[Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma].
To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM). The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed. APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively. The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.


Recognition of Toxoplasma gondii by TLR11 prevents parasite-induced immunopathology.
TLRs are thought to play a critical role in self/non-self discrimination by sensing microbial infections and initiating both innate and adaptive immunity. In this study, we demonstrate that in the absence of TLR11, a major TLR involved in recognition of Toxoplasma gondii, infection with this protozoan parasite induces an abnormal immunopathological response consisting of pancreatic tissue destruction, fat necrosis, and systemic elevations in inflammatory reactants. We further show that this immunopathology is the result of non-TLR dependent activation of IFN-gamma secretion by NK cells in response to the infection. These findings reveal that in addition to triggering host resistance to infection, TLR recognition can be critical for the prevention of pathogen-induced immune destruction of self tissue.


EFFECT OF SCORPION VENOM TOXINS ON STRUCTURAL AND FUNCTIONAL PARAMETERS OF INTERNAL ORGANS, INCLUDING KIDNEYS (REVIEW).
The aim: To establish patterns of structural and functional changes in internal organs, including kidneys, under the conditions of exposure to scorpion venom toxins. Materials and methods: A thorough literature analysis was conducted on the basis of PubMed, Google Scholar, Web of Science, and Scopus databases. When processing the search results, we chose the newest publications up to 5 years old or the most thorough publications that vividly described the essence of our topic. Conclusions: The venom of various species of scorpions exhibits a wide range of biological activity. Acting on the structures of the central and peripheral nervous system, the toxins of scorpion venom cause the development of paralysis, convulsions, brain inflammation, hemorrhagic and ischemic strokes. Under conditions of influence on the cardiovascular system, damage to the endothelial lining of the vascular wall, disturbances in heart rhythm, conduction, and the development of destructive changes in the myocardium are characteristic. Data on kidney damage due to scorpion bites require a more detailed study, as information on microscopic and submicroscopic changes in the structure of the organ is too limited. However, cases of the development of tubular necrosis, interstitial nephritis, and kidney infarction are currently known.


Enhancing user acceptance of mandated mobile health information systems: the ePOC (electronic point-of-care project) experience.
From a clinical perspective, the use of mobile technologies, such as Personal Digital Assistants (PDAs) within hospital environments is not new. A paradigm shift however is underway towards the acceptance and utility of these systems within mobile-based healthcare environments. Introducing new technologies and associated work practices has intrinsic risks which must be addressed. This paper contends that intervening to address user concerns as they arise throughout the system development lifecycle will lead to greater levels of user acceptance, while ultimately enhancing the deliverability of a system that provides a best fit with end user needs. It is envisaged this research will lead to the development of a formalised user acceptance framework based on an agile approach to user acceptance measurement. The results of an ongoing study of user perceptions towards a mandated electronic point-of-care information system in the Northern Illawarra Ambulatory Care Team (TACT) are presented.


Dual Role of Gold Nanorods: Inhibition and Dissolution of Aβ Fibrils Induced by Near IR Laser.
Extracellular plaques of amyloid beta (Aβ) fibrils and neurofibrillary tangles are known to be associated with neurological diseases such as Alzheimer's disease. Studies have shown that spherical nanoparticles inhibit the formation of Aβ fibrils by intercepting the nucleation and growth pathways of fibrillation. In this report, gold nanorods (AuNRs) are used to inhibit the formation of Aβ fibrils and the shape-dependent plasmonic properties of AuNRs are exploited to faciliate faster dissolution of mature Aβ fibrils. Negatively charged, lipid (DMPC) stabilized AuNRs inhibit the formation of fibrils due to selective binding to the positevly charged amyloidogenic sequence of Aβ protein. The kinetics of inhibition is characterized by thioflavin T (ThT) fluorescence, transmission electronic microscopy (TEM), atomic force microscopy (AFM), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). An increase in the aspect ratio of DMPC-AuNR in the range of 2.2-4.2 decreased the fibrils content proportionally. Further, the fibrils content is decreased by increasing the concentration of AuNR for all aspect ratios. As AuNR absorb near-infrared (NIR) light and creates a localized hotspot, NIR laser (800 nm) is applied for 2 min to facilitate the thermal dissolution of mature Aβ fibrils. Majority of Aβ fibrils are disintegrated into smaller fragments after exposure to NIR in the presence of AuNR. Thus, the DMPC-AuNRs exhibit a dual effect: inhibition of fibrillation and NIR laser facilitated dissolution of mature amyloid fibrils. This study essentially provides guidelines to design efficient nanoparticle-based therapeutics for neurodegenerative diseases.


Green sulfur bacteria from hypersaline Chiprana Lake (Monegros, Spain): habitat description and phylogenetic relationship of isolated strains.
The 'Salada de Chiprana' (Chiprana Lake) is a hypersaline (30-73 per thousand), permanent and shallow lake of endorheic origin in a semi-arid region of the Ebro depression (Aragon, Spain). Magnesium sulfate and sodium chloride represent the main salts of this athalassohaline environment. Anoxic conditions occurred periodically in the bottom layers of the lake during the study period. When stratified, high sulfide concentrations (up to 7 mM) were measured in the hypolimnion. Physical and chemical conditions gave rise to the development of very dense green sulfur bacteria blooms (10.7 mg l(-1) of BChl c and 16.7 mg l(-1) of BChl d) at 0.5-1 m from the bottom. Microscopic observations revealed that cells morphologically similar to Chlorobium vibrioforme were dominant in the phototrophic bacterial community, but Prosthecochloris aestuarii was also found sometimes at lower concentrations, as revealed by both microscopic observation and flow cytometric analyses. Deep agar dilution series allowed to obtain several axenic cultures of phototrophic bacteria. They were identified according to their morphology, pigment composition and phylogenetic relationships (16S rDNA sequence analysis). Two of the sequenced strains (CHP3401 and CHP3402) belonged to the green sulfur bacteria and were related to Prosthecochloris aestuarii SK413(T) and Chlorobium vibrioforme DSM260(T), respectively. HPLC analyses of both natural samples and Chlorobium vibrioforme isolates indicated that these strains contained both BChl c and BChl d. Phylogenetic results suggested that Chlorobium vibrioforme strains DSM260(T) and CHP3402, all sequenced strains of Prosthecochloris aestuarii and strain CIB2401 constitute a separate cluster of green sulfur bacteria, all of them isolated from marine to hypersaline habitats.


Epidemiology of hyperadrenocorticism among 210,824 dogs attending primary-care veterinary practices in the UK from 2009 to 2014.
To estimate prevalence and risk factors for diagnosis with hyperadrenocorticism in dogs attending primary-care veterinary practices in the UK from 2009 to 2014. Cases were identified by searching the de-identified electronic patient records from UK primary-care veterinary practices participating in the VetCompass Programme. The estimated prevalence for hyperadrenocorticism diagnosis in dogs was 0·28% (95% confidence interval: 0·25 to 0·31). Multivariable logistic regression analysis revealed four associated risk factors: breed, breed-relative bodyweight, age and insurance status. The bichon frise had 6·5 times the odds (95% CI: 3·5 to 12·1, P<0·001) of hyperadrenocorticism compared with crossbreds. Dogs weighing more than or equal to their breed mean had 1·7 times the odds (95% CI: 1·3 to 2·3, P<0·001) of hyperadrenocorticism compared with dogs weighing less than the breed mean. Dogs aged 12·0 years and above showed 5·7 times the odds (95% CI: 3·7 to 8·7, P<0·001) of hyperadrenocorticism compared with dogs aged 6·0 to 8·9 years. Insured dogs had 4·0 times the odds (95% CI: 2·8 to 5·6, P<0·001) of hyperadrenocorticism compared with non-insured dogs. This is the first epidemiological report of a non-referral hospital population of dogs diagnosed with hyperadrenocorticism in the UK and describes important breed, age and bodyweight associations with this disorder which may improve diagnosis and enhance understanding of the underlying pathophysiology.


Argatroban: for a few selected patients.
Type II heparin-induced thrombocytopenia is currently managed by withdrawing heparin and replacing it with danaparoid sodium. Argatroban, a direct thrombin inhibitor anticoagulant (like lepirudin), is now authorised for this indication in France, following authorisation in several other countries since the early 2000s. Argatroban has not been compared with danaparoid in clinical trials. About 700 patients treated with argatroban in 2 trials were compared to historical controls managed by simple withdrawal of heparin and, in some cases, switching to an oral anticoagulant. Argatroban had no apparent advantages in terms of death or the need for amputation. Argatroban did not appear to increase the risk of bleeding in these trials, but evidence provided by historical comparisons is weak. The adverse effect profile includes hepatic disorders (notably fulminant hepatitis). The risk of pharmacokinetic interactions appears to below. In practice, given the absence of a proven therapeutic advantage, it is better to continue to use danaparoid for first-line treatment, reserving argatroban for the rare situations in which danaparoid is inappropriate.


