as a reduction in duration of the active phase of labor.


[Mechanism of acetate accumulation during sludge anaerobic digestion].
To investigate the organic carbon metabolism during sludge anaerobic digestion and to clarify the mechanism of acetate accumulation. We Used inhibitors 2-bromoethanesulfonate (BES) and chloroform (CHCl3) to block the methanogesis to investigate the accumulation of various fermentation intermediates. We determined the bacterial number of homoacetogen and syntrophic acetogen and calculated the thermodynamics of the acetogenesis reaction to identify the directions of organic carbon metabolism and acetate accumulation during sludge anaerobic digestion. With the addition of BES, the acetate concentration was 27 mmol/L, the gene copy number of fhs was 2-3 folds of the control group and the number of sytroph acetogen was slightly decreased. In the group of chloroform addition, the acetate was 22 mmol/L, while the copy number of fhs gene was one order of magnitude lower than that in the BES model. The two inhibitors lead to acetate accumulation from the anaerobic digestion of sludge. BES inhibited the methanogen and had no effect on other anaerobic acetogens. The accumulation of the acetate came from the hydrolysis acidogenesis, homoacetogenesis and syntrophic acetogenesis. Chloroform inhibited not only methanogen but also the homoacetogen and syntrophic acetogen severely. The acetate accumulation mainly came from the hydrolysis acidogenesis fermentation.


Leveraging the Role of the Metastatic Associated Protein Anterior Gradient Homologue 2 in Unfolded Protein Degradation: A Novel Therapeutic Biomarker for Cancer.
Effective diagnostic, prognostic and therapeutic biomarkers can help in tracking disease progress, predict patients' survival, and considerably affect the drive for successful clinical management. The present review aims to determine how the metastatic-linked protein anterior gradient homologue 2 (AGR2) operates to affect cancer progression, and to identify associated potential diagnostic, prognostic and therapeutic biomarkers, particularly in central nervous system (CNS) tumors. Studies that show a high expression level of AGR2, and associate the protein expression with the resilience to chemotherapeutic treatments or with poor cancer survival, are reported. The primary protein structures of the seven variants of AGR2, including their functional domains, are summarized. Based on experiments in various biological models, this review shows an orchestra of multiple molecules that regulate AGR2 expression, including a feedback loop with p53. The AGR2-associated molecular functions and pathways including genomic integrity, proliferation, apoptosis, angiogenesis, adhesion, migration, stemness, and inflammation, are detailed. In addition, the mechanisms that can enable the rampant oncogenic effects of AGR2 are clarified. The different strategies used to therapeutically target AGR2-positive cancer cells are evaluated in light of the current evidence. Moreover, novel associated pathways and clinically relevant deregulated genes in AGR2 high CNS tumors are identified using a meta-analysis approach.


Myosin transitions in developing fast and slow muscles of the rat hindlimb.
Myosin isozymes from the slow soleus and fast EDL muscles of the rat hindlimb were analyzed by pyrophosphate gel electrophoresis, by peptide mapping of heavy chains, and by antibody staining. At the earliest stage examined, 20 days gestation, distinctions between the developing fast and slow muscles were seen by all these criteria; all fibers in the distal hindlimb reacted strongly with antibody to adult fast myosin. Some fibers also reacted with antibody to adult slow myosin; these fibers had a precise, axial distribution in the hindlimb. This pattern of staining which includes the entire soleus, foreshadows the adult distribution of slow fibers and may indicate that the specific pattern of innervation of the limb is already determined. In the early developing soleus there are four fetal and neonatal isozymes plus two isozymes present in equal proportions in the 'slow' area of the pyrophosphate gel. The mobility of these two slow isozymes decreases with maturity and the slowest moving isozyme gradually becomes the dominant species. Thus early diversity between the soleus and EDL is expressed by myosins which are distinct from the mature isozymes. The relative proportion of slow isozymes significantly increases with development and as this occurs the fetal and neonatal isozymes are progressively eliminated. Transiently at least one mature fast isozyme appears in the soleus. This is present at 15 days postpartum and probably correlates with the population of fast, type II fibers, which comprise 50% of this muscle cell population at 15 days. The EDL contained three fetal and neonatal isozymes and only one slow isozyme which does not change in mobility with age.(ABSTRACT TRUNCATED AT 250 WORDS)


