Survival Impact of Secondary Cytoreductive Surgery for Recurrent Ovarian Cancer in an Asian Population.
The aim of this study was to evaluate the role of secondary cytoreductive surgery in Asian patients with recurrent ovarian cancer and to assess prognostic variables on overall post-recurrence survival time. We conducted a retrospective review of patients with recurrent ovarian cancer who underwent secondary cytoreduction at the Gynaecological Cancer Center at the KK Women's and Children's Hospital, Singapore, between 1999 and 2009. Eligible patients included those who had been firstly treated by primary cytoreductive surgery and followed by adjuvant chemotherapy and had a period of clinical remission of at least six months and subsequently underwent secondary cytoreductive surgery for recurrence. Univariate analysis was performed to evaluate various variables influencing the overall survival. Twenty-five patients met our eligibility criteria. The median age was 52 years (range=31-78 years). The median time from completion of primary treatment to recurrence was 25.1 months (range=6.4-83.4). Secondary cytoreduction was optimal in 20 of 25 patients (80%). The median follow-up duration was 38.9 months (range=17.8-72.4) and median overall survival time was 33.1 months (95% confidence interval, 15.3-undefined.). Ten (40.0%) patients required bowel resection, but no end colostomy was performed. One (4.0%) patient had wedge resection of the liver, one (4.0%) had a distal pancreatectomy, one (4.0%) had a unilateral nephrectomy, and one (4.0%) had adrenalectomy. There were no operative deaths. The overall survival of patients who responded to secondary cytoreductive surgery and adjuvant chemotherapy was significantly longer than those patients who did not respond to the treatment. Of those patients who responded to the surgical management, patients with clear cell carcinoma fared well compared to those with the endometrioid, mucinous adenocarcinoma, and papillary serous type (p<0.001). Complete secondary cytoreductive surgery appeared to have some relationship to overall survival but was not statistically significant. In carefully selected patients with recurrent ovarian cancer, optimal cytoreductive surgery is possible and in a subgroup of patients who respond to surgery and chemotherapy survival is significantly longer.


Antioxidant and anticytolytic action as the basis of the Pancreo-Plant® hepatoprotective effect in acute liver ischemia.
In this experimental study, the effects of the combined herbal drug Pancreo-Plant® at a dose of 72 mg/kg and the comparison drug silymarin at a dose of 25 mg/ kg on animal mortality, cytolysis activity, free radical oxidation, and functional activity of the liver in the conditions of acute experimental ischemia have been studied. A pronounced antioxidant effect of the studied agent has been found which was manifested in the reduction of the lipid peroxidation products content, namely thiobarbituric acid products and diene conjugates and normalization of the enzymatic and non-enzymatic chains of endogenous antioxidant protection (reduced glutathione, catalase). In the case of acute liver failure, Pancreo-Plant® exhibited a significant anti-cytolytic effect, restored carbohydrate metabolism and protein-synthetic function of the liver. It was found that the total hepatoprotective activity of the combined herbal drug Pancreo-Plant® exceeded the activity of the comparison drug silymarin.


Anti-glomerular basement membrane (GBM)-antibody-mediated disease with normal renal function.
This study compared the clinical and laboratory characteristics of patients with anti-glomerular basement membrane (GBM) disease and normal renal function, with those of patients with anti-GBM disease where there was renal impairment. The medical records of the 14 patients who had presented with anti-GBM disease to our hospital in the past 20 years were reviewed. Five (36%) had a normal serum creatinine or creatinine clearance at presentation. Other features were haemoptysis (2/5, 40%), macroscopic haematuria (2/5, 40%) or systemic symptoms (1/5, 20%). All five (100%) had some degree of haematuria, four (80%) had proteinuria of at least 1 g/day, and none was hypertensive. Anaemia, a raised WCC, or elevated ESR (> 35 mm/h) occurred less often than in patients with impaired renal function (P<0.05). Two of the five (40%) with normal renal function had circulating anti-GBM antibodies, which were present at low or moderate levels; but seven of the nine with renal impairment (77%) had circulating antibodies, with high levels in five. Renal biopsies from patients with normal renal function were normal (1/5, 20%), showed mesangial proliferation (4/5, 80%) or had more than 20% glomeruli sclerosed (1/5, 20%). Complement deposition was present in 2/4 biopsies (50%). The kidneys from patients with renal impairment had crescents in more than 50% glomeruli (9/9, 100%), and four had more than 20% glomeruli sclerosed (44%). All four kidneys from patients with renal impairment that were examined had complement deposits (100%). Treatment was identical in both groups; patients with normal renal function were followed for a median of 48 months, and those with renal impairment for 180 months. There were no further episodes of haemoptysis, haematuria, or other symptoms of relapse in either group. All five patients with normal renal function are alive, and the serum creatinine is less than 0.2 mmol/l in all (100%), but haematuria persists in one (20%), and proteinuria >1 g/day in two (40%). Eight of the nine (89%) patients with impaired renal function survive, but all are currently being dialysed or have had a renal transplant. Patients with anti-GBM disease with normal renal function are not uncommon, and often have a good prognosis. There is less renal damage, possibly because of lower levels of circulating anti-GBM antibodies and less glomerular complement deposition.


Foundations of idiographic methods in psychology and applications for psychotherapy.
Researchers have long called for greater recognition and use of longitudinal, individual-level research in the study of psychopathology and psychotherapy. Much of our current research attempts to indirectly investigate individual-level, or idiographic, psychological processes via group-based, or nomothetic, designs. However, results from nomothetic research do not necessarily translate to the individual-level. In this review, we discuss how idiographic analyses can be integrated into psychotherapy and psychotherapy research. We examine and review key statistical methods for conducting idiographic analyses. These methods include factor-based and vector autoregressive approaches using longitudinal data. The theoretical framework behind each approach is reviewed and critically evaluated. Empirical examples of each approach are discussed, with the aim of helping interested readers consider how they may use idiographic methods to analyze longitudinal data and psychological processes. Finally, we conclude by citing key limitations of the idiographic approach, calling for greater development of these analyses to ease their successful integration into clinical settings.


A comparison of different compressive forces on graft materials during alveolar ridge preservation.
Following tooth extraction, alveolar ridge preservation (ARP) can maintain the dimensions of ridge height and width. Although previous studies have demonstrated the effects of ARP, few if any studies have investigated the compressive force applied during grafting. The aim of this study was to determine the effects of different compressive forces on the graft materials during ARP. After tooth extraction, sockets were filled with deproteinized bovine bone mineral with 10% porcine collagen and covered by a resorbable collagen membrane in a double-layered fashion. The graft materials were compressed using a force of 5 N in the test group (n=12) and a force of 30 N in the control group (n=12). A hidden X suture was performed to secure the graft without primary closure. Cone-beam computed tomography (CBCT) was performed immediately after grafting and 4 months later, just before implant surgery. Tissue samples were retrieved using a trephine bur from the grafted sites during implant surgery for histologic and histomorphometric evaluations. Periotest values (PTVs) were measured to assess the initial stability of the dental implants. Four patients dropped out from the control group and 20 patients finished the study. Both groups healed without any complications. The CBCT measurements showed that the ridge volume was comparably preserved vertically and horizontally in both groups (P>0.05). Histomorphometric analysis demonstrated that the ratio of new bone formation was significantly greater in the test group (P<0.05). The PTVs showed no significant differences between the 2 groups (P>0.05). The application of a greater compressive force on biomaterials during ARP significantly enhanced new bone formation while preserving the horizontal and vertical dimensions of the alveolar ridge. Further studies are required to identity the optimal compressive force for ARP.


[Coagulation parameters associated with inhaled glucocorticosteroid therapy in stable asthma].
The aim of this study was to determine if there are changes in laboratory investigations which allow to recognize coagulation disturbances associated with inhaled glucocorticoid therapy. The study group consist of 26 patients with stable asthma (5 male, 21 female) without risk factors of venous thrombosis, mean age 45 +/- 14 years. 15 patients were treated with 500-1000 mg beclomethasone daily, 11 patients received a daily dose of 1000-2000 microg of beclomethasone. The laboratory investigations included: hemoglobin concentration (Hb), hematocrit (Ht), platelet count (PLT), red blood cell count (E), white blood cell count (L), percentage of eosinophils (Eos%), fibrinogen (Fib), D-dimer concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), prothrombin index (Quick), INR and von Willebrand factor (vWF). An elevated concentration of D-dimers was detected in 4 patients (15%) the others investigated coagulation parameters were within normal range. We found a significant correlation between the dose of inhaled glucocorticosteroid and the PT, prothrombin index and INR. The results revealed no evidence of increased fibrinolytic activity in subjects with stable bronchial asthma treated with inhaled glucocorticosteroids.


Ambient and laboratory observations of organic ammonium salts in PM1.
Ambient measurements of PM1 aerosol chemical composition at Cabauw, the Netherlands, implicate higher ammonium concentrations than explained by the formation of inorganic ammonium salts. This additional particulate ammonium is called excess ammonium (eNH4). Height profiles over the Cabauw Experimental Site for Atmospheric Research (CESAR) tower, of combined ground based and airborne aerosol mass spectrometric (AMS) measurements on a Zeppelin airship show higher concentrations of eNH4 at higher altitudes compared to the ground. Through flights across the Netherlands, the Zeppelin based measurements furthermore substantiate eNH4 as a regional phenomenon in the planetary boundary layer. The excess ammonium correlates with mass spectral signatures of (di-)carboxylic acids, making a heterogeneous acid-base reaction the likely process of NH3 uptake. We show that this excess ammonium was neutralized by the organic fraction forming particulate organic ammonium salts. We discuss the significance of such organic ammonium salts for atmospheric aerosols and suggest that NH3 emission control will have benefits for particulate matter control beyond the reduction of inorganic ammonium salts.


Selective Synthesis of (Z)-Diazadiphosphafulvalene from 2,2'-bis-Azaphosphindole.
The unprecedented 2,2'-bis(azaphosphindole) has been synthesized via a new route. Reaction with NaH afforded a dianion derivative 5, which is easily transformed to alkylated bis(azaphosphindole) or (Z)-P,P,N,N-cisoid diazadiphosphafulvalene. The reaction features good regioselectivity and high steroselectivity. Relatively strong fluorescence is observed with diazadiphosphafulvalenes. The X-ray crystal structure analysis showed that dianion ligand 5 is bonded to two Na atoms in a bridging cis-fashion, which allows the synthesis of diazadiphosphafulvalene in a highly stereoselective approach.


Flow cytometric isolation of drug-like conformational antibodies specific for amyloid fibrils.
Antibodies that recognize specific protein conformational states are broadly important for research, diagnostic and therapeutic applications, yet they are difficult to generate in a predictable and systematic manner using either immunization or in vitro antibody display methods. This problem is particularly severe for conformational antibodies that recognize insoluble antigens such as amyloid fibrils associated with many neurodegenerative disorders. Here we report a quantitative fluorescence-activated cell sorting (FACS) method for directly selecting high-quality conformational antibodies against different types of insoluble (amyloid fibril) antigens using a single, off-the-shelf human library. Our approach uses quantum dots functionalized with antibodies to capture insoluble antigens, and the resulting quantum dot conjugates are used in a similar manner as conventional soluble antigens for multi-parameter FACS selections. Notably, we find that this approach is robust for isolating high-quality conformational antibodies against tau and α-synuclein fibrils from the same human library with combinations of high affinity, high conformational specificity and, in some cases, low off-target binding that rival or exceed those of clinical-stage antibodies specific for tau (zagotenemab) and α-synuclein (cinpanemab). This approach is expected to enable conformational antibody selection and engineering against diverse types of protein aggregates and other insoluble antigens (e.g., membrane proteins) that are compatible with presentation on the surface of antibody-functionalized quantum dots.


Superior mesenteric artery syndrome.
An obstruction of the distal part of the duodenum can occur because of the superior mesenteric artery syndrome (SMAS) after a surgical correction of scoliosis. It is essential to evaluate the risk factors and diagnose the SMAS in time because complications of this condition are life-threatening and it is associated with a high rate of morbidity. Diagnostics of the SMAS is challenging, because it is rare and its symptoms are non-specific. Therefore, in order to better understand the essence of this pathology and to make diagnosis easier we present a rare clinical case of the superior mesenteric artery syndrome after a surgical correction of neuromuscular scoliosis. A 12-year-old girl with a specific development disorder, sensory neuropathy and progressive kypho-scoliosis was admitted to Vilnius University Children's Hospital. The patient had right side 50-degree thoracic scoliosis and an 80-degree thoracic kyphosis. She underwent posterior spinal fusion with hooks and screws from Th1 to L2. On the fourth day after the surgery the patient developed nausea and began to vomit each day 1-2 times per day, especially after meals. The SMAS was suspected and a nasogastric tube was inserted, stomach decompression and the correction of electrolytes disbalance were made. After the treatment, the symptoms did not recur and a satisfactory correction and balance of the spine were made in coronal and sagittal planes. It is extremely important to identify the risk factors of the SMAS and begin preoperative diet supplements before surgical correction of scoliosis for patients with a low body mass index. After the first episode of vomiting following the surgery, we recommend to investigate these patients for a gastrointestinal obstruction as soon as possible. Decompression of the stomach, enteral or parenteral nutrition, and fluid therapy are essential in treating the SMAS.


Antimicrobial resistance status of Enterococcus from Australian cattle populations at slaughter.
Antimicrobial agents are used in cattle production systems for the prevention and control of bacterial associated diseases. A consequence of their use is the potential development of antimicrobial resistance (AMR). Enterococcus faecium and Enterococcus faecalis that are resistant to antimicrobials are of increased concern to public health officials throughout the world as they may compromise the ability of various treatment regimens to control disease and infection in human medicine. Australia is a major exporter of beef; however it does not have an ongoing surveillance system for AMR in cattle or foods derived from these animals. This study examined 910 beef cattle, 290 dairy cattle and 300 veal calf faecal samples collected at slaughter for the presence of enterococci. Enterococcus were isolated from 805 (88.5%) beef cattle faeces, 244 (84.1%) dairy cattle faeces and 247 (82.3%) veal calf faeces with a total of 800 enterococci subsequently selected for AMR testing. The results of AMR testing identified high levels of resistance to antimicrobials that are not critically or highly important to human medicine with resistance to flavomycin (80.2%) and lincomycin (85.4-94.2%) routinely observed. Conversely, resistance to antibiotics considered critically or highly important to human medicine such as tigecycline, daptomycin, vancomycin and linezolid was not present in this study. There is minimal evidence that Australian cattle production practices are responsible for disproportionate contributions to AMR development and in general resistance to antimicrobials of critical and high importance in human medicine was low regardless of the isolate source. The low level of antimicrobial resistance in Enterococcus from Australian cattle is likely to result from comprehensive controls around the use of antimicrobials in food-production animals in Australia. Nevertheless, continued monitoring of the effects of all antimicrobial use is required to support Australia's reputation as a supplier of safe and healthy food.


[Immunochemical studies of human cathepsin D].
Rabbit antiserum against human liver cathepsin D was raised. The antiserum did not cross-react with cathepsins D from tissues of other species (bovine liver, bovine spleen, chicken liver). The study of cathepsins D isolated from human pathologically altered tissues showed that cathepsins from kidney malignant tumor and from myeloleucosis-induced spleen tumor were immunologically identical to the enzyme from normal liver. Cathepsins from liposarcoma and uterine myoma were characterized by partial identity with the enzyme from normal liver. Cathepsins D isolated from various human livers exhibited individual quantitative differences in antigenic properties, a fact to be taken into account in development of an immunochemical method for identification of cathepsin D. The low immunogenicity of human cathepsin D for rabbits and inadequate suitability of these animals for raising appropriate antisera was also considered.


Monte Carlo method based QSAR modelling of natural lipase inhibitors using hybrid optimal descriptors.
Obesity is one of the most provoking health burdens in the developed countries. One of the strategies to prevent obesity is the inhibition of pancreatic lipase enzyme. The aim of this study was to build QSAR models for natural lipase inhibitors by using the Monte Carlo method. The molecular structures were represented by the simplified molecular input line entry system (SMILES) notation and molecular graphs. Three sets - training, calibration and test set of three splits - were examined and validated. Statistical quality of all the described models was very good. The best QSAR model showed the following statistical parameters: r2 = 0.864 and Q2 = 0.836 for the test set and r2 = 0.824 and Q2 = 0.819 for the validation set. Structural attributes for increasing and decreasing the activity (expressed as pIC50) were also defined. Using defined structural attributes, the design of new potential lipase inhibitors is also presented. Additionally, a molecular docking study was performed for the determination of binding modes of designed molecules.


Spontaneous alternation: A potential gateway to spatial working memory in Drosophila.
Despite their ubiquity in biomedical research, Drosophila have yet to be widely employed as model organisms in psychology. Many complex human-like behaviors are observed in Drosophila, which exhibit elaborate displays of inter-male aggression and female courtship, self-medication with alcohol in response to stress, and even cultural transmission of social information. Here, we asked whether Drosophila can demonstrate behavioral indices of spatial working memory in a Y-maze, a classic test of memory function and novelty-seeking in rodents. Our data show that Drosophila, like rodents, alternate their visits among the three arms of a Y-maze and spontaneously favor entry into arms they have explored less recently versus ones they have just seen. These findings suggest that Drosophila possess some of the information-seeking and working memory facilities mammals depend on to navigate through space and might be relevant models for understanding human psychological phenomena such as curiosity.


Using Ecological Momentary Assessment to Identify Common Smoking Situations Among Korean American Emerging Adults.
The present study provides detailed contextual information about smoking habits among young Korean American smokers with the goal of characterizing situations where they are most at risk for smoking. Relevant situational factors included location, social context, concurrent activities, time of day, affective states, and food and beverage consumption. Using ecological momentary assessment (EMA) over 7 days, participants (N = 78) were instructed to respond to smoking prompts (n = 2614) and non-smoking prompts (n = 2136) randomly scheduled throughout the day. At each prompt, participants completed a short survey about immediate contextual factors. We used multilevel models to evaluate the association between contextual factors and smoking and further explored the distribution of smoking locations and concurrent activities across each social context and reason for smoking. Compared to non-smoking events, smoking events were associated with being outside, the presence of Korean friends, socializing, consuming alcohol, and experiencing more stress relative to one's average stress level (all ps < .01). Further analyses involving only smoking events showed that when participants smoked alone, they were most commonly at home (50 %) and most often studying/working (28 %). When smoking with Korean friends, participants were most often outside (38 %) and socializing (54 %). When smoking to reduce craving, participants were most often at home (39 %) and studying/working (25 %). To our knowledge, this is the first study to provide detailed descriptions of real-time smoking contexts among young Korean American smokers. Information with this level of granularity is needed to develop effective just-in-time adaptive interventions (JITAIs) for smoking cessation.


Formulation and statistical optimization of a novel crosslinked polymeric anti-tuberculosis drug delivery system.
The crux of this research was the pragmatic investigation into the formulation of a reconstitutable multiparticulate anti-tuberculosis drug delivery system for facilitated administration for the attainment of segregated gastrointestinal (GI) delivery of rifampicin (RIF) and isoniazid (INH) in order to address issues of unacceptable RIF bioavailability on coadministration with INH. Ionotropically crosslinked polymeric enterospheres for delivery of INH to the small intestine were developed via a response surface methodology for the design and optimization of the formulation and processing variables. A 3(4) Box-Behnken statistical design was constructed. The concentration of zinc sulfate salting-out and crosslinking electrolyte, the crosslinking reaction time, the drying temperature (DT), and the concentration of triethyl citrate plasticizer were varied for determination of their effect on the molar amount of zinc (n(Zn)) incorporated in the crosslinked enterosphere, drug entrapment efficiency (DEE), and mean dissolution time (MDT) at t(2h) in acidic media (0.1 M HCl). Complexometric determination of zinc cations (Zn(2+)) revealed that 23.70-287.89 mol of Zn(2+) per mole of polymer were implicated in crosslink formation. DEE of 27.92% to 99.77% were obtained. Drug release at t(2h) ranged from 1.67% to 73.04%. The salting-out and crosslinking agent significantly affected n(Zn) (p = 0.034) and the DEE (p = 0.000), as did the concentration of plasticizer employed (p = 0.000 and 0.002, respectively). High DTs (>42.5 degrees C) also significantly improved DEE (p = 0.029). ZnSO(4) had a significant effect on the MDT (p = 0.000). A dry dispersible multiparticulate system incorporating the optimally designed INH-loaded enterospheres and RIF was developed. Bivariate regression analysis of UV spectrophotometric absorbance data allowed in vitro resolution of RIF and INH release at simulated gastric pH.


Rapid development of chylothorax in patient with propofol-induced coma.
A woman presented with new onset of a progressive ataxia. Subsequently, she underwent resection of a ponto-cerebellar maeningioma. Ten days later a chylothorax developed. Although the exact aetiology of the chylothorax is unclear, an acute obstruction of common chyle duct with a concomitant lipophilic infusion of propofol seems most likely to be a culprit for rapid increase in the size of the pleural effusions.


Vulnerabilities of the mentalization-based models of vulnerability: A rejoinder to commentaries on the special issue on mentalization in borderline personality disorder.
Fonagy and Sharp read the commentaries with interest, respect, and deep gratitude. Interest, because, consistent with their mentalization-based approach, they discover most about themselves through the eyes of others. Respect, because all the commentators are major contributors to the field whose contributions deserve special issues in their own right. And finally, deep gratitude for the time and effort they took to review our contributions with thoughtfulness and insight. Fonagy and Sharp hope that the set of articles that they have brought together for this special section, in combination with the thoughtful commentaries previously discussed, will further stimulate constructive dialogue around the potential of mentalizing as a translational target. They are grateful to the editors of this journal for their assistance in laying the foundation for this continued dialogue.


Acute cardiovascular exercise promotes functional changes in cortico-motor networks during the early stages of motor memory consolidation.
A single bout of cardiovascular exercise performed immediately after practicing a visuo-motor tracking task has been shown to improve the long-term retention of this motor skill through an optimization of the memory consolidation process. The mechanisms underlying the time-dependent effects of acute cardiovascular exercise on motor memory consolidation, however, remain poorly understood. In this study, we sought to determine the impact of a single bout of cardiovascular exercise performed immediately after motor skill practice on those mechanisms using electroencephalography (EEG) and electromyography (EMG). Specifically, we assessed exercise-induced changes in the activity and connectivity of cortico-motor networks during early consolidation and the impact of these changes on skill retention. Participants practiced a visuo-motor tracking task followed by either a short bout of intense exercise or a rest period. EEG along with EMG data of hand muscles were collected during the production of low-force isometric contractions. Event-related desynchronization, functional connectivity and corticomuscular coherence were measured at baseline, 30, 60 and 90 min after the bout of exercise or the rest period. Improvements in motor memory were inferred via retention tests of the motor skill performed 8 and 24 h after motor practice. We found that participants who performed the single bout of exercise showed better motor skill retention 24 h after motor practice. This improvement in skill retention in the exercise group was associated with significant decreases in beta-band event-related desynchronization in EEG electrodes located over the left sensorimotor areas. We also found that after exercise, alpha-, and even more significantly, beta-band functional connectivity, increased between EEG electrodes located over left and right sensorimotor areas. The exercise group also showed greater beta-band corticomuscular coherence but only in a small number of electrodes. Neither functional connectivity nor corticomuscular coherence measures correlated with skill retention scores. This is the first study exploring brain mechanisms underlying the summative effects of motor learning and cardiovascular exercise on motor memory consolidation. We have identified potential neural substrates through which a single bout of acute exercise, when performed in close temporal proximity to motor practice, strengthens motor memories. Our findings provide new mechanistic insights into a better understanding of the complex temporal relationship existing between cardiovascular exercise and motor memory consolidation.


[Rotavirus and malabsorption. Immunofluorescence microscopy studies of small intestine specimens].
Only 20% of the total of diarrheas in childhood are caused by bacteria . Compared to it, very often the causes for such diseases are viruses, especially rotavirus. The virus - localisation is known to be in enterocytes of the duodenal or jejunal mucosa. So it is probable that a destruction of villous structure linked with diminishing of enzyme activities-especially of lactase--can occur. 53 mucosa specimens were investigated from children by means of fluorescence microscopy. Cryo-cut-slices (8-10 mu) were fixed in acetone and marked with self-prepared rotavirus-hyperimmuneserum (against SA11-virus) and examined using the microscope Fluoval. The distribution of fluorescence along the villi or flat surface was semiquantitatively evaluated. All the investigated children - aged 1-15 years - had been suspected for malabsorption. In 23 of them rotavirus antigen was detected and partly a low activity of disaccharidases, especially of lactase, but also there were simultaneously 7 cases of confirmed coeliac disease in this group. So we conclude: In some patients the rotavirus infection is a complication of malabsorption syndromes; or in other cases it is an asymptomatic accidental finding in the small intestine mucosa.


Transecting the hypogastric nerve to uncover the bladder-inhibitory pathways involved with saphenous nerve stimulation in anesthetized rats.
Saphenous (SAFN) nerve stimulation was recently shown in anesthetized rats to elicit bladder-inhibitory responses in a frequency-dependent manner; however, the mechanism of action is unknown. The goal of this study was to investigate the potential role of the hypogastric nerve (HGN) in this inhibitory pathway by examining stimulation-evoked changes in bladder function under four different experimental conditions: (1) HGN intact, saline infusion (HGNi-s), (2) HGN transected, saline infusion (HGNt-s), (3) HGN intact, acetic acid (AA) infusion (HGNi-a), and (4) HGN transected, AA infusion (HGNt-a). Experiments were conducted in 33 urethane-anesthetized female rats, where continuous bladder infusion was provided through a suprapubic catheter. The experimental protocol involved two, 40-min stimulation trials in which electrical pulses were applied to the SAFN at a set frequency (10 Hz) and two different amplitudes (50 μA and 100 μA). In all experimental groups, SAFN stimulation resulted in complete suppression of bladder activity with an incidence rate of 25% to 50%. However, significant changes in the measured urodynamic changes (e.g., basal pressure, contraction amplitude, and inter-contraction interval) were found only in the HGNt-a animals. Our findings suggest that the HGN does not mediate the inhibitory effects of SAFN stimulation and that bladder inhibition is achieved through a different mechanism of action.


Dermatologic problems in the elderly.
Age-related skin changes place older adults at risk for a variety of dermatologic problems, ranging from xerosis, or dry skin, to malignant melanoma, a life-threatening condition. Primary care providers must differentiate rashes caused by fungal infections, eczematous conditions, viral infections, drug reactions, and other common causes in this age group. Providers should be familiar with dermatologic therapy that may involve topical preparations, oral medications, and surgical methods. In addition, patient education about symptom treatments, skin hygiene, and preventive measures can greatly improve the clinical condition and quality of life of older adults.


Plasmon-induced oxidation of gold nanoparticles on TiO2 in the presence of ligands.
The mechanism of plasmon-induced charge separation of gold nanoparticles (Au NPs) on TiO2 was investigated with the help of anionic ligands. Au NPs are oxidized in the presence of KX (X = SCN, Br or Cl), chiefly via direct oxidation to [AuX4](-). The reactivity of Au NPs depends on the solution pH, the type of anion ligands and the excitation wavelength, suggesting that the photopotential of Au NPs during plasmon-induced charge separation depends on both the flatband potential of TiO2 and the energy of irradiated photons. The results indicate that the reactivity and efficiency of the plasmon-induced charge separation and accompanying reactions can be tuned and optimized by changing those factors.


Fluorescence of aromatic amines and their fluorescamine derivatives for detection of explosive vapors.
Nitroaromatics (such as dinitrotoluene, trinitrotoluene, and nitrobenzene) found in explosive vapors from buried landmines can be reduced to aminoaromatics by a novel process involving Pd metal nanocatalysts prepared in supercritical fluid carbon dioxide and supported on multi-walled carbon nanotubes. These aminoaromatics are fluorescent and, if desired, the fluorescence yield can be increased and the fluorescence maxima shifted further toward the red by reaction with appropriate derivatizing agents such as fluorescamine. Corrected spectra for these chemicals and their derivatives are included. Subpicomolar detection limits have already been achieved using a laboratory spectrofluorometer with a 150 W Xe arc lamp. Using lasers as excitation sources, this approach has the potential for developing a field sensor competitive with other methods currently used for detecting explosive vapors from land mines.


Pharmacokinetics of ketamine in man.
A method for the analysis of ketamine and of its metabolites is described using gas-liquid chromatography for separation and flame ionization detection. The lower limit of detection for ketamine in serum was 0.025 mug/ml. The pharmacokinetic behaviour of ketamine after intravenous injection may be described in terms of an open two-compartment model. The serum half-life of ketamine was in alpha-phase about 11 min, the predominant half-life for the beta-phase 2.5 h. The half-life of ketamine and its metabolities in urine was comparable to that in serum. It could be shown that the duration of anaesthesia is not only correlated ti ist rapid metabolic breakdown and elimination, but also to the distribution of the drug peripheral tissue.


Telemedicine and its transformation of emergency care: a case study of one of the largest US integrated healthcare delivery systems.
Innovative methods for delivering healthcare via the use of technology are rapidly growing. Despite the passage of the Affordable Care Act, emergency department visits have continued to rise nationally. Healthcare systems must devise solutions to face these increasing volumes and also deliver high quality care. In response to the changing healthcare landscape, New York Presbyterian Hospital has implemented a comprehensive enterprise wide digital health portfolio which includes the first mobile stroke treatment unit on the east coast and the first emergency department-based digital emergency care program in New York City.


Quality of Life Following Salvage Endoscopic Nasopharyngectomy in Patients With Recurrent Nasopharyngeal Carcinoma: A Prospective Study.
Background: This study aimed to assess the effect of endoscopic nasopharyngectomy in patients with recurrent nasopharyngeal carcinoma (NPC) on site-specific and sinonasal-related quality of life (QoL) before and after surgery using validated instruments. Methods: Consecutive adult patients with recurrent NPC, who were treated via salvage endoscopic nasopharyngectomy, were prospectively enrolled at a single institution from January 2018 to December 2019. Each patient completed the Anterior Skull Base Questionnaire (ASBQ) and the 22-Item Sino-Nasal Outcome Test (SNOT-22) preoperatively, and then at regular intervals after surgery to assess their perceived QoL. Results: Forty patients fulfilled the inclusion criteria. The median follow-up was 12 months (range, 2-24 months). Overall scores on the ASBQ and SNOT-22 at 3 or 12 weeks after surgery decreased significantly compared with before surgery (p < 0.05). At 6 months and 1 year postoperatively, there was no significant difference from the preoperative score. Subtotal resection was associated with worse overall ASBQ scores at 6 months and 1 year after endoscopic nasopharyngectomy (p < 0.05). Worse QoL was also associated with advanced T stage (rT3 and rT4) and pathological World Health Organization type III. Sex, age (<50 years), tumor necrosis, lymph node metastasis, and use of a nasoseptal flap approach did not impact postoperative QoL. Conclusions: Site-specific and sinonasal-related QoL, measured using validated tools, demonstrated an overall maintenance of postoperative compared with preoperative QoL. Endoscopic endonasal resection is a valuable management choice in patients with recurrent NPC. In addition, subtotal resection was an important factor that negatively influenced postoperative QoL; as such, gross-total resection should be attempted in all patients to optimize QoL after surgery.


Inhibition by divalent metal ions of human histidine triad nucleotide binding protein1 (hHint1), a regulator of opioid analgesia and neuropathic pain.
Human histidine triad nucleotide binding protein 1 (hHint1) is a purine nucleoside phosphoramidase and adenylate hydrolase that has emerged as a potential therapeutic target for the management of pain. However, the molecular mechanism of Hint1 in the signaling pathway has remained less clear. The role of metal ions in regulating postsynaptic transmission is well known, and the active site of hHint1 contains multiple histidines. Here we have investigated the effect of divalent metal ions (Cd2+, Cu2+, Mg2+, Mn2+, Ni2+, and Zn2+) on the structural integrity and catalytic activity of hHint1. With the exception of Mg2+, all the divalent ions inhibited hHint1, the rank of order was found to be Cu2+ >Zn2+ >Cd2+ ≥Ni2+ >Mn2+ based on their IC50 and kin/KI values. A crystal structure of hHint1 with bound Cu2+ is described to explain the competitive reversible inactivation of hHint1 by divalent cations. All the metal ions exhibited time- and concentration- dependent inhibition, with the rate of inactivation highly dependent on alterations of the C-terminus. With the exception of Cu2+; restoration of inhibition was observed for all the metal ions after treatment with EDTA. Our studies reveal a loss in secondary structure and aggregation of hHint1 upon incubation with 10-fold excess of copper. Thus, hHint1 appears to be structurally sensitive to irreversible inactivation by copper, which may be of neurotoxicological and pharmacological significance.


Roles of Fas/FasL-mediated apoptosis and inhibin B in the testicular dysfunction of rats with left-side varicocele.
We investigated the role of the Fas/FasL signalling pathway and inhibin B expression in rats with an experimentally induced left-side varicocele. Forty-five Sprague Dawley (SD) male rats were randomly divided into three groups in average: control group, sham group and experimental group. The expression of inhibin B in the rat left testis was analysed at the mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting respectively. The expressions of Fas, FasL and caspase-3 in the left testis were measured by RT-PCR and immunofluorescence. The apoptosis index (AI) was measured by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Both the mRNA and protein of inhibin B were significantly reduced in the experimental group compared with that in the control group or the sham group. The expression of Fas, FasL and caspase-3 in the experimental group was significantly increased compared to that in the control group or the sham group. The concentration of serum inhibin B was also inversely related to circulating FSH concentrations and positively correlated with sperm count. It is concluded that Fas/FasL system may play an important role in apoptosis of rats with experimental varicocele and inhibin B could reflect spermatogenesis function.


Nurses' perceptions of the content, relevance and usefulness of the quality of life concept in relation to nursing practice.
The aim of this study was to investigate how nurses define the quality of life concept and if they find it relevant and useful for their daily practice. Eighteen nurses recruited from a neurological and rheumatologic unit at a Norwegian University Hospital filled in a questionnaire consisting of four open-ended questions in relation to the definition of quality of life, the concept's relevance for their daily practice, characteristics of a patient experiencing good vs. bad quality of life and ways to improve quality of life. The findings showed that nurses associated quality of life with the individual's experience of meaning in life. Meaning in life was associated with good mood, positive self-concept, being solution-oriented, initiative to self-care and having a close relationship to significant others. Further, the nurses expressed that their way of being towards the patients in terms of give time, encourage, inspire confidence, be present and listen was the most important intervention to maintain or increase patients' quality of life.


Prescription drug misuse: quantifying the experiences of New Zealand GPs.
The misuse of prescription drugs for their psychoactive effects is an international problem. To date, there is a paucity of quantitative data on prescription drug misuse (PDM) in New Zealand, especially data investigating the experiences of general practitioners (GPs). To quantify GPs' experiences regarding PDM in New Zealand in terms of the extent of the problem, challenges faced, problem drugs, and actions taken by GPs once PDM is suspected. A cross-sectional postal survey of a random sample of 300 GPs in New Zealand was undertaken. A 45.7% response rate was achieved. Approximately two-thirds of GPs (65.9%) had diagnosed at least one patient with a PDM problem in the last 12 months. Thirty percent of respondents indicated that they had been faced with at least one challenge in the past 12 months, with 'verbal threats' being the most common of these (16.3%). Benzodiazepines and opioids were identified as the most problematic drug classes. The action usually taken by the greatest number of GPs once they suspected PDM was to 'document it' (97.9%) followed closely by 'suggest an alternative drug' (96.7%) and 'refrain from prescribing the drug' (91.9%). PDM is an issue for GPs. The findings from this study have highlighted the need for further research into this concerning issue, specifically further quantification of the size of the problem in the New Zealand general population. There is also a need for the development and implementation of interventions to help minimise and better manage PDM in New Zealand.


Substance use and mild traumatic brain injury risk reduction and prevention: a novel model for treatment.
Traumatic brain injury (TBI) and substance use disorders (SUDs) frequently co-occur. Individuals with histories of alcohol or other drug use are at greater risk for sustaining TBI, and individuals with TBI frequently misuse substances before and after injury. Further, a growing body of literature supports the relationship between comorbid histories of mild TBI (mTBI) and SUDs and negative outcomes. Alcohol and other drug use are strongly associated with risk taking. Disinhibition, impaired executive function, and/or impulsivity as a result of mTBI also contribute to an individual's proclivity towards risk-taking. Risk-taking behavior may therefore, be a direct result of SUD and/or history of mTBI, and risky behaviors may predispose individuals for subsequent injury or continued use of substances. Based on these findings, evaluation of risk-taking behavior associated with the co-occurrence of SUD and mTBI should be a standard clinical practice. Interventions aimed at reducing risky behavior among members of this population may assist in decreasing negative outcomes. A novel intervention (Substance Use and Traumatic Brain Injury Risk Reduction and Prevention (STRRP)) for reducing and preventing risky behaviors among individuals with co-occurring mTBI and SUD is presented. Areas for further research are discussed.


Life course impacts of mild intellectual deficits.
We identified 201 individuals who obtained IQs of 85 or below in high school and participated in the Wisconsin Longitudinal Study (a prospective longitudinal study that followed sample members from age 18 through age 53). Their life course development was contrasted with their siblings who obtained IQs above 100. Life course outcomes were assessed in five domains: Education and Occupational Attainment, Family Formation, Social Participation and Support, Physical Health, and Psychological Well-Being. Compared to their higher IQ sibling, low-IQ individuals completed less schooling, had less prestigious occupations, rated themselves less physically healthy, and reported lower levels of psychological well-being. Differences were not evident, however, in patterns of family formation, social support, job satisfaction, or objective measures of physical health.


Pressurized water extraction of β-glucan enriched fractions with bile acids-binding capacities obtained from edible mushrooms.
A pressurized water extraction (PWE) method was developed in order to extract β-glucans with bile acids-binding capacities from cultivated mushrooms (Agaricus bisporus, Lentinula edodes, and Pleurotus ostreatus) to be used as supplements to design novel foods with hypocholesterolemic properties. Extraction yields were higher in individual than sequential extractions being the optimal extraction parameters: 200°C, 5 cycles of 5 min each at 10.3 MPa. The crude polysaccharide (PSC) fractions, isolated from the PWE extracts contained mainly β-glucans (including chitooligosaccharides deriving from chitin hydrolysis), α-glucans, and other PSCs (hetero-/proteo-glucans) depending on the extraction temperature and mushroom strain considered. The observed bile acids-binding capacities of some extracts were similar to a β-glucan enriched fraction obtained from cereals.


Coronary heart disease. Differential hemodynamic, metabolic, and electrocardiographic effects in subjects with and without angina pectoris during atrial pacing.
Right atrial pacing was performed in 41 subjects with coronary heart disease. Twenty developed angina pectoris during pacing, while 21 did not. The extent of coronary artery disease, as judged by selective cinearteriography, was similar in the two groups. Both had significant increases in heart rate and pressure-time per minute, but there was no significant difference in either of these parameters between groups. Among the hemodynamic parameters measured, the only statistically significant change was in the cardiac index which fell slightly but significantly in the angina group. There were no differences in myocardial oxygen extraction either within each group or between groups. In the angina group, however, 14 of 20 subjects exhibited abnormal myocardial lactate metabolism during pacing. The mean change was highly significant (P < 0.01). In the nonangina group, eight of 21 subjects had abnormal lactate metabolism during pacing and the mean change was significant (P < 0.05). There was no correlation between abnormal lactate metabolism and electrocardiographic evidence of myocardial ischemia in either group. Sublingual nitroglycerin, given to five subjects with angina while pacing was continued, resulted in prompt relief of symptoms, but abnormal lactate metabolism and ST-segment depression were unaffected after 10 min. By contrast, when anginal symptoms were relieved in five subjects by cessation of pacing, symptomatic improvement was accompanied by marked improvement in lactate metabolism after 10 min. Although angina pectoris appears to be related statistically to subnormal left ventricular function and abnormal lactate metabolism, there is significant individual variation.


Refining the World Health Organization Definition: Predicting Autopsy-Defined Sudden Arrhythmic Deaths Among Presumed Sudden Cardiac Deaths in the POST SCD Study.
Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs. Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors-an emergency medical system set and a comprehensive set adding medical record data-to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts. Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67-0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70-0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36-0.57), and specificity was 0.90 (0.79-0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64-0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71-0.79]) added use of β-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases <1 hour (n=59) were classified as SAD, sensitivity was 0.18 (0.13-0.22) and specificity was 0.95 (0.90-0.97). Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to <1 hour since last normal, at the cost of sensitivity.


Affective Processing in Pediatric Bipolar Disorder and Offspring of Bipolar Parents.
Bipolar disorder (BD) is characterized by biased processing of emotional information. However, little research in this area has been conducted in youth with BD and at-risk individuals. The goal of this study was to determine whether children with BD displayed comparable or more severe manifestations of this bias relative to offspring of parents with BD. The sample (n = 57 children and adolescents) included 18 individuals with BD (age: 13.63 ± 2.99; 8 females), 16 offspring of parents with BD (age: 11.83 ± 2.96; 9 females) and 23 healthy controls (HC) (age: 12.789 ± 3.087; 8 females). All participants performed the Affective Go/No-Go (AGN) and the Rapid Visual Processing (RVP) tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Relative to HC, individuals with BD responded faster to correct trials and committed an elevated number of commission errors across all affective conditions of the AGN task. By contrast, BD offspring showed intact performance accuracy but quicker response times than HC. Post-hoc analyses revealed that this behavioral pattern was observed in BD offspring with mental health problems but not in healthy BD offspring. Overall, mean reaction times and total number of errors in the RVP task were comparable across groups. In line with previous findings, subjects with BD encountered difficulties in processing affective information. The tendency toward faster but accurate responses to affective stimuli observed in BD offspring may be a marker of attentional bias toward affective information and constitute a vulnerability marker for mood disorder.


Marchiafava-Bignami-like injury of the corpus callosum in an infant.
We report on a 16-month-old boy who presented with truncal ataxia and intermittent nystagmus. Magnetic resonance imaging (MRI) at 19 months showed a T (2)-hyperintensity of the splenium and the genu of the corpus callosum with extension into the adjacent frontal white matter. Diffusion tensor imaging (DTI) revealed a corresponding area of restricted diffusion, suggesting cytotoxic oedema. The extent and localisation of the signal abnormalities mimic tissue injury as seen in Marchiafava-Bignami disease (MBD). Metabolic investigations were normal. Follow-up imaging at 24 months showed a similar T (2)-hyperintensity of the corpus callosum and white matter while on DTI the cytotoxic oedema had resolved. Clinically a remaining truncal and gait ataxia, clumsiness and a developmental delay is seen. Goal of this case report is (a) to present a rare case of Marchiafava-Bignami-like injury of the corpus callosum in an infant and (b) to discuss the neuroradiological imaging findings including MRI and DTI.


[Determination of trace selenium in herbs of invigorating circulation blood and removing blood stasis by fluorometry].
Selenium in herbs of invigorating circulation blood and removing blood stasis was analysed by fluorometry. The RSD was less than 4.9%, the rate of recovery varied from 96% to 102%. The method has better selectivity. It is operated simply, and is suited for selenium of herbs analysis.


Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor.
Norisoboldine (NOR) is a benzylisoquinoline alkaloid isolated from Radix Linderae, a traditional Chinese medicine. Our previous studies have demonstrated that it produces anti-inflammatory and anti-rheumatoid arthritis effects. The present study was undertaken to explore the analgesic effects of NOR and its potential mechanism in the formalin test and the acetic acid writhing test. Oral administration of NOR dose dependently attenuated the formalin-induced pain responses in the second phase, and reduced formalin-induced paw oedema. It also diminished acetic acid-induced writhing responses but had no effect on acute thermal pain in the hotplate test. The mechanistic studies suggested that the adenosine system, but not the opioid receptor system, is involved in NOR-induced antinociception. Naloxone, a non-selective opioid receptor antagonist, had no effect on NOR-induced analgesic action. However, caffeine (a non-selective adenosine receptor antagonist) completely reversed the analgesic effect of NOR in formalin-induced nociceptive responses in the second phase, and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, a selective adenosine A1 receptor antagonist) completely inhibited NOR-induced analgesia in both formalin-induced nociceptive responses and acetic acid-induced writhing responses. In addition, NOR reduced formalin-induced activation of extracellular signal-regulated kinase and calcium/calmodulin-dependent protein kinase II in the spinal cord, which is also blocked by DPCPX. Furthermore, NOR decreased forskolin-evoked cyclic adenosine monophosphate levels in mouse spinal cord neuronal cultures through the adenosine A1 receptor. Our data demonstrate that NOR produces the analgesic effect in inflammatory pain by a mechanism related to the adenosine system.


Deep learning algorithms to detect diabetic kidney disease from retinal photographs in multiethnic populations with diabetes.
To develop a deep learning algorithm (DLA) to detect diabetic kideny disease (DKD) from retinal photographs of patients with diabetes, and evaluate performance in multiethnic populations. We trained 3 models: (1) image-only; (2) risk factor (RF)-only multivariable logistic regression (LR) model adjusted for age, sex, ethnicity, diabetes duration, HbA1c, systolic blood pressure; (3) hybrid multivariable LR model combining RF data and standardized z-scores from image-only model. Data from Singapore Integrated Diabetic Retinopathy Program (SiDRP) were used to develop (6066 participants with diabetes, primary-care-based) and internally validate (5-fold cross-validation) the models. External testing on 2 independent datasets: (1) Singapore Epidemiology of Eye Diseases (SEED) study (1885 participants with diabetes, population-based); (2) Singapore Macroangiopathy and Microvascular Reactivity in Type 2 Diabetes (SMART2D) (439 participants with diabetes, cross-sectional) in Singapore. Supplementary external testing on 2 Caucasian cohorts: (3) Australian Eye and Heart Study (AHES) (460 participants with diabetes, cross-sectional) and (4) Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) (265 participants with diabetes, cross-sectional). In SiDRP validation, area under the curve (AUC) was 0.826(95% CI 0.818-0.833) for image-only, 0.847(0.840-0.854) for RF-only, and 0.866(0.859-0.872) for hybrid. Estimates with SEED were 0.764(0.743-0.785) for image-only, 0.802(0.783-0.822) for RF-only, and 0.828(0.810-0.846) for hybrid. In SMART2D, AUC was 0.726(0.686-0.765) for image-only, 0.701(0.660-0.741) in RF-only, 0.761(0.724-0.797) for hybrid. There is potential for DLA using retinal images as a screening adjunct for DKD among individuals with diabetes. This can value-add to existing DLA systems which diagnose diabetic retinopathy from retinal images, facilitating primary screening for DKD.


Gastric emptying and orocaecal transit time of meals containing lactulose or inulin in men.
The H(2) breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H(2) which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of (13)C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85.3 (sd 42.8) min) compared with L-S (162.4 (sd 62.6) min) and inulin (292.4 (sd 66.7) min; P = 0.007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0.005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0.05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H(2) breath test.


[Detection of heroin metabolites: 6-monoacetylmorphine and morphine in human hair by GC/MS].
This paper presents a method to detect the main metabolites of heroin: 6-monoacetylmorphine (6-MAM) and morphine (MOR) in human hair using GC/MS-SIM. The hair specimens were washed with special solvents and cut into about 0.5 mm pieces. Ethylmorphine was added as internal standard and HCl solution for hydrolysis. After hydrolysis, 6-MAM and MOR were extracted by a mixture of solvents (chloroform-isopropyl alcohol-heptane 50:17:33). The residue of the extract was derivatized with N-methyl-N-trimethylsilyl trifluoroacetamide(MSTFA), then the trimethylsilyl(TMS)-derivatives were qualitatively and quantitatively analyzed using GC/MS-SIM. The correlation coefficients for 6-MAM and MOR were 0.9996 and 0.9997, respectively. The recoveries of both 6-MAM and MOR were over 50%. The RSD of within-day and between-day was less than 8% and 10%, respectively. The lower limit of detection of both 6-MAM and MOR was 0.5 ng.mg-1. Hair samples of 12 drug abusers were analyzed using this method, 8 of them gave positive results. This method is simple, accurate and sensitive. It is very suitable for routine case work.


Involvement of Prolyl Hydroxylase Domain Protein in the Rosiglitazone-Induced Suppression of Osteoblast Differentiation.
Rosiglitazone is a well-known anti-diabetic drug that increases insulin sensitivity via peroxisome proliferator-activated receptor γ (PPARγ) activation, but unfortunately it causes bone loss in animals and humans. A previous study showed that prolyl hydroxylase domain protein (PHD) plays a role in rosiglitazone-induced adipocyte differentiation. Based on the inverse relationship between adipocyte and osteoblast differentiation, we investigated whether PHD is involved in the effects of rosiglitazone on osteoblast differentiation. Rosiglitazone inhibited osteoblast differentiation in a concentration-dependent manner, and in parallel induced three PHD isoforms (PHD1, 2, and 3). PHD inhibitors and knockdown of each isoform prevented the inhibitory effects of rosiglitazone on osteoblast differentiation and increased the expression of Runx2, a transcription factor essential for osteoblastogenesis. MG-132, a proteasomal inhibitor also prevented the rosiglitazone-induced degradation of Runx2. Furthermore, both increased PHD isoform expressions and reduced osteoblast differentiation by rosiglitazone were prevented by PPARγ antagonists, indicating these effects were mediated via PPARγ activation. In vivo oral administration of rosiglitazone to female ICR mice for 8 weeks reduced bone mineral densities and plasma alkaline phosphatase (ALP) activity, and increased PHD expression in femoral primary bone marrow cells and the ubiquitination of Runx2. Together, this suggests that the rosiglitazone-induced suppression of osteoblast differentiation is at least partly induced via PPARγ-mediated PHD induction and subsequent promotion of the ubiquitination and degradation of Runx2.


Application of an optimized total N-nitrosamine (TONO) assay to pools: placing N-nitrosodimethylamine (NDMA) determinations into perspective.
Although N-nitrosodimethylamine (NDMA) has been the most prevalent N-nitrosamine detected in disinfected waters, it remains unclear whether NDMA is indeed the most significant N-nitrosamine or just one representative of a larger pool of N-nitrosamines. A widely used assay applied to quantify nitrite, S-nitrosothiols, and N-nitrosamines in biological samples involves their reduction to nitric oxide by acidic tri-iodide, followed by chemiluminescent detection of the evolved nitric oxide in the gas phase. We here describe an adaptation of this method for analyzing total N-nitrosamine (TONO) concentrations in disinfected pools. Optimal sensitivity for N-nitrosamines was obtained using a reduction solution containing 13.5 mL glacial acetic acid and 1 mL of an aqueous 540 g/L iodide and 114 g/L iodine solution held at 80 degrees C. The method detection limit for N-nitrosamines was 110 nM using 100 microL sample injections and NDMA as a standard. N-nitrosamines featuring a range of polarities were converted to nitric oxide with 75-103% efficiency compared to NDMA. Evaluation of potential interfering species indicated that only nitrite and S-nitrosothiols were a concern, but both interferences were effectively eliminated using group-specific sample pretreatments previously employed for biological samples. To evaluate the low TONO concentrations anticipated for pools, 1 L samples were extracted by continuous liquid-liquid extraction with ethyl acetate for 24 h, and concentrated to 1 mL. N-nitrosamine recovery during extraction ranged from 37-75%, and there was a potential for artifactual nitrosation of amines during solvent reflux in the presence of significant nitrite concentrations, but not at the low nitrite concentrations prevalent in most pools. Using the 1000-fold concentration factor and 56% average extraction efficiency, the method detection limit would be 62 pM (5 ng/L as NDMA). The TONO assay was applied to six pools and their common tap water source in conjunction with analysis for specific nitrosamines. Even accounting for the range of N-nitrosamine extraction recoveries, NDMA accounted for an average of only 13% (range 3-46%) of the total nitrosamine pool.


Warfarin Quality Metrics for Hospitalized Older Adults.
Background Warfarin's adverse drug events are dangerous, common, and costly. While outpatient warfarin management tools exist, there is a dearth of guidance for inpatients. Objectives We sought to describe a health system's chronic warfarin quality metrics in older inpatients, defined by international normalized ratio (INR) control, explore associations between INR overshoots and clinical outcomes, and identify factors associated with overshoots. Patients/Methods Data on patients 65 years and older who were prescribed chronic warfarin and admitted during January 1, 2014, to June 30, 2016, were extracted through retrospective chart review. We defined overshoots as INRs 5 or greater after 48 hours of hospitalization. Logistic regression modeling was used to determine risks for overshoots and multivariate analysis for overshoots' association with length of stay (LOS), bleeding, and mortality. Results Of the 12,107 older inpatients on chronic warfarin, most were 75 years or older (75.7%), female (51.2%), and white (70.0%). While 1,333 (11.0%) of patients had overshoots during the admission, 449 (33.7%) of these reached overshoots after 48 hours. When stratified by overshoots versus no overshoots, LOS more than doubled (15.6 vs. 6.8 days) and the bleed rate was significantly higher (27.4 vs. 8.3%) in the overshoot group. While overall mortality was small (0.4%), the overshoot group's mortality was significantly higher (3.12 vs. 0.28%). Black race and weight were protective against overshoots; history of heart failure and antibiotic/amiodarone exposure were predictive of overshoots. Conclusion This is the largest study examining warfarin quality metrics for hospitalized adults, specifically older inpatients. Our model may serve as the basis for identifying high-risk warfarin patients to target interventions to reduce adverse drug events.


Determination of body image and sexual adjustment in women with breast cancer after surgery.
The aim of the study is to determine body image, sexual adjustment and the factors affecting them in women with breast cancer after surgery. This descriptive and cross-sectional study was conducted with breast cancer patients admitted to a foundation hospital. Data were collected with the Sexual Adjustment and Body Image Scale, evaluated with t-test, MWU, Kruskall Wallis and correlation analysis. Sexual Adjustment Body Image scale subdimension scores of the patients were 10.81±2.32 for Prior Body Image, 9.69±2.69 for Postbody Image,7.04±1.73 for Prior Sexual Adjustment,7.4±2.34 for Sexual Importance of Breasts and -4.28±2.63 for Impact on Sexual Functioning. A weak positive correlation was found between the patients' body image scores and their sexual adjustment scores. It was found that having a child significantly affected the Prior and Postbody Image scores. There was a significant difference between Prior Sexual Adjustment scores according to income level. Employment had an effect on the Impact on Sexual Functioning subdimension score and presence of a chronic disease affected the Postbody Image and Prior Sexual Adjustment subdimension scores. Having a chronic disease, having children, being employed, and having poor income affect sexual adjustment and body image in women with breast cancer after surgery.


Conceptual problems in the definition and interpretation of attributable fractions.
We have argued that the concept of attributable fraction requires separation into the concepts of excess fraction, etiologic fraction, and incidence-density fraction. These quantities do not necessarily approximate one another, and the etiologic fraction is not generally estimable without strong biologic assumptions. For these reasons, care is needed in deciding which (if any) of the concepts is appropriate for a particular application. It appears that the excess fraction (like incidence proportion) will be most relevant in situations that require only consideration of whether disease occurs by a particular time. In situations that require consideration of when disease occurs, direct measures of effect on incidence time may be as relevant as or more relevant than any attributable fraction. To avoid technical complications, we have not discussed additional problems of causal attribution that can arise when exposure has multiple levels or is sustained over time, and the estimation problems that can arise when considering case-control studies, competing risks, or differential censoring. For more detailed discussions of such problems and proposed solutions, see references 11-20.


Strain engineering of monoclinic domains in K x Na1-x NbO3 epitaxial layers: a pathway to enhanced piezoelectric properties.
A novel concept to obtain a ferroelectric material with enhanced piezoelectric properties is proposed. This approach is based on the combination of two pathways: (i) the evolution of a ferroelectric monoclinic phase and, (ii) the coexistence of different types of ferroelectric domains leading to polarization discontinuities at the domain walls. Each of these pathways enables polarization rotation in the material which is responsible for giant piezoelectricity. Targeted incorporation of anisotropic epitaxial lattice strain is used to implement this approach. The feasibility of our concept is demonstrated for K0.9Na0.1NbO3 epitaxial layers grown on NdScO3 substrates where the coexistence of (100)pc and (001)pc pseudocubic oriented monoclinic domains is experimentally verified. This coexistence results in a complex periodic domain pattern with alternating emergence of ferroelectric in-plane a 1 a 2 and inclined M C monoclinic phases, which differ in the direction of the electrical polarization vector. Our approach opens the possibility to exploit ferroelectric properties in both vertical and lateral directions and to achieve enhanced piezoelectric properties in lead-free material caused by singularities at the domains walls.


The STANISLAS Cohort: a 10-year follow-up of supposed healthy families. Gene-environment interactions, reference values and evaluation of biomarkers in prevention of cardiovascular diseases.
The description of this familial longitudinal cohort was published in this journal 10 years ago, in 1998. To date, 117 publications on the STANISLAS Cohort (SC) have appeared, corresponding to five main categories of results: familial resemblance and heritability; genetics and gene-environment interactions; mRNA and proteins as gene products; reference values and biological variations of proteins; and finally preventive medicine and prepathological epidemiological data. More than 600 data values on demographic and laboratory data have been collected on each individual taking part out of the 1006 families at the beginning and for all three recruitments. Serum and plasma are stored in liquid nitrogen for all participants for all three recruitments. DNA has been extracted from all participants and mRNA from 357 families. They are stored at -80 degrees C. Owing to the SC study, heritability and many gene-environment interactions have been described. The expression of 166 genes related to cardiovascular diseases was measured in peripheral blood mononuclear cells RNA. Reference values for proteins and vitamins have been established in addition to reference values for the carotid and femoral intima media thickness in adults and children. The data obtained contribute to a better understanding of the relation between the studied polymorphisms (161 polymorphic sites) and health, and predisposition to obesity, high blood pressure and metabolic syndrome. To the best of our knowledge, the SC study is internationally the only longitudinal family cohort of subjects who are presumed to be healthy, which enables the study of the chain DNA-RNA-proteins.


Rheological properties, oxidative stability, and tocopherol content during storage of fried dough made with Silky fowl egg: comparison with hen egg.
Eggs from Silky fowl and White Leghorn hens were used to prepare fried dough. The rheological properties, lipid oxidative stability, and trans, trans-2,4-decadienal and tocopherol content of fried dough made with Silky fowl egg were compared with dough made with hen egg. The fried dough was stored in a glass bottle at 50 degrees C in the dark for 12 d. The fried dough made with Silky fowl egg showed little change in hardness and adhesion for 12 d at 50 degrees C. However, in the fried dough made with hen egg, hardness increased drastically and adhesion decreased. The fried dough made with Silky fowl egg showed restricted generation of hydroperoxides during 12 d in storage at 50 degrees C. In contrast, the fried dough made with hen egg showed an increased amount of hydroperoxides during the 12-d storage. The lowest concentration of trans, trans-2,4-decadienal was observed in fried dough made with Silky fowl egg, whereas the concentration of trans, trans-2,4-decadienal in fried dough made with hen egg was significantly increased. Total tocopherols in fried dough made with Silky fowl egg were degraded 23.3 mg/100 g of fried dough by the end of the experimental period at 50 degrees C. In contrast, total tocopherols in the fried dough made with hen egg were degraded 40 mg/100 g of fried dough. The ratio of unsaturated fatty acids to saturated fatty acids decreased and the hydroperoxide content increased with storage time. The unsaturated fatty acid:saturated fatty acid ratio and hydroperoxide and tocopherol contents were lower in fried dough made with Silky fowl egg than in that made with hen egg, indicating decreased lipid oxidation. The present experiment suggests that the use of Silky fowl egg could improve the rheological properties, oxidative stability, and trans, trans-2,4-decadienal and tocopherol contents of fried dough.


Comparative Proteome Reveals Metabolic Changes during the Fruiting Process in Flammulina velutipes.
Understanding the molecular mechanisms regulating the fruiting process in macro-fungi, especially industrially cultivated mushrooms, has long been a goal in mycological research. To gain insights into the events accompanying the transformation of mycelia into fruit-bodies in Flammulina velutipes, proteins expressed characteristically and abundantly at primordium and fruit-body stages were investigated by using the iTRAQ labeling technique. Among the 171 differentially expressed proteins, a total of 68 displayed up-regulated expression levels that were associated with 84 specific KEGG pathways. Some up-regulated proteins, such as pyruvate carboxylase, aldehyde dehydrogenase, fatty acid synthase, aspartate aminotransferase, 2-cysteine peroxiredoxin, FDS protein, translation elongation factor 1-alpha, mitogen-activated protein kinases (MAPKs), and heat-shock protein 70 that are involved in carbohydrate metabolism, carotenoid formation, the TCA cycle, MAPK signaling pathway, and the biosynthesis of fatty acids and branched-chain amino acids, could serve as potential stage-specific biomarkers to study the fruiting process in F. velutipes. Knowledge of the proteins might provide valuable evidence to better understand the molecular mechanisms of fruit-body initiation and development in basidiomycete fungi. Furthermore, this study also offers valuable evidence for yield improvement and quality control of super golden-needle mushroom in practice.


Relaxin and progesterone during pregnancy and the post-partum period in association with live and stillborn calves in bottlenose dolphins (Tursiops truncatus).
The objectives of this study were to validate a relaxin and progesterone RIA for use in bottlenose dolphins, and quantify and characterize both hormones in extracts of placental tissue and serum collected during pregnancy and the post-partum period, and compare the results between dolphins with live and stillborn calves. In Experiment 1, validation of a heterologous relaxin and progesterone RIA involved specific displacement of antibody-bound radiolabeled human relaxin or progesterone in response to increasing volumes of pooled pregnant dolphin serum and amounts of respective hormone standards added to a fixed volume of serum. The displacement curves were considered parallel and additive relative to respective standard curves. In Experiment 2, immunoreactive relaxin and progesterone were detected in placental extracts and, in corresponding serum samples, concentrations of both hormones were higher during the pre-partum than post-partum periods. Circulatory concentrations of progesterone decreased (P < 0.05) from relatively high concentrations during early and mid-pregnancy to intermediate concentrations by late pregnancy (month effect, P < 0.0001) in dolphins with live births, whereas, in dolphins with stillbirths, the decrease in progesterone began earlier (month-by-birth status interaction, P < 0.007); mean concentrations were lower at mid- (37%, P < 0.06) and late (25%) pregnancy. Temporally, relaxin increased (P < 0.05) progressively from relatively low concentrations during early pregnancy to high concentrations during late pregnancy (month effect, P < 0.0001) and was not different between birth statuses (birth status effect, P = 0.76; month-by-birth status interaction, P = 0.17). Even though the interaction did not reach significance, mean relaxin concentrations were 42%, 29%, and 34% lower at early, mid-, and late pregnancy, respectively, in dolphins with stillbirths than in those with live births. In conclusion, the pregnancy-specific increase in serum concentrations of relaxin and lower concentrations of both relaxin and progesterone in association with stillbirths suggest the potential for relaxin to be used diagnostically to determine pregnancy status, and one or both hormones to be used to assess placental function, and, perhaps, fetal well-being in bottlenose dolphins and other cetaceans.


Genomewide association mapping and pathway analysis of meat tenderness in Polled Nellore cattle.
Brazil is one of the world's largest beef exporters, although the product has a low price due to quality issues. The meat exported by Brazil is considered medium and low quality by international buyers, mainly due to lack of tenderness. The predominant Zebu breeds (80% Nellore) are known for producing tougher beef than taurine breeds. Nonetheless, some studies have shown that there is substantial genetic variability for tenderness within the Nellore breed, although it is a difficult trait to improve by conventional selection methods. Therefore, the aim of this study was to perform a genomewide association study (GWAS) and a gene set enrichment analysis to identify genomic regions and biologically relevant pathways associated with meat tenderness in Polled Nellore cattle. Data consisted of Warner-Bratzler shear force values of LM from 427 Polled Nellore animals divided into 3 experimental slaughters (years 2005, 2008, and 2010). The animals were genotyped with either the Illumina BovineHD BeadChip (777k, on 61 samples) or the GGP Indicus HD chip (77k, on 366 samples). Single nucleotide polymorphisms were excluded when the call rate was <90%, the Hardy-Weinberg proportions -value was <1% (Fisher exact test, Bonferroni adjusted), and the minor allele frequency was <1%. Imputation from the GGP Indicus HD chip to the Illumina BovineHD BeadChip was performed using the FImput program. Genomewide association analysis was performed using the Efficient Mixed Model Association eXpedited (EMMAx) and the population parameters previously determined (P3D) methods. The GWAS was complemented with a gene set enrichment analysis performed using the FatiGO procedure. Significant markers ( < 0.0001) explaining a larger proportion of variation than other significant SNPs were located on chromosomes 3, 13, 17, 20, 21, and 25, indicating QTL associated with meat tenderness throughout the genome. Additionally, gene set analysis identified 22 Gene Ontology functional terms and 2 InterPro entries that showed significant enrichment of genes associated with tenderness. The functional categories included protein tyrosine and serine/threonine kinase activity, calcium ion binding, lipid metabolic process, and growth factors, among others. These results help to elucidate the genetic architecture and metabolic pathways underlying this trait, which is of extreme economic and social importance to Brazil, because Nellore is the dominant beef cattle breed in the country.


Electrospun Nanofibrous UV Filters with Bidirectional Actuation Properties Based on Salmon Sperm DNA/Silk Fibroin for Biomedical Applications.
In this study, we dissolved Bombyx mori degummed silk [i.e., silk fibroin (SF)] and salmon sperm deoxyribonucleic acid (DNA) in water and used a bioinspired spinning process to obtain an electrospun nanofibrous SF-based patch (ESF). We investigated the bidirectional macroscale actuation behavior of ESF in response to water vapor and its UV-blocking properties as well as those of ESF/DNA films. Fourier transform infrared (FTIR) results suggest that the formation of β-sheet-rich structures promotes the actuation effect. ESF/DNA film with high-ordered and β-sheet-rich structures exhibits higher electrical conductivity and is water-insoluble. Given the intrinsic ability of both SF and DNA to absorb UV radiation, we performed biological experiments on the viability of keratinocyte HaCaT cells after exposure to solar spectrum components. Our findings indicate that the ESF/DNA patch is photoprotective and can increase the cellular viability of keratinocytes after UV exposure. Furthermore, we demonstrated that ESF/DNA patches treated with water vapor can serve as suitable scaffolds for tissue engineering and can improve tissue regeneration when cellularized with HaCaT cells. The 3D shape morphing capability of these patches, along with their potential as UV filters, could offer significant practical advantages in tissue engineering.


Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants.
The ubiquitin proteasome system (UPS) has garnered much attention due to its potential for the development of therapeutics. Following a successful clinical application of general proteasome inhibitors much effort has been devoted to targeting individual UPS components including E3 enzymes and deubiquitinases that control specificity of ubiquitination. Our group has developed a novel approach for targeting the UPS proteins using engineered ubiquitin variants (Ubvs). These drug-like proteins can serve as valuable tools to study biological function of UPS components and assist in the development of small molecules for clinical use. In this review, we summarize studies of Ubvs targeting members of three major families, including deubiquitinases, HECT E3 ligases, and CRL E3 ligases. In particular, we focus on Ubv binding mechanisms, structural studies, and effects on enzyme function. Furthermore, new insights gained from the Ubvs are discussed in the context of small molecule studies.


Factors Contributing to Patient Satisfaction and Expectations following Computer-Assisted Total Knee Arthroplasty.
The purpose of this study was to determine which factors contribute to patient satisfaction and expectations after total knee arthroplasty (TKA). A total of 109 patients (130 knees) with knee osteoarthritis who underwent primary TKA with navigation were studied. Intraoperative mediolateral laxity was measured. The factors including mediolateral laxity that affected patient satisfaction and expectations were evaluated using the 2011 Knee Society Score. Patient satisfaction after TKA correlated positively with symptoms and functional activities, and negatively with old age in univariate analysis. Multivariate analysis showed that symptoms and functional activities remained statistically significant; however, old age showed no difference. Patient expectations after TKA correlated positively with symptoms and functional activities, and negatively with mediolateral laxity at 60 degrees in univariate analysis. Multivariate analysis showed that symptoms, functional activities, and mediolateral laxity at 60 degrees remained statistically significant. In conclusion, midflexion instability was associated with worse expectations.


[Determination of 7 bio-active alkaloids in Stephania plants by RP-HPLC].
Seven bio-active alkaloids (stepholidine, sinoacutine, isocorydine, l-tetrahydropalmatine, crebanine, fanchinoline and tetrandrine) in Stephania plants were determined by RP-HPLC, using UV detection (282 nm) and gradient elution. The reversed phase system consisted of ODS column and methanol-water-triethylamine as mobile phase. The flow rate was 1.0 ml.min-1. Good linearity between peak heights and concentrations of the alkaloids was obtained in the concentration range. The HPLC method proved accurate, precise and sensitive. The results showed that there were some differences in the occurrence and content of the alkaloids between various species and between the same species from different habitats and collecting time. Based on the results, some species with high content of the 7 bio-active alkaloids were selected. The study provided some useful information for the utilization of medicinal plant resources in the genus Stephania.


Purification and characterization of extracellular poly(beta-D-1,4-mannuronide) lyase from Dendryphiella salina IFO 32139.
An extracellular endo poly(beta-D-1,4-mannuronide) lyase of Dendryphiella salina IF 32139 was purified to homogeneity by Q Sepharose FF and Sephacryl S-200 HR column chromatographies. The purified enzyme had a molecular weight of 35,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric point of 3.65 by isoelectric focusing. The optimum pH and temperature for enzyme activity were pH 5.0 and 45 degrees C, respectively. The enzyme was stable from pH 4 to 10 and at temperature below 40 degrees C. Some divalent cations, Ca2+, Mn2+, and Zn2+, increased the enzyme activity. Hg2+ and NBS strongly inhibited the activity. This enzyme susceptibly degraded poly-M, produced a wide range of 4,5-unsaturated oligomannuronic acids, and further degraded these unsaturated oligomannuronic acids to produce the unsaturated monomer and dimer as final products.


Advancing microbial sciences by individual-based modelling.
Remarkable technological advances have revealed ever more properties and behaviours of individual microorganisms, but the novel data generated by these techniques have not yet been fully exploited. In this Opinion article, we explain how individual-based models (IBMs) can be constructed based on the findings of such techniques and how they help to explore competitive and cooperative microbial interactions. Furthermore, we describe how IBMs have provided insights into self-organized spatial patterns from biofilms to the oceans of the world, phage-CRISPR dynamics and other emergent phenomena. Finally, we discuss how combining individual-based observations with IBMs can advance our understanding at both the individual and population levels, leading to the new approach of microbial individual-based ecology (μIBE).


Effect of calf age and dam breed on intake, energy expenditure, and excretion of nitrogen, phosphorus, and methane of beef cows with calves.
The effects of calf age and dam breeds of different milk yield potential on turnover of energy and nutrients were followed in 16 Simmental and 16 Angus beef cows with Angus-sired calves. Calf ages investigated were 1, 4, 7, and 10 mo. The forage offered for ad libitum access consisted of hay for the calves and of a constant mixture of grass silage, meadow hay, and straw (1:0.7:0.3 on a DM basis) for the cows. Calves of 10 mo of age received an additional 2.6 kg DM/d of crushed barley. The animals were kept in groups of four cows and four calves except in the respiration chambers, where only one cow (tethered) and her calf (loose) were grouped together. Indicator techniques were applied to obtain individual data on feces and urine volumes during group housing. In the Simmental cows, heavier on average by 22 kg, voluntary DMI was higher than in the Angus cows (14.0 vs 12.3 kg/d). In calves, DMI from supplementary feeds was 1.6, 3.9, and 6.3 kg/d, on average, at 4, 7, and 10 mo of age, respectively. Dam breed had no significant effect on DMI and ADG of calves and on BW changes of cows. System retention of energy, N, and P showed a curvilinear development with calf age. System energy expenditure, which linearly increased with calf age, was higher with Simmental than with Angus dams (11%), even when adjusted for metabolic BW (8%). Energy loss through methane linearly increased with NDF intake and, consequently, with calf age from 18 to 30 MJ/d (446 to 751 L/d) for cows and calves together. Similarly, fecal and urinary N excretion and fecal P excretion steadily increased with calf age. In calves, the easily volatile N percentage of manure N rapidly decreased from very high levels in young calves. The resulting changes in inclination to gaseous N loss during manure storage for 8 wk were more than compensated by alterations in N intake of the calves, resulting in an increased total system N loss with progressing lactation. Overall, the present results indicate a difference between Angus and Simmental in efficiency of nutrient and energy utilization that might be explained by the difference in amount of delivery of nutrients to the calves via milk vs forage. Suggestions are made as to how the emissions of N, P, and methane, which were excessive in relation to productivity, could be reduced by nutritional means.


Behavioural characterization of C57BL/6N and BALB/c female mice in social home cage - Effect of mixed housing in complex environment.
Developing reliable mouse models for social behaviour is challenging. Different tests have been proposed, but most of them consist of rather artificial confrontations of unfamiliar mice in novel arenas or are relying on social stress induced by aggressive conspecifics. Natural social interaction in home cage in laboratory has not been investigated well. IntelliCage is a fully automated home-cage system, where activity of the group-housed mice can be monitored along with various cognitive tasks. Here we report the behavioural profile of C57BL/6N (B6) and BALB/c (BALB) female mice in IntelliCage when separated by strain, followed by monitoring of activity and formation of 'home-base' after mixing two strains. For that purpose, 3 cages were connected. Significant differences between the strains were established in baseline behaviour in conventional tests and in IntelliCage. The B6 mice showed reduced anxiety-like behaviour in open field and light-dark box, slightly enhanced exploratory activity in IntelliCage during initial adaptation and clearly distinct circadian activity. Mixing of two strains resulted in reduction of body weight and anhedonia in B6 mice. In addition, the B6 mice showed clear preference to previous home-cage, and formed a new home-base faster than BALB mice. In contrast, BALB mice showed enhanced activity and moving between the cages without showing any preference to previous home-cage. It could be argued that social challenge caused changes in both strains and different coping styles are responsible for behavioural manifestations. Altogether, this approach could be useful in modelling and validating mouse models for disorders with disturbed social behaviour.


Evidence of Rickettsia and Orientia Infections Among Abattoir Workers in Djibouti.
Of 49 workers at a Djiboutian abattoir, eight (16%, 95% confidence interval [CI]: 9-29) were seropositive against spotted fever group rickettsiae (SFGR), two (4%, 95% CI: 1-14) against typhus group rickettsiae, and three (6%, 95% CI: 2-17) against orientiae. One worker (9%, 95% CI: 2-38) seroconverted against orientiae during the study period. This is the first evidence of orientiae exposure in the Horn of Africa. SFGR were also identified by polymerase chain reaction in 32 of 189 (11%, 95% CI: 8-15) tick pools from 26 of 72 (36%) cattle. Twenty-five (8%, 95% CI: 6-12) tick pools were positive for Rickettsia africae, the causative agent of African tick-bite fever. Health-care providers in Djibouti should be aware of the possibility of rickettsiae infections among patients, although further research is needed to determine the impact of these infections in the country.


Accuracy of imaging the menisci on an in-office, dedicated, magnetic resonance imaging extremity system.
Magnetic resonance imaging effectively defines and characterizes musculoskeletal pathologic lesions, particularly meniscal tears. Most studies comparing the efficacy of magnetic resonance imaging and arthroscopic evaluation have been performed on high-field (1.5-T) systems. The effectiveness of a low-field (0.2-T), dedicated, extremity magnetic resonance imaging device in diagnosing meniscal tears was studied prospectively on 35 patients with knee symptoms who subsequently had arthroscopic evaluation. Magnetic resonance imaging examinations were performed before surgery and were read by an experienced radiologist who was blinded to the results of the arthroscopic evaluations. Specificity was 100% for both the medial and lateral menisci. Sensitivity was 86% for the medial menisci, 89% for the lateral menisci, and 87% for both. Accuracy was 91% for the medial menisci, 97% for the lateral menisci, and 94% overall. The positive predictive values were 100% for the medial menisci, 100% for the lateral menisci, and 100% for both. The negative predictive values were 81% for the medial menisci, 96% for the lateral menisci, and 91% for both. The low-field magnetic resonance imaging system provided specificity and sensitivity that were equal to or better than previous reports with high-field systems. In particular, this low-field system eliminated the problem of false-positive results that has been found in some studies using high-field systems.


Neutrophil Extracellular Traps (NETs): An unexplored territory in renal pathobiology, a pilot computational study.
In the age of modern medicine and artificial intelligence, image analysis and machine learning have revolutionized diagnostic pathology, facilitating the development of computer aided diagnostics (CADs) which circumvent prevalent diagnostic challenges. Although CADs will expedite and improve the precision of clinical workflow, their prognostic potential, when paired with clinical outcome data, remains indeterminate. In high impact renal diseases, such as diabetic nephropathy and lupus nephritis (LN), progression often occurs rapidly and without immediate detection, due to the subtlety of structural changes in transient disease states. In such states, exploration of quantifiable image biomarkers, such as Neutrophil Extracellular Traps (NETs), may reveal alternative progression measures which correlate with clinical data. NETs have been implicated in LN as immunogenic cellular structures, whose occurrence and dysregulation results in excessive tissue damage and lesion manifestation. We propose that renal biopsy NET distribution will function as a discriminate, predictive biomarker in LN, and will supplement existing classification schemes. We have developed a computational pipeline for segmenting NET-like structures in LN biopsies. NET-like structures segmented from our biopsies warrant further study as they appear pathologically distinct, and resemble non-lytic, vital NETs. Examination of corresponding H&E regions predominantly placed NET-like structures in glomeruli, including globally and segmentally sclerosed glomeruli, and tubule lumina. Our work continues to explore NET-like structures in LN biopsies by: 1.) revising detection and analytical methods based on evolving NETs definitions, and 2.) cataloguing NET morphology in order to implement supervised classification of NET-like structures in histopathology images.