Klotho-FGF23, Cardiovascular Disease, and Vascular Calcification: Black or White?
Patients affected by Chronic Kidney Disease and Mineral Bone Disorder (CKD-MBD) have a high risk of cardiovascular (CV) mortality that is poorly explained by traditional risk factors. The newest medical treatments for CKD-MBD have been associated with encouraging, but still inconsistent, improvement in CV disease complications and patient survival. A better understanding of the biomarkers and mechanisms of left ventricular hypertrophy (LVH), atherosclerosis, and vascular calcification (VC) may help with diagnosis and treatment of the organ damage that occurs secondary to CKD-MBD, thus improving survival. Recent insights about fibroblast growth factor-23 (FGF23) and its co-receptor, Klotho, have led to marked advancement in interpreting data on vascular aging and CKDMBD. This review will discuss the current experimental and clinical evidence regarding FGF23 and Klotho, with a particular focus on their roles in LVH, atherosclerosis, and VC.


Effects of procedure on memory scanning of mildly mentally retarded adults.
The performance of mildly mentally retarded adults on recognition memory tasks was compared with that of nonretarded control subjects. Following Sternberg's (1969) procedure, material to be remembered was presented in a fixed-set procedure, during which subjects were tested repeatedly on the same well-learned set of material, and a varied-set procedure, during which they were only tested on a memory set once before having to learn a new set. Mean reaction times (RTs) in all groups increased linearly as the number of items in the fixed memorized set increased; but "no" RTs of retarded adults tested under the varied-set procedure did not show this pattern. There was a gradation of slopes for the linear regression functions of RT on memory set size in both procedures, from less steep for nonretarded adults to increasingly steep values for nonretarded children and retarded adults. These results suggest that retarded adults use different processing strategies in the two procedures and that rate of processing increases with increasing mental age.


Quality of life following laparoscopic anterior 90 degrees versus Nissen fundoplication: results from a multicenter randomized trial.
The short-term clinical outcomes from a multicenter prospective randomized trial of laparoscopic Nissen versus anterior 90 degrees partial fundoplication have been reported previously. These demonstrated a high level of satisfaction with the overall outcome following anterior 90 degrees fundoplication. However, the results of postoperative objective tests and specific clinical symptoms are not always consistent with an individual patient's functional status and general well being following surgery, and quality of life (QOL) is also an important outcome to consider following surgery for reflux. Hence, QOL information was collected in this trial to investigate the hypothesis: improvements in QOL following laparoscopic antireflux surgery are greater after anterior 90 degrees partial fundoplication than after Nissen fundoplication. Patients undergoing a laparoscopic fundoplication for gastro-esophageal reflux at one of nine university teaching hospitals in six major cities in Australia and New Zealand were randomized to undergo either laparoscopic Nissen or anterior 90 degrees partial fundoplication. Quality of life before and after surgery was assessed using validated questionnaires - the Short Form 36 general health questionnaire (SF36) and an Illness Behavior Questionnaire (IBQ). Patients were asked to complete these questionnaires preoperatively and at 3, 6, 12 and 24 months postoperatively. One hundred and twelve patients were randomized to undergo a Nissen fundoplication (52) or a 90 degrees anterior fundoplication (60). Patients who underwent anterior fundoplication reported significant improvements in eight of the nine SF36 scales compared to four of the nine following a Nissen fundoplication. The majority of these improvements occurred early in the postoperative period. With respect to the illness behavior data, there were no significant differences between the two procedures. Both groups had a significant improvement in disease conviction scores at all time points compared to their preoperative scores. Patients undergoing laparoscopic anterior 90 degrees partial fundoplication reported more QOL improvements in the early postoperative period than patients undergoing a Nissen fundoplication. However, the QOL outcome for both procedures was similar at later follow-up.


Cathepsin D in a murine model of frontotemporal dementia with Parkinsonism-linked to chromosome 17.
Tauopathies, such as Alzheimer's disease (AD) and Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), are characterized by tau accumulation. This accumulation could result from alterations in tau degradation by either the ubiquitin-proteasome system or the autophagy-lysosomal pathway. To analyze a possible alteration of the autophagy-lysosomal pathway in transgenic mice expressing human tau with three FTDP-17 missense mutations (TauVLW mice), we studied the lysosomal enzyme Cathepsin D. The hippocampi of TauVLW mice, where the human mutant tau accumulates, showed both increased Cathepsin D and partial colocalization of Cathepsin D with human mutant tau. At the ultrastructural level, some multivesicular bodies showed human mutant tau-immunopositive vesicles. This finding could provide insights into the molecular mechanisms of tau degradation in human tauopathies.


A high efficiency membrane separator for donor plasmapheresis.
The shortfall in human plasma for therapeutic use can be met satisfactorily only by donor plasmapheresis. Membrane blood plasma separators of conventional design work poorly at low rates of blood flow, and performance decreases rapidly as the membrane becomes fouled. To overcome these problems, membrane separators have been developed that employ vortex mixing to prevent blood cells obstructing the membrane pores. These separators consist of a single blood channel 160 mm long by 62.5 mm wide. The two membranes that act as boundaries for the blood channel are thermoformed to provide a closely packed array of outward facing dimples. The membranes are seated on rigid support plates, and flexible diaphragms are attached to each end of the blood channel. The diaphragms were oscillated in antiphase at 3 to 6 Hz, with a stroke volume of 2.8 ml. In 24 clinical trials, mean plasma filtration rate was 18 ml/min at a blood inlet flow of 48 ml/min. In 10 experiments using bovine blood, mean plasma filtration rate was 35 ml/min at a blood inlet flow of 90 ml/min. Little reduction in performance was observed over 80 min. The membrane area was 200 sq cm, which gave a filtration velocity of 1.75 L/min/m2, higher by a factor of five than is reported for hollow fiber or flat plate designs.


First report of a simultaneous transcatheter mitral valve-in-valve and aortic valve replacement in a left ventricular assist device patient.
Transcatheter aortic valve replacement is standard of care for patients with severe aortic stenosis at high risk for surgical aortic valve replacement. Although not intended for treatment of primary aortic insufficiency, several transcatheter aortic valve prostheses have been used to treat patients with severe aortic insufficiency (AI), including patients with left ventricular assist devices (LVAD), in whom significant AI is not uncommon. Similarly, transcatheter valve replacements have been used for valve-in-valve treatment, in the pulmonary, aortic, and mitral positions, either via a retrograde femoral approach or antegrade transseptal approach (mitral valve-in-valve). In this case report, we report an LVAD patient with severe aortic insufficiency and severe bioprosthetic mitral prosthetic stenosis, in whom we successfully performed transfemoral aortic valve replacement and transfemoral mitral valve-in-valve replacement via a transseptal approach. © 2017 Wiley Periodicals, Inc.


Preparation, isolation, and characterization of Nalpha-Fmoc-peptide isocyanates: solution synthesis of oligo-alpha-peptidyl ureas.
The N(alpha)-Fmoc-peptide isocyanates 3a-q, 4a-c, and 5a-c were prepared by the Curtius rearrangement of N(alpha)-Fmoc-peptide acid azides in toluene under thermal, microwave, and ultrasonic conditions. All the N(alpha)-Fmoc-oligo-peptide isocyanates made were isolated as stable crystalline solids with 71 to 94% yield and were fully characterized by 1H NMR, 13C NMR, and mass spectroscopy. Their utility for the synthesis of oligo-alpha-peptidyl ureas 7a-f and 8a-c by the divergent coupling approach was demonstrated. The coupling of N(alpha)-Fmoc-dipeptide isocyanates with amino acid ester or with N,O-bis(trimethylsilyl)amino acids resulted in N(alpha)-Fmoc-tripeptidyl urea ester and acids containing one each of peptide bond and urea bond. The divergent approach is extended to the synthesis of tetrapeptidyl ureas by the 2 + 2 strategy using bis-TMS-peptide acid as an amino component. To incorporate urea bonds in adjacent positions, N(alpha)-Fmoc-peptidyl urea isocyanates 9a-d were prepared and employed in the synthesis of three tetrapeptidyl ureas 10a-b and 11 containing one peptide bond and two urea bonds in series from the N-terminal end. The protocol was then employed for the synthesis of five urea analogues 13-15, 18, and 21 of [Leu5]enkephalin containing urea bonds at the 2, 3, 4 positions as well as at the 2, 4 and 2, 3, 4 positions. The analogue 2l was made by the convergent synthesis by the N --> C terminal chain extension. Finally, two urea analogues 22 and 23 of repeat units of bioelasto polymers, namely Val-Pro-Gly-Val-Gly-OH and Pro-Gly-Val-Gly-Val-OH, were synthesized incorporating the urea bond by the concomitant isocyanate generation and urea bond formation under thermal conditions.


Study of Imidazolium Salt Derivatives as PIK3CA Inhibitors Using a Comprehensive in Silico Method.
A series of imidazolium salt derivatives have demonstrated potent antitumor activity in prior research. A comprehensive in silicon method was carried out to identify the putative protein target and detailed structure-activity relationship of the compounds. The Topomer CoMFA and CoMSIA techniques were implemented during the investigation to obtain the relationship between the properties of the substituent group and the contour map of around 77 compounds; the Topomer CoMFA and CoMSIA models were reliable with the statistical data. The protein-protein interaction network was constructed by combining the Pharmmapper platform and STRING database. After generating the sub-network, the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA with protein data bank ID: 3ZIM) was selected as the putative target of imidazolium salt derivatives. A docking study was carried out to correlate interactions of amino acids in protein active pockets surrounded by the ligand with contour maps generated by the structure-activity relationship method. Then the molecular dynamics simulations demonstrated that the imidazolium salt derivatives have potent binding capacity and stability to receptor 3ZIM, and the two ligand-receptor complex was stable in the last 2 ns. Finally, the ligand-based structure-activity relationship and receptor-based docking were combined together to identify the structural requirement of the imidazolium salt derivatives, which will be used to design and synthesize the novel PIK3CA inhibitors.