Principles of managing children with asthma in the emergency department.
INTRODUCTION: Paediatric asthma exacerbations comprise a significant portion of emergency department (ED) visits and hospitalizations. Recognition of diagnostic symptoms and signs, and timely use of appropriate medications may reduce the need of hospitalizations and the impact of this disease on the lives of children and their families. OBJECTIVE: To review the pathophysiology of asthma, the current recommendations for conventional medical treatment in the ED, the controversies surrounding adjunct therapies, and the importance of discharge planning and follow-up. CONCLUSIONS: Paediatric asthma exacerbations may be successfully treated in the ED with the use of appropriate inhaled and systemic medications.


Is ethanol a pro-drug? Acetaldehyde contribution to brain ethanol effects.
This article presents the proceedings of a symposium at the 2004 meeting of the International Society for Biomedical Research on Alcoholism, held in Mannheim, Germany. The symposium was organized by Etienne Quertemont and chaired by C. J. Peter Eriksson. The presentations were (1) Brain ethanol metabolism and its behavior consequences, by Sergey M. Zimatkin and P. S. Pronko; (2) Acetaldehyde increases dopaminergic neuronal activity: a possible mechanism for acetaldehyde reinforcing effects, by Marco Diana and Milena Pisano; (3) Contrasting the reinforcing actions of acetaldehyde and ethanol within the ventral tegmental area (VTA) of alcohol-preferring (P) rats, by Zachary A. Rodd and Richard R. Bell; (4) Molecular and biochemical changes associated with acetaldehyde in human alcoholism and alcohol abuse, by C. J. Peter Eriksson.


Observations of human behavior influencing the use of insecticide-impregnated bednets to control malaria in Sabah, Malaysia.
Observational and survey methodologies were used to probe human behavioral factors influencing the use of insecticide-impregnated bednets to control malaria in rural Sabah, Malaysia. One aim was to investigate why a field trial of such nets in an interior area yielded disappointing results. A second aim was to gather baseline data prior to a field trial proposed for a coastal area. Interior villagers reported a significantly higher net usage rate than that observed directly, suggesting that subject self-reports need to be validated in some way. The poor results of the interior field trial appeared related to reluctance to regularly use nets, which were not in wide use previously. Prospects for reducing malaria transmission through bednets appeared better for the coastal area since nearly half of observed villagers were sleeping in them. However, significantly more coastal than interior villagers were observed watching television at night, an activity that may increase malaria risk by keeping villagers awake and out of bednets.


From teratocarcinomas to embryonic stem cells.
The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so-called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem-cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential.


Closing Post-orthodontic Spaces Between Anterior Teeth Using Sequential 3D-printed Direct Composite Injection Guides.
Restorative treatment of anterior teeth is sometimes required to improve esthetic and functional occlusal outcomes of orthodontic therapy. This case report presents a direct, noninvasive approach to close post-orthodontic gaps in anterior teeth using a 3D-printed composite resin injection guide with a full digital workflow. The composite injection technique using 3D-printed guides is a full digital workflow that can transfer the design precisely, save chair time, and simplify the direct composite restoration procedure.


Genetic Associations and Interactions Between the NR3C1 (GR) and NR3C2 (MR) Genes and Aggressive Behavior in a Central South Chinese Han Population.
The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play important roles in the hypothalamic-pituitary-adrenal axis and stress regulation. The current study aimed to address the genetic association and gene-gene interactions between GR and MR gene polymorphisms and aggressive behavior. A haplotype-based, case-control study was designed to examine the association between human MR and GR genes and aggressive behaviors, including robbery and intentional interpersonal injury, in a central south Chinese Han population. Eight well-studied polymorphisms of the MR gene (rs2070951, rs2871, rs5522, and rs5525) and the GR gene (rs10482605, rs6190, rs1800445, and rs6196) were genotyped using SNaPshot. The MR and GR gene polymorphisms were not associated with aggressive behaviors, including in robbery and intentional interpersonal injury subgroups (p > 0.05). The frequency of haplotype TAAT of GR was significantly higher in the control group than that in the case group (p = 0.004, padj = 0.02). In addition, a two-way interaction between GR rs1800445 and MR rs2070951 and aggressive behavior was also found (p = 0.01). The haplotype TAAT of GR might be a protective factor against aggressive behavior, while gene-gene interactions between GR rs1800445 and MR rs2070951 might be a risk factor for aggressive behavior in the Central South Chinese Han population.


