Chewing on the trees: Constraints and adaptation in the evolution of the primate mandible.
Chewing on different food types is a demanding biological function. The classic assumption in studying the shape of feeding apparatuses is that animals are what they eat, meaning that adaptation to different food items accounts for most of their interspecific variation. Yet, a growing body of evidence points against this concept. We use the primate mandible as a model structure to investigate the complex interplay among shape, size, diet, and phylogeny. We find a weak but significant impact of diet on mandible shape variation in primates as a whole but not in anthropoids and catarrhines as tested in isolation. These clades mainly exhibit allometric shape changes, which are unrelated to diet. Diet is an important factor in the diversification of strepsirrhines and platyrrhines and a phylogenetic signal is detected in all primate clades. Peaks in morphological disparity occur during the Oligocene (between 37 and 25 Ma) supporting the notion that an adaptive radiation characterized the evolution of South American monkeys. In all primate clades, the evolution of mandible size is faster than its shape pointing to a strong effect of allometry on ecomorphological diversification in this group.


Ligand-induced 5-HT3 receptor internalization in enteric neurons in rat ileum.
Release of 5-hydroxytryptamine (5-HT) from mucosal enterochromaffin cells and activation of 5-HT(3) receptors (5-HT(3)Rs) on neurons in the gut wall is important in the response of the gut to the luminal environment. Intestinal inflammation is associated with increased levels of mucosal 5-HT. The aims of the study were to determine the following: (1) if 5-HT(3)R undergoes ligand-induced internalization in myenteric neurons, and (2) the effect of long-term increase of mucosal 5-HT on 5-HT(3)Rs. Acute effects of exogenous 5-HT or endogenous release of 5-HT by luminal glucose on cellular localization of 5-HT(3)Rs was determined by immunohistochemistry and confocal microscopy. Treatment with the serotonin re-uptake inhibitor, fluoxetine, for 6 days (20 mg/kg daily orally) was used to increase mucosal 5-HT chronically in rats. Net ileal fluid movement was measured in anesthetized rats by the weight change of a 2.5% agarose cylinder. Acute increases in 5-HT induced by exogenous or endogenous 5-HT decreased 5-HT(3)R immunoreactivity at the neuronal cell membrane by 70% and 60%, respectively. Chronic fluoxetine treatment increased mucosal levels of 5-HT and decreased membrane 5-HT(3)R immunoreactivity by 27%. Net fluid absorption was decreased by a 5-HT(3)R agonist or by luminal glucose; this was attenuated 88% and 99%, respectively, by fluoxetine treatment. Long-term increase in 5-HT in the intestinal mucosa results in increased 5-HT(3)R internalization in myenteric neurons. Chronic changes in mucosal 5-HT may alter gastrointestinal secretory and motor function via ongoing loss of receptor from neuronal membrane, causing a mismatch between luminal content and absorption.


A Novel Oxidative Stress Mediator in Acute Appendicitis: Thiol/Disulphide Homeostasis.
Aim. To investigate the role of a novel oxidative stress marker, thiol/disulphide homeostasis, in patients diagnosed with acute appendicitis (AA). Methods. In this study, seventy-one (43 male and 28 female) patients diagnosed with AA and 71 (30 male and 41 female) healthy volunteers were included. Age, gender, body mass index (BMI), haemoglobin (Hb), white blood cell (WBC), c-reactive protein (CRP), and thiol/disulphide homeostasis parameters (native thiol, total thiol, disulphide, disulphide/native thiol, native thiol/total thiol, and disulphide/total thiol ratios) were compared between the groups. Thiol/disulphide homeostasis was determined by a newly developed method by Erel and Neselioglu. Results. The native thiol, total thiol, and the native thiol/total thiol ratio levels were statistically significantly decreased in the AA compared with the control group (p < 0.001). Disulphide level and the ratios of disulphide/native thiol and disulphide/total thiol were higher in the AA group than in the control group (p < 0.001). There was a negative correlation of CRP with native thiol, total thiol, and native thiol/total thiol ratio while there was a positive correlation of CRP with disulphide/native thiol and disulphide/total thiol in the AA group. In the stepwise regression model, risk factors as disulphide/native thiol (OR = 1.368; p = 0.018) and CRP (OR = 1.635; p = 0.003) were determined as predictors of perforated appendicitis compared to the nonperforated group. Conclusion. This is the first study examining the thiol/disulphide homeostasis as a diagnostic aid in AA and establishing thiol/disulphide homeostatis balance shifted towards the disulphide formation due to thiol oxidation. Further studies are needed to optimize the use of this novel oxidative stress marker in AA.


TP induces hepatic intolerance to FasL-mediated hepatocyte apoptosis by inhibiting XIAP.
Triptolide (TP) is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF). Its severe toxic side effects, especially hepatotoxicity, have limited the clinical application of TP-related drugs. In this study, we investigated the mechanism of the hepatotoxic effects of TP from the perspective that TP inhibited the expression of the pro-survival protein X-linked inhibitor of apoptosis protein (XIAP) and enhanced FasL-mediated apoptosis of hepatocytes. TP and CD95/Fas antibody (Jo-2) were administered by gavage to C57BL/6 mice for 7 consecutive days. After co-administration of TP and Jo-2, mouse livers showed large areas of necrosis and apoptosis and significantly increased Caspase-3 activity. KEGG pathway enrichment analysis indicated that TP may cause the development of liver injury through the apoptotic signaling pathway. Proteinprotein interaction networks showed that XIAP played an essential role in this process. TP reduced the protein expression of XIAP after combination treatment with Jo-2/FasL in vivo/in vitro. TP and FasL co-stimulation significantly increased microRNA-137 (miR-137) levels in AML12 cells, while inhibition of miR-137 expression induced a rebound in XIAP protein expression. In conclusion, TP presensitizes hepatocytes and enhances the sensitivity of hepatocytes to the Fas/FasL pathway by inhibiting the protein expression of XIAP, leading to hepatocyte apoptosis.


What influences home delivery among women who live in urban areas? Analysis of 2014 Ghana Demographic and Health Survey data.
In Ghana, home delivery among women in urban areas is relatively low compared to rural areas. However, the few women who deliver at home in urban areas still face enormous risk of infections and death, just like those in rural areas. The present study investigated the factors associated with home delivery among women who live in urban areas in Ghana. Data for this study was obtained from the 2014 Ghana Demographic and Health Survey. We used data of 1,441 women who gave birth in the 5 years preceding the survey and were dwelling in urban areas. By the use of Stata version 14.2, we conducted both descriptive and multivariable logistic regression analyses. We found that 7.9% of women in urban areas in Ghana delivered at home. The study revealed that, compared to women who lived in the Northern region, women who lived in the Brong Ahafo region [AOR = 0.38, CI = 0.17-0.84] were less likely to deliver at home. The likelihood of home delivery was high among women in the poorest wealth quintile [AOR = 2.02, CI = 1.06-3.86], women who professed other religions [AOR = 3.45; CI = 1.53-7.81], and those who had no antenatal care visits [AOR = 7.17; 1.64-31.3]. Conversely, the likelihood of home delivery was lower among women who had attained secondary/higher education [AOR = 0.30; 0.17-0.53], compared to those with no formal education. The study identified region of residence, wealth quintile, religion, antenatal care visits, and level of education as factors associated with home delivery among urban residents in Ghana. Therefore, health promotion programs targeted at home delivery need to focus on these factors. We also recommend that a qualitative study should be conducted to investigate the factors responsible for the differences in home delivery in terms of region, as the present study could not do so.


[Detection of longitudinal electric currents in frog nerves].
The data on transversal potential difference (V-x) in the sciatic nerve of a frog under the influence of the magnetic field are presented. The amplitude of the registered signal has a linear rise with an increase of the magnetic field tension. (H), while a change of (H) direction leads to a change of polarity of the signal (V-x). The presence of (V-x) is connected with the existence of the longitudinal directed stream of the light charged particles in the nerve.


Use of self home-made diaphragm for protection against pregnancy and sexually-transmitted infections: case report.
This is a case report of a 44-year-old woman who used a home-made diaphragm for 16 years to protect herself from pregnancy and sexually-transmitted infections. The woman stitched a piece of cloth with folded polythene inside. This case report provides a vivid illustration of the limitations of available methods of protection for women. It consists of an introduction to the topic, a description of her experiences using her home-made diaphragm and a discussion of the significance of the case. This report supports the need for additional research on female-controlled methods of protection against sexually-transmitted infections, methods that can be used without male knowledge and co-operation, such as vaginal microbicides and cervical barriers against infection, including the diaphragm.