[Dose distribution from kV-cone beam computed tomography in image-guided radiotherapy].
Image-guided radiotherapy (IGRT) is an increasingly commonly adopted technique. As a result, however, total patient dose is increasing rapidly, especially when kV-cone beam computed tomography (CBCT) is applied. This study investigated the dosimetry of kV-CBCT using a Farmer ionization chamber with a (60)Co absorbed-dose calibration factor. The absorbed-dose measurements were performed using an I'mRT phantom (RW3, IBA) which is employed for dose verification of intensity-modulated radiotherapy (IMRT). The I'mRT phantom was used as a substitute for head and pelvis phantoms. The kV-CBCT absorbed dose was evaluated from a beam quality conversion factor of kV to (60)Co and the ionization ratio of the I'mRT phantom and water, calculated using the Monte Carlo method. The dose distribution in the I'mRT phantom was also measured using a radiophotoluminescent glass dosimeter (RGD). The absorbed doses for the pelvis phantom (full scan) ranged from 2.5-4 cGy for kV-CBCT and 4-8 cGy for MV-CBCT. TomoTherapy resulted in a lower dose of approximately 1.3 cGy due to fan-beam. For the head phantom (half scan), the doses ranged from 0.1-0.7 cGy for kV-CBCT and 3-5 cGy for MVCBCT. The results for RGD were similar to ion chamber measurements. It is necessary to decrease the absorbed dose of the organs at risk every time IGRT is applied.


Impact of National Institutes of Health Gastrointestinal PROMIS Measures in Clinical Practice: Results of a Multicenter Controlled Trial.
The National Institutes of Health (NIH) created the Patient Reported Outcomes Measurement Information System (PROMIS) to allow efficient, online measurement of patient-reported outcomes (PROs), but it remains untested whether PROMIS improves outcomes. Here, we aimed to compare the impact of gastrointestinal (GI) PROMIS measures vs. usual care on patient outcomes. We performed a pragmatic clinical trial with an off-on study design alternating weekly between intervention (GI PROMIS) and control arms at one Veterans Affairs and three university-affiliated specialty clinics. Adults with GI symptoms were eligible. Intervention patients completed GI PROMIS symptom questionnaires on an e-portal 1 week before their visit; PROs were available for review by patients and their providers before and during the clinic visit. Usual care patients were managed according to customary practices. Our primary outcome was patient satisfaction as determined by the Consumer Assessment of Healthcare Providers and Systems questionnaire. Secondary outcomes included provider interpersonal skills (Doctors' Interpersonal Skills Questionnaire (DISQ)) and shared decision-making (9-item Shared Decision Making Questionnaire (SDM-Q-9)). There were 217 and 154 patients in the GI PROMIS and control arms, respectively. Patient satisfaction was similar between groups (P>0.05). Intervention patients had similar assessments of their providers' interpersonal skills (DISQ 89.4±11.7 vs. 89.8±16.0, P=0.79) and shared decision-making (SDM-Q-9 79.3±12.4 vs. 79.0±22.0, P=0.85) vs. This is the first controlled trial examining the impact of NIH PROMIS in clinical practice. One-time use of GI PROMIS did not improve patient satisfaction or assessment of provider interpersonal skills and shared decision-making. Future studies examining how to optimize PROs in clinical practice are encouraged before widespread adoption.


Communicate About Quality and Safety: Let's Think Outside the Box! Experience From a Cancer Center.
While the priority of caregivers in any health care establishment is patient care, they are often constrained by time and cannot fully devote themselves to projects aiming at improving the quality and safety of care. Although the culture of quality is widespread in health care establishments, the quality and safety department team must continue to improve existing procedures and develop new ones, in order to reinforce the take-home message that safety is of paramount importance. Since good communication is a key factor in the success of quality plans, the quality and safety team in our establishment is placing special emphasis on "out of the ordinary" activities that take professional carers out of their daily routines, arouse their curiosity, and increase their adherence to quality procedures. The issues addressed during these activities are based on the year-round continuous assessment of in-house procedures. Only those that have been deemed essential for safe care are focused upon. Most of the activities that are implemented have already been tried and tested in the fields of industry and aviation, and they all have a fun, collaborative, and creative component. Their impact and effect are assessed by carrying out the same assessments as those used at the beginning on the project. These innovative activities, which have received strong support from the staff, have had a positive effect on interdepartmental cooperation, on the adherence to the new methods presented, and on ensuring that information is made available to the greatest number of professionals. They have allowed the staff to acquire and consolidate new professional knowledge and have promoted good practice. This new program of activities has considerably improved the safety culture within our establishment. While the relationship between the skills of professionals and patient safety is clear to all, the message needs to be delivered in an original way that makes a lasting impression, in addition to using "standard" communication methods such as plenary meetings. The bottom line is to get as many professionals as possible fully adherent to the culture of quality, since quality is everyone's business and health care procedures are constantly evolving. Based on our experience, we provide a set of activities that can be improved and adapted according to the setting in which it is used.


Fluid absorption during transurethral prostatectomy.
A study of 39 patients having a transurethral resection (TUR) of prostate for benign prostatic hyperplasia was carried out. Large quantities of mannitol, which was used as the irrigating fluid during the procedure, were found to enter the circulation. A corresponding fall in the serum sodium levels was noted. Those patients with serum mannitol levels greater than 4000 mg/l were noted to be hypotensive and have a bradycardia. These patients were nearly all hypovolaemic and the bradycardia was felt to be inappropriate. The possibility of this being due to a combination of factors including intravascular mannitol is considered.


A Case of COVID-19 Induced Thrombotic Thrombocytopenic Purpura.
Thrombotic Thrombocytopenic Purpura (TTP) is a challenging thrombotic diathesis which requires prompt diagnosis and therapeutic intervention in order to avoid life-threatening consequences. There are two forms of TTP, congenital and acquired, with the acquired form constituting about 90% of cases. Both forms are associated with a deficiency of ADAMTS-13, a metalloproteinase enzyme responsible for cleaving ultra-large von Willebrand factor (uLvWF), preventing its pathologic accumulation. Within the last year, many of the diverse and serious effects of the COVID-19 virus have come to recognition, with some of the most dire consequences involving devastating vascular and hematologic complications. As with many viruses, it seems that the endothelium and the vasculature are often prime targets. Here, we report a case of a 30 year old male who was diagnosed with TTP approximately one week after a positive COVID-19 test result. He responded appropriately to plasma exchange (PLEX), caplacizumab, and steroids. We believe it is important to investigate a potential link between these two conditions, as TTP has significant morbidity and mortality risk if left unattended. We hope that our report will contribute to a better understanding of this potential link.


Cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in endothelial cells.
Endothelial cells have the ability to change their complement of cell surface proteins in response to inflammatory cytokines. We hypothesized that the expression of the coxsackievirus-adenovirus receptor (CAR), a viral receptor and putative cell-cell adhesion molecule, may be altered during the response of endothelial cells to inflammation. To test this hypothesis, we evaluated CAR protein and mRNA levels in human umbilical vein endothelial cells after they were exposed to tumor necrosis factor alpha, gamma interferon, or a combination of the two cytokines. Flow cytometric and Western blot analyses indicated that cytokine treatment led to a synergistic decrease in CAR protein expression. A Western blot analysis showed that CAR levels decreased to 16% +/- 4% or 1% +/- 4% of the CAR protein levels in untreated cells with either 24 or 48 h of cytokine treatment, respectively. Quantitative reverse transcription-PCR demonstrated that the combination treatment caused CAR mRNA levels to decrease to 21% +/- 12% or 5% +/- 3% of the levels in untreated cells after a 24- or 48-h cytokine treatment, respectively. Reduced CAR expression led to a decrease in adenovirus (Ad) binding of 80% +/- 3% (compared with untreated endothelial cells), with a subsequent decrease in Ad-mediated gene transfer that was dependent on the dose and duration of cytokine treatment but not on the dose of Ad. A similar decrease in CAR protein level and susceptibility to Ad infection was observed in human microvascular endothelial cells, while CAR expression on normal human bronchial epithelial cells or A549 lung epithelial cells was less affected by cytokine treatments. Taken together, the data demonstrate that inflammatory cytokines decrease CAR mRNA and protein expression with a concomitant decrease in Ad binding, reflecting the impact of cell physiology on the function of CAR and the potential effect of inflammation on the ability of Ad to transfer genes to endothelial cells.


Achieving self-sufficiency: training Australia's future medical workforce.
There is an oversupply of Australian junior doctors, but significant training bottlenecks are developing, and geographical maldistribution in rural and remote areas remains. Last year, the Federal Minister for Immigration rejected a Department of Health recommendation for the removal of 41 health roles from the Skilled Occupation List after concerns that rural and regional communities would be left without access to medical services in areas currently serviced by international medical graduates. In an effort to achieve workforce self-sufficiency, Australia must ensure access to high-quality vocational training places in rural and regional settings while managing immigration of overseas-trained health professionals.


Monoclonal antibody-based enzyme immunoassay for detection of ricin.
A sensitive and specific enzyme-linked immunoadsorbent assay (ELISA) was developed to detect ricin in biological fluids. The assay is based on the sandwich format using monoclonal antibodies (MAbs) of two distinct specificities. An affinity-purified anti-ricin B chain MAb (1G7) is utilized to adsorb ricin from solution and the second anti-ricin A chain MAb (5E11) conjugated with peroxidase is then used to form a sandwich, and peroxidase allows color development and measurement of optical density at 450 nm. Standard curves were linear over the range of 2.5-100 ng/mL ricin. The limit of detection was below 5 ng/mL in assay buffer as well as in a 1:10 dilution of urine or 1:50 dilution of human serum spiked with ricin.