Distributive and phagocytic characteristics of hepatic macrophages in five cetaceans belonging to Delphinidae and Ziphiidae.
Details of morphology and distribution of hepatic macrophages in cetaceans were investigated using the immunohistochemistry with an antibody (SRA-E5) generated against human macrophage scavenger receptor antigen. Liver samples were obtained from five species of cetaceans (Baird's beaked whales, short-finned pilot whales, Risso's dolphins, bottlenose dolphins, and pantropical spotted dolphins). Except for two species of whales, the number of SRA-E5-positive Kupffer cells was greatest in the perivenous zone (zone 3), followed by the mid-zonal (zone 2) and periportal (zone 1) zones; this distribution pattern was different from that in cattle examined here and previously reported rodents with the highest number in zone 1. The frequency of Kupffer cell in each of zones was significantly different among species, and interestingly, the total mean of the Kupffer cell number in three zones increased as the body-length of species was small. In cetaceans, Kupffer cells in zone 1 appeared larger and more stellate in shape, whereas those in zone 3 were smaller and rounder. All cetaceans but Baird's beaked whales had the black pigment-containing Kupffer cells, with the greatest number in zone 3, and macrophages with the similar pigments were also seen in the hepatic intermediate septa, indicating an active phagocytosis. Most of the black pigments were considered to be lipofuscin and such pigments were not seen in the bovine livers. These results indicate that cetacean hepatic macrophages show differences in the distribution and phagocytosis among hepatic lobular zones, or between cetacean species and terrestrial animals.


Cloning and expression of N-acetylglucosaminyltransferase I, the medial Golgi transferase that initiates complex N-linked carbohydrate formation.
This laboratory has previously identified a human gene encoding N-acetylglucosaminyltransferase I (GlcNAc-TI; EC 22.214.171.124) by complementation of the glycosylation defect in the Lec1 Chinese hamster ovary (CHO) cell mutant. A phage lambda library prepared from genomic DNA of a tertiary Lec1 transfectant (3 degrees T) has now been used to obtain clones encoding an active GlcNAc-TI enzyme. A small genomic DNA fragment [approximately 4.6 kilobases (kb)], isolated from an Alupositive lambda clone, conferred human GlcNAc-TI activity upon transfection into Lec1 cells. An approximately 1.3-kb probe generated from this DNA fragment detected unique but distinct DNA fragments in human and CHO genomic DNA. The probe also hybridized to a poly(A)+ RNA of approximately 2.7 kb in human and CHO cells and allowed the isolation of a full-length cDNA encoding human GlcNAc-TI activity. The overall features of the cDNA and deduced protein sequence (445 amino acids) are typical of other Golgi transferases that are type II transmembrane proteins. Northern blot analysis with the same probe showed that Lec1 mutant cells also possessed an approximately 2.7-kb poly(A)+ RNA, indicating that the lec1 mutation is a point mutation.


cDNA cloning, tissue distribution, and subcellular localization of horseshoe crab big defensin.
A full-length cDNA for horseshoe crab big defensin with a strong antimicrobial activity was obtained from a hemocyte cDNA library. The open reading frame of the cDNA coded for an NH2-terminal signal sequence followed by a propeptide and the mature big defensin. The propeptide is linked to the mature protein through an -Arg-X-Lys/Arg-Arg- motif, the processing site for Kex2-like proteases. Northern blot analysis revealed that big defensin is expressed in all the tissues tested, suggesting that big defensin plays an important role not only in hemocytes but also in other tissues for host defense. The subcellular localization, determined by immunocytochemistry at ultrastructural level, confirmed the previous findings obtained by biochemical analysis that big defensin locates in both small and large granules in hemocytes. Big defensin is the first example to demonstrate the existence of broad tissue distribution in horseshoe crab.


Atractylodes lancea Rhizome Polysaccharide Alleviates Immunosuppression and Intestinal Mucosal Injury in Mice Treated with Cyclophosphamide.
Plant-derived polysaccharides, such as Atractylodes lancea rhizome polysaccharide (ALP), are good immune regulators. However, the immune regulatory mechanism of the ALP is unknown. This study aimed to evaluate the effects of ALP on the intestinal mucosal barrier and intestinal mucosal immunity of immunosuppressed mice. We also compared the activity of raw Atractylodes lancea rhizome polysaccharide (SALP) with wheat bran processed bran-fried Atractylodes lancea rhizome polysaccharide (FALP; both at 1.2 g/kg/d for mice). Our results showed that ALP effectively increased the immune organ index and blood cell count, stimulated the secretion of cytokines, and promoted the expression of occludin and zonula occludens-1 (ZO-1). ALP also promoted the expression of T cells and the secretion of sIgA. Furthermore, ALP alleviated the gut microbiota disorder in Cy-treated mice and increased the relative abundances of Lactobacillus and Faecalibaculum. ALP reversed the decrease in the level of SCFAs and promoted the expression of G protein-coupled receptor 43 (GPR43). To our knowledge, this study was the first to explore how the ALP protects the intestinal mucosal barrier and enhances intestinal mucosal immunity by alleviating the gut microbiota imbalance and metabolic disorders of SCFAs. FALP was more therapeutic than SALP, suggesting that FALP could be developed as a promising functional food component.


Haptens, prohaptens and prehaptens, or electrophiles and proelectrophiles.
It is argued that the term 'hapten', and derived terms such as 'pro-hapten' and 'pre-hapten' are ambiguous and unnecessary. It is proposed that their use be abandoned. Instead, when considering the chemical basis of skin sensitization, it is preferable to classify compounds according to the chemical reaction mechanisms by which they can modify proteins.


Improved performance of collagen scaffolds crosslinked by Traut's reagent and Sulfo-SMCC.
Collagen scaffolds are frequently employed for applications in regenerative medicine. In previous studies, we affirmed that Traut's reagent (2-Iminothiolane hydrochloride) and Sulfo-SMCC (4-(N-Maleimidomethyl) cyclohexane-1-carboxylic acid 3-sulpho-N-hydroxysuccinimide ester sodium salt) could covalently bind growth factors on collagen scaffolds. We also observed that crosslinking formed within the collagen scaffolds with excess dosage of Sulfo-SMCC, which improved the biological performance of collagen scaffolds together with growth factors. In order to evaluate changes in capacity caused by crosslinking, Traut's reagent and adjusted different concentrations of Sulfo-SMCC (0.263, 1.315, 2.63 and 5.26 mM) were used to construct collagen scaffolds with differing extents of crosslinking in this study. The results demonstrated that resistance of collagen scaffolds to enzymatic digestion, cellularization and vascularization in vivo were enhanced by the crosslinking procedure. The cell culture studies indicated that the crosslinking procedure did not influence biocompatibility. Moreover, there were no statistical differences in the degradation rate, cellularization or vascularization among 1.315, 2.63 and 5.26 mM crosslinked groups. These results demonstrated that crosslinking collagen scaffolds with an appropriate amount of Traut's reagent and Sulfo-SMCC was an effective and safe method to modify naturally derived collagen scaffolds with notable potential uses in tissue regeneration.


Interscalene brachial plexus blocks in the management of shoulder dislocations.
Interscalene brachial plexus block is a simple and effective alternative to intravenous benzodiazepines or general anaesthesia for manipulation of the dislocated shoulder. Thirty interscalene brachial plexus blocks were performed on 29 patients with dislocations of the shoulder to provide regional anaesthesia for reduction. Pain was abolished by 14 out of the 30 blocks performed, improved by 13 and unchanged by three. Muscle relaxation (MRC grade 3 or less) occurred in 21 patients. In 26 cases the block allowed reduction of the dislocation without additional analgesia or sedative. Reduction was not possible in four cases. There were no significant complications.


Diamond quantum thermometry: from foundations to applications.
Diamond quantum thermometry exploits the optical and electrical spin properties of colour defect centres in diamonds and, acts as a quantum sensing method exhibiting ultrahigh precision and robustness. Compared to the existing luminescent nanothermometry techniques, a diamond quantum thermometer can be operated over a wide temperature range and a sensor spatial scale ranging from nanometres to micrometres. Further, diamond quantum thermometry is employed in several applications, including electronics and biology, to explore these fields with nanoscale temperature measurements. This review covers the operational principles of diamond quantum thermometry for spin-based and all-optical methods, material development of diamonds with a focus on thermometry, and examples of applications in electrical and biological systems with demand-based technological requirements.


Ultrasound guided brain abscess aspiration.
A brain abscess is a neurosurgical emergency and frequently requires drainage to relieve intracranial pressure and identify the offending organism. Surgical adjuncts including neuronavigation and intra-operative CT and MRI facilitate surgery, but have limitations, including cost and not offering real time intracranial views. Intra-operative ultrasound is a fast and relatively cheap tool which offers live, real time imaging and visualisation of an abscess being aspirated, but is less frequently used. We describe our technique of ultrasound guidance as an adjunct with neuronavigation for brain abscess aspiration, review the literature on surgical adjuncts and remind the neurosurgical community of its value in this and other cranial procedures. We summarise our recent experience in its use in six patients with a brain abscess. There is a learning curve to using intra-operative ultrasound, but we recommend its routine use in abscess drainage surgery.