The Characterization and Study of Antibacterial, Free Radical Scavenging, and Anticancer Potential of Livistona chinensis-Mediated Silver Nanoparticles.
In the present research, Livistona chinensis leaf extracts were utilized as reductants to bio-fabricate silver nanoparticles (LC-AgNPs) and this was followed by the evaluation of their antioxidant, antibacterial, and anticancer potential. Multiple parameters were optimized for the formation and fidelity of LC-AgNPs. The color shift of the reaction mixture from yellow to dark brown confirmed the LC-AgNPs formation. UV/VIS spectroscopy exhibited a surface plasmon resonance (SPR) band at 436 nm. The Fourier transform infrared (FTIR) spectroscopy spectrum depicted phytochemicals in the plant extract acting as bio-reducers for LC-AgNPs synthesis. The XRD pattern confirmed the presence of LC-AgNPs by showing peaks corresponding to 2θ angle at 8.24° (111), 38.16° (200), 44.20° (220), and 64.72° (311). Zetasizer analysis exhibited size distribution by intensity of LC-AgNPs with a mean value of 255.7 d. nm. Moreover, the zeta potential indicated that the AgNPs synthesized were stable. The irregular shape of LC-AgNPs with a mean average of 38.46 ± 0.26 nm was found by scanning electron microscopy. Furthermore, the antioxidant potential of LC-AgNPs was examined using a DPPH assay and was calculated to be higher in LC-AgNPs than in leaf extracts. The calculated IC50 values of the LC-AgNPs and plant extract are 85.01 ± 0.17 and 209.44 ± 0.24, respectively. The antibacterial activity of LC-AgNPs was investigated against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis as well as Staphylococcus aureus, and maximum potential was observed after 24 h against P. aeruginosa. Moreover, LC-AgNPs exhibited maximum anticancer potential against TPC1 cell lines compared to the plant extract. The findings suggested that LC-AgNPs could be used as antioxidant, antibacterial, and anticancer agents for the cure of free-radical-oriented bacterial and oncogenic diseases.


Low UPB1 Level Correlates With Poor Prognosis in Lung Adenocarcinoma.
Lung adenocarcinoma (LUAD) is a critical cancer with high mortality, worse prognosis, and crucial lymphatic metastasis. Consequently, prognostic biomarkers for LUAD are truly required. β-Ureidopropionase (UPB1) is abnormally expressed in various cancers. However, the function of UPB1 in LUAD is still ambiguous. This study aimed to explore the expression profile and prognostic significance of UPB1 in LUAD. The differential UPB1 levels in pan cancers and their prognostic significance were comprehensively investigated through Gene Expression Profiling Interactive Analysis, UALCAN, Tumor Immune Estimation Resource, and Kaplan-Meier plotter platform. The correlation between UPB1 and tumor infiltration immune cells was explored using Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions and Drug Bank database databases. The UPB1 level was abnormally expressed in pan-tumor tissue than in adjacent tissue from The Cancer Genome Atlas tool. Low UPB1 level was correlated with poor overall survival in patients with LUAD. Furthermore, a comparison of the various pathologic characteristics of LUAD between high and low UPB1 level subgroups revealed that low UPB1 expression was correlated with lymph node metastasis. Kaplan-Meier survival analysis indicated that a low UPB1 level was associated with worse progression‑free survival and overall survival in patients with LUAD. Univariate and multivariate analyses suggested that UPB1 could be a useful prognostic indicator for LUAD. Abnormal UPB1 may be correlated with aberrant LUAD immune infiltration, prompting a worse survival outcome. Results showed that low UPB1 is correlated with a worse prognosis of LUAD and may be a valuable prognostic indicator for LUAD.


miR-630 overexpression in hepatocellular carcinoma tissues is positively correlated with alpha-fetoprotein.
MicroRNA-630 (miR-630) has been shown to be involved in various human malignancies. However, its role in hepatocellular carcinoma (HCC) remains unknown. TaqMan qRT-PCR assay was performed to detect the expression of miR-630 in 42 pairs of HCC tissues and corresponding noncancerous hepatocellular tissues, and its correlations with clinicopathologic features and serum alpha-fetoprotein (AFP) level of patients were analyzed. The present study found that miR-630 expression was significantly increased in HCC tissues and cells compared with their normal counterparts. miR-630 expression level did not significantly chang at stage I but was markedly increased at advanced TNM stage (stage II~III). In addition, the increased expression of miR-630 in tissues of HCC appeared in patients who exhibited elevated serum levels of AFP (>25 ng/ml), but not in those with normal AFP levels (≤25 ng/ml). The miR-630 expression in carcinoma tissues revealed a positive correlation with the levels of serum alpha-fetoprotein (AFP; R2=0.768). These results suggest that miR-630 is associated with tumor progression of hepatocellular carcinoma and may be a potential prognosis indicator.


[Endocrine regulators of calcium metabolism (calcitonin and parathormone) in patients with myocardial infarction during various periods of observation].
The purpose of the study was a comprehensive analysis of the level of calcitonin and parathormone in patients with acute myocardial infarction (MI) and postinfarction cardiosclerosis as compared to similar data on healthy persons and coronary patients without a previous history of myocardial infarction. A total of 122 persons were examined using a radioimmunoassay and biochemical methods. The data obtained demonstrated an increase in the level of circulating calcitonin in patients with chronic CHD including postinfarction cardiosclerosis. The phasing of changes was revealed in the patients with acute MI: hypercalcitoninemia and hyperparathyrinemia on the 1st and 27-th-30th day of disease. Hypocalcemia was noted on the 14th-16th day of disease in the presence of normalization of the level of both hormones.


Increased skin cancer mortality in Chile beyond the effect of ageing: Temporal analysis 1990 to 2005.
Chile has a medium-to-high skin cancer mortality rate. Previous studies have shown an increasing rate of skin cancer mortality. We evaluated skin cancer mortality characteristics and their temporal evolution in Chile from 1990 to 2005 in a mixed ecological study using death certificate databases. Age, sex, year and region of residence were obtained for melanoma and non-melanoma deaths. Crude and age-sex-adjusted rates were calculated using the national projections and WHO 2000 standard population data. Descriptive and temporal analyses, using a Prais-Winsten regression, were computed. A total of 3588 deaths were registered, of which 55% were melanoma and 54% occurred in men (median age 71 years; women were older). The adjusted rate was 1.75 deaths per 100,000 inhabitants (2.22 in men vs. 1.39 in women). Melanoma skin cancer and non-melanoma skin cancer mortality had a tendency to increase. In conclusion, skin cancer mortality is rising beyond the rate predicted by ageing. An increased incidence due to changes in modifiable factors, such as exposure to ultraviolet radiation and arsenic, might explain the increase in skin cancer mortality.


Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.
Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia. In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level. During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.


Towards Identifying Optimal Biased Feedback for Various User States and Traits in Motor Imagery BCI.
Neural self-regulation is necessary for achieving control over brain-computer interfaces (BCIs). This can be an arduous learning process especially for motor imagery BCI. Various training methods were proposed to assist users in accomplishing BCI control and increase performance. Notably the use of biased feedback, i.e. non-realistic representation of performance. Benefits of biased feedback on performance and learning vary between users (e.g. depending on their initial level of BCI control) and remain speculative. To disentangle the speculations, we investigate what personality type, initial state and calibration performance (CP) could benefit from a biased feedback. We conduct an experiment (n = 30 for 2 sessions). The feedback provided to each group (n = 10) is either positively, negatively or not biased. Statistical analyses suggest that interactions between bias and: 1) workload, 2) anxiety, and 3) self-control significantly affect online performance. For instance, low initial workload paired with negative bias is associated to higher peak performances (86%) than without any bias (69%). High anxiety relates negatively to performance no matter the bias (60%), while low anxiety matches best with negative bias (76%). For low CP, learning rate (LR) increases with negative bias only short term (LR = 2%) as during the second session it severely drops (LR = -1%). We unveil many interactions between said human factors and bias. Additionally, we use prediction models to confirm and reveal even more interactions. This paper is a first step towards identifying optimal biased feedback for a personality type, state, and CP in order to maximize BCI performance and learning.


[Are non-literal language comprehension deficits related to a theory of mind deficit in Parkinson's disease?].
Theory of mind (TOM), i.e. the capacity to attribute mental states to oneself and others, would be impaired in Parkinson's disease (PD). Nonliteral language (NLL) comprehension would also be impaired in this disease. The goal of this study was to verify the presence of an association between the TOM and NLL comprehension deficits. We assessed 15 individuals in the early stages of PD and 17 healthy controls (HC), comparable on gender, age and education. Each subject completed a TOM evaluation task and a NLL task (i.e. metaphor comprehension). They also completed executive functioning (mental flexibility, inhibition and working memory) evaluation tasks. Our results showed that patients with PD had significant difficulties in the TOM and NLL comprehension tasks compared to HC participants. A significant relationship was found between TOM and NLL comprehension results. Moreover, NLL scores were associated with a task evaluating mental flexibility. Thus, PD might cause both TOM and NLL comprehension deficit even in the early stages of the disease. Our results showed that there would be a close relationship between TOM and NLL in people with PD.