Potential for differential diagnosis of autoimmune pancreatitis and pancreatic cancer using carbonic anhydrase II antibody.
Pancreatic ductal epithelia contain an abundance of carbonic anhydrase (CA), and the presence of antibodies to this enzyme has been described in autoimmune disorders. We previously found a small amount of an immunoglobulin G-like material in purchased CAII reagents, which led to pseudopositive reactions. We determined the optimum measurement conditions for detecting anti-CAII antibody using an enzyme-linked immunosorbent assay and sera from 140 patients with pancreatic diseases. Compared with the prevalence of anti-CAII antibody in healthy subjects, a significantly higher seroprevalence of the antibody was detected in patients with autoimmune pancreatitis (AIP) (88.9%, P < 0.02), Sjögren syndrome (67.6%, P < 0.01), and alcoholic chronic pancreatitis (45.8%, P < 0.01). No positive results were obtained among patients with pancreatic cancer. Moreover, the antibody value obtained in the pancreatic cancer patients was actually lower than that obtained in healthy subjects. The anti-CAII antibody is probably not a specific marker of AIP because it was present at a higher frequency in the sera of patients with other pancreatic diseases. Nevertheless, the anti-CAII antibody may be a useful tool for the differential diagnosis of AIP and pancreatic cancer.


[Expressions and Clinical Significance of Autophagy-related Genes ATG2B, ATG4D, ATG9B in Breast Carcinoma].
To investigate the expressions and clinical significance of autophagy-related gene 2B (ATG2B), autophagy-related gene 4D (ATG4D), autophagy-related gene 9B (ATG9B) in breast cancer cell lines and breast cancer. Cancer Browser screening was applied to study the differential expressions of ATG2B, ATG4D, ATG9B genes in breast cancer. Quantitative Real-time PCR was used to measure the expressions of these three genes in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435S and ZR-75-30) as well as 83 cases of breast cancer samples with paired normal breast tissues. The relationships between the expressions of these genes and clinicopathological characteristics were further analyzed. Cancer Browser screening found abnormal expressions of ATG2B, ATG4D, ATG9B in breast cancer (P = 0.015, P = 0.028, P = 0.040). All four breast cancer cell lines expressed ATG2B, ATG4D, ATG9B, and the expression of ATG2B, ATG9B was significantly lower than positive control (P < 0.001), but ATG4D expression was higher than positive control (P < 0.001). The expressions of ATG2B, ATG4D, ATG9B in breast cancer were all lower than those in the adjacent normal tissues (P < 0.001, P = 0.031, P < 0.001). Furthermore, the expression of ATG2B was correlated with ER (r = 0.949, P = 0.015), and the expression of ATG4D was related to age (r = -0.449, P = 0.005), the expression of ATG9B was correlated to lymph node metastasis and cytokeratin 5/6 status (r = 0.339, P = 0.043; r = 0.533, P = 0.043). ATG2B, ATG4D, ATG9B genes shows low expressions in breast cancer, which may become new molecular markers for the prognosis of breast cancer.


An integrative literature review exploring the clinical management of delirium in patients with advanced cancer.
To present the findings of an integrative literature review of the evidence for the clinical management of delirium in patients with advanced cancer. Patients with advanced cancer frequently experience delirium which can be distressing for both patients and their families. Current guidelines recommend that underlying causes of the delirium be addressed and a course of antipsychotics considered. However, the research into the effectiveness of treatments for delirium in people with advanced cancer is limited. Integrative literature review. Systematic searches of the MEDLINE, CINAHL, ProQuest Nursing and Allied Health and PsychInfo databases were conducted in April 2016 to include papers published in 2000 and later. The returns were screened using inclusion and exclusion criteria, and the seven studies found to be suitable were subject to review. Findings of the seven papers were extracted, appraised critically and reviewed using a narrative approach. A number of interventions, including the use of atypical antipsychotics, opioid rotation, methylphenidate hydrochloride and coeliac plexus block, were reported; however, there was limited evidence of their effectiveness. One study reported the use of exercise therapy as a nonpharmacological intervention. A variety of interventions to treat delirium in patients with advanced cancer have been tested through nonblinded, nonrandomised trials which have not produced a clear evidence base for practice. The clinical management of delirium in patients with advanced cancer is poorly understood and remains a clinical issue which requires further research (particularity randomized control trials) in order to determine more effective treatments and management strategies.


[Thymoma with Multilocular Cystic Change;Report of a Case].
A 21-year-old male was pointed out an abnormal shadow on chest X-ray. Chest computed tomography showed a multilocular cystic mass of 10×4×4 cm in size in the anterior mediastinum. The tumor and the left lobe of the thymus was resected by median sternotomy. Pathologically, type AB thymoma as found in the wall of the cyst.


Structural and functional properties of plasma membranes from the filamentous fungus Penicillium chrysogenum.
Functional plasma membranes from the filamentous fungus Penicillium chrysogenum have been isolated with the objective of studying transport processes. The isolation procedure consists of three steps, namely homogenization of cells with a Braun MSK homogenizer, followed by Percoll gradient centrifugation and floatation of membranes in a three-step Nycodenz gradient. This method can be applied to strains which differ significantly in morphology and penicillin-production capacity. Plasma membranes were fused with liposomes containing the beef heart mitochondrial cytochrome-c oxidase. In the presence of reduced cytochrome c, the hybrid membranes maintained a high proton motive force that functions as a driving force for the uptake of the amino acids arginine and valine via distinct transport systems.


Ruminal ammonia load affects leucine utilization by growing steers.
Six ruminally cannulated Holstein steers (initial BW = 189 +/- 11 kg) housed in metabolism crates were used in a 6 x 6 Latin square to study effects of ruminal ammonia load on Leu utilization. All steers received a diet based on soybean hulls (2.7 kg of DM/d), ruminal infusions of 200 g of acetate/d, 200 g of propionate/d, and 50 g of butyrate/d, as well as an abomasal infusion of 300 g of glucose/d to provide energy without increasing microbial protein supply and an abomasal infusion of a mixture (238 g/d) of all essential AA except Leu. Treatments were arranged as a 3 x 2 factorial and included Leu (0, 4, or 8 g/d) infused abomasally and urea (0 or 80 g/d) infused ruminally. Abomasal Leu infusion linearly decreased (P < 0.05) both urinary and fecal N excretions and linearly increased (P < 0.05) retained N, but the decreases in urinary N excretion in response to Leu tended (P = 0.07) to be greater, and the increases in retained N in response to Leu were numerically greater in the presence of the urea infusion. Although urea infusions increased (P < 0.05) plasma urea concentrations, urinary N excretions, and urinary urea excretions, retained N also was increased (P < 0.05). The efficiency of deposition of supplemental Leu ranged from 24 to 43% when steers received 0 or 80 g of urea/d, respectively. Under our experimental conditions, increasing ammonia load improved whole-body protein deposition in growing steers when Leu supply was limiting.


Patient expectations prior to coloplast titan penile prosthesis implant predicts postoperative satisfaction.
Managing and understanding expectations of patients prior to inflatable penile prosthesis (IPP) surgery is a critical. Clinicians vary in the way they explain the operation, and patients have varied expectations prior to surgery. The goal is to understand the role that preoperative counseling and patients' realistic understanding of IPP surgery play in determining postoperative satisfaction. 21 Patients underwent IPP surgery, and received a preoperative expectations survey, then, 4 months later, gave a single score of 1-100 (1 is very dissatisfied, 100 is extremely satisfied). The results were correlated with an R(2) value and visualized on a scatter plot. This significance is tested using a two-tailed test. Lower preoperative expectations scores correlated almost linearly with higher satisfaction scores after surgery. The R (Pearson) value was -0.489, with an R(2) of 0.239. This was significant using a two-tailed test, with a P value of 0.0245. Giving patients an accurate description of the procedure and setting realistic expectations leads to higher postoperative satisfaction.


Lymphokines in sensitized rats. I. Migration inhibitory factor(s) from specifically stimulated thymocytes in vitro.
Cell-mediated immune responses were studied in Wistar rats by migration inhibition factor (MIF) assays in vitro of lymphoid cells derived from thymus, spleen and peripheral blood and peritoneal exudates and by delayed cutaneous hypersensitivity reactions in vivo. Using PPD and purified diphtheria toxoid as soluble test antigens it appeared that significant migration inhibition was observed only when sensitized thymus and peritoneal exudate cells were used in the direct capillary migration system. Indirect MIF assays, using both capillary and agarose techniques, showed that migration inhibitory activity was found in thymus culture supernatants as well as in spleen culture supernatants of sensitized animals. The MIF activity in thymic cell culture supernatants seemed to be antigen-independent, although in this respect no definitive conclusions can be drawn from the present results. Migration inhibition in direct and indirect techniques always correlated with a positive delayed-type skin reaction. It is suggested that a population of thymus cells of sensitized animals is able to produce MIF on specific antigenic stimulation in vitro. This might support the idea that a cell population within the thymus possesses characteristics of peripheral T cells.


Halogen bonding and rotational disorder in chlorine clathrate hydrate cages.
We present a detailed theoretical characterization of the structure and interactions in dichlorine clathrate hydrate cages. In the case of the dodecahedral cage, there is clear evidence of the presence of halogen bonding, whereas in the tetrakaidecahedral cage, the expected signatures are there but in a weaker form. Comparison is made with the available structural data from x-ray experiments, where the rotational motion of dichlorine has been taken into account through Monte Carlo simulations illustrating delocalization effects associated with sampling multiple minima, specifically for the larger cage. Finally, the intermolecular potentials have been calculated with local correlation methods, and energy decomposition analysis has been applied to shed light on the nature of the interactions.


The Vanderbilt Professional Nursing Practice Program, part 2: Integrating a professional advancement and performance evaluation system.
Developing a performance-based advancement system requires evaluation tools that capture essential behaviors and outcomes reflective of key nursing functions. To ensure relevance to clinical practice and enhance buy-in from nursing staff, the behaviors and outcomes were defined by a broad cross-section of nursing staff and administrators. The first article (September 2003) in this 3-part series described the foundation for and the philosophical background of the Vanderbilt Professional Nursing Practice Program (VPNPP), the career advancement program under way at Vanderbilt University Medical Center. This second article describes the development of the evaluation tools used in the VPNPP, the implementation and management of this new system, program evaluation, and improvements since the inception of the program. Additionally, the authors present the challenges and lessons we learned in development and implementation of a dynamic evaluation system that supports our career advancement program. The process of advancing within the program will be described in part 3.


Partial purification of L-ascorbate:ferricytochrome b5 oxidoreductase from rat liver microsomes.
L-Ascorbate:ferricytochrome b5 oxidoreductase from rat liver microsomes was enriched about 750-fold after treatment with a non-ionic detergent with a yield of about 15%. The enriched enzyme still shows four bands in sodium dodecylsulfate polyacrylamide-gel electrophoresis and is a hydrophobic membrane protein.