The Concave Faces of the Great Pyramid: An Explanation.
A construction methodology proposed by the author in 2003 to explain how the Great Pyramid was built suggested that workers used the angled faces of the pyramid as surfaces on which to transport block and sledge assemblies. This methodology however would leave few material traces behind making it more difficult to conclusively prove. This article argues that the known concavity of the outer packing blocks of the Great Pyramid provides meangingful archaeological evidence to add weight to the author's proposed construction methodology.


Idiopathic Carpal Spasm (Trousseau's Sign) After Intraoperative Arm Tourniquet Inflation in an Intubated Patient.
We present a case of a 38-year-old male who sustained a laceration from a knife to the volar aspect of his left index and middle fingers. He had clinical injury to his flexor digitorum profundus tendons to both digits. He underwent operative exploration and repair of the tendons under general anaesthetic. An arm tourniquet was inflated to allow for haemostasis in the operative field. A few minutes after inflation, the patient's hand went into carpal spasm. The tourniquet was deflated and the spasm resolved. Intraoperative serum calcium and carbon dioxide levels were normal. The operation proceeded with the tourniquet deflated. Postoperatively serum calcium and magnesium levels were within normal limits, as was serum vitamin D and parathyroid hormone levels. It has been reported that carpal spasm can occur with tourniquet use in the anxious patient due to hyperventilation and resultant metabolic alkalosis. This however is the first reported case of carpal spasm in the setting of tourniquet use and normal serum electrolytes and respiratory parameters in an intubated patient.


Portobiliary fistula following laparoscopic cholecystectomy.
The laparoscopic approach has replaced open surgery as the gold standard for cholecystectomy. This technique is, however, associated with a greater incidence of bile duct injuries (BDIs). We report a case of portobiliary fistula (PBF), a rare complication of BDI, occurring post laparoscopic cholecystectomy (LC). PBF has been reported after procedures such as endoscopic retrograde cholangiopancreatography and pathologies such as liver abscesses, but only once previously in the setting of LC. We discuss the management of this patient with apparent dual pathology, and summarise other aetiologies that may give rise to this condition.


Subcutaneous Administration of Medications and Fluids by Nonprofessional Caregivers at Home.
Background: Patients requiring home-based palliative care have advanced complex illnesses with functional limitations and decline. This retrospective study reviewed caregiver administration of subcutaneous (SQ) medications and fluids when symptom control could not be achieved using the oral route. Methods: Medical records from September 1, 2017 to February 28, 2018 were reviewed for 272 consecutive patients who received SQ administration of medications or fluids at a home-based palliative care program. We analyzed the clinical characteristics of patients and caregivers, medications administered, and catheter outcomes. Results: Patients' median age was 74 years, and 163 (60%) were women. The most common cancer diagnoses were stomach 26 (12%), lung 22 (10%), and colorectal 20 (9%). Dementia 24 (44%), cerebrovascular disease 9 (16%), and congestive heart failure 7 (13%) were the most frequent nonmalignant diseases. Poor symptom control 162 (60%) and impaired oral intake 107 (39%) were the most common indications for an SQ route of administration. Nonprofessional caregivers trained by a nurse administered medications to 218 patients (80%). During interventions, the patients received a mean of 4 medications (±2 standard deviation). A total of 903 catheters were inserted, 15/732 (2%) catheters handled by nonprofessional caregivers caused a local infection, compared with 3/171 (1.8%) of catheters handled by nurses. Hydromorphone was the most common opioid used (57%), followed by morphine (35%). The median length of stay in the program was 24 days (interquartile range: 11-60). Conclusions: SQ administration of medications and fluids by nonprofessional caregivers trained by health care professionals is feasible and promising, but additional testing is needed.


The Risk Factor of Age in Construction Accidents: Important at Present and Fundamental in the Future.
Occupational accidents in the construction sector are analyzed in this study of the relation between the age of the injured worker, days off work due to the injury, and accident severity. A further aim is to establish whether accumulated fatigue during the working day and throughout the week has a similar effect on all workers, regardless of age. A total of three million four hundred and thirty-eight thousand, one hundred and forty-five (3,438,145) accidents are analyzed in this study; the total of all accidents are notified in Spain by workers from the sector over the period 1996-2015. The results confirmed a direct link between worker age and both days off work due to the injury and accident severity. They also confirmed that the workers injured in accidents in the afternoon hours were older than the workers injured in the morning hours. In consequence, the average number of days off work due to injury following an accident of the older workers was also larger and the accidents are more severe. Likewise, the workers injured on a Friday were of an older average age than those injured on a Monday. In consequence, the average number of days off work due to injury on the last day of the week was also higher and the accidents were of more severity. All the above-mentioned differences were statistically significant.


Comparison of muscle fatty acid profiles and cholesterol concentrations of bison, beef cattle, elk, and chicken.
The objective of this study was to compare fatty acid weight percentages and cholesterol concentrations of longissimus dorsi (LD), semitendinosus (ST), and supraspinatus (SS) muscles (n = 10 for each) of range bison (31 mo of age), feedlot-finished bison (18 mo of age), range beef cows (4 to 7 yr of age), feedlot steers (18 mo of age), free-ranging cow elk (3 to 5 yr of age), and chicken breast. Lipids were analyzed by capillary GLC. Total saturated fatty acids (SFA) were greater (P < 0.01) in range bison than in feedlot bison and were greater (P < 0.01) in SS of range beef cattle than in feedlot steers. Muscles of elk and range bison were similar (P > 0.05) in SAT. In LD, polyunsaturated fatty acids (PUFA) were highest (P < 0.01) for elk and range bison and lowest (P < 0.01) for feedlot steers within each muscle. Range bison and range beef cows had greater (P < 0.01) PUFA in LD and ST than feedlot bison or steers, respectively. Range-fed animals had higher (P < 0.01) n-3 fatty acids than feedlot-fed animals or chicken breast. Chicken breast n-6 fatty acids were greater (P < 0.01) than for muscles from bison, beef, or elk. Elk had higher (P < 0.01) n-6 fatty acids than bison or beef cattle; however, range-fed animals had higher (P < 0.01) n-6 fatty acids than feedlot-fed animals in ST. Conjugated linoleic acid (CLA, 18:2cis-9, trans-11) in LD was greatest (P < 0.01) for range beef cows (0.4%), and lowest for chicken breast and elk (mean = 0.1%). In ST, CLA was greatest (P < 0.01) for range and feedlot bison and range beef cows (mean = 0.4%) and lowest for elk and chicken breast (mean = 0.1%). Also, SS CLA was greatest (P < 0.01) for range beef cows (0.5%) and lowest for chicken breast (0.1%). Mean total fatty acid concentration (g/100 g tissue) for all muscles was highest (P < 0.01) for feedlot bison and feedlot cattle and lowest (P < 0.01) for range bison, range beef cows, elk, and chicken. Chicken breast cholesterol (mg/100 g tissue) was higher (P < 0.01) than LD and ST cholesterol, which were lowest (P < 0.01; 43.8) for range bison and intermediate for the other species. Cholesterol in SS was highest (P < 0.01) for feedlot bison and steers, which were similar to chicken breast (mean = 61.2 vs 52.8 for the mean of the other species). We conclude that lipid composition of bison muscle varies with feeding regimen, and range-fed bison had muscle lipid composition similar to that of forage-fed beef cows and wild elk.


Heterotrimeric G proteins-mediated resistance to necrotrophic pathogens includes mechanisms independent of salicylic acid-, jasmonic acid/ethylene- and abscisic acid-mediated defense signaling.
Heterotrimeric G proteins are involved in the defense response against necrotrophic fungi in Arabidopsis. In order to elucidate the resistance mechanisms involving heterotrimeric G proteins, we analyzed the effects of the Gβ (subunit deficiency in the mutant agb1-2 on pathogenesis-related gene expression, as well as the genetic interaction between agb1-2 and a number of mutants of established defense pathways. Gβ-mediated signaling suppresses the induction of salicylic acid (SA)-, jasmonic acid (JA)-, ethylene (ET)- and abscisic acid (ABA)-dependent genes during the initial phase of the infection with Fusarium oxysporum (up to 48 h after inoculation). However, at a later phase it enhances JA/ET-dependent genes such as PDF1.2 and PR4. Quantification of the Fusarium wilt symptoms revealed that Gβ- and SA-deficient mutants were more susceptible than wild-type plants, whereas JA- and ET-insensitive and ABA-deficient mutants demonstrated various levels of resistance. Analysis of the double mutants showed that the Gβ-mediated resistance to F. oxysporum and Alternaria brassicicola was mostly independent of all of the previously mentioned pathways. However, the progressive decay of agb1-2 mutants was compensated by coi1-21 and jin1-9 mutations, suggesting that at this stage of F. oxysporum infection Gβ acts upstream of COI1 and ATMYC2 in JA signaling.