The shaping effects of three nickel-titanium rotary instruments in simulated S-shaped canals.
The purpose of this study was to compare the shaping effects of three nickel-titanium rotary instruments, ProTaper, K3, and RaCe, with emphasis on canal transportation. Simulated canals with an S-shaped curvature in clear resin blocks were prepared with a torque-control, low-speed engine. Canals were prepared using the crown-down technique to the size of #30. Canal aberrations were assessed by comparing the pre- and postinstrumentation images under a stereomicroscope. ProTaper instruments caused greater widening of canals compared to K3 or RaCe. Furthermore, ProTaper files showed a tendency to ledge or zip formation at the end-point of preparation. These canal aberrations may be caused by ProTaper finishing files, which appear to be less flexible than other files of the same tip-size, because of their greater taper-size. These results suggest that nickel-titanium file systems including less tapered, more flexible instruments, like K3 and RaCe should be used in the apical preparation of canals with a complicated curvature.


Cost benefit of emerging technology in localized carcinoma of the prostate.
In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.


Perylene diimide-Cu2+ based fluorescent nanoparticles for the detection of spermine in clinical and food samples: a step toward the development of a diagnostic kit as a POCT tool for spermine.
The sustainable development of point-of-care testing (POCT) for spermine detection is important to check for food spoilage, early diagnosis of various malignancies and diminished anticonvulsant drug carbamazepine response in chronic epilepsy. Herein, the synthesis, characterization and spectroscopic properties of perylene diimide EA-PDI∩Cu2+ complex based nanoparticles towards spermine were studied in detail. This EA-PDI∩Cu2+ complex can be used for the ultrasensitive detection of spermine as low as 86.3 nM (UV-vis) and 90 pM (fluorescence) in aqueous medium, in urine and blood serum samples (recovery 99 ± 3) and in the solid state (0.1 μg L-1), and EA-PDI shows minimal cytotoxicity to cells and can easily enter into Human Osteosarcoma MG-63 cells for bio-imaging of Cu2+ and spermine. This EA-PDI∩Cu2+ complex can be established as a cost-effective method to develop a diagnostic kit for POCT of spermine in terms of a solution-based test kit for real time detection of spermine in vapor and solution form released from fermented food samples.


Effects of passive transfer of immunity on results of diagnostic tests for antibodies against feline immunodeficiency virus in kittens born to vaccinated queens.
To determine whether passive transfer of immunity affects results of diagnostic tests for antibodies against FIV in kittens born to vaccinated queens. Experimental trial. 12 specific-pathogen-free queens and their 55 kittens. Queens were vaccinated with a whole-virus FIV vaccine prior to breeding. Serum was obtained from the queens on the day of parturition and from the kittens on days 2 and 7, then weekly until results of tests for antibodies against FIV were negative for 2 consecutive weeks. Milk was collected from the queens daily for the first week and then weekly. Serum and milk were tested for antibodies against FIV with 2 commercial assays. Antibodies against FIV were detected in serum obtained from the queens on the day of parturition and in the milk throughout lactation. All kittens tested positive for antibodies against FIV at 2 days of age. At 8 weeks of age, 30 (55%) kittens tested positive with 1 of the commercial assays, and 35 (64%) tested positive with the other. All kittens tested negative for antibodies against FIV by 12 weeks of age. Results suggest that kittens readily absorb antibodies against FIV in colostrum from vaccinated queens and that these antibodies may interfere with results of commercially available tests for FIV infection past the age of weaning. Currently licensed diagnostic tests for FIV infection are unable to distinguish among kittens with antibodies against FIV as a result of infection, passive transfer from infected queens, and passive transfer from vaccinated queens.


[Chronic liver disease associated with cystic fibrosis in the Hospital Alberto Sabogal Sologuren, Lima, Peru: report of a case].
Cystic fibrosis (CF) is the most frequent recessive genetic disorder in the caucasian population and is produced by the alteration of electrolyte and water transport in the epithelial cell membrane. Liver disease is a frequent complication towards the end of the first decade of life, being weird its onset, except in patients with a history of meconium ileus. The characteristic liver injury in CF is focal biliary cirrhosis, but fatty infiltration can also be found. The diagnosis is made considering the clinical, laboratory and imaging results having in consideration that the normal liver function tests do not rule out the disease. Ultrasound is the most widely used and can detect the presence of steatosis, stones, fibrosis, cirrhosis, portal hypertension or abnormalities of the biliary tree. There is an also available technique such as computed tomography or magnetic resonance imaging, which allows a morphological study. Important aspects in the treatment are nutritional management, administration of soluble vitamins and the use of ursodeoxycholic acid (UDCA). In cases of advanced cirrhosis, transplantation, isolated or combined with the lung, is an option to consider, with acceptable survival rates. We report the case of an 11 year old patient with a diagnosis of chronic liver disease associated with cystic fibrosis.


Opioid Prescribing for Opioid-Naive Patients in Emergency Departments and Other Settings: Characteristics of Prescriptions and Association With Long-Term Use.
We explore the emergency department (ED) contribution to prescription opioid use for opioid-naive patients by comparing the guideline concordance of ED prescriptions with those attributed to other settings and the risk of patients' continuing long-term opioid use. We used analysis of administrative claims data (OptumLabs Data Warehouse 2009 to 2015) of opioid-naive privately insured and Medicare Advantage (aged and disabled) beneficiaries to compare characteristics of opioid prescriptions attributed to the ED with those attributed to other settings. Concordance with Centers for Disease Control and Prevention (CDC) guidelines and rate of progression to long-term opioid use are reported. We identified 5.2 million opioid prescription fills that met inclusion criteria. Opioid prescriptions from the ED were more likely to adhere to CDC guidelines for dose, days' supply, and formulation than those attributed to non-ED settings. Disabled Medicare beneficiaries were the most likely to progress to long-term use, with 13.4% of their fills resulting in long-term use compared with 6.2% of aged Medicare and 1.8% of commercial beneficiaries' fills. Compared with patients in non-ED settings, commercial beneficiaries receiving opioid prescriptions in the ED were 46% less likely, aged Medicare patients 56% less likely, and disabled Medicare patients 58% less likely to progress to long-term opioid use. Compared with non-ED settings, opioid prescriptions provided to opioid-naive patients in the ED were more likely to align with CDC recommendations. They were shorter, written for lower daily doses, and less likely to be for long-acting formulations. Prescriptions from the ED are associated with a lower risk of progression to long-term use.


Effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats.
The purpose of this study was to examine the effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats. The "linked animals" experiments provided evidence that diflunisal exhibits an enterohepatic circulation. Within 26 hr after iv administration of diflunisal (10 mg/kg) to rats, excretion was as follows: 42.2% of the dose, bile; 2.3%, unchanged drug; 27.8%, ester glucuronide; and 12.1%, ether glucuronide. On the average, approximately 65% of the amount of the drug and its glucuronides excreted in bile was reabsorbed from the gut. Biliary excretion and plasma data showed that biotransformation of diflunisal to its glucuronides is the rate-limiting step in their elimination. A concentration-dependent decrease in the partial formation clearance to ester glucuronide was observed with decreased concentration of diflunisal. These concentration-dependent kinetics can be at least partly explained by the nonlinear protein binding of diflunisal.


[Decreased alpha fetoprotein in maternal serum in relation to increased alpha fetoprotein in amniotic fluid in a case of fetal trisomy 21 associated with esophageal atresia].
A subnormal maternal serum alpha-fetoprotein level associated with elevated alpha-fetoprotein level in amniotic fluid was found in a case of trisomy 21 combined with esophageal atresia in a fetus at 36 + 5 weeks of gestation. The significance of this observation is discussed in view of the possible biologic mechanisms resulting in maternal serum alpha-fetoprotein reduction in cases of fetal autosomal trisomies. The most likely hypotheses seem to be a reduced fetal alpha-fetoprotein production and/or an alteration of the placental regulation of the alpha-fetoprotein transfer from fetal to maternal blood via the placenta.


Dynamics of ascorbate in the aqueous humor and tissues surrounding ocular chambers.
The level of ascorbate in the aqueous humor and surrounding intraocular structures in enucleated arterially perfused rabbit eye was investigated. The enucleated eye preparation was shown to be capable of secreting ascorbate from the perfusate into the aqueous humor. Ascorbate in the iris, ciliary body and cornea was released into the aqueous humor when the eye was perfused with ascorbate-free solution. Failure to obtain aqueous flow rates from the decay of ascorbate in the anterior chamber was due to the contribution of ascorbate from these ocular tissues during the perfusion. Histochemically, ascorbate was localized in the pigmented epithelial layer in the valleys between the ciliary processes and the pars plana of the ciliary body and in the iris. In the cornea, distinct localization of ascorbate was observed in the endothelium and basal cell layer of the epithelium.