UHRF2 promotes intestinal tumorigenesis through stabilization of TCF4 mediated Wnt/β-catenin signaling.
Intestinal tumors mainly originate from transformed crypt stem cells supported by Wnt signaling, which functions through downstream critical factors enriched in the intestinal stem/progenitor compartment. Here, we show Uhrf2 is predominantly expressed in intestinal crypts and adenomas in mice and is transcriptionally regulated by Wnt signaling. Upregulated UHRF2 correlates with poor prognosis in colorectal cancer patients. Although loss of Uhrf2 did not affect intestinal homeostasis and regeneration, tumor initiation and progression were inhibited, leading to a markedly prolonged life span in Uhrf2 null mice on an ApcMin background. Uhrf2 deficiency also strongly reduced primary tumor organoid formation suggesting impairment of tumor stem cells. Moreover, ablation of Uhrf2 suppressed tumor cell proliferation through downregulation of the Wnt/β-catenin pathway. Mechanistically, Uhrf2 directly interacts with and sumoylates Tcf4, a critical intranuclear effector of the Wnt pathway. Uhrf2 mediated SUMOylation stabilized Tcf4 and further sustained hyperactive Wnt signaling. Together, we demonstrate that Wnt-induced Uhrf2 expression promotes tumorigenesis through modulation of the stability of Tcf4 for maintaining oncogenic Wnt/β-catenin signaling. This is a new reciprocal feedforward regulation between Uhrf2 and Wnt signaling in tumor initiation and progression.


[Non-iodine-absorbing metastasis of differentiated thyroid cancer--therapeutic probe with 13-cis retinoic acid].
The absence of iodine uptake in metastases of differentiated thyroid carcinoma makes them unresponsive to treatment with radioiodine 131I. In many of such cases symptomatic treatment remains the only available therapy. The results of studies on partial redifferentiation of metastases of thyroid cancer achieved after cis-retinoid acid therapy have drawn attention to the possibility of restoration of iodine uptake in metastases after pretreatment with cis-retinoic acid (Roaccutane). 5 patients with iodine uptake-negative metastases of differentiated thyroid carcinoma were given Roaccutane in a dose 1.5 mg/kg/24 h daily for 6 weeks before the therapy with radioiodine. In none of the patients restoration of radioiodine uptake in metastases has occurred as shown in post-therapeutic total body scintigraphy.


Mitral valve prosthesis for correction of mitral regurgitation in a dog.
Mitral regurgiation with atrial fibrillation in a 3-year-old St. Bernard dog was corrected by digitalization, placement of a mitral valve prosthesis, and direct current cardioversion. The atrial fibrillation eventually returned and became refractory to cardioversion.