The effect of depression on academic achievement in children with epilepsy.
In this cross-sectional study our aim was to evaluate the effect of depression on academic achievement in children with epilepsy and low school performance. Fifty-one children with epilepsy and low school performance were evaluated with the Children's Depression Inventory (CDI) to measure depressive symptoms. School performance was evaluated with Achenbach's Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). Children diagnosed with depressive spectrum disorders received medical therapy. All tests were administered in the first interview and repeated at the end of 6 months of therapy. Forty-three children completed the study. The patients were evaluated with DSM-IV diagnostic criteria. Accordingly, 9 (20.9%) children had Major Depressive Disorder (MDD) and 4 (9.3%) had Depressive Disorder, Not Otherwise Specified (DD-NOS). All children with MDD and DD-NOS received antidepressant medication, but only seven of them completed treatment. Posttreatment CDI scores were significantly lower, and TRF scores also improved. Pediatric neurologists should be aware of the possibility of depressive disorders in children with epilepsy, especially in those with low school performance.


Effectiveness of individualized, integrative outpatient treatment for females with anorexia nervosa and bulimia nervosa.
The effectiveness of an individualized outpatient program was investigated in the treatment of bulimia nervosa (BN) and anorexia nervosa (AN). Participants included 151 females who received outpatient eating disorder treatment in the partial hospitalization program, the intensive outpatient program, or a combination of the two programs. Outcome measures included the Eating Disorder Inventory (EDI-2), Beck Depression Inventory (BDI-II), frequency of binge eating and purging, and mean body weight. Findings included significant increases in weight for the AN group, reductions in binge eating frequency for the BN group, and reductions in EDI-2 and BDI-II scores and purging frequency for both groups. This study provides preliminary support for the efficacy of a multimodal program for the treatment of both anorexia nervosa and bulimia nervosa.


Sleep quality of endometrial cancer survivors and the effect of treatments.
Sleep disorders affect 54.9% of gynaecologic cancer survivors. The effect of treatment methods on sleep quality is not clear. This study evaluated the sleep quality of survivors of endometrial cancer and compared the effects of different treatments on sleep quality. Patients were categorised as surgery (group 1), surgery + brachytherapy (BRT) (group 2), surgery + external beam radiation therapy (EBRT) (group 3), and surgery + EBRT + BRT + chemotherapy (group 4). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The PSQI was completed by the participants before surgery, 1, 3, and 6 months after each treatment was completed. The PSQI scores were compared between the different measurement times and different study groups. This study enrolled 114 patients with a mean age of 58.1±11 years. The number of participants in each group was 53 (46.5%), 14 (12.3%), 12 (10.5%), and 35 (30.7%), respectively. At baseline, 28 (24.6%) patients reported poor sleep quality. The mean PSQI score reached the maximum level at the second measurement and decreased slightly during follow-up and the change in the PSQI score was significant (p=0.001). Group 3 and group 4 had significantly higher scores from baseline (p<0.008). At time point 3, the differences between the groups were significant. At time point 4, the most prominent effect of treatment on sleep quality was observed in patients with combined chemo-radiotherapy when compared with the other study groups. Most survivors of endometrial cancer are affected by poor sleep quality during their treatment. To improve these patients' quality of life, this disorder must be considered at each visit and tailored care plans should be developed to meet the women's needs. Further studies are needed to evaluate the long-term results of sleep quality on patients with endometrial cancer.


Characterization of a new pathogenic Acanthamoeba Species, A. byersi n. sp., isolated from a human with fatal amoebic encephalitis.
Acanthamoeba spp. are free-living amoebae that are ubiquitous in natural environments. They can cause cutaneous, nasopharyngeal, and disseminated infection, leading to granulomatous amebic encephalitis (GAE) in immunocompromised individuals. In addition, they can cause amoebic keratitis in contact lens wearers. Acanthamoeba GAE is almost always fatal because of difficulty and delay in diagnosis and lack of optimal antimicrobial therapy. Here, we report the description of an unusual strain isolated from skin and brain of a GAE patient. The amoebae displayed large trophozoites and star-shaped cysts, characteristics for acanthamoebas belonging to morphology Group 1. However, its unique morphology and growth characteristics differentiated this new strain from other Group 1 species. DNA sequence analysis, secondary structure prediction, and phylogenetic analysis of the 18S rRNA gene confirmed that this new strain belonged to Group 1, but that it was distinct from the other sequence types within that group. Thus, we hereby propose the establishment of a new species, Acanthamoeba byersi n. sp. as well as a new sequence type, T18, for this new strain. To our knowledge, this is the first report of a Group 1 Acanthamoeba that is indisputably pathogenic in humans.


Factor structure of the Bern Psychopathology Scale in a sample of patients with schizophrenia spectrum disorders.
The Bern Psychopathology Scale (BPS) is based on a system-specific approach to classifying the psychopathological symptom pattern of schizophrenia. It consists of subscales for three domains (language, affect and motor behaviour) that are hypothesized to be related to specific brain circuits. The aim of the study was to examine the factor structure of the BPS in patients with schizophrenia spectrum disorders. One hundred and forty-nine inpatients with schizophrenia spectrum disorders were recruited at the Department of Psychiatry II, Ulm University, Germany (n=100) and at the University Hospital of Psychiatry, Bern, Switzerland (n=49). Psychopathology was assessed with the BPS. The VARCLUS procedure of SAS(®) (a type of oblique component analysis) was used for statistical analysis. Six clusters were identified (inhibited language, inhibited motor behaviour, inhibited affect, disinhibited affect, disinhibited language/motor behaviour, inhibited language/motor behaviour) which explained 40.13% of the total variance of the data. A binary division of attributes into an inhibited and disinhibited cluster was appropriate, although an overlap was found between the language and motor behaviour domains. There was a clear distinction between qualitative and quantitative symptoms. The results argue for the validity of the BPS in identifying subsyndromes of schizophrenia spectrum disorders according to a dimensional approach. Future research should address the longitudinal assessment of dimensional psychopathological symptoms and elucidate the underlying neurobiological processes.


Reconstruction of the lower lid.
As the lower eyelid is frequently the site of malignant disease, lower lid replacement is a common task in oculoplastic surgery. As a rule the reconstruction of larger defects (more than one-third) can be accomplished with free grafts or with flaps. Different forms of pedicle flaps (full thickness, tarsoconjunctival, combined) from the upper lid provide better results than free grafts. A convenient method of lower lid replacement is the use of a medial pedicle rotation flap of the cheek. This has advantages over the temporal pedicle cheek flap or the frontal flap.


Right ventricular myxoma with heart failure.
Cardiac myxomas are histologically benign tumors but they may be lethal because of their strategic position. These are mostly located in the left atrium and uncommonly in the right atrium. We report a case of a large right ventricular myxoma presenting with heart failure.


Sleep and breathing patterns in patients with Prader Willi syndrome (PWS): effects of age and gender.
Patients with Prader Willi syndrome (PWS) often complain of daytime hypersomnolence. Because of reported daytime sleepiness and high prevalence of morbid obesity, these patients have been considered at risk for sleep related disordered breathing, but polysomnographic studies have been limited. We evaluated sleep and breathing polysomnographically in 24 PWS patients including 15 adults and 9 children. All adult patients completed MSLT testing on the day following the nocturnal sleep study. Both adult and children groups showed little or no sleep apnea, but REM related oxygen desaturation was quite common, its severity significantly correlated with increased obesity. Sleep patterns in both groups showed abnormal REM sleep cycles with variable REM latency (at times significantly shortened) and fragmented REM sleep with multiple brief REM periods. REM sleep abnormalities were still present in some patients without REM related desaturation. As a group, patients with PWS demonstrated pathological somnolence as measured by MSLT, which correlated with nocturnal sleep efficiency but not with nocturnal REM latency. It is hypothesized that the abnormal sleep findings in PWS reflect an underlying hypothalamic dysfunction characteristic of this syndrome.


Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma.
Programmed death-ligand 1 (PD-L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down-regulation of antitumour T cell responses and is a target for immunotherapy. PD-L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut-offs. We assessed pathologist consistency in evaluating PD-L1 immunopositivity by examining the inter- and intraobserver agreement using various antibody clones and different cancer types. PD-L1 expression in TC and immune cells (IC) was manually scored in 27 head and neck squamous cell carcinoma (HSCC), 30 urothelial carcinoma (UC) and breast carcinoma (BC) using three commercial clones (SP263, SP142, 22C3) and one platform-independent test (E1L3N). For interobserver agreement, PD-L1 status was evaluated blindly by three pathologists. For intraobserver agreement, PD-L1 expression was re-evaluated following a wash-out period. Intraclass correlation coefficient (ICC), overall percentage agreement (OPA) and κ-values were calculated. Using clinical algorithms, the percentage of PD-L1-positive cases in HSCC, BC and UC were 15-81%, 47-67% and 7-43%, respectively. The percentage of PD-L1 positive cases relied heavily on the algorithm/cut-off values used. Almost perfect interobserver agreement was achieved using SP263 and E1L3N in HSCC, 22C3, SP142 and E1L3N in BC and 22C3 in UC. The SP142 clone in UC and HSCC showed moderate agreement and was associated with lower ICC and decreased intraobserver concordance. Excellent inter- and intraobserver agreement can be achieved using SP263, 22C3 and E1L3N, whereas PD-L1 scoring using SP142 clone is associated with a higher level of subjectivity.