Challenge seeking and the type A coronary-prone behavior pattern.
The present investigation sought to further delineate the Type A coronary-prone behavior pattern and to elucidate the psychophysiological process through which this behavioral disposition is translated into heart disease. Type A and Type B male subjects engaged in tasks that required varying degrees of activity before an assessment of challenge-seeking tendencies. Type A participants sought greater degrees of challenge than did their Type B counterparts. In addition, the more active the person with Pattern A had been immediately before the challenge-seeking opportunity, the greater the degree of challenge sought. Precedent activity level did not significantly influence challenge seeking in the Type B population. The Type A subjects also had significantly faster heart rates during performance of a challenging task. Pattern A behavior may be translated into heart disease through the cumulative deleterious effects of chronic and excessive challenge-induced cardiovascular excitation.


The state of play in tools for predicting immunoglobulin resistance in Kawasaki disease.
Intravenous immunoglobulin (IVIG) resistance is an independent risk factor for the development of coronary artery lesions (CAL) in patients with Kawasaki disease (KD). Accurate identification of IVIG-resistant patients is one of the biggest clinical challenges in the treatment of KD. In this review article, we will go over current IVIG resistance scoring systems and other biological markers of IVIG resistance, with a particular focus on advances in machine-based learning techniques and high-throughput omics data. Traditional scoring models, which were developed using logistic regression, including the Kobayashi score and Egami score, are inadequate at identifying IVIG resistance in non-Japanese populations. Newer machine-learning methods and high-throughput technologies including transcriptomic and epigenetic arrays have identified several potential targets for IVIG resistance including gene expression of the Fc receptor, and components of the interleukin (IL)-1β and pyroptosis pathways. As we enter an age where access to big data has become more commonplace, interpretation of large data sets that are able take into account complexities in patient populations will hopefully usher in a new era of precision medicine, which will enable us to identify and treat KD patients with IVIG resistance with increased accuracy.


Selective anticancer activity of superparamagnetic iron oxide nanoparticles (SPIONs) against oral tongue cancer using in vitro methods: The key role of oxidative stress on cancerous mitochondria.
Today, it has been proven that the nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs) have widespread use in biomedical applications, for instance, in magnetic resonance imaging and targeted delivery of drugs. Despite many studies on SPIONs in diagnosing some diseases like cancer, it has not been investigated on the oral tongue squamous cell carcinoma (OTSCC) detection by the NPs. Hence, the present study has been designed to assess the in vitro cytotoxicity of SPIONs on the isolated mitochondria of OTSCC by mitochondrial tests. Isolated mitochondria were removed from the separated cancer and control tissues from the squamous cells of tango in male Wistar rats (6 or 8 weeks) and exposed to the different concentrations of SPIONs (30, 60, and 120 nM). A rise in the production of reactive oxygen species is one of the significant mechanisms of this study, followed by a collapse of mitochondrial membrane potential, the escape of mitochondrial cytochrome c, and mitochondrial swelling in the exposed isolated mitochondria of OTSCC with SPIONs. Furthermore, our results indicated that the exposure to the SPIONs reduced the activity of succinate dehydrogenase in complex II of the mitochondria obtained from cancerous oral tongue squamous. So the SPIONs can induce selective cytotoxicity on the OTSCC mitochondria without significant effects on the control mitochondria. Based on the results and further studies about in vivo experiments in this regard, it is concluded the SPIONs may be a hopeful therapeutic candidate for the treatment of OTSCC.


Towards Sustainable North American Wood Product Value Chains, Part I: Computer Vision Identification of Diffuse Porous Hardwoods.
Availability of and access to wood identification expertise or technology is a critical component for the design and implementation of practical, enforceable strategies for effective promotion, monitoring and incentivisation of sustainable practices and conservation efforts in the forest products value chain. To address this need in the context of the multi-billion-dollar North American wood products industry 22-class, image-based, deep learning models for the macroscopic identification of North American diffuse porous hardwoods were trained for deployment on the open-source, field-deployable XyloTron platform using transverse surface images of specimens from three different xylaria and evaluated on specimens from a fourth xylarium that did not contribute training data. Analysis of the model performance, in the context of the anatomy of the woods considered, demonstrates immediate readiness of the technology developed herein for field testing in a human-in-the-loop monitoring scenario. Also proposed are strategies for training, evaluating, and advancing the state-of-the-art for developing an expansive, continental scale model for all the North American hardwoods.


[Percutaneous revision of shunt with obstructed ventricular catheter (author's transl)].
Shunt dysfunction due to an obstructed ventricular catheter can be avoided, at least in part, by placing the of the catheter anteriorly to the Foramen of Monro. However, once the catheter is obstructed, surgical removal under general anesthesia is almost inevitable. Irrigation method for an obstructed ventricular catheter enables us to gain scarcely anything and accumulation of instilled fluid in the ventricle often causes the dangerously increased intracranial pressure. 1) Technique for placement of the ventricular catheter. The skin incision is a semicircular. After the skin flap is reflected, "8-shaped" burr hole is placed (Fig. 1 in the text). At first, two openings, large and small, are made in the skull. At 1/4 inch drill is used for making a small hole and a regular perforator for an adjacent large one, then, with a small Schlessinger roungeur, a thin wall dividing these two holes is removed. Two to 3 cm lateral from the midline and also posterior to the frontal hair line is usually chosen for placement of burr holes. A straight ventricular catheter with multiple small perforations at its tip is connected to the Rickham reservoir and inserted in the ventricle anteriorly to the Foramen Monro, through the small hole of the "8-shaped" burr hole. Rest of surgical procedure is performed according to a routine manner. 2) Technique for release of ventricular catheter obstruction by percutaneous management through the "8-shaped" burr hole. A 20-gaze modified spinal needle is inserted through the Rickham reservoir under fluoroscopic control and gradually progressed to the tip of the obstructed catheter. Simple aspiration through the needle may occasionally open the catheter by removing small obstruents, but in many instances, insertion of an another ventricular needle through the large hole and combined irrigation are indispensable. 3) Results. Ten of 72 patients who had placement of the ventricular catheter by this technique developed obstructions of the catheter. Percutaneous technique was successful in releasing the obstructions in 12 times of these 8 patients and remaining 2 patients were subsequently operated upon for the following reasons. One patient, because of dislodging of the reservoir cap after successful release of obstruction and the other, due to extraventricular location of the tip of the catheter prior to the percutaneous management. No serious complications has been encountered and the technique was proved to be safe and simple ensuring good functional return of the shunt in long-term follow-up.


Use of prescribing indicators as a means of identifying variation in the prevalence of valproate prescribing between health communities: a cross-sectional study.
To determine the appropriateness of valproate prescribing indicators in England and Wales as a means of identifying variation in the prevalence of valproate use among women and girls of childbearing potential between health communities. Cross-sectional study using an ecological design using routinely published, publicly available valproate prescribing data for the period January to March 2019 and 2018 mid-year population estimates. In England and Wales, 87.7 people in every 1000 people prescribed valproate were women or girls aged 14-45 years (range 60.4-133.2). The prevalence of valproate use among all women and girls of childbearing age was 1.49 cases per 1000 women and girls aged 14-45 years (range 0.47-3.13). Considerable variation in prevalence was observed depending on which of two measures was used. The relative risk of exposure between health communities increased from 2.2 to 6.6 depending on the measure used, leading to the identification of different health communities being a priority for action. Wide variation was observed in the prevalence of valproate use among individuals other than women and girls aged 14-45 years (mean prevalence 3.89 cases per 1000 population, range 2.42-7.78). The prevalence of valproate use in all Clinical Commissioning Groups and Local Health Boards was lower in the at-risk population than in the rest of the population (p=0.046) with a strong positive correlation observed between the prevalence of valproate use in these two groups (p<0.001). Current indicators may lead to a failure to systematically review women and girls of childbearing age prescribed valproate. Urgent consideration should be given to changing the indicators used in England and Wales.


Increased cerebral blood volume pulsatility during head-down tilt with elevated carbon dioxide: the SPACECOT Study.
Astronauts aboard the International Space Station (ISS) have exhibited hyperopic shifts, posterior eye globe flattening, dilated optic nerve sheaths, and even optic disk swelling from spaceflight. Elevated intracranial pressure (ICP) consequent to cephalad fluid shifts is commonly hypothesized as contributing to these ocular changes. Head-down tilt (HDT) is frequently utilized as an Earth-based analog to study similar fluid shifts. Sealed environments like the ISS also exhibit elevated CO2, a potent arteriolar vasodilator that could further affect cerebral blood volume (CBV) and cerebral blood flow, intracranial compliance, and ICP. A collaborative pilot study between the National Space Biomedical Research Institute and the German Aerospace Center tested the hypotheses that 1) HDT and elevated CO2 physiologically interact and 2) cerebrovascular pulsatility is related to HDT and/or elevated CO2 In a double-blind crossover study (n = 6), we measured CBV pulsatility via near-infrared spectroscopy, alongside noninvasive ICP and intraocular pressure (IOP) during 28-h -12° HDT at both nominal (0.04%) and elevated (0.5%) ambient CO2 In our cohort, CBV pulsatility increased significantly over time at cardiac frequencies (0.031 ± 0.009 μM/h increase in total hemoglobin concentration pulsatility amplitude) and Mayer wave frequencies (0.019 ± 0.005 μM/h increase). The HDT-CO2 interaction on pulsatility was not robust but rather driven by one individual. Significant differences between atmospheres were not detected in ICP or IOP. Further work is needed to determine whether individual differences in pulsatility responses to CO2 relate to visual changes in space.NEW & NOTEWORTHY Cerebral blood volume (CBV) pulsatility-as measured by near-infrared spectroscopy-increases over time during -12° head-down tilt at both cardiac and Mayer wave frequencies. CBV pulsatility appeared to increase more under elevated (0.5%) CO2 at Mayer wave frequencies in some individuals. If similar dynamic pulsatility increases occur in astronauts, there is the potential to initiate vascular and possibly other remodeling processes that lead to symptoms associated with sustained increases in intracranial pressure.


YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers.
The Hippo/YAP signaling pathway is a crucial regulator of tissue growth, stem cell activity, and tumorigenesis. However, the mechanism by which YAP controls transcription remains to be fully elucidated. Here, we utilize global chromatin occupancy analyses to demonstrate that robust YAP binding is restricted to a relatively small number of distal regulatory elements in the genome. YAP occupancy defines a subset of enhancers and superenhancers with the highest transcriptional outputs. YAP modulates transcription from these elements predominantly by regulating promoter-proximal polymerase II (Pol II) pause release. Mechanistically, YAP interacts and recruits the Mediator complex to enhancers, allowing the recruitment of the CDK9 elongating kinase. Genetic and chemical perturbation experiments demonstrate the requirement for Mediator and CDK9 in YAP-driven phenotypes of overgrowth and tumorigenesis. Our results here uncover the molecular mechanisms employed by YAP to exert its growth and oncogenic functions, and suggest strategies for intervention.


Improved Prodigiosin Production by Relieving CpxR Temperature-Sensitive Inhibition.
Prodigiosin (PG) is a typical secondary metabolite mainly produced by Serratia marcescens. CpxR protein is an OmpR family transcriptional regulator in Gram-negative bacteria. Firstly, it was found that insertion mutation of cpxR in S. marcescens JNB 5-1 by a transposon Tn5G increased the production of PG. Results from the electrophoretic mobility shift assay (EMSA) indicated that CpxR could bind to the promoter of the pig gene cluster and repress the transcription levels of genes involved in PG biosynthesis in S. marcescens JNB 5-1. In the ΔcpxR mutant strain, the transcription levels of the pig gene cluster and the genes involved in the pathways of PG precursors, such as proline, pyruvate, serine, methionine, and S-adenosyl methionine, were significantly increased, hence promoting the production of PG. Subsequently, a fusion segment composed of the genes proC, serC, and metH, responsible for proline, serine, and methionine, was inserted into the cpxR gene in S. marcescens JNB 5-1. On fermentation by the resultant engineered S. marcescens, the highest PG titer reached 5.83 g/L and increased by 41.9%, relative to the parental strain. In this study, we revealed the role of CpxR in PG biosynthesis and provided an alternative strategy for the engineering of S. marcescens to enhance PG production.


A rabbit model of cerebral microembolic signals for translational research: preclinical validation for aspirin and clopidogrel.
Essentials Microembolic signal (MES) is an independent predictor of stroke risk in patients. A rabbit model of cerebral microembolic signals was established. Therapeutic efficacy was demonstrated for aspirin and clopidogrel on microembolic signals. Potential translational value of this preclinical model of MES was demonstrated. Objectives Cerebral microembolic signals (MESs) detected by transcranial Doppler (TCD) ultrasound constitute an independent predictor of stroke risk and prognosis. The aim of this study was to develop a novel preclinical model of MESs to facilitate translational research. Methods A clinical TCD ultrasound machine was used to detect MESs in the cerebral circulation of New Zealand White rabbits. Technical feasibility was assessed for the measurement of MESs in the middle cerebral artery (MCA) by TCD. FeCl3 -induced carotid arterial thrombosis was optimized for the generation of endogenous microemboli. Ascending doses of two antithrombotic agents (aspirin and clopidogrel) were evaluated individually and in combination for their effects on both arterial thrombosis and MESs in a 30% FeCl3 -induced carotid arterial thrombosis model, along with ex vivo functional assays. Results Dose-dependent FeCl3 -induced arterial thrombosis studies showed that 30% FeCl3 resulted in the most consistent and reproducible MESs in the MCA (3.3 ± 0.7 MESs h(-1) ). Ascending-dose studies showed that the effective doses for 50% inhibition (ED50 ) of thrombus formation, based on integrated blood flow and thrombus weight, respectively, were 3.1 mg kg(-1) and 4.2 mg kg(-1) orally for aspirin, and 0.3 mg kg(-1) and 0.28 mg kg(-1) orally for clopidogrel. The ED50 values for MES incidence were 12.7 mg kg(-1) orally for aspirin, and 0.25 mg kg(-1) orally for clopidogrel. Dual treatment with aspirin (5 mg kg(-1) ) and clopidogel (0.3 mg kg(-1) ) resulted in significant reductions in cerebral MESs (P < 0.05) as compared with monotherapy with either agent. Conclusions Our study demonstrated the successful establishment of the MES model in rabbits, and it may provide translational value for MESs and ischemic stroke research.


[Soluble forms of adenylyl cyclases of spermatozoa].
Soluble (cytosolic) forms of adenylyl cyclases (sAC), the enzymes catalyzing the conversion of ATP to the second messenger cAMP, play a key role in the regulation of spermatogenesis, control maturation of spermatozoa in the epididymis and their capacitation in the female genital tract, which determines their ability to fertilize. In the last years the significant progress was made in the study of the structural and functional organization and regulatory properties of sAC, their localization in the spermatozoa as well as in the investigation of intracellular cascades functionally coupled with sAC, including protein kinase A, cAMP-dependent phosphodiesterase, non-receptor tyrosine kinases, tyrosine phosphatases, transcription factors of CREB/CREM-family. The molecular mechanisms involved in the regulation of the intracellular concentration of bicarbonate anions, the main endogenous activators of sAC, were deciphered. Many evidences were obtained that the decrease of functional activity of sAC and signaling cascades and effector proteins coupled to it, as well as bicarbonate anion transporters lead to disturbances of spermatogenesis. As a consequence, the development of approaches for controlling the activity of sAC in spermatozoa is one of the priority ways to treat dysfunctions of the male reproductive system. Present review is devoted to advances in the study of soluble forms of AC and functionally coupled to them signaling cascades and effector proteins in the spermatozoa, as well as to the unresolved issues in this area.


Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials.
Semaglutide shows significant performance on weight reduction in several clinical trials. However, it is not clear what kind of administration frequency or dosage will achieve better effects. This study aims to explore the different therapeutic effect of semaglutide on weight control under the diverse administration circumstances. The PubMed, Embase, Web of Science, Cochrane Library, and the Clinical Trials.gov were searched from inception until 6 June, 2022 to include randomized controlled trials evaluating the Efficacy and safety of subcutaneous semaglutide in overweight or obese adults. Random effects or fixed effects model was conducted based on the heterogeneity among trials. Subgroup analysis was performed to identify the detailed effects under different intervention situations. Our study included 13 RCTs involving 5,838 participants with 3,794 ones in semaglutide group and 2,044 in placebo group. Semaglutide was associated with a significant reduction on weight loss related outcomes, including the absolute value of weight loss (WMD -8·97, 95% CI -10·73 to -7·21), percentage of weight loss (WMD -10·00, 95% CI -11·99 to -8·00), body mass index (WMD-3·19, 95% CI -4·02 to -2·37) and waist circumference (WMD -7·21,95% CI -8·87 to -5·56). Subgroup analyses illustrated participants with high weekly dosage, long-term treatment duration and severe baseline BMI (Class II obesity) had a more remarkably decreasing on the main outcomes of weight loss (P for interaction<0·05). Total adverse reactions occurred more frequently in the daily administration group than that in the weekly group (P for interaction =0·01). During the treatment, the incidence rate of hypoglycemia was higher in the group without lifestyle intervention compared with that with lifestyle intervention (P for interaction =0·04). Interpretation Subcutaneous semaglutide had significant benefits on weight loss with reasonable safety in overweight or obese adults. Moreover, additional benefits on cardiometabolic profiles were also seen. We recommended semaglutide treatment to be coupled with lifestyle interventions, and target dose of 2·0 mg or more subcutaneously once weekly. Clinicians can choose suitable treatment schemes based on diverse individual situations. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337099, identifier PROSPERO (CRD42022337099).


Role of seminal osmolarity in the reduction of human sperm motility.
Mammalian sperm at ejaculation are suspended in the seminal plasma, a heterogeneous mixture deriving from the testicular/epididymal fluid and from secretions of seminal vesicles, prostate and bulbourethral glands. Biochemical characteristics of seminal fluid change along the male reproductive tract when considering its inorganic and organic composition and pH but it is known that in each region of the male genital tract seminal osmolarity is higher than that of serum. It has been previously demonstrated that in invertebrate and vertebrate sperm, seminal plasma osmolarity influences sperm motility and activity, and human sperm have been shown to possess osmosensitive calcium entry pathway that controls important functions such as acrosome reaction and oocyte penetration. In the present study, we have determined seminal plasma osmolarity in a large number of normozoospermic fertile and asthenozoospermic infertile subjects correlating it with sperm motility percentages and kinematic characteristics determined utilizing a computerized motion analysis system. Our results confirm that seminal plasma osmolarity is higher than that of serum (336.1 +/- 20.2 vs. 291.1 +/- 6.9 mOsm/L, respectively). Normozoospermic subjects show seminal osmolarity values that are significantly lower with respect to asthenozoospermic patients (317.8 +/- 12.2 vs. 345.2 +/- 22.6 mOsm/L, p<0.001), irrespective of the cause of asthenozoospermia. Seminal plasma osmolarity negatively correlates with sperm progressive motility percentages and kinetic characteristics (curvilinear velocity, linear velocity, linear coefficient and lateral displacements of sperm head). Furthermore, when sperm from fertile subjects were suspended in medium with an osmolarity increasing from 300 to 600 mOsm, sperm motility percentages and kinetics characteristics were progressively reduced and nearly abolished when medium osmolarity was 600 mOsm. On the contrary, when sperm from asthenozoospermic subjects with high semen osmolarity were resuspended in medium with lower osmolarity, sperm motility parameters improved significantly. Sperm motility parameters did not correlate with seminal plasma concentrations of sodium, potassium, chloride with a weak correlation only with seminal calcium concentration. No correlations are present between seminal plasma osmolarity and ionic composition. In conclusion, the present study confirms and extends the knowledge that, in human, seminal plasma osmolarity is higher than that of serum and demonstrates that seminal osmolarity influences sperm motility characteristics and then it may contribute to the pathogenesis of some forms of asthenozoospermia and male infertility.


Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte tissue factor expression.
The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis, pregnancy loss, and thrombocytopenia associated with the production of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). The mechanisms of thrombus formation remain unknown. Tissue factor (TF), an inducible cell glycoprotein, is a major initiator of coagulation in vivo. The present study was therefore undertaken to investigate TF expression and procoagulant activity on monocytes from patients with primary APS and its correlation with thrombotic events. Three groups of patients were studied: group 1 comprised 23 primary APS patients with thrombosis, group 2 consisted of 10 primary APS patients without thrombosis, and group 3 contained 20 patients with thrombosis but without antiphospholipid antibodies. Twenty age- and sex-matched healthy blood donors were used as controls (group 4). Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and LAC by standard methodology. Cell surface expression of TF on monocytes was assessed by flow cytometry. The amount of TF in cell lysates (TF(Ag)) and soluble TF(Ag) plasma levels were analyzed by ELISA, and the TF-related procoagulant activity (PCA-TF) on intact cells and cell lysates by a chromogenic assay. Levels of the cytokines that influence TF production, i.e., tumor necrosis factor alpha (TNF alpha) and interleukin-1beta (IL-1beta), were determined by ELISA. Cell surface expression of TF was increased in group 1 (mean +/- SEM 50.2 +/- 4% positive cells) compared with group 2 (14.6 +/- 1.6%), group 3 (16.8 +/- 3.7%), and group 4 (14.1 +/- 1.6%). TF(Ag) levels were also elevated in group 1 (215.8 +/- 11.2 pg/10(6)) compared with group 2 (150.8 +/- 15.2), group 3 (101.4 +/- 14.8), and group 4 (80.32 +/- 5.5). PCA-TF on intact cells and cell lysates was significantly increased in group 1 (148.8 +/- 16.3 units/10(5) lysate cells, compared with 54.5 +/- 11.5, 38.6 +/- 9.7, and 22.5 +/- 3.1 in groups 2, 3, and 4, respectively). Among group 1 patients, there was a significant increase in the degree of TF expression in those positive for IgG aCL, but not in those positive for IgM aCL or LAC. TNF alpha and IL-1beta plasma levels did not differ significantly between any of the groups. These results suggest that monocyte TF expression is directly involved in the pathogenesis of thrombotic complications in patients with the primary APS.


Calculation model and bearing capacity optimization method for the soil settlement between piles in geosynthetic-reinforced pile-supported embankments based on the membrane effect.
The geosynthetic-reinforced pile-supported embankment (GRPSE) system has been widely used in road construction on soft soil. However, the application of the GRPSE system is often restricted by its high-cost. The reason is that they are designed for bearing control as defined in the past. During the construction process, the pile spacing is reduced to meet the requirements for the embankment bearing capacity and settlement. These factors cause the membrane effect to not be exploited. As a result, the utilization efficiency of the bearing capacity of the soil between the piles is low and the project cost is high. Therefore, in order to solve the problem of insufficient bearing capacity of soil between piles, we established a settlement calculation model of soil between piles based on membrane effect. The model considers the relationship between the geosynthetic reinforcement (GR) and the pile spacing. Based on the obtained model, a method for optimizing the soil bearing capacity of GRPSEs is proposed. By controlling the settlement of soil between piles, the bearing capacity of soil between piles and the membrane effect of embankment can be fully utilized. Therefore, the project cost can be reduced. Finally, the method is applied to field tests for comparison. The results show that the method is reasonable and applicable. This method can effectively exploit the membrane effect and improve the utilization efficiency of the bearing capacity of the soil between piles. An economical and reasonable arrangement scheme for the piles and GR was obtained. This scheme can not only ensure the safety of the project, but also fully utilize the bearing capacity of the soil between the piles and provide a new method for engineering design.


Critical amino acid residues of maurocalcine involved in pharmacology, lipid interaction and cell penetration.
Maurocalcine (MCa) is a 33-amino acid residue peptide that was initially identified in the Tunisian scorpion Scorpio maurus palmatus. This peptide triggers interest for three main reasons. First, it helps unravelling the mechanistic basis of Ca(2+) mobilization from the sarcoplasmic reticulum because of its sequence homology with a calcium channel domain involved in excitation-contraction coupling. Second, it shows potent pharmacological properties because of its ability to activate the ryanodine receptor. Finally, it is of technological value because of its ability to carry cell-impermeable compounds across the plasma membrane. Herein, we characterized the molecular determinants that underlie the pharmacological and cell-penetrating properties of maurocalcine. We identify several key amino acid residues of the peptide that will help the design of cell-penetrating analogues devoid of pharmacological activity and cell toxicity. Close examination of the determinants underlying cell penetration of maurocalcine reveals that basic amino acid residues are required for an interaction with negatively charged lipids of the plasma membrane. Maurocalcine analogues that penetrate better have also stronger interaction with negatively charged lipids. Conversely, less effective analogues present a diminished ability to interact with these lipids. These findings will also help the design of still more potent cell penetrating analogues of maurocalcine.


Symposium on allergic lung disease. IV. Immunologic mechanisms for release of chemical mediators of anaphylaxis from human lung tissue.
The antigen-induced, IgE-dependent release of chemical mediators from human lung tissue in vitro is modulated by a variety of pharmacologic maneuvers involving alterations in the intracellular levels of cyclic nucleotides. Increase in the level of cyclic AMP inhibits the immunologic release of histamine, SRS-A and ECF-A; beta-adrenergic agents, prostaglandins, cholera toxin and methylxanthines all produce accumulations of cAMP in human lung tissue. Depletion of cAMP after alpha-adrenergic, low-dose prostaglandin and imidazole stimulation is associated with enhancement of the release of mediators. Studies involving purified preparations of rat peritoneal mast cells confirm that alterations in the cAMP levels of a homogeneous population of target cells indeed influence histamine release in a fashion analogous to that of human lung tissue.Furthermore, cholinergic stimuli produce a marked enhancement of the antigen-induced release of mediators from human lung through an apparently independent mechanism, presumably acting through alterations in the tissue concentration of cyclic GMP. This latter observation suggests an important interaction between endogenously released parasympathetic neurohormones and the immunologic release of the chemical mediators of asthma.


Retrospective cine 3He ventilation imaging under spontaneous breathing conditions: a non-invasive protocol for small-animal lung function imaging.
A non-invasive and free-breathing hyperpolarized (HP) (3)He imaging protocol for small animals was implemented and validated on rats for lung function imaging. Animals were allowed to breathe a mixture of air and (3)He from a mask and a gas reservoir fitted to their heads. Radial imaging sequences were used, and MRI signal intensity changes were monitored for retrospective cine image reconstruction. The ventilation cycle of the animals was imaged with a 100 ms temporal resolution. The sliding window imaging technique was applied to reconstruct 5 ms time-shifted image series covering the complete breathing cycle. Image series were processed to extract quantitative ventilation parameters such as the gas arrival time. The reproducibility and the non-invasiveness of this ventilation imaging protocol were evaluated by multiple acquisitions on the same animals.


VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease.
The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease-MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1 gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability. We developed a computational pipeline, VNtyper, for reliable detection of MUC1 VNTR pathogenic variants and demonstrated its clinical utility in two distinct cohorts: (1) a historical cohort including 108 families with ADTKD and (2) a replication naive cohort comprising 2,910 patients previously tested on a panel of genes involved in monogenic renal diseases. In the historical cohort all cases known to carry pathogenic MUC1 variants were re-identified, and a new 25bp-frameshift insertion in an additional mislaid family was detected. In the replication cohort, we discovered and validated 30 new patients.


[Zinc balance in malnourished children given prolonged total parenteral feeding].
Zinc balances were performed in five different occasions in three children receiving prolonged total parenteral nutrition (TPN) for 4 or more weeks. Excessive urinary zinc loss was a constant finding and one patient also presented increased fecal loss. It is concluded that TPN solutions when administered for long periods must be supplemented with zinc in order to obtain positive balances and a retention of zinc between 50-100 micrograms kg/day. In children without abnormal losses supplements recommended by the American Medical Association (100 micrograms/kg/day up to 5 years and from 2.5 to 4 mg/day in old children) seem adequate. In case of deficit in Zn and/or high digestive losses supplement of Zn in TPN must be increased up to 200 to 500 micrograms/kg/day.


Low-grade inflammation, obesity, and insulin resistance in adolescents.
Low-grade inflammation is associated with insulin resistance and precedes the onset of type 2 diabetes mellitus in adults, but there are no comparable data in youth. The objective of the study was to characterize the pattern of subclinical immune activation that is associated with indices of obesity and insulin resistance in youth and analyze whether this association is explained by obesity. This was a cross-sectional study. Medical check-up of schoolchildren was conducted by the Public Health Office in Düsseldorf (Germany). Participants included 519 adolescents (mean age 15.5 +/- 0.8 yr). Measures included body mass index (BMI) and waist circumference (WC) as indices of obesity; fasting glucose, insulin, and homeostasis model assessment of insulin resistance; serum concentrations of TNFalpha, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1, interferon-gamma-inducible protein (IP)-10 and adiponectin as immunological variables. In age-, sex-, and lipid-adjusted analyses, IL-6, IL-18, IP-10, and adiponectin (inversely) were associated with both BMI and WC (all P <or= 0.002). None of the immune markers was related to glucose, but IL-6, IL-18, and adiponectin (inversely) were associated with insulin and homeostasis model assessment of insulin resistance in age- and sex-adjusted models. Adjustment for BMI or WC indicated that a considerable proportion of these associations may be mediated by obesity. We found that a differential low-grade immune activation is associated with parameters of obesity in adolescents. Moreover, there is evidence that IL-6, IL-18, IP-10, and adiponectin (inversely) are associated with insulin resistance and that these associations can mainly be attributed to obesity.