Laparoscopic Sacrocolpopexy Plus Colporrhaphy With a Small Intestine Submucosa Graft Versus Total Pelvic Floor Reconstruction for Advanced Prolapse: A Retrospective Cohort Study.
Transvaginal mesh (TVM) results in a greater anatomic cure but more complications. We aimed to compare laparoscopic sacrocolpopexy (LSC) plus colporrhaphy with the small intestine submucosa (SIS) graft versus TVM for advanced pelvic organ prolapse (POP). Patients with advanced POP who underwent LSC plus colporrhaphy with the SIS graft or TVM at a center between September 2015 and November 2016 were studied. Anatomical outcomes were evaluated using POP quantification. Functional outcomes related to POP and sexual life were evaluated using the Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12). Data regarding surgical procedures and patient demographic variables were recorded. Chi-square and Student t -tests were used for 2 independent samples. A total of 76 patients were enrolled in this study with 26 patients in the LSC plus colporrhaphy with the SIS graft group (group A) and 50 patients with TVM group (group B). All patients in both groups demonstrated significant improvement in anatomical outcomes (P<0.05) after surgery. PFDI-20 scores were significantly improved 12 months after operation in both groups (P<0.001). PISQ-12 scores were significantly improved in patients after surgery, especially patients in group A (P<0.001). Mesh exposure occurred in both groups as follows: 8 patients (30.7%) in group A and 5 patients (10%) in group B. Even though both surgeries showed excellent results for subjective and objective outcomes, the use of an SIS graft might increase the exposure of polypropylene mesh. We do not recommend LSC plus colporrhaphy with the SIS graft for advanced multiple-compartments prolapse.


Investigating Neurologic Improvement After IV Thrombolysis: The Effect of Time From Stroke Onset vs Imaging-Based Tissue Clock.
Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time. Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90. Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5 hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/p = 0.03), whereas early treatment window did not modify the effect of IVT. CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved.


A compression force comparison study among three staple fixation systems.
Traditional staples have recently been redesigned with both new materials and engineering techniques to facilitate interfragmentary compression in theory, resulting in greater friction between bone fragments to counteract shearing forces. In the current study, the biomechanical properties of 3 different staples were investigated. The interfacial force at 2 different sites within a calcaneal bone model was measured after insertion and activation of the OSStaple, the UNI-CLIP, and the Smith and Nephew Standard Large Staple after precompression with the SYNTHES Small Distractor. Additionally, the ability of each staple to maintain compression over a short period of time was investigated. In the current bench study, the OSStaple consistently generated the greatest and most uniform compression across the bone model osteotomy and was also capable of sustaining the compression over the duration of all of the trials.


Determination of Residues of Phenicol Drugs in Ayu (Plecoglossus altivelis) by LC-MS/MS.
An analytical method for the determination of residues of 3 phenicol drugs (chloramphenicol, thiamphenicol and florfenicol) in Ayu (Plecoglossus altivelis) by LC-MS/MS was developed. We used the whole body of Ayu, including the bones and internal organs, in addition to muscle. Phenicols were extracted with 90% acetonitrile and an aliquot of the crude extract was cleaned up on a Florisil column (2 g), followed by defatting with n-hexane. The acetonitrile extract was evaporated and the solvent was replaced with phosphate buffer, then the extract was purified on a hydroxylated styrene-divinylbenzene copolymer column (200 mg). Finally, sample solution was passed through a deproteination cartridge filter with a lipid removal function. Chloramphenicol was quantitated by means of a calibration curve corrected with salogate standard (chloramphenicol-d5) and thiamphenicol and florfenicol were quantitated based on absolute calibration curves. This method was validated in accordance with the notification of the Ministry of Health, Labour and Welfare of Japan. As a result of the validation study, the trueness, repeatability and within-laboratory reproducibility were 85-103, 5-13 and 8-13%, respectively. This method is useful for inspecting residues of 3 phenicol drugs in whole body of Ayu efficiently. Moreover, when chloramphenicol and thiamphenicol are detected by this method, the quantitated value is applicable to decide the compliance of the sample with the specifications and standards of the Food Sanitation Law.


[Outpatient clinic for abnormal uterine blood loss: diagnosis and treatment in one visit].
Many women aged 40-55 years suffer from abnormal uterine bleeding or heavy menstrual bleeding. Not all general practitioners and specialists, however, are aware of the developments in diagnostic and therapeutic possibilities for abnormal uterine bleeding. We present 3 patients with heavy menstrual bleeding who were treated at our one-stop clinic. In one patient, a 45-year-old woman, a small fibroid was removed with a Twizzle bipolar electrode. The second patient, a 47-year-old woman, opted for an endometrial ablation which was performed directly under local anaesthesia. The third patient, a 42-year-old woman, had an endometrial polyp removed with a duckbill snare. The clinic for diagnosis and therapy in one consult has advantages for the patient. Today, technological advances in instruments and equipment have made it possible to treat many types of intracavitary abnormalities directly in the ambulatory setting, for example, the resection of small fibroids or intrauterine polyps and use of the second-generation endometrial ablation technique.


Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018.
To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.


HLA antigens in patients with giant cell arteritis, compared with two control groups of different ages.
The prevalence of 39 HLA antigens of series A, B and C was determined in 63 patients with Giant cell arteritis. In 44 patients the diagnosis was established by means of temporal artery biopsy and in 19 it was based on clinical criteria. The prevalence of the antigens was compared with that in two control groups of different ages. No significantly increased antigen prevalence was seen in our patients, as compared with controls. There were no differences in the prevalence of HLA antigens between groups of patients with different clinical forms of GCA. Nor was any difference in the prevalence of HLA antigens found between younger and older healthy individuals.


[Observation on therapeutic effect of comprehensive therapy on optic atrophy complicated by cerebral palsy].
To assess therapeutic effect of combined treatment of Chinese medicine and western medicine on optic atrophy complicated by cerebral palsy. One hundred and seventeen cases were divided into an observation group (n = 79) and a control group (n = 38). The control group were treated with routine western medicine treatment including neurotrophic drugs and high pressure oxygen, etc. and the observation group with acupuncture at Ganshu (BL 18), Pishu (BL 20), Chengqi (ST 1), etc. and injection of 0.2-0.3 mL Compound Danshen Injectio into Qiuhou (EX-HN 7), on the basis of the same treatment of western medicine as that in the control group. Fundus examination and the tracing body angle detection were conducted before and after treatment and the therapeutic effects were assessed in the two groups. The total effective rate was 91.1% in the observation group and 60.5% in the control group with a significant difference between the two groups (P < 0.001); after treatment the angle of tracing body significantly increased in the two groups (P < 0.01) with the observation group better than the control group (P < 0.01). The combined treatment of Chinese medicine and western medicine is an effective therapy for optic atrophy complicated by cerebral palsy.


Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level.
Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression. Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses. We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02). Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential.


Anti-proliferative potential of Glucosamine in renal cancer cells via inducing cell cycle arrest at G0/G1 phase.
Renal cell carcinoma (RCC) is one of the most common types of cancer in urological system worldwide. Recently, the anticancer role of Glucosamine has been studied in many types of cancer. The aim of this study was to investigate the effects of Glucosamine on RCC. The effects of Glucosamine on RCC cell proliferation and apoptosis were investigated by MTT assay and Annexin V-FITC Apoptosis assay, respectively in vitro. Cell cycle was detected by flow cytometry after treatment with Glucosamine. Protein levels of several cell cycle associated markers were examined by Western Blot. Our data showed that Glucosamine significantly inhibited the proliferation of renal cancer 786-O and Caki-1 cells in a dose-dependent manner. Besides, Glucosamine treatment resulted in cell cycle arrest at G0/G1 phase in both cell lines. Meanwhile, the expression of several regulators that contribute to G1/S phased transition, such as Cyclin D1, CDK4 and CDK6, were significantly down-regulated with the up-regulation of cell cycle inhibitors, p21 and p53, after treatment with glucosamine. However, the apoptosis rate of RCC cells was down-regulated when treatment with Glucosamine at 1 mM and 5 mM, while up-regulated at 10 mM. Our findings indicated that Glucosamine inhibited the proliferation of RCC cells by promoting cell cycle arrest at G0/G1 phase, but not promoting apoptosis. The present results suggested that Glucosamine might be a potential therapeutic agent in RCC treatment in the future.


Evolving educational objectives of library schools.
Library school objectives are characterized in terms of research, teaching, and student recruitment. The absence of a theoretical framework for much of what is being taught, the small amount of research in library schools, and the shortage of library school teachers are cited as major problems of library schools. Increased interest in the problems of librarianship by researchers in other areas, higher salaries for library school teachers and beginning librarians, and increased financial support for research and scholarships are given as encouraging signs of progress toward the solution of these problems.