Assessing compatibility and viral fitness between poultry-adapted H9N2 and wild bird-derived neuraminidases.
Exchange of viral segments between one or more influenza virus subtypes can contribute to a shift in virulence and adaptation to new hosts. Among several influenza subtypes, H9N2 is widely circulating in poultry populations worldwide and has the ability to infect humans. Here, we studied the reassortant compatibility between chicken H9N2 with N1-N9 gene segments of wild bird origin, either with an intact or truncated stalk. Naturally occurring amino acid deletions in the NA stalk of the influenza virus can lead to increased virulence in both mallard ducks and chickens. Our findings show extended genetic compatibility between chicken H9Nx gene segments and the wild-bird NA with and without 20 amino acid stalk deletion. Replication kinetics in avian, mammalian and human cell lines revealed that parental chH9N2 and rH9N6 viruses with intact NA-stalk replicated significantly better in avian DF1 cells compared to human A549 cells. After introducing a stalk deletion, an enhanced preference for replication in mammalian and human cell lines could be observed for rH9N2Δ(H6), rH9N6Δ and rH9N9Δ compared to the parental chH9N2 virus. This highlights the potential emergence of novel viruses with variable phenotypic traits, warranting the continuous monitoring of H9N2 and co-circulating subtypes in avian hosts.


Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis.
Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-beta release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-beta can activate pancreatic stellate cells and their synthesis of collagen I and III. This study evaluates the role of endogenous IL-10 in the modulation of the regeneration phase following acute pancreatitis and in the development of pancreatic fibrosis. IL-10 knockout (KO) mice and their C57BL/6 controls were submitted to repeated courses (3/wk, during 6 wk, followed by 1 wk of recovery) of cerulein-induced acute pancreatitis. TGF-beta(1) release was measured on plasma, and its pancreatic expression was assessed by quantitative RT-PCR and immunohistochemistry. Intrapancreatic IL-10 gene expression was assessed by semiquantitative RT-PCR, and intrapancreatic collagen content was assessed by picrosirius staining. Activated stellate cells were detected by immunohistochemistry. S phase intrapancreatic cells were marked using tritiated thymidine labeling. After repeated acute pancreatitis, IL-10 KO mice had more severe histological lesions and fibrosis (intrapancreatic collagen content) than controls. TGF-beta(1) plasma levels, intrapancreatic transcription, and expression by ductal and interstitial cells, as well as the number of activated stellate cells, were significantly higher. IL-10 KO mice disclosed significantly fewer acinar cells in S phase, whereas the opposite was observed for pseudotubular cells. Endogenous IL-10 controls the regeneration phase and limits the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.


Long-term outcomes and transmission rates in hepatitis C virus-positive donor to hepatitis C virus-negative kidney transplant recipients: Analysis of United States national data.
The use of kidneys from hepatitis C virus (HCV)-positive (D+) deceased donors for HCV-negative recipients (R-) might increase the donor pool. We analyzed the national Organ Procurement and Transplant Network (OPTN) registry from 1994 to 2014 to compare the outcomes of HCV D+/R- (n = 421) to propensity-matched HCV-negative donor (D-)/R- kidney transplants, as well as with waitlisted patients who never received a transplant, in a 1:5 ratio (n = 2105, per matched group). Both 5-year graft survival (44% vs 66%; P < .001) and patient survival (57% vs 79%; P < .001) were inferior for D+/R- group compared to D-/R-. Nevertheless, 5-year patient survival from the time of wait listing was superior for D+/R- when compared to waitlisted controls (68% vs 43%; P < .001). Of the 126 D+/R- with available post-transplant HCV testing, HCV seroconversion was confirmed in 62 (49%), likely donor-derived. Five-year outcomes were similar between D+/R- that seroconverted vs D+/R- that did not (n = 64). Our analysis shows inferior outcomes for D+/R- patients although detailed data on pretransplant risk factors was not available. Limited data suggest that HCV transmission occurred in half of HCV D+/R- patients, although this might not have been the primary factor contributing to the poor observed outcomes.


U.S. Small-area Life Expectancy Estimates Project: Methodology and Results Summary.
Statistically reliable, abridged, period life tables were produced for 88.7% of U.S. census tracts (65,662). A battery of tests revealed that the census-tract life table functions followed expected patterns; their distribution about state and U.S. values showed no aberrations; and their weighted mean values compared well with state- and national-level estimates. The weighted mean life expectancy at birth for the 65,662 census tracts was 78.7 years compared with the official U.S. estimate of 78.8 years in midyear 2013. The results of this study concur with previous research showing that a minimum population size of 5,000 is acceptable, with the caveat that missing age-specific death counts cannot be ignored. The methodology developed for this study addressed the issues of small populations and zero deaths as robustly as possible, although it is not without error.


Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms.
The present study aimed to examine the enantiomer-selective pharmacokinetics (PK), relative bioavailability (Frel), and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA). In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females) received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200); two 300 mg tablets (T 300); one 600 mg tablet (T 600); and a racemic ALA solution (OS). All tablet formulations (Thioctacid HR) were considered test treatments, while the OS (Thioctacid, 600 T) served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+)- and S-(-)-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax) and total exposure (area under the curve [AUC]0-t) were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax) values ranging from 0.33-0.5 hours. The Frel of all tablet formulations was comparable, with R-(+)-enantiomer Cmax test/reference ratios ranging from 36% (T 600) to 43% (T 200), and R-(+)-enantiomer AUC test/reference ratios ranging from 64% (T 600) to 79% (T 300), indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC). An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA enantiomers indicated the absence of a significant sex effect for Cmax, as well as 20%-26% and 25%-32% higher R-(+)- and S-(-)-ALA enantiomer AUC outcomes in females when compared to males. The observed modest sex effect was comparable for both ALA enantiomers and across all formulations, and it did not appear to require a dose adjustment in clinical practice.


Antifungal activity of Coriaria nepalensis essential oil by disrupting ergosterol biosynthesis and membrane integrity against Candida.
Fungal diseases in humans have increased significantly with the advent of an expanding population of immunosuppressed patients and with the introduction of sophisticated life-saving medical procedures. Plant extracts and products have been used in traditional medicine for centuries. Coriaria nepalensis essential oil (CNEO) is known to possess antimicrobial activity. This study was an attempt to examine CNEO against various fluconazole-sensitive and -resistant Candida isolates. Insight into the mechanism of action was elucidated by flow cytometric analysis and ergosterol biosynthesis studies. The susceptibility tests for CNEO were carried out in terms of MIC and by disc diffusion assays against all Candida isolates, employing standard protocols. Insight into the mechanism of action was elucidated by propidium iodide cell sorting (FACS) and by assessing ergosterol content in treated and untreated isolates with the test entity. CNEO was found effective against all Candida isolates, including the resistant strains. While CNEO inflicts fungal cell death by disrupting membrane integrity, significant impairment of ergosterol biosynthesis was induced by the test entity. CNEO showed a strong antifungal effect against all the Candida isolates. Mechanisms of action appear to originate from the inhibition of ergosterol biosynthesis and the disruption of membrane integrity. It can be concluded that the observed antimicrobial characteristics of C. nepalensis indicate that it might be a promising antimicrobial agent.


Adhesion enhancement of steel fibers to acrylic bone cement through a silane coupling agent.
The use of a silane coupling agent (methacryloxypropyl-trichlorosilane) to improve the mechanical properties of steel fiber-reinforced acrylic bone cements was assessed. Changes to the tensile and fracture properties of bone cements reinforced with silane-coated or uncoated 316L stainless steel fibers of different aspect ratios were studied. Contact-angle measurements indicated that the coupling agent coats the metal surface through room temperature treatments in a short time (within 2 h). Push-out tests indicated that the interfacial shear strength of silane-coated 316L stainless steel rods is 141% higher than the uncoated rods. The elastic moduli, ultimate stresses, and fracture toughness of the silane-coated, steel fiber-reinforced bone cements are significantly higher than the bone cements reinforced with uncoated steel fibers. There were no differences in the tensile mechanical properties of the silane-coated or uncoated, steel fiber-reinforced cements after aging in a physiological saline solution, indicating that the bonding effectiveness is decreased by the intrusion of water at the metal-polymer interface. Because of possible biocompatibility issues with leaching of the silane coupling agent and no long-term mechanical benefit in simulated aging experiments, the use of these agents is not recommended for in vivo use.


Living with pain: the experience of children and adolescents in palliative care.
A qualitative study was conducted with semi-structured interviews with the aim of understanding the experience of children and adolescents under palliative care when managing pain daily and how they describe the intensity, quality and location of pain. We used Piaget's theory of cognitive development as a theoretical framework and oral history as a methodological framework. We found four themes: describing pain; seeking a life closer to normality, despite pain and disease; using a variety of alternatives for pain control; and living with damaged physical appearance. Although pain is a limiting factor in the lives of children and adolescents, we found that they faced their daily pain and still had a life beyond pain and illness. In addition, we highlight the relevance of nurses' understanding that effective management of pain in children is essential for a normal life and less suffering.


Respiratory Function Changes as Early Signs of Amyotrophic Lateral Sclerosis.
The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking. The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines. We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in 35 patients with unspecific neurological symptoms at the time of the visit and those were subsequently diagnosed with ALS 2 years after the initial visit ("pre-ALS"); we compared these patients with 29 patients with established ALS and with 28 control subjects. Spirometric parameters were not different between the three groups. However, MIP was significantly lower and P0.1 was significantly increased (with the ratio P0.1/MIP significantly higher) in both established and pre-ALS patients compared to controls, while both MIP and P0.1 were similar between established ALS and pre-ALS. Changes in MIP, P0.1, and P0.1/MIP ratio are highly suggestive of preclinical ALS when the spirometry and neurodiagnostic tests are still inconclusive. MIP and P0.1 are noninvasive measurements that can be easily assessed in an ambulatory setting. Future studies on larger cohorts are needed to validate the use of these parameters in the preclinical diagnosis of ALS as well as in other neuromuscular diseases.


Clinical and histopathological examination of experimental bite marks in-vivo.
Under rigorously controlled laboratory conditions, mechanically induced simulated human bite marks were made on pig skin to enable the clinical and histopatholgical study of experimental bite marks in-vivo. A series of bite marks were created on the abdomen and thorax of live anaesthetized juvenile pigs at specific times just prior to and after death. Following the release of the biting force clinical observations of antemortem wounds revealed slow diminishment of the bite indentations presumably due to dermal elastic recovery. Minutes after euthanasia of the animals, the indentations of the teeth from the postmortem bite marks faded rapidly. After the biting process the animals were placed on either the right or left side and this side was maintained until necropsy to examine for dependant and non-dependent side differences. All bite mark injuries located on the non-dependent side revealed specific pattern characteristics. However, on the dependent side whether the bite mark was antemortem or postmortem in areas of livor mortis, no clear pattern was visible. Histologically, the observations for each bite mark specimen were categorised by the presence or absence of extravasated red blood cells in the fatty or muscle layers. The histopathological findings correlate with the clinical observations of antemortem and postmortem bite marks located on the non-dependent side in regard to muscular erythema and extravasated red blood cells. It is clinically difficult to comment on temporal relationship of a bite mark in relation to time of death in areas affected by blood-pooling seen on the dependent side. In these situations, histopathological studies could be a reliable alternative to provide information regarding antemortem or postmortem injuries.


A functional promoter polymorphism of IFITM3 is associated with susceptibility to pediatric tuberculosis in Han Chinese population.
A susceptibility locus for tuberculosis, a re-emerging infectious disease throughout the world, was previously discovered to exist on chromosome 11p15. IFITM3 gene encoding for interferon inducible transmembrane protein 3, is located at 11p15. It acts as an effector molecule for interferon-gamma, which is essential for anti-tuberculosis immune response. In order to investigate the association between susceptibility to TB and genetic polymorphisms of the IFITM3 core promoter, a case-control study including 368 TB patients and 794 healthy controls was performed in Han Chinese children in northern China. The rs3888188 polymorphism showed significant association with susceptibility to TB. The rs3888188 G allele, acting recessively, was more frequent in TB patients (95% confidence interval: 1.08-1.56, Bonferroni P-value: 0.039). We further assessed the effect of rs3888188 polymorphism on IFITM3 transcription in vitro. As based on luciferase promoter assays, the promoter activity of haplotypes with rs3888188 G allele was lower than that of haplotypes with rs3888188 T allele. Moreover, peripheral-blood mononuclear cells carrying rs3888188 GG genotype showed a reduced IFITM3 mRNA level compared to cells carrying TT or GT genotype. In conclusion, rs3888188, a functional promoter polymorphism of IFITM3, was identified to influence the risk for pediatric TB in Han Chinese population.


Intrinsic penicillin resistance in enterococci.
Penicillin resistance development in enterococci has been associated with overproduction of a low-affinity penicillin-binding protein (PBP) that is a normal component of the PBP pattern of these bacteria and is apparently able to substitute the functions of the other PBPs. In resistant mutants of Enterococcus hirae ATCC 9790 the low-affinity PBP (PBP5) overproduction was associated with a deletion in a genetic element, located 1 kb upstream of the pbp5 gene, which negatively controlled PBP5 synthesis. Hypersusceptibility to penicillin was associated with a point mutation in the pbp5 gene, which causes premature termination of translation. Structural homologies between low-affinity PBPs of the different enterococcal species have been suggested by cross-reactivity of antibodies raised against E. hirae PBP5 with PBP5 of Enterococcus faecium and Enterococcus faecalis. Acquisition of a high-level ampicillin resistance in E. faecium was associated with overproduction of PBP5, which, compared with PBP5 of moderately resistant strains, appeared to be modified in its penicillin-binding capability. The modified phenotype of PBP5 was found to be associated to some amino acid substitutions in the region between the SDN and KTG motifs. In particular, the substitution converting a polar residue (T) in a nonpolar one (A or I) could play an important role in remodeling the penicillin-binding domain and determining the decrease in penicillin affinity.


Investigation of an anatomically variant isolated bicuspid pulmonary valve: A case report.
We provide a discussion of the anatomical characteristics of the bicuspid pulmonary valve (BPV) in this paper. We performed an autopsy of an isolated BPV found in the heart of a deceased individual. The deceased was a man in his 60s and had no previous history of cardiovascular disease. The heart weighed 260 g and had mild right ventricular hypertrophy. The pulmonary valve had a fish-mouth-like shape that was convex to the pulmonary trunk and both cusps were thickened and hardened. The anterior and left semilunar cusps of the pulmonary valve were fused. Post-stenotic dilatation was noted. In comparing the present case with previous reports, we found that, in human BPVs, cusps are fused in at least 2 patterns.


Precise analyses of the structure of the thymus for establishing details of the mechanisms underlying thymocyte proliferation and maturation.
Details of thymocyte proliferation and maturation are important for understanding the variability of T cell functions. The following aspects need to be clarified in this context: 1) Ascertaining why hematopoietic committed pre-T cells migrating in the blood stream are trapped and proliferate in the subcapsular region of the thymus. Further morphological and functional studies of stromal cells in situ in the thymus should be conducted. The factors responsible for thymocyte proliferation should be also analysed. 2) How phenotypic maturation of thymocytes takes place and how T-cell receptor (TCR) expression is processed and controlled. 3) Subsequently, how does the selection of thymocytes take place? Is negative selection in fact responsible for the unresponsiveness of the body to self antigens? Further morphological analyses of thymic epithelial cells, thymocytes themselves and macrophages need to be conducted, together with immunohistochemical analyses using many monoclonal antibodies directed against these cells and the extracellular matrix, in order to analyse the cellular dynamics and cell-to-cell interactions occurring in thymus tissues in situ. 4) How mature thymocytes migrate to the periphery: Perivascular structures and the cells accumulating in this space should be intensively analysed morphologically and phenotypically. Lymphatic structures related to the thymus tissues also remain to be studied. To understand these questions, several useful experimental systems can also be employed: 1) Phylogenetical analyses, 2) ontogenical analyses, 3) thymus tissues regenerating from radiation or thymotoxic drugs, 4) thymomas, and 5) thymus tissues from transgenic animals. These important problems could be further studied in such experimental models both morphologically and immunohistochemically, since many useful tools are now available for studies of phenotypic and other markers of thymocytes and thymic epithelial cells. Subsequently, further detailed analyses of thymic structures may shed more light on the mechanisms underlying thymocyte proliferation and maturation.


[Iron deficiency anemia in childhood. A case with associated deficiency of folic acid (author's transl)].
The case of a six year and ten months old girl with an iron deficiency anemia of long duration is reported. The lack of iron was associated with folic acid deficiency, which disguished the hematologic pattern, presenting a normocromic and aniso-poiquilocytic anemia. Long duration of iron deficiency allowed for evaluation of the iron deficiency effects on weight and height growth which were diminished as well as on the functioning and morphology of the gastrointestinal system, showing malabsorption syndrome which improve with iron supply.


Femtosecond bulk transparent material processing and recovery.
Femtosecond lasers have a unique ability of processing bulk transparent materials for various applications such as micromachining, waveguide manufacturing, and photonic bandgap structures, just to name a few. These applications depend on the formation of micron or submicron size features are known to be index modifications to the bulk substrate [2, 11], which were thought to persist indefinitely. However, it has been observed that some of these bulk transparent materials recover or "heal" with time. This "healing" process is studied and quantified using Nomarski Differential Interference Contrast optical microscopy and diffraction efficiency measurements of micro-machined gratings. We find healing to be accelerated in dye doped polymers.


Plasmonic smart dust for probing local chemical reactions.
Locally probing chemical reactions or catalytic processes on surfaces under realistic reaction conditions has remained one of the main challenges in materials science and heterogeneous catalysis. Where conventional surface interrogation techniques usually require high-vacuum conditions or ensemble average measurements, plasmonic nanoparticles excel in extreme light focusing and can produce highly confined electromagnetic fields in subwavelength volumes without the need for complex near-field microscopes. Here, we demonstrate an all-optical probing technique based on plasmonic smart dust for monitoring local chemical reactions in real time. The silica shell-isolated gold nanoparticles that form the smart dust can work as strong light concentrators and optically report subtle environmental changes at their pinning sites on the probed surface during reaction processes. As a model system, we investigate the hydrogen dissociation and subsequent uptake trajectory in palladium with both "dust-on-film" and "film-on-dust" platforms. Using time-resolved single particle measurements, we demonstrate that our technique can in situ encode chemical reaction information as optical signals for a variety of surface morphologies. The presented technique offers a unique scheme for real-time, label-free, and high-resolution probing of local reaction kinetics in a plethora of important chemical reactions on surfaces, paving the way toward the development of inexpensive and high-output reaction sensors for real-world applications.


Detection of metastatic lesions from malignant pheochromocytoma and paraganglioma with diffusion-weighted magnetic resonance imaging: comparison with 18F-FDG positron emission tomography and 123I-MIBG scintigraphy.
To investigate the diagnostic features of whole-body diffusion-weighted magnetic resonance imaging (DWI) as compared with 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and (123)I-meta-iodo-benzyl guanidine scintigraphy (MIBG) on metastatic lesions of patients with malignant pheochromocytoma or paraganglioma. We prospectively studied 11 patients with histologically confirmed pheochromocytoma/paraganglioma and possible metastatic lesions. FDG-PET, MIBG, and DWI examinations were performed within 1 week, and the images were visually interpreted. Abnormal positive uptake either on MIBG or on FDG-PET was considered as metastases. Abnormal high signal intensities on DWI were considered as metastases using conventional T1-and T2-weighted images as reference. FDG-PET and DWI demonstrated metastatic lesions in all 11 patients, but MIBG showed no metastatic lesions in two patients. The numbers of lymph node metastases depicted on FDG-PET, MIBG, and DWI were 19, 6, and 39; bone metastases were 50, 49, and 60; liver metastases were 9, 9, and 15; lung metastases were 5, 7, and 5, respectively. MIBG failed to demonstrate many metastatic lesions, which were demonstrated on FDG-PET or DWI, although two mediastinal lymph node metastases, three lung metastases, and six bone metastases, which were not seen on DWI, were clearly demonstrated on MIBG. DWI showed 15 liver metastases, but 6 of them were not seen on FDG-PET or MIBG. DWI may be particularly advantageous in depicting lymph node and liver metastases and may have a higher rate of detecting metastatic lesions when compared with MIBG or FDG-PET. The limitations of DWI were possible false-positive finding, and probable lower detectability of mediastinal lymph node and lung metastasis.


Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches.
The search for molecular underpinnings of human vocal communication has focused on genes encoding forkhead-box transcription factors, as rare disruptions of FOXP1, FOXP2, and FOXP4 have been linked to disorders involving speech and language deficits. In male songbirds, an animal model for vocal learning, experimentally altered expression levels of these transcription factors impair song production learning. The relative contributions of auditory processing, motor function or auditory-motor integration to the deficits observed after different FoxP manipulations in songbirds are unknown. To examine the potential effects on auditory learning and development, we focused on female zebra finches (Taeniopygia guttata) that do not sing but develop song memories, which can be assayed in operant preference tests. We tested whether the relatively high levels of FoxP1 expression in forebrain areas implicated in female song preference learning are crucial for the development and/or maintenance of this behavior. Juvenile and adult female zebra finches received FoxP1 knockdowns targeted to HVC (proper name) or to the caudomedial mesopallium (CMM). Irrespective of target site and whether the knockdown took place before (juveniles) or after (adults) the sensitive phase for song memorization, all groups preferred their tutor's song. However, adult females with FoxP1 knockdowns targeted at HVC showed weaker motivation to hear song and weaker song preferences than sham-treated controls, while no such differences were observed after knockdowns in CMM or in juveniles. In summary, FoxP1 knockdowns in the cortical song nucleus HVC were not associated with impaired tutor song memory but reduced motivation to actively request tutor songs.


[Effect of ionizing radiation on O2 generation by cytochrome P-450].
A study was made of generation of superoxide anion-radical (O2-) by cytochrome P-450 in a microsomal membrane of rat liver. Using spectrophotometry (by oxidation of adrenaline to adrenochrome) and ESR (with a spin-trap, tiron) the authors showed the ability of O2- generation by P-450 through decomposition of organic peroxides. During the first 24 h following irradiation of rats with doses of 7 and 10 Gy, the generation of O2- by cytochrome P-450 of rat liver microsomes was increased. Mechanisms of the postirradiation modification of O2- generation rate are discussed.


Age-related patterns of injury in children involved in all-terrain vehicle accidents.
All-terrain vehicle (ATV) accidents are considerable sources of morbidity and mortality for children and adolescents. This study was done to investigate the types and severity of injuries and the role of age and body mass index on the types of fractures sustained in children younger than 16 years. A retrospective chart review was done on 96 consecutive children who sustained injuries in ATV-related accidents during a 30-month period. Sixty-four patients were boys and 32 were girls. The mean age of the children was 11.0 years. To determine differences in fracture type, Glasgow Coma Scale, Pediatric Trauma Score, and length of hospitalization, the 96 patients were divided into 2 groups: group A, 54 children (56%) 12 years or younger, and group B, 42 children (44%) 13 years or older. Sixty-one children (64%) required hospital admission. No statistically significant difference between the 2 groups was noted. Fifty-four (56%) children required surgical treatment. One fatality occurred. No statistically significant differences between the 2 groups were noted regarding the Glasgow Coma Scale and the Pediatric Trauma Score. Orthopaedic injuries were the most common, occurring in 58 (60%) children, followed by head injury in 34 (35%) and intraabdominal/intrathoracic injuries in 23 (24%). Nineteen (20%) children had more than 1 system involved, and 1 had 3 systems involved. Sixty-eight fractures occurred in 58 children (38 in group A and 30 in group B) including 9 open fractures. As expected, older children had a significantly increased body mass index compared with younger children (P < 0.02). Age-related patterns of fracture were observed. Younger children (<or=12 years) were more likely to sustain an isolated fracture (odds ratio 2.9, P < 0.02) and were more likely to sustain a lower extremity fracture (odds ratio 3.2, P < 0.03), specifically a femoral fracture (odds ratio 6.5, P < 0.01), than older children (>or=13 years). Older children were more likely to sustain a pelvic fracture (odds ratio 1.108, P < 0.04). To our knowledge, this is the first study to evaluate age-related patterns of fractures in ATV-related accidents. It is our hope that increased awareness of the severity and types of injuries and fracture patterns will lead to more rapid diagnosis and help to bring about improved safety measures, increased public awareness, and even legislation concerning the use of ATVs by children. Level IV.


Neurilemoma of the median nerve - surgical strategies based on a case report.
The study presented a case of a patient with a neurilemoma of the median nerve. It presented as a six centemeters tumor, at the level of the proximal one third of the arm with only mild paraesthesias within first to third ray of the hand. MRI showed the relationship of the tumor and the median nerve, and allowed for the preliminary diagnose of a benign peripheral neural sheath tumor (neurilemoma or neurofibroma). During the first operation the tumor has not been excised, because nerve reconstruction technique was not available. During the second procedure excision of the tumor has been performed without resection of the median nerve trunk with no postoperative deficiencies. The paper provides a detailed description of a surgical procedure. The presented case, like current publications shows that peripheral neural sheath tumor may be usually excised without resection of the nerve trunk, although the possibility of nerve fascicles injury or the need to excise them in the case of neurofibroma clearly suggest that these type of operations should be carried out in centers with microsurgical facilities.


Changes in the immunophenotype of recurrent pituitary adenomas.
Only two cases have been reported of a pituitary adenoma that changed phenotype between its initial resection and recurrence. To determine the frequency of such cases among our patients, we examined the clinical course of these tumors and characterized any patterns. We reviewed the charts of 1023 patients with pituitary adenomas who underwent surgery between 1984 and 1992 at the University of California at San Francisco. Of the 65 patients (6.4%) who had operations for or clinical evidence of tumor recurrence, five (7.7%) had tumors that changed phenotype. The female-to-male ratio was 4:1, and age at the onset of symptoms was 33.2 +/- 15.3 years (mean +/- standard deviation). Changes occurred in hormone production and hormone release after 6.4 +/- 3.4 years. At some point, all five tumors were invasive and four were macroadenomas. Two patients had more than one operation for tumor recurrence; three had silent or symptomatic pituitary apoplexy; and three had undergone sellar irradiation before the changes in phenotype occurred. The behavior of these tumors therefore seems to be aggressive. We do not yet know whether phenotypic changes in pituitary adenomas have any treatment implications. Therefore, we advocate the complete immunostaining of primary and recurrent pituitary adenomas so that additional data about their clinical course can be collected.


Improved Sensing Capability of Integrated Semiconducting Metal Oxide Gas Sensor Devices.
Semiconducting metal oxide (SMO) gas sensors were designed, fabricated, and characterized in terms of their sensing capability and the thermo-mechanical behavior of the micro-hotplate. The sensors demonstrate high sensitivity at low concentrations of volatile organic compounds (VOCs) at a low power consumption of 10.5 mW. In addition, the sensors realize fast response and recovery times of 20 s and 2.3 min, respectively. To further improve the baseline stability and sensing response characteristics at low power consumption, a novel sensor is conceived of and proposed. Tantalum aluminum (TaAl) is used as a microheater, whereas Pt-doped SnO₂ is used as a thin film sensing layer. Both layers were deposited on top of a porous silicon nitride membrane. In this paper, two designs are characterized by simulations and experimental measurements, and the results are comparatively reported. Simultaneously, the impact of a heat pulsing mode and rubber smartphone cases on the sensing performance of the gas sensor are highlighted.


Transitioning from lateral to the prone transpsoas approach: flatten the learning curve by knowing the nuances.
Prone transpsoas lateral lumbar interbody fusion is the newest frontier in surgical approach to the lumbar spine. Prone positioning facilitates segmental lordosis and facile posterior segmental fixation. However, even in experienced hands, transitioning from a lateral decubitus to prone position necessitates alterations to the traditional technique. In this video, the authors highlight the nuances of adopting the prone transpsoas lateral lumbar interbody fusion technique and strategies to overcome them. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2224.


Fungal nanoscale metal carbonates and production of electrochemical materials.
Fungal biomineralization of carbonates results in metal removal from solution or immobilization within a solid matrix. Such a system provides a promising method for removal of toxic or valuable metals from solution, such as Co, Ni, and La, with some carbonates being of nanoscale dimensions. A fungal Mn carbonate biomineralization process can be applied for the synthesis of novel electrochemical materials.


The OXIMAPA Study: Hypertension Control by ABPM and Association with Sleep Apnea Syndrome by Pulse Oximetry.
Ambulatory blood pressure monitoring by automatic device is the best blood pressure evaluation method and sleep apnea syndrome is the leading cause of poor control. Oximetry allows screening these individuals but its usefulness has been poorly explored in Primary Health Care. The aim was to evaluate the blood pressure control at the office and with ambulatory blood pressure monitoring by automatic device and to relate it to sleep apnea syndrome. We selected a sample of 50 participants, representative of 3036 hypertensive patients. The variables were: blood pressure value at the office and blood pressure with ambulatory blood pressure monitoring by automatic device; presence of criteria of sleep apnea syndrome in oximetry. The prevalence of uncontrolled blood pressure was 56% on office evaluation and 68% on ambulatory blood pressure monitoring by automatic device. It was found: 36% of daytime hypertension, 52% nocturnal hypertension, 40% non-dipper profile, 16% of white coat hypertension and 28% masked hypertension. The prevalence of sleep apnea syndrome was 16%. Blood pressure in ambulatory blood pressure monitoring by automatic device and blood pressure in office showed no statistically significant association (p = 0.761). We found a statistically significant association between sleep apnea syndrome and daytime hypertension (p = 0.019) and non-dipper profile (p = 0.005). Ambulatory blood pressure monitoring by automatic device detected more 12% of uncontrolled hypertension than office blood pressure. Sleep apnea syndrome is strongly associated with uncontrolled hypertension and oximetry may be a good screening method, but should be studied further.


Pollinex Quattro: a novel and well-tolerated, ultra short-course allergy vaccine.
Pollinex Quattro is a novel, ultra short-course vaccine for treatment of seasonal allergic rhinitis from grass, tree or ragweed pollen allergy. Its unique formulation combines chemically modified allergens adsorbed onto a L-tyrosine depot to enhance tolerability with the novel adjuvant, monophosphoryl lipid A, to improve efficacy. Controlled clinical studies indicate that four preseasonal injections with grass or tree formulations significantly reduce rhinoconjunctivitis symptoms and medication use, as well as elevate allergen-specific immunoglobulin G and blunt elevation of immunoglobulin E upon allergen exposure. Postmarketing surveillance studies indicate similar clinical outcomes. In all cases, the allergy vaccine was well tolerated with minimal local reactions, while systemic reactions were rare and mild. Results from recent investigational trials with grass and ragweed formulations are consistent with previous efficacy and safety outcomes, and will be used toward product registration in North America.


The relationship between idiopathic cytopenias/dysplasias of uncertain significance (ICUS/IDUS) and autoimmunity.
This review examines the several lines of evidence that support the relationship between myelodysplasia and autoimmunity, i.e. their epidemiologic association, the existence of common immune-mediated physiopathologic mechanisms, and the response to similar immunosuppressive therapies. The same relationship is reviewed here considering idiopathic cytopenia of uncertain significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), two recently recognized provisional conditions characterized by isolated/unexplained cytopenia and/or dysplasia in <10% bone marrow cells. Areas covered: The review focuses on alterations of cytokine profiles, telomere/telomerase and toll-like receptors, and on increased myelosuppressive mediators and apoptotic markers in both myelodysplasia and autoimmunity. In addition, the presence of an autoimmune reaction directed against marrow precursors is described in refractory/relapsing autoimmune cytopenias (autoimmune hemolytic anemia, immune thrombocytopenia, chronic idiopathic neutropenia), possibly contributing to their evolution to ICUS/IDUS/bone marrow failure syndromes. Expert commentary: The increasing availability of omics methods has fuelled the discussion on the role of somatic mutations in the pathogenesis of IDUS/ICUS, clonal hematopoiesis of indeterminate potential, and clonal cytopenias of undetermined significance, and in their possible evolution. Even more attracting is the involvement of the genetic background/accumulating somatic mutations in cytopenias with autoimmune alterations.


The trend of parasitic diseases among the population of Osjecko-baranjska County during the period 1996-2010--Croatia.
Our manuscript shows infestation of the different population (by age groups, and by sex) with endoparasites and ectoparasites from 1996 till 2010, through seasons (spring, summer, autumn, winter).Parasitological examinations which were done at "Public health Institute" of Osjecko-baranjska county, and which were done at total of 3667 patients, were the methods of direct parasitological diagnostic for proof of parasitic elements in clinical samples, and the methods of indirect parasitological diagnostic, serological examination for proof of antibodies to antigens in the serum of the patients or of the asymptomatic parasite carriers. Development of causers of the diseases (parasites) is depending on the season. Results of our researches were processed with statistical program called Statistica 8.0 (StatSoft. Inc 1984-2008). From statistical parameters arithmetic middle (x), standard deviation (s), and standard error of the arithmetic middle (sx), are shown. Testing of the significance of differences between independent samples was done with t-test (ANOVA), and is shown in the chart using the appropriate letters (a,b,c). Determined parameters of total infestation and endoparasitic infestation, and total infestation and ectoparasitic infestation show statistically significant difference on the risk level of 0.05 regardless of the age or the sex group of the population of Osjecko-baranjska county. Determined parameters of monitoring infestation (endoparasitosis and ectoparasitosis) have shown statistically significant difference on the risk level of 0.05.


Long-term persistence of low-molecular-weight material with anti-factor Xa activity contributes to anticoagulant and antithrombotic effects after subcutaneous injection of CY 216 in the rabbit.
This study was done to document further the mechanism of the antithrombotic effect of CY 216 after subcutaneous injection in the rabbit. We first measured the circulating anti-factor Xa and anti-thrombin activities expressed in either International Unit or Standard Independent Unit and from these activities we calculated the above critical length material (ACLM) and below critical length material (BCLM) levels. The clearance of the BCLM was half that of the ACLM. Then we determined the inhibitory effect of CY 216 on thrombin generation (TG) in platelet-poor plasma (PPP) and in whole blood. TG was both inhibited and delayed in whole blood, while it was only inhibited in PPP. The IC50 on TG in PPP and in whole blood were 1.80 +/- 0.16 and 4.33 +/- 1.01 micrograms.ml-1 respectively. After the injection, the inhibition of TG was significant as long as BCLM was detectable. The duration of the antithrombotic effect was essentially correlated to the ACLM level in the Wessler-thromboplastin model and to the BCLM level in the Wessler-serum model. Taken together, these results demonstrate that both ACLM and BCLM components of CY 216 are involved in its anticoagulant effect ex vivo as well as in its antithrombotic activity in vivo, and that the relative contribution of BCLM increases with the time after administration.


Successful endoscopic closure with endoscopic clips for endoscopic ultrasound related large duodenal perforation.
Objectives: Duodenal perforation as a complication of endoscopic ultrasound-guided fine needle aspiration may progress to acute peritonitis and septic shock. Open surgery, the standard treatment, can be avoided by performing closure during endoscopy using endoscopic clips. Patient: A 77-year-old woman was referred to our hospital with salivary gland swelling. She had elevated hepatobiliary enzymes and jaundice. Computed tomography (CT) revealed pancreatic head swelling and bile duct dilation. Endoscopic ultrasonography revealed a hypoechoic mass in the pancreatic head. The pancreatic head mass was punctured twice using a 22-gauge Franchine-type puncture needle at the duodenal bulb. The endoscope was advanced to the descending part of the duodenum, and part of the superior duodenal angle was perforated (diameter approximately 15 mm) with the endoscope. The duodenal mucosa around the perforation was immediately closed using endoscopic clips. Results: Abdominal CT showed gas in the peritoneal and retroperitoneal spaces. The patient experienced abdominal pain and fever and was treated with fasting and antibiotics. The gas gradually decreased, symptoms