Automatic smoke evacuation in laparoscopic surgery: a simplified method for objective evaluation.
Although its theoretical usefulness has been reported, the true value of automatic smoke evacuation system in laparoscopic surgery remains unknown. This is mainly due to the lack of objective evaluation. The purpose of this study was to determine the efficacy of the automatic smoke evacuator in laparoscopic surgery, by real-time objective evaluation system using an industrial smoke-detection device. Six pigs were used in this study. Three surgical ports were placed and electrosurgical smoke was generated in a standard fashion, using either a high-frequency electrosurgical unit (HF-ESU) or laparosonic coagulating shears (LCS). The smoke was evacuated immediately in the evacuation group but not in the control nonevacuation group. The laparoscopic field-of-view was subjectively evaluated by ten independent surgeons. The composition of the surgical smoke was analyzed by mass spectrometry. The residual smoke in the abdominal cavity was aspirated manually into a smoke tester, and stains on a filter paper were image captured, digitized, and semiquantified. Subjective evaluation indicated superior field-of-view in the evacuation group, compared with the control, at 15 s after activation of the HF-ESU (P < 0.05). The smoke comprised various chemical compounds, including known carcinogens. The estimated volume of intra-abdominal residual smoke after activation of HF-ESU was significantly lower in the evacuation group (47.4 ± 16.6) than the control (76.7 ± 2.4, P = 0.0018). Only marginal amount of surgical smoke was detected in both groups after LCS when the tissue pad was free from burnt tissue deposits. However, the amount was significantly lower in the evacuation group (21.3 ± 10.7) than the control (75 ± 39.9, P = 0.044) when the tissue pad contained tissue sludge. Automatic smoke evacuation provides better field-of-view and reduces the risk of exposure to harmful compounds.


Adverse effects from inappropriate medication administration via a jejunostomy feeding tube.
Numerous complications can arise when administering medications to patients receiving continuous enteral feeding. We report a case of a patient who could not be fed by mouth and was receiving continuous jejunal enteral feeding who had an adverse event associated with inappropriate administration of a medication via his jejunostomy tube. He had taken an extended-release niacin product before hospitalization for type IIb hyperlipidemia. The patient was inappropriately given a single dose of 750 mg of niacin as the short-acting tablets that were crushed and administered via the jejunostomy tube. He experienced severe cutaneous flushing, a feeling of warmth, itching, nausea, and emesis. He was noted to have "prickly heat" to the forehead, according to the nursing notes. A discussion of problems and guidelines for medication administration in adult patients receiving continuous tube feeding is provided.


Sleep patterns and cardiometabolic risk in schoolchildren from Cuenca, Spain.
Sleep seems to have a significant influence on the metabolic syndrome (MetS). However, results in this association are still inconsistent in children. The aim of this study was to examine the influence of sleep characteristics in the MetS (index and factors) in Spanish children. Cross-sectional study including a sample of 210 children aged 8-to-11-years belonging to 20 schools from the province of Cuenca, Spain was conducted. Cardiometabolic risk and actigraphy sleep patterns were determined and analysed using correlation coefficients, ANCOVA models and a propensity score derivation model. Overall, children in the lower time in bed category and those who went to bed later (> 23:15h) showed worse values in the cardiometabolic profile and risk index. Differences were observed when the total time in bed was below 9h 15mins. Our study shows that short sleep duration could be a risk factor for cardiometabolic risk in children, and bedtime may independently influence this risk. In addition, our data suggests that children's sleep hygiene should be incorporated in parenting educational programs.


Amplification of the telomerase reverse transcriptase (hTERT) gene in cervical carcinomas.
The expression of telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex, is required for activation of telomerase during immortalization and transformation of human cells. However, the biochemical and genetic mechanisms governing hTERT expression remain to be elucidated. In the present study, we examined hTERT amplification as a potential genetic event contributing to telomerase activation in cervical carcinomas. An amplification of the hTERT gene was found in 1/4 cervical cancer cell lines and 21/88 primary tumor samples derived from the patients with cervical carcinomas. An increase in the hTERT copy number was significantly correlated with higher levels of hTERT protein expression. Moreover, the hTERT alterations with the enhanced hTERT expression were exclusively observed in those tumors with high-risk human papillomavirus infection. Taken together, the hTERT gene amplification, directly or indirectly targeted by human papillomavirus, may be one of the driving forces responsible for upregulation of hTERT expression and activation of telomerase in cervical cancers.


[Spontaneous urinary extravasation from the renal pelvis associated with ureteral fibroepithelial polyp: report of a case].
A 26-year-old woman presented with a colicky right flank pain. Retrograde pyelogram showed extravasation of the contrast medium from the right renal pelvis and a filling defect in the right ureter 4.5 cm proximal to the ureteral orifice. Urinary cytology was negative for malignancy. A partial ureterectomy with a vesicoureteroneostomy was performed. Gross inspection of the resected distal ureter revealed a 3-mm polyp with a grayish-white smooth surface as well as a ureteral stenosis of 2 cm in length just distal to the polyp. Pathological diagnosis was a fibroepithelial polyp. In our case, urinary extravasation probably resulted from an impacted polyp in the stenotic ureter.


Formation of Volatile Tea Constituent Indole During the Oolong Tea Manufacturing Process.
Indole is a characteristic volatile constituent in oolong tea. Our previous study indicated that indole was mostly accumulated at the turn over stage of oolong tea manufacturing process. However, formation of indole in tea leaves remains unknown. In this study, one tryptophan synthase α-subunit (TSA) and three tryptophan synthase β-subunits (TSBs) from tea leaves were isolated, cloned, sequenced, and functionally characterized. Combination of CsTSA and CsTSB2 recombinant protein produced in Escherichia coli exhibited the ability of transformation from indole-3-glycerol phosphate to indole. CsTSB2 was highly expressed during the turn over process of oolong tea. Continuous mechanical damage, simulating the turn over process, significantly enhanced the expression level of CsTSB2 and amount of indole. These suggested that accumulation of indole in oolong tea was due to the activation of CsTSB2 by continuous wounding stress from the turn over process. Black teas contain much less indole, although wounding stress is also involved in the manufacturing process. Stable isotope labeling indicated that tea leaf cell disruption from the rolling process of black tea did not lead to the conversion of indole, but terminated the synthesis of indole. Our study provided evidence concerning formation of indole in tea leaves for the first time.


Fatty acid solubilizer from the oral disk of the blowfly.
Blowflies are economic pests of the wool industry and potential vectors for epidemics. The establishment of a pesticide-free, environmentally friendly blowfly control strategy is necessary. Blowflies must feed on meat in order to initiate the cascade of events that are involved in reproduction including juvenile hormone synthesis, vitellogenesis, and mating. During feeding blowflies regurgitate salivary lipase, which may play a role in releasing fatty acids from triglycerides that are found in food. However, long-chain fatty acids show low solubility in aqueous solutions. In order to solubilize and ingest the released hydrophobic fatty acids, the blowflies must use a solubilizer. We applied native PAGE, Edman degradation, cDNA cloning, and RT-PCR to characterize a protein that accumulated in the oral disk of the black blowfly, Phormia regina. In situ hybridization was carried out to localize the expression at the cellular level. A fluorescence competitive binding assay was used to identify potential ligands of this protein. A protein newly identified from P. regina (PregOBP56a) belonged to the classic odorant-binding protein (OBP) family. This gene was expressed in a cluster of cells that was localized between pseudotracheae on the oral disk, which are not accessory cells of the taste peg chemosensory sensilla that normally synthesize OBPs. At pH 7 and pH 6, PregOBP56a bound palmitic, stearic, oleic, and linoleic acids, that are mainly found in chicken meat. The binding affinity of PregOBP56a decreased at pH 5. We propose that PregOBP56a is a protein that solubilizes fatty acids during feeding and subsequently helps to deliver the fatty acids to the midgut where it may help in the process of reproduction. As such, PregOBP56a is a potential molecular target for controlling the blowfly.


Searching for value: the influence of policy and reform on nurses' sense of value in long-term aged care in Australia.
Contemporary literature on long-term aged care focuses heavily on issues associated with the recruitment and retention of nursing staff, such as job satisfaction and attitudes towards caring for older people. This paper aims to highlight one aspect of a larger study of registered nurses' experiences in long-term aged care in Australia and the influence that government policy and reform has in shaping that experience. This insight into aspects of nurses' everyday experience also contributes to a broader understanding of job satisfaction in long-term care. Findings from this study suggest that registered nurses experience tension in their search for value in their practice, which incorporates professional, political and social mediators of value and worth. These issues are discussed in relation to the impact of policy and reform on nurses' sense of value in long-term aged care and highlight the need for sensitive policy initiatives that support issues of value in nursing practice.


PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).
To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.


Adaptation of acaricide stress facilitates Tetranychus urticae expanding against Tetranychus cinnabarinus in China.
The two-spotted spider mite, Tetranychus urticae, and the carmine spider mite, Tetranychus cinnabarinus, are invasive and native species in China, respectively. Compared with T. cinnabarinus, T. urticae has expanded into most parts of China and has become the dominant species of spider mite since 1983, when it was first reported in China. However, the mechanism of the demographic conversion has not been illuminated. In this study, one T. urticae field population and one T. cinnabarinus field population were isolated from the same plant in the same field, and the toxicological characteristics were compared between these two species. Laboratory bioassays demonstrated that T. urticae was more tolerant to commonly used acaricides than T. cinnabarinus. The activities of detoxification enzymes were significantly greater in T. urticae, and the fold changes of enzymes activities in T. urticae were also greater following exposure to acaricides. Furthermore, more metabolism-related genes were upregulated at a basal level, and more genes were induced in T. urticae following exposure to acaricides. The comparison of proteins and genes between both species led credence to the hypothesis that T. urticae was more resistant to acaricides, which was the reason explaining the expansion of invasive T. urticae against native T. cinnabarinus. Laboratory simulation experiments demonstrated that following the application of acaricides, the composition of a mixed T. urticae/T. cinnabarinus population would change from a T. cinnabarinus-dominant to a T. urticae-dominant population. This study not only reveals that T. urticae possesses stronger detoxification capacity than its sibling species T. cinnabarinus, which facilitated its persistent expansion in China, but also points to the need to accurately identify Tetranychus species and to develop species-specific management strategies for these pests.


THE EVOLUTIONARILY STABLE PHENOTYPE DISTRIBUTION IN A RANDOM ENVIRONMENT.
In an unpredictably changing environment, phenotypic variability may evolve as a "bet-hedging" strategy. We examine here two models for evolutionarily stable phenotype distributions resulting from stabilizing selection with a randomly fluctuating optimum. Both models include overlapping generations, either survival of adults or a dormant propagule pool. In the first model (mixed-strategies model) we assume that individuals can produce offspring with a distribution of phenotypes, in which case, the evolutionarily stable population always consists of a single genotype. We show that there is a unique evolutionarily stable strategy (ESS) distribution that does not depend on the amount of generational overlap, and that the ESS distribution generically is discrete rather than continuous; that is, there are distinct classes of offspring rather than a continuous distribution of offspring phenotypes. If the probability of extreme fluctuations in the optimum is sufficiently small, then the ESS distribution is monomorphic: a single type fitted to the mean environment. At higher levels of variability, the ESS distribution is polymorphic, and we find stability conditions for dimorphic distributions. For an exponential or similarly broad-tailed distribution of the optimum phenotype, the ESS consists of an infinite number of distinct phenotypes. In the second model we assume that an individual produces offspring with a single, genetically determined phenotype (pure-strategies model). The ESS population then contains multiple genotypes when the environmental variance is sufficiently high. However the phenotype distributions are similar to those in the mixed-strategies model: discrete, with an increasing number of distinct phenotypes as the environmental variance increases.


Water-Dependent Blending of Pectin Films: The Mechanics of Conjoined Biopolymers.
Biodegradable pectin polymers have been recommended for a variety of biomedical applications, ranging from the delivery of oral drugs to the repair of injured visceral organs. A promising approach to regulate pectin biostability is the blending of pectin films. To investigate the development of conjoined films, we examined the physical properties of high-methoxyl pectin polymer-polymer (homopolymer) interactions at the adhesive interface. Pectin polymers were tested in glass phase (10-13% w/w water content) and gel phase (38-41% w/w water content). The tensile strength of polymer-polymer adhesion was measured after variable development time and compressive force. Regardless of pretest parameters, the adhesive strength of two glass phase films was negligible. In contrast, adhesion testing of two gel phase films resulted in significant tensile adhesion strength (p < 0.01). Adhesion was also observed between glass phase and gel phase films-likely reflecting the diffusion of water from the gel phase to the glass phase films. In studies of the interaction between two gel phase films, the polymer-polymer adhesive strength increased linearly with increasing compressive force (range 10-80 N) (R2 = 0.956). In contrast, adhesive strength increased logarithmically with time (range 10-10,000 s) (R2 = 0.913); most of the adhesive strength was observed within minutes of contact. Fracture mechanics demonstrated that the adhesion of two gel phase films resulted in a conjoined film with distinctive physical properties including increased extensibility, decreased stiffness and a 30% increase in the work of cohesion relative to native polymers (p < 0.01). Scanning electron microscopy of the conjoined films demonstrated cross-grain adhesion at the interface between the adhesive homopolymers. These structural and functional data suggest that blended pectin films have emergent physical properties resulting from the cross-grain intermingling of interfacial pectin chains.


Surfactant Protein B Suppresses Lung Cancer Progression by Inhibiting Secretory Phospholipase A2 Activity and Arachidonic Acid Production.
Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B). To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to evaluate the downstream signaling pathway. The in vivo effects of SP-B were assessed through mouse xenograft model with intratumoral injection of CM. In response to IR, NSCLC cell lines showed decreased SP-B regulated by the TGF-β signaling and decreased SP-B stimulated cell survival and epithelial-mesenchymal transition. Treatment with CM from irradiated cells activated sPLA2, enhanced protein kinase Cδ-MAPKs signaling pathway, and increased arachidonic acid production. We confirmed the in vivo roles of SP-B through mouse xenograft model. Our results revealed that down-regulation of SP-B was involved in the radiation-induced metastatic conversion of NSCLC and provided evidence that SP-B acted as a suppressor of NSCLC progression.


Cost-minimization analysis of a wide-area teleradiology network in a French region.
The objective of our study was to perform a cost-minimization analysis of a wide-area teleradiology network. A prospective analysis of all transmissions over 1 year (data transmitted at the time of the remote consultation, and health outcomes of patients from medical record). The inter-hospital teleradiology network of the Aquitaine area (RIHRA) is a telemedicine system enabling the management of remote emergencies and elective radiology consultations. A cost-minimization study enabled a comparison of care procedures following the use of the network with those which would have been implemented without the network. The outcome measures of effectiveness were the transfers, hospitalizations, and consultations avoided or added. Fixed and variable costs were estimated. Among the 664 transmissions included in the study, 562 (85%) were performed in emergency and 102 (15%) for elective (non-emergency) cases. In emergency, 48% of transfers were avoided. For elective teleconsultations, a transfer was avoided for 37% of the patients and hospitalization for 12%. An extra consultation occurred after remote consultation for 2% of the patients. Annual saving can be estimated at 102,779 EUR for the Aquitaine area. This study underlines the efficiency of an inter-hospital teleradiology network. A qualitative evaluation of the impact of the use of the system should be carried out to improve technical and organizational operations.


Recombinant interleukin-2 acts as an adjuvant and helps to increase the efficacy of tumour vaccines.
To examine augmentation of the resistance-inducing effect of tumour vaccines with IL-2, we have used the cytokine produced by genetically modified somatic cells, and a conventional experimental model of TRA-expressing, MC-induced murine fibrosarcoma transplanted in histocompatible mice. We have found that the effect of s.c. immunization with irradiated tumour vaccines can be substantially enhanced by IL-2 injected repeatedly at the site of vaccination. To investigate the kinetics of local and systemic immunocyte populations during the course of immunization with vaccine plus IL-2, some of the vaccinated mice were sacrificed and their regional LNC and spleen cells were used for phenotypic analysis. It has been found that local (s.c.) administration of the irradiated tumour vaccine plus IL-2 was accompanied by an early depletion of CD4+ and CD8+ cells in regional lymph nodes followed by subsequent rebound lymphocytosis. The local reaction was followed by a systemic response in the spleen characterized with an increase in TCR alpha beta + CD4+ lymphocytes.


Carbon nanosphere synthesis and applications for rechargeable batteries.
Carbon nanospheres (CNSs) have attracted great interest in energy conversion and storage technologies due to their excellent chemical and thermal stability, high electrical conductivity and controllable size structure characteristics. In order to further improve the energy storage properties, many efforts have been made to design suitable nanocarbon spherical materials to improve electrochemical performance. In this overview, we summarize the recent research progress on CNSs, mainly focusing on the synthesis methods and their application as high-performance electrode materials in rechargeable batteries. As for the synthesis methods, hard template methods, soft template methods, the extension of the Stöber method, hydrothermal carbonization, aerosol-assisted synthesis are described in detail. In addition, the use of CNSs as electrodes in energy storage devices (mainly concentrated on lithium-ion batteries (LIBs)), sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are also discussed in detail in this article. Finally, some perspectives on the future research and development of CNSs are provided.


Heats of hydrogenation of compounds featuring main group elements and with the potential for multiply bonding.
Reaction enthalpies are calculated for the hydrogenation reactions of main group hydrides with the potential for multiple bonding, and thus the unsaturated character of these species is determined. In addition to the global minimum structures, which leave in some cases no hope for even a single E-E bond (E=Group 13, 14, or 15 element), calculations are also performed for geometries with maximum potential for multiple bonding. The trends down the groups and the periods are established. Interpretations have to take several factors into account. These factors sometimes work hand in hand but also against each other. We also include in our survey the species [HGaGaH]2- as a free anion and Na2[HGaGaH] as well as their hydrogenation products [H2GaGaH2]2- and Na2[H2GaGaH2]2-. The results show that the presence of the Na+ ions has a significant impact on their chemistry, and thus suggests that they are involved to a large extent in the bonding. Our results indicate that the compounds should be described as cluster compounds.


Developing treatment guidelines for myasthenia gravis.
A task force of the Myasthenia Gravis Foundation of America recently published a formal consensus statement intended to be a treatment guide for clinicians caring for myasthenia gravis (MG) patients worldwide. Its development was stimulated by the fact that there is generally no accepted standard of care for MG, and no one treatment is best for all MG patients. Also, there are few randomized trials of treatments in current use, and the generalizability of the few trials that have been successful may be difficult. Fifteen international experts in MG participated in the consensus process, which used a simple consensus to develop preliminary definitions and the RAND/UCLA Appropriateness Method to quantify agreement on treatment guidance statements for seven topics: symptomatic and immunosuppressive treatment, intravenous immunoglobulin and plasma exchange, impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG with muscle-specific tyrosine kinase antibodies, and MG in pregnancy. The executive summary of the guidance statement was published with open access to facilitate access by patients and healthcare professionals, and the full statement, with extensive background information, is available online. The guidance statement is a living document that will require updates as new treatments and new information on current treatments become available.


The effect of different foot and hand set-up positions on backstroke start performance.
Foot and hand set-up position effects were analysed on backstroke start performance. Ten swimmers randomly completed 27 starts grouped in trials (n = 3) of each variation, changing foot (totally immersed, partially and totally emerged) and hand (lowest, highest horizontal and vertical) positioning. Fifteen cameras recorded kinematics, and four force plates collected hands and feet kinetics. Standardised mean difference and 95% confidence intervals were used. Variations with feet immersed have shown lower vertical centre of mass (CM) set-up position (0.16 m), vertical impulse exerted at the hands, horizontal and vertical impulse exerted at the feet (0.28, 0.41, 0.16 N/BW.s, respectively) than feet emerged with hands horizontal and vertically positioned. Most variations with feet partially emerged exhibited higher and lesser vertical impulse exerted at hands than feet immersed and emerged (e.g. vertical handgrip, 0.13, 0.15 N/BW.s, respectively). Variation with feet emerged and hands on the lowest horizontal handgrip depicted shorter horizontal (0.23, 0.26 m) and vertical CM positioning at flight (0.16, 0.15 m) than the highest horizontal and vertical handgrip, respectively. Start variations have not affected 15-m time. Variations with feet partially or totally emerged depicted advantages, but focusing on the entry and underwater biomechanics is relevant for a shorter start time.