Increased expression of interleukin 36 in chronic rhinosinusitis and its contribution to chemokine secretion and increased epithelial permeability.
IL-36 family, a recently reported member of the IL-1 cytokine family, plays an essential role in nonspecific innate immune response to infection. This study aims at investigating the expression of IL-36 family members (α, β, and γ) in normal and inflammatory sinus mucosa of patients with chronic rhinosinusitis (CRS), their effects on chemokine secretion and on the barrier function of epithelial and endothelial cells, and the effect of Toll-like receptors on the expression of IL-36 in epithelial cells. The expression of IL-36 family in normal and inflammatory sinus mucosa, the production of chemokines or the expression levels of IL-36 family in epithelial cells treated with IL-36 family members or stimulated with TLR3, TLR4, TLR5, or TLR7/8 agonists were measured with real time PCR, ELISA, immunohistochemistry, or Western blot. The epithelial and endothelial permeability, and transendothelial leukocyte migration were investigated using cultured epithelial and endothelial cells. IL-36α, IL-36β, and IL-36γ were localized in epithelial cells of sinonasal mucosa. Their levels increased in inflammatory mucosa of CRS patients and are up-regulated by TLR3, TLR4, or TLR5 agonists. IL-36α, or IL-36γ induced CXCL1, CXCL2, and CXCL3 production. Epithelial and endothelial permeability, transendothelial leukocyte migration were increased in cells treated with IL-36α, IL-36β, or IL-36γ. These results suggest that IL-36α, IL-36β, and IL-36γ localized in superficial epithelium may act as a responder to microbial and nonmicrobial elements through TLR and subsequently produce CXC chemokines, playing an interplay between innate and adaptive immune response.


Hydroethanolic plant extracts from Cameroon positively modulate enzymes relevant to carbohydrate/lipid digestion and cardio-metabolic diseases.
Cardiovascular diseases are the greatest cause of death globally and are frequently associated with type 2 diabetes mellitus and metabolic syndrome, a condition including visceral obesity, hypertension, elevated triglycerides and low HDL cholesterol and hyperglycaemia. Several medicinal plants, including spices, are used in Cameroon as herbal medicines and are traditionally employed for the treatment of several ailments such as diabetes and related diseases. In this study, we chemically characterized eleven Cameroonian spice extracts and evaluated their effects on some enzyme activities relevant to carbohydrate and lipid digestion and cardio-metabolic diseases. Hydroethanolic spice extracts were characterized by GC-MS analysis and screened for their ability to modulate the activity of α-glucosidase, α-amylase, pancreatic lipase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and angiotensin-converting enzyme (ACE). Among the spice extracts tested, those from Xylopia parviflora showed the widest inhibitory spectrum, with a relevant effect on all enzyme activities. Dichrostachys glomerata and Aframomum citratum extracts were more selective. The selected and strong activity of some plants, such as that of Aframomum citratum on pancreatic lipase and that of Xylopia aethiopica on ACE, suggests their specific use in obesity and hypertension, respectively. Chemical analysis indicated that for some spice extracts such as Xylopia parviflora and Aframomum citratum their secondary metabolites (chlorogenic acid, pimaric acid, and catechin and its derivatives) could potentially justify the biological properties observed. Our findings clearly show significant inhibition of cardio-metabolic enzymes by hydroethanolic Cameroonian spice extracts, suggesting the potential usefulness of nutraceuticals derived from these plants to develop novel management strategies for obesity and diabetes complications.


Whole-Body Vibration or Aerobic Exercise in Patients with Bronchiectasis? A Randomized Controlled Study.
Background and Objectives: The whole-body vibration (WBV) technique is an exercise training method. It has been reported to improve muscle strength, exercise capacity, and the quality of life. However, there is no study on the use of the WBV technique in bronchiectasis. The aim of the present study is to compare the effect of aerobic exercise with whole-body vibration on exercise capacity, respiratory function, dyspnea, and quality of life (QoL) in bronchiectasis patients. Materials and Methods: Clinically stable bronchiectasis patients aged 18−74 years participated in this study. A pulmonary function test, 6 minute walk test (6MWT), five times sit-to-stand test (FTSST), Modified Medical Research Council (mMRC) Scale, an, St. Georges Respiratory Questionnaire (SGRQ) were used in the evaluation. In total, 41 patients (WBV group: 20, aerobic group: 21) completed the study. The patients were treated for eight weeks. Results: When the two groups were compared after the treatment, there was a significant difference between the mMRC scores in favor of the WBV group (p < 0.05). When the results of the WBV group were examined before and after treatment, a significant difference was found between the 5SST and 6MWT (p < 0.05). When the aerobic group was compared before and after the treatment, it was observed that there was a significant difference in FVC, FVC%, 5SST, 6MWT, and SGRQ total score, and activity and impact scores, which are the sub-parameters (p < 0.05). Conclusions: Eight weeks of WBV exercise can lead to significant improvements in patients with bronchiectasis, exercise capacity, and dyspnea. Larger studies are needed to define the optimal intensity and duration of WBV, as well as to investigate its possible long-term effects.


Electrochemistry of Alzheimer Disease Amyloid Beta Peptides.
Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterization. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation are electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates, protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, particularly zinc, copper and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed.


Intercellular calcium signalling between chondrocytes and synovial cells in co-culture.
Intercellular communication allows the co-ordination of cell metabolism between tissues as well as sensitivity to extracellular stimuli. Paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex cellular networks that favour the intercellular exchange of nutrients and second messengers. Heterologous intercellular communication was studied in co-cultures of articular chondrocytes and HIG-82 synovial cells by measuring mechanically induced cytosolic changes in Ca2+ ion levels by digital fluorescence video imaging. In confluent co-cultures, mechanical stimulation induced intercellular Ca2+ waves that propagated to both cell types with similar kinetics. Intercellular wave spreading was inhibited by 18alpha-glycyrrhetinic acid and by treatments inhibiting the activation of purinoreceptors, suggesting that intercellular signalling between these two cell types occurs both through gap junctions and ATP-mediated paracrine stimulation. In rheumatoid arthritis the formation of the synovial pannus induces structural changes at the chondrosynovial junction, where chondrocyte and synovial cells come into close apposition: these results provide the first evidence for direct intercellular communication between these two cell types.


[Gastrointestinal tract in diseases of the adrenal cortex].
Clinico-roentgenological study of the gastrointestinal tract was carried out in 86 patients with diseases of the adrenal cortex. A hyperplastic relief of the gastric mucosa was revealed in the adreno-genital syndrome, Itsenko-Cushing's disease, androsteroma and glucosteroma; the relief was hypoplastic in Addison's disease. Ulcerative lesions found in Addison's disease were erosive and associated with the corticosteroid therapy instituted. Functional changes in small intestine in Itsenko--Cushing's disease, glucosteroma and Addison's disease were chiefly hypomotor-hypotonic in character, and in the adreno-genital syndrome and androsteromas--hypermotor-normotonic. Electrogastrography revealed different disturbances in the rhythm and amplitude of oscillations in the gastric biopotentials pointing to the changes in the vegetative innervation.


Recent Advances of Curcumin and its Analogues in Breast Cancer Prevention and Treatment.
More than 230,000 diagnosed cases of invasive breast cancer in women was estimated in 2014 and an expected 40,000 deaths attributed to the aggressive carcinoma. An effective approach to diminish the morbidity and mortality of breast cancer is the development of chemopreventive and chemotherapeutic agents. Nutraceuticals have demonstrated their ability to proficiently halt carcinogenesis. The administration of natural compounds able to effectively serve as chemoprevention and chemotherapeutics without causing harm or adverse effects is imperative. Curcumin derived from the rhizome of Curcuma longa L., is a common spice of India, used for centuries because of its medicinal properties. The main component of curcumin possesses a wide range of biological activities; anti-proliferative, anti-inflammatory, and apoptotic characteristics modulated through the inactivation of pathways such as EGK and Akt/mTOR. In addition, curcumin alters the expression of cytokines, transcription factors, and enzymes involved in cell vitality. The in vivo application of curcumin in breast cancer is hindered by its limited bioavailabiity. The synthesis of curcumin analogues and delivery via nanoparticles has demonstrated enhanced bioavailability of curcumin in the malignancy. This review focuses on recent developments in the use of curcumin, curcumin analogues, and novel delivery systems as a preventive and therapeutic method for breast cancer.


[Recognize the frailty: A challenge in general medicine].
Frailty is the most problematic expression of population ageing. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime leading to functional dependence. It is before the onset of functional dependence that detection of the frailty by the general practitioner is essential in order to tend to compress morbidity. After an attempt for operational definition of frailty this paper reviews methodological, semantic and logistical pitfalls of screening for frailty in general medicine. The use of frailty would allow general practitioners to introduce early interventions in the care for the older person, thus shifting the care towards a preventive course and thereby reducing the adverse outcomes as well as the public costs.


Purification and characterization of UDP-GlcNAc: GlcNAcbeta 1-6(GlcNAcbeta 1-2)Manalpha 1-R [GlcNAc to Man]-beta 1, 4-N-acetylglucosaminyltransferase VI from hen oviduct.
A new beta1,4-N-acetylglucosaminyltransferase (GnT) responsible for the formation of branched N-linked complex-type sugar chains has been purified 64,000-fold in 16% yield from a homogenate of hen oviduct by column chromatography procedures using Q-Sepharose FF, Ni(2+)-chelating Sepharose FF, and UDP-hexanolamine-agarose. This enzyme catalyzes the transfer of GlcNAc from UDP-GlcNAc to tetraantennary oligosaccharide and produces pentaantennary oligosaccharide with the beta1-4-linked GlcNAc residue on the Manalpha1-6 arm. It requires a divalent cation such as Mn(2+) and has an apparent molecular weight of 72,000 under nonreducing conditions. The enzyme does not act on biantennary oligosaccharide (GnT I and II product), and beta1,6-N-acetylglucosaminylation of the Manalpha1-6 arm (GnT V product) is essential for its activity. This clearly distinguishes it from GnT IV, which is known to generate a beta1-4-linked GlcNAc residue only on the Manalpha1-3 arm. Based on these findings, we conclude that this enzyme is UDP-GlcNAc:GlcNAcbeta1-6(GlcNAcbeta1-2)Manalpha1-R [GlcNAc to Man]-beta1,4-N-acetylglucosaminyltransferase VI. This is the only known enzyme that has not been previously purified among GnTs responsible for antenna formation on the cores of N-linked complex-type sugar chains.


Symposium on infections in the compromised host. Significance of fever in the compromised host.
The febrile response is a normal, nonspecific manifestation of nearly all infectious disease processes. However, in the compromised host, this response is often diminished or absent, thus depriving the clinician of an important diagnostic indicator. This article describes various clinical entities that present with fever and outlines the therapeutic considerations used in patients with impaired defense mechanisms.


Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis.
We studied 25-hydroxyvitamin D (vitamin D) levels in patients with amyotrophic lateral sclerosis (ALS) and the effect of vitamin D supplementation. Vitamin D levels were checked in 37 consecutive patients with ALS. Demographic data, vitamin D supplementation, change in Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score, and side effects from vitamin D were noted over a 9 month follow-up period. ALSFRS-R scores were compared between patients who took vitamin D and those who did not. The median age was 55 years and median time since symptom onset was 61 months. The mean vitamin D level was 22.3 ng/mL (normal range, 30-80 ng/mL). Eighty-one percent of patients had a vitamin D level lower than 30 ng/mL and 43% had a vitamin D level lower than 20 ng/mL. Twenty patients took 2000 international units of vitamin D daily. After adjustment for age and baseline vitamin D levels in a linear regression model, the ALSFRS-R score decline was smaller in patients taking vitamin D at 9 months (p=0.02) but was not significantly different at 3 or 6 months. Median vitamin D levels rose from 18.5 to 31.0 ng/mL at 6 months in the group taking vitamin D. No side effects secondary to vitamin D supplementation were reported. Vitamin D supplementation at 2000 international units daily was safe over a period of 9 months and may have a beneficial effect on ALSFRS-R scores. Further studies are warranted to determine whether there is a benefit in vitamin D supplementation for all ALS patients.


Two tropical conifers show strong growth and water-use efficiency responses to altered CO2 concentration.
Conifers dominated wet lowland tropical forests 100 million years ago (MYA). With a few exceptions in the Podocarpaceae and Araucariaceae, conifers are now absent from this biome. This shift to angiosperm dominance also coincided with a large decline in atmospheric CO2 concentration (ca). We compared growth and physiological performance of two lowland tropical angiosperms and conifers at ca levels representing pre-industrial (280 ppm), ambient (400 ppm) and Eocene (800 ppm) conditions to explore how differences in ca affect the growth and water-use efficiency (WUE) of seedlings from these groups. Two conifers (Araucaria heterophylla and Podocarpus guatemalensis) and two angiosperm trees (Tabebuia rosea and Chrysophyllum cainito) were grown in climate-controlled glasshouses in Panama. Growth, photosynthetic rates, nutrient uptake, and nutrient use and water-use efficiencies were measured. Podocarpus seedlings showed a stronger (66 %) increase in relative growth rate with increasing ca relative to Araucaria (19 %) and the angiosperms (no growth enhancement). The response of Podocarpus is consistent with expectations for species with conservative growth traits and low mesophyll diffusion conductance. While previous work has shown limited stomatal response of conifers to ca, we found that the two conifers had significantly greater increases in leaf and whole-plant WUE than the angiosperms, reflecting increased photosynthetic rate and reduced stomatal conductance. Foliar nitrogen isotope ratios (δ15N) and soil nitrate concentrations indicated a preference in Podocarpus for ammonium over nitrate, which may impact nitrogen uptake relative to nitrate assimilators under high ca SIGNIFICANCE: Podocarps colonized tropical forests after angiosperms achieved dominance and are now restricted to infertile soils. Although limited to a single species, our data suggest that higher ca may have been favourable for podocarp colonization of tropical South America 60 MYA, while plasticity in photosynthetic capacity and WUE may help account for their continued persistence under large changes in ca since the Eocene.


Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer.
The peritoneal surfaces of the abdomen and pelvis are important sites for the dissemination of gastrointestinal and gynecologic malignancy. Transcoelomic dissemination of cancer cells gives rise to carcinomatosis, which, without special treatment, is a fatal manifestation of these diseases. To treat peritoneal carcinomatosis, cytoreductive surgery removes gross disease plus perioperative intraperitoneal and perioperative intravenous chemotherapy eradicates microscopic residual disease and chemical compatibilities. Chemotherapy agents are administered either by the intraperitoneal or intravenous route, based on their pharmacologic properties. A peritoneal-plasma barrier, which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity, results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration of the intraperitoneal chemotherapy is facilitated by moderate hyperthermia (41-42°C). Targeting of intravenous chemotherapy to the peritoneal surface is facilitated by the intraperitoneal heat. A constant dose of chemotherapy agent and volume of carrier solution, based on body surface area, allows prediction of systemic drug exposure and systemic toxicity. Timing of the hyperthermic chemotherapy as a scheduled part of the surgical procedure to uniformly expose all peritoneal surfaces is crucial to success.


Traditional Beliefs, Practices, and Migration: A Risk to Malaria Transmission in Rural Nepal.
The study aimed to explore sociocultural factors influencing the risk of malaria and practices and beliefs towards malaria prevention, transmission and treatment in a remote village in Khatyad Rural Municipality (KRM) of Nepal. A sequential exploratory mixed methods approach was used. Qualitative data were collected through 25 one-on-one, in-depth interviews followed by a face-to-face household survey (n = 218) among people from a village in KRM believed to have a high risk of malaria. Traditional practices such as Chhaupadi requiring the seclusion of women during menstruation and post-partum, transhumance, and reliance on traditional healers for the management of malaria were common practices in the village. The household survey found 98.1% of women faced menstrual exile either inside the house or in a separate hut, with 64.2% not having access to Long-lasting Insecticidal Nets (LLINs). Hardships and economic constraints compelled villagers to migrate seasonally for work to malaria-endemic areas in India, thereby exposing themselves to the risk of malaria. Persistent traditional beliefs and seasonal migration could threaten the elimination goals set by the national malaria program.


The impact of diagnosis of hepatitis C virus on quality of life.
The aim of this study was to examine the effects of diagnosis of hepatitis C virus (HCV) infection on quality of life in a cohort admitted to Fairfield Infectious Diseases Hospital with acute hepatitis from 1971 to 1975. Sera stored from the original admission were tested for antibody to HCV. Systematic approaches were used to locate anti-HCV-positive individuals and outcomes assessed by the Short Form 36 (SF-36) scale and a study-specific questionnaire as well as clinical review. Study subjects' SF-36 scores were compared with Australian population norms. Anti-HCV and HCV-RNA positive individuals (n = 15) aware of their serostatus rated significantly worse on 7 of 8 SF-36 scales compared with population norms. However, HCV-seropositive and RNA-positive individuals unaware of their HCV serostatus (n = 19) scored significantly worse in only 3 scales. Those aware of their serostatus did not differ sociodemographically, clinically, virologically, or serologically from those who were unaware, nor was there a link between quality of life (QOL) scores and objective measures of ill health. All subjects had injected drugs in the past. In conclusion, HCV-RNA and anti-HCV-positive individuals in our study have significantly poorer subjective health status 26 years after original infection compared with population norms. QOL measures were significantly worse for HCV-seropositive individuals aware of their serostatus compared with those unaware. We feel that the reduced QOL in the diagnosed group may be partially an effect of labeling and that the impact of the diagnostic process per se on QOL in individuals with HCV requires further evaluation.


Determination of nitrate in forages by using selective ion electrode: collaborative study.
Each of 10 collaborating laboratories analyzed 4 blind duplicate pairs of forage samples for nitrate, by using a potentiometric method. Two forage controls and a 100 000 mg KNO3/L standard were also provided. Nitrate was extracted into an aqueous Al2(SO4)3 solution containing 70 mg KNO3/L and quantitated with a nitrate-selective electrode. Standards were prepared using extracting solution as diluent. Nitrate concentrations in forage samples ranged from less than 0.50 to 4.35% KNO3. Repeatability coefficients of variation (CVo) ranged from 1.74 to 3.61%, and reproducibility coefficients of variation (CVx) ranged from 6.92 to 7.66%. Mean recovery of a 0.55% KNO3 spike was 94.5%. The method has been adopted official first action.


Intra-Regional Glu-GABA vs Inter-Regional Glu-Glu Imbalance: A 1H-MRS Study of the Neurochemistry of Auditory Verbal Hallucinations in Schizophrenia.
Glutamate (Glu), gamma amino-butyric acid (GABA), and excitatory/inhibitory (E/I) imbalance have inconsistently been implicated in the etiology of schizophrenia. Elevated Glu levels in language regions have been suggested to mediate auditory verbal hallucinations (AVH), the same regions previously associated with neuronal hyperactivity during AVHs. It is, however, not known whether alterations in Glu levels are accompanied by corresponding GABA alterations, nor is it known if Glu levels are affected in brain regions with known neuronal hypo-activity. Using magnetic resonance spectroscopy (MRS), we measured Glx (Glu+glutamine) and GABA+ levels in the anterior cingulate cortex (ACC), left and right superior temporal gyrus (STG), and left inferior frontal gyrus (IFG), in a sample of 77 schizophrenia patients and 77 healthy controls. Two MRS-protocols were used. Results showed a marginally significant positive correlation in the left STG between Glx and AVHs, whereas a significant negative correlation was found in the ACC. In addition, high-hallucinating patients as a group showed decreased ACC and increased left STG Glx levels compared to low-hallucinating patients, with the healthy controls in between the 2 hallucinating groups. No significant differences were found for GABA+ levels. It is discussed that reduced ACC Glx levels reflect an inability of AVH patients to cognitively inhibit their "voices" through neuronal hypo-activity, which in turn originates from increased left STG Glu levels and neuronal hyperactivity. A revised E/I-imbalance model is proposed where Glu-Glu imbalance between brain regions is emphasized rather than Glu-GABA imbalance within regions, for the understanding of the underlying neurochemistry of AVHs.


The Impact of Immersion on Cluster Identification Tasks.
Recent developments in technology encourage the use of head-mounted displays (HMDs) as a medium to explore visualizations in virtual realities (VRs). VR environments (VREs) enable new, more immersive visualization design spaces compared to traditional computer screens. Previous studies in different domains, such as medicine, psychology, and geology, report a positive effect of immersion, e.g., on learning performance or phobia treatment effectiveness. Our work presented in this paper assesses the applicability of those findings to a common task from the information visualization (InfoVis) domain. We conducted a quantitative user study to investigate the impact of immersion on cluster identification tasks in scatterplot visualizations. The main experiment was carried out with 18 participants in a within-subjects setting using four different visualizations, (1) a 2D scatterplot matrix on a screen, (2) a 3D scatterplot on a screen, (3) a 3D scatterplot miniature in a VRE and (4) a fully immersive 3D scatterplot in a VRE. The four visualization design spaces vary in their level of immersion, as shown in a supplementary study. The results of our main study indicate that task performance differs between the investigated visualization design spaces in terms of accuracy, efficiency, memorability, sense of orientation, and user preference. In particular, the 2D visualization on the screen performed worse compared to the 3D visualizations with regard to the measured variables. The study shows that an increased level of immersion can be a substantial benefit in the context of 3D data and cluster detection.


Analysis of geometric morphometrics and molecular phylogeny for Anopheles species in the Republic of Korea.
Human malaria, transmitted by Anopheles mosquitoes, is the most predominant mosquito-borne disease that is responsible for hundreds of thousands of deaths worldwide each year. In the Republic of Korea (ROK), there are currently several hundred malaria cases annually, mostly near the demilitarized zone (DMZ). Eight species of Anopheles mosquitoes are currently known to be present in the ROK. Similar to other major malaria vectors in Africa and India, it is very challenging to morphologically differentiate Anopheles mosquitoes in the ROK due to their extremely similar morphology. In this study, wing geometric morphometrics (WGM) were used to differentiate the eight Anopheles species collected at six locations near the DMZ, Seoul and Pyeongtaek from April-October 2021. Phylogenetic analysis was also performed using cytochrome c oxidase subunit 1 (COI), internal transcribed spacer 2 (ITS2), and tyrosine hydroxylase (TH) genes for comparison with WGM analysis and to infer evolutionary relationships. The results of cross-validation (overall accuracy = 74.8%) demonstrated that species identification using WGM alone was not possible with a high accuracy for all eight species. While phylogenetic analyses based on the COI region could not clearly distinguish some species, the analysis based on ITS2 and TH was more useful for resolving the phylogenetic correlation of the eight species. Our results may improve Anopheles species identification strategies for effective identification and control of malaria vectors in the ROK.


Outcomes of Endovascular Management of Late Vascular Hemorrhage After Pancreatic Transplant.
The aim of this retrospective study is to evaluate the endovascular treatment of hemorrhage in the nonperioperative setting in pancreas transplant recipients. All angiograms performed between January 1, 1999, and June 1, 2016, to treat hemorrhage after pancreatic transplant at a single large-volume transplant center were reviewed. Fourteen patients who underwent 21 angiograms were identified. The patients' charts were reviewed for clinical indications, technical aspects of the endovascular interventions, outcomes, and complications. The mean number of angiograms was 1.5 per patient. The primary and primary assisted clinical success rates were 64.3% (9/14 patients) and 71.4% (10/14 patients), respectively. Five patients (35.7%) experienced complications. At presentation, eight patients had functioning grafts and seven of these eight patients (87.5%) maintained graft function. It is critical to recognize transplant-related hemorrhage after pancreas transplant. Endovascular management is associated with high clinical success and rarely results in loss of graft function, suggesting that it should be a consideration for first-line therapy in this patient population.


Comparison of optical coherence tomography in diabetic macular edema, with and without reading center manual grading from a clinical trials perspective.
To analyze the value of reading center error correction in automated optical coherence tomography (OCT; Stratus; Carl Zeiss Meditec, Inc., Dublin, CA) retinal thickness measurements in eyes with diabetic macular edema (DME). OCT scans (n=6522) obtained in seven Diabetic Retinopathy Clinical Research Network (DRCR.net) studies were analyzed. The reading center evaluated whether the automated center point measurement appeared correct, and when it did not, measured it manually with calipers. Center point standard deviation (SD) as a percentage of thickness, center point thickness, signal strength, and analysis confidence were evaluated for their association with an automated measurement error (manual measurement needed and exceeded 12% of automated thickness). Curves were constructed for each factor by plotting the error rate against the proportion of scans sent to the reading center. The impact of measurement error on interpretation of clinical trial results and statistical power was also assessed. SD was the best predictor of an automated measurement error. The other three variables did not augment the ability to predict an error using SD alone. Based on SD, an error rate of 5% or less could be achieved by sending only 33% of scans to the reading center (those with an SD >or= 5%). Correcting automated errors had no appreciable effect on the interpretation of results from a completed randomized trial and had little impact on a trial's statistical power. In DME clinical trials, the error involved with using automated Stratus OCT center point measurements is sufficiently small that results are not likely to be affected if scans are not routinely sent to a reading center, provided adequate quality control measures are in place.


Miniaturised acoustofluidic tactile haptic actuator.
Tactile haptic feedback is an important consideration in the design of advanced human-machine interfaces, particularly in an age of increasing reliance on automation and artificial intelligence. In this work, we show that the typical nanometer-order surface displacement amplitudes of piezoelectric transducers-which are too small to be detectable by the human touch, and constitute a significant constraint in their use for tactile haptic surface actuation-can be circumvented by coupling the vibration into a liquid to drive the deflection of a thermoplastic membrane. In particular, transmission of the sound energy from the standing wave vibration generated along a piezoelectric transducer into a microfluidic chamber atop which the membrane is attached is observed to amplify the mechanical vibration signalling through both the acoustic radiation pressure and the viscous normal stress acting on the membrane-the latter arising due to the acoustic streaming generated as the sound wave propagates through the liquid-to produce 100 μm-order static deflections of the membrane, upon which approximately 0.5 μm dynamic vibrations at frequencies around 1 kHz are superimposed; both these static and dynamic responses are within the perception range for human finger sensation. The large static deformation, the relatively fast response time, and the ability to incorporate a dynamic vibrotactile response together with the small size and potential for integration of the device into large scale arrays make this mechanism well suited for driving actuation in devices which require tactile haptic responses.


Invited review: Cattle lameness detection with accelerometers.
Locomotion scoring is time consuming and is not commonly completed on farms. Farmers also underestimate their herds' lameness prevalence, a knowledge gap that impedes lameness management. Automation of lameness detection could address this knowledge gap and facilitate improved lameness management. The literature pertinent to adding lameness detection to accelerometers is reviewed in this paper. Options for lameness detection systems are examined including the choice of sensor, raw data collected, variables extracted, and statistical classification methods used. Two categories of variables derived from accelerometer-based systems are examined. These categories are behavior measures such as lying and measures of gait. For example, one measure of gait is the time a leg is swinging during a gait cycle. Some behavior-focused studies have reported accuracy levels of greater than 80%. Cow gait measures have been investigated to a lesser extent than behavior. However, classification accuracies as high as 91% using gait measures have been reported with hardware likely to be practical for commercial farms. The need for even higher accuracy and potential barriers to adoption are discussed. Significant progress is still required to realize a system with sufficient specificity and sensitivity. Lameness detection systems using 1 accelerometer per cow and a resolution lower than 100 Hz with gait measurement functions are suggested to balance cost and data requirements. However, gait measurement using accelerometers is rather underdeveloped. Therefore, a high priority should be given to the development of novel gait measures and testing their ability to differentiate lame from nonlame cows.


Human and mouse introns are linked to the same processes and functions through each genome's most frequent non-conserved motifs.
We identified the most frequent, variable-length DNA sequence motifs in the human and mouse genomes and sub-selected those with multiple recurrences in the intergenic and intronic regions and at least one additional exonic instance in the corresponding genome. We discovered that these motifs have virtually no overlap with intronic sequences that are conserved between human and mouse, and thus are genome-specific. Moreover, we found that these motifs span a substantial fraction of previously uncharacterized human and mouse intronic space. Surprisingly, we found that these genome-specific motifs are over-represented in the introns of genes belonging to the same biological processes and molecular functions in both the human and mouse genomes even though the underlying sequences are not conserved between the two genomes. In fact, the processes and functions that are linked to these genome-specific sequence-motifs are distinct from the processes and functions which are associated with intronic regions that are conserved between human and mouse. The findings show that intronic regions from different genomes are linked to the same processes and functions in the absence of underlying sequence conservation. We highlight the ramifications of this observation with a concrete example that involves the microsatellite instability gene MLH1.


[A survey on AIDS knowledge rate and sexual behavior among men who have sex with men population at sexually transmitted disease clinic].
To survey on men who have sex with men (MSM) population's sexual behaviors, condom-service condition, HIV related knowledge and other issues among MSM population at sexually transmitted disease (STD) clinics to understand the characteristics of behaviors and offer suggestions for effective health education and behavior intervention. From January to December, 2009, we used anonymous questionnaires which involved in their mastery of demographic characteristics, sexual behavior, condom-service condition, HIV related knowledge, and so one, to investigate 200 MSM at 3 STD clinics of comprehensive hospital. The average age of informant was (26.7+/- 8.9) years and 121 individuals (62.6%) had confirmed with STD in recent one year. In the recent 6 months, the average number of homosexual partners was 9.2+/- 4.8 and 102 (52.8%) had heterosexual partners. In the sexual intercourse with homosexual, 123 individuals had anal intercourse (63.7 %) and 117 had oral intercourse (60.6%). In the sexual intercourse with heterosexual, 92 (90.2%) individuals had vaginal intercourse, 37 (36.2%) had anal intercourse, and 59 (57.8%) had oral sex behavior.There were a statistical difference between heterosexual and homosexual sex behaviors (P<0.01). The condom-using frequency had statistic difference in different sexual behaviors(χ²=188.396, P<0.001). There was no linear correlation between HIV related knowledge and condom-using condition in sexual behaviors except the heterosexual anal intercourse. High AIDS knowledge mastery rate is found in our survey. The respondents get HIV/AIDS knowledge through various ways actively. There is no obvious relation between the mastery of HIV related knowledge and condom-using frequency. The ratio of non-protected sexual behaviors is high in heterosexuals. How to adopt effective methods for behavior intervention to MSM at STD clinic needs to be further studied.


Placenta Accreta Spectrum.
Placenta accreta spectrum (PAS) is one of the most dangerous conditions in pregnancy and is increasing in frequency. The risk of life-threatening bleeding is present throughout pregnancy but is particularly high at the time of delivery. Although the exact cause is unknown, the result is clear: Severe PAS distorts the uterus and surrounding anatomy and transforms the pelvis into an extremely high-flow vascular state. Screening for risk factors and assessing placental location by antenatal ultrasonography are essential for timely diagnosis. Further evaluation and confirmation of PAS are best performed in referral centers with expertise in antenatal imaging and surgical management of PAS. In the United States, cesarean hysterectomy with the placenta left in situ after delivery of the fetus is the most common treatment for PAS, but even in experienced referral centers, this treatment is often morbid, resulting in prolonged surgery, intraoperative injury to the urinary tract, blood transfusion, and admission to the intensive care unit. Postsurgical complications include high rates of posttraumatic stress disorder, pelvic pain, decreased quality of life, and depression. Team-based, patient-centered, evidence-based care from diagnosis to full recovery is needed to optimally manage this potentially deadly disorder. In a field that has relied mainly on expert opinion, more research is needed to explore alternative treatments and adjunctive surgical approaches to reduce blood loss and postoperative complications.


Downregulation of the Na(+)-creatine cotransporter in failing human myocardium and in experimental heart failure.
The failing myocardium is characterized by depletion of phosphocreatine and of total creatine content. We hypothesized that this is due to loss of creatine transporter protein. Creatine transporter protein was quantified in nonfailing and failing human myocardium (explanted hearts with dilated cardiomyopathy [DCM; n=8] and healthy donor hearts [n=8]) as well as in experimental heart failure (residual intact left ventricular tissue, rats 2 months after left anterior descending coronary artery ligation [MI; n=8] or sham operation [sham; n=6]) by Western blotting. Total creatine content was determined by high-performance liquid chromatography. Donor and DCM hearts had total creatine contents of 136.4+/-6.1 and 68.7+/-4.6 nmol/mg protein, respectively (*P<0.05); creatine transporter protein was 25.4+/-2.2 optical density units in donor and 17.7+/-2.5 in DCM (*P<0.05). Total creatine was 87.5+/-4.2 nmol/mg protein in sham and 65.7+/-4.2 in MI rats (*P<0.05); creatine transporter protein was 139.0+/-8.7 optical density units in sham and 82.1+/-4.0 in MI (*P<0.05). Both in human and in experimental heart failure, creatine transporter protein content is reduced. This mechanism may contribute to the depletion of creatine compounds and thus to the reduced energy reserve in failing myocardium. This finding may have therapeutic implications, suggesting a search for treatment strategies targeted toward creatine transport.


Multiple minute digitate hyperkeratosis: 10 years from Caccetta's algorithm. A case report and narrative review.
To date, the clinical appearance and histological features of multiple minute digitate hyperkeratosis have been well characterized. However, there is no consensus on its treatment. After a comprehensive search of the databases MEDLINE, EMBASE, Web of Science, and the Cochrane Library and Database of Systematic Reviews, we have summarized the available clinical evidence regarding the therapeutic approaches already reported for this entity since its first description in 1967. Additional publications were identified within the references of retrieved papers. Sixty-five articles have been revised, resulting in a total of 73 compatible cases. The histopathological features and different classifications used through history have also been considered, updating and completing the available knowledge. Ultimately, we propose topical treatment with 5 % 5-fluorouracil formulated with 10 % salicylic acid as a potential treatment that has been used successfully in a 51-year-old woman at our facility. Further research in form of prospective or comparative studies is encouraged for a better conceptualization of the therapeutics of this disease.


New insights into the regulatory mechanisms of ppGpp and DksA on Escherichia coli RNA polymerase-promoter complex.
The stringent response modulators, guanosine tetraphosphate (ppGpp) and protein DksA, bind RNA polymerase (RNAP) and regulate gene expression to adapt bacteria to different environmental conditions. Here, we use Atomic Force Microscopy and in vitro transcription assays to study the effects of these modulators on the conformation and stability of the open promoter complex (RPo) formed at the rrnA P1, rrnB P1, its discriminator (dis) variant and λ pR promoters. In the absence of modulators, RPo formed at these promoters show different extents of DNA wrapping which correlate with the position of UP elements. Addition of the modulators affects both DNA wrapping and RPo stability in a promoter-dependent manner. Overall, the results obtained under different conditions of ppGpp, DksA and initiating nucleotides (iNTPs) indicate that ppGpp allosterically prevents the conformational changes associated with an extended DNA wrapping that leads to RPo stabilization, while DksA interferes directly with nucleotide positioning into the RNAP active site. At the iNTPs-sensitive rRNA promoters ppGpp and DksA display an independent inhibitory effect, while at the iNTPs-insensitive pR promoter DksA reduces the effect of ppGpp in accordance with their antagonistic role.


Prevalence of sleep apnoea and snoring in hypertensive men: a population based study.
Several studies have reported an association between sleep disordered breathing (SDB) and hypertension (HT) but there is still a debate as to whether this is an effect of confounders. Some researchers have found an age dependent relationship between SDB and HT with higher risk at lower ages. A case-control study was performed in hypertensive men and non-hypertensive male controls matched for age and body mass index to assess whether there is an independent association between SDB and HT. If so, we further wanted to investigate whether this effect is age dependent. An overnight sleep study was performed in a population based, age stratified sample of 102 hypertensive men aged 43-82 years and 102 non-hypertensive controls. Hypertensive subjects had a significantly higher prevalence of SDB than non-hypertensive subjects (apnoea-hypopnoea index (AHI): 10.8 v 7.3; desaturation index (DI): 8.5 v 5.2; AHI >or=10: 37% v 24%, p<0.05; DI >or=10: 29% v 12%; lowest desaturation: mean (SD) 81.9 (7.3) v 84.7 (6.1), p<0.01). After adjusting for neck circumference and physical inactivity, DI >or=10 and lowest desaturation were still independent predictors of HT with adjusted odds ratios of 2.3 (95% CI 1.0 to 5.3) and 0.94 (95% CI 0.89 to 0.99), respectively. When the subjects were split into two groups according to age (<60 and >or=60 years), the influence of DI >or=10 on HT was strongest in the younger men (adjusted OR 4.3 (95% CI 1.0 to 19.3 v 2.1 (95% CI 0.7 to 6.5)) and the association between minimum oxygen saturation (SaO(2)) and HT reached statistical significance in the younger men only. SDB is more prevalent in men with HT than in controls. DI >or=10 and lowest desaturation are independent predictors of HT irrespective of confounders. The results indicate that the influence of SDB on HT is more pronounced in younger and middle aged men than in those above 60 years.


Plasma cell-free DNA methylation analysis for ovarian cancer detection: Analysis of samples from a case-control study and an ovarian cancer screening trial.
Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.


Localization of Na+,K+-ATPase alpha-subunit to the sinusoidal and lateral but not canalicular membranes of rat hepatocytes.
Controversy has recently developed over the surface distribution of Na+,K+-ATPase in hepatic parenchymal cells. We have reexamined this issue using several independent techniques. A monoclonal antibody specific for the endodomain of alpha-subunit was used to examine Na+,K+-ATPase distribution at the light and electron microscope levels. When cryostat sections of rat liver were incubated with the monoclonal antibody, followed by either rhodamine or horseradish peroxidase-conjugated goat anti-mouse secondary, fluorescent staining or horseradish peroxidase reaction product was observed at the basolateral surfaces of hepatocytes from the space of Disse to the tight junctions bordering bile canaliculi. No labeling of the canalicular plasma membrane was detected. In contrast, when hepatocytes were dissociated by collagenase digestion, Na+,K+-ATPase alpha-subunit was localized to the entire plasma membrane. Na+,K+-ATPase was quantitated in isolated rat liver plasma membrane fractions by Western blots using a polyclonal antibody against Na+,K+-ATPase alpha-subunit. Plasma membranes from the basolateral domain of hepatocytes possessed essentially all of the cell's estimated Na+,K+-ATPase catalytic activity and contained a 96-kD alpha-subunit band. Canalicular plasma membrane fractions, defined by their enrichment in alkaline phosphatase, 5' nucleotidase, gamma-glutamyl transferase, and leucine aminopeptidase had no detectable Na+,K+-ATPase activity and no alpha-subunit band could be detected in Western blots of these fractions. We conclude that Na+,K+-ATPase is limited to the sinusoidal and lateral domains of hepatocyte plasma membrane in intact liver. This basolateral distribution is consistent with its topology in other ion-transporting epithelia.


Botulinum toxin for the treatment of bruxism.
Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.


Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality.
We describe an approach for anticoagulation and transfusions in veno-venous-extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.


Are Your Patients Satisfied A Systematic Review of Treatment Satisfaction Measures in Psoriasis.
Treatment satisfaction is paramount to the field of dermatology. Treatment dissatisfaction directly impacts patient outcomes and health care delivery. A critical need exists for standardized, validated treatment satisfaction measures in dermatology. Comprehensive evaluation of the performance of treatment satisfaction instruments used in psoriasis is lacking. We sought to critically appraise the literature on measurement properties of treatment satisfaction instruments used in psoriasis. We performed a systematic review to identify treatment satisfaction instruments used in psoriasis and corresponding studies on their measurement properties. We followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology to inform a best evidence synthesis. Eleven instruments were identified. Six achieved positive content validity ratings, 2 achieved positive reliability and structural validity ratings, and 1 achieved a positive internal consistency rating. The REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) and the Spanish Satisfaction With Treatment of Psoriasis Questionnaire (SSWTPQ) had the highest overall performance. Measurement property data for treatment satisfaction instruments were found to be insufficient in identifying a single best treatment satisfaction instrument for psoriasis. Additional studies are required to better characterize the measurement properties of treatment satisfaction measures and allow for standardized assessments across psoriasis clinical trials and clinical practice.


Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins.
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin- or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders.


Improved general-purpose five-point model for water: TIP5P/2018.
A new five point potential for liquid water, TIP5P/2018, is presented along with the techniques used to derive its charges from ab initio per-molecule electrostatic potentials in the liquid phase using the split charge equilibration of Nistor et al. [J. Chem. Phys. 125, 094108 (2006)]. By taking the density and diffusion dependence on temperature as target properties, significant improvements to the behavior of isothermal compressibility were achieved along with improvements to other thermodynamic and rotational properties. While exhibiting a dipole moment close to ab initio values, TIP5P/2018 suffers from a too small quadrupole moment due to the charge assignment procedure and results in an overestimation of the dielectric constant.


Frequency of Adverse Events Following Q Fever Immunisation in Young Adults.
Q fever is a zoonosis of concern in many countries. Vaccination is the most effective means of prevention, and since 1989, Australia has had a licensed Q fever vaccine, Q-VAX®. This vaccine was also used in the Netherlands in 2011 following the largest recorded Q fever outbreak globally. There is a paucity of available data regarding adverse events following immunisation (AEFI) for young adult females. Such data are important for informing future vaccination recommendations both within Australia and internationally. This study collected Q fever vaccine (Q-VAX®) AEFI data in veterinary and animal science students at Australian universities. Students were enrolled at the time of vaccination and were emailed a link to an online AEFI survey one week later. Of the 60% (499/827) that responded, 85% were female and the median age was 18 years. Local injection site reactions (ISRs) occurred in 98% (95%; CI 96⁻99%) of respondents, of which 30% (95% CI 24⁻32%) were severe. Systemic AEFI occurred in 60% (95%; CI 55⁻64%) of respondents within the seven days following immunisation. Medical attention was sought by 19/499 (3.8%) respondents, of whom one sought treatment at a hospital emergency department. Females were more likely than males to experience any local ISR (odds ratio [OR] 9.3; 95% CI 2.5⁻33.8; p < 0.001), ISRs of greater severity (OR 2.5; 95% CI 1.5⁻4.2; p < 0.001), and any systemic AEFI (OR 1.9; 95% CI 1.1⁻3.1; p = 0.016). These safety data suggest that a high frequency of adverse events following immunisation should be expected in young adults, particularly females. However, the consequences of Q fever disease are potentially far more debilitating.


Peptidoglycan analysis reveals that synergistic deacetylase activity in vegetative Clostridium difficile impacts the host response.
Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15-25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N-deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N-deacetylases, and this N-deacetylation modulates host-pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N-deacetylases; however, which of these N-deacetylases are involved in peptidoglycan N-deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N-deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N-deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N-deacetylase. However, its impact on N-deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N-deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence.


Identification of soybean microRNAs involved in soybean cyst nematode infection by deep sequencing.
Soybean cyst nematode (SCN), Heterodera glycines, is the most devastating pathogen of soybean worldwide. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are known to play important role in plant stress response. However, there are few reports profiling the miRNA expression patterns during pathogen stress. We sequenced four small RNA libraries from two soybean cultivar (Hairbin xiaoheidou, SCN race 3 resistant, Liaodou 10, SCN race 3 susceptible) that grown under un-inoculated and SCN-inoculated soil. Small RNAs were mapped to soybean genome sequence, 364 known soybean miRNA genes were identified in total. In addition, 21 potential miRNA candidates were identified. Comparative analysis of miRNA profiling indicated 101 miRNAs belong to 40 families were SCN-responsive. We also found 20 miRNAs with different express pattern even between two cultivars of the same species. These findings suggest that miRNA paly important role in soybean response to SCN and have important implications for further identification of miRNAs under pathogen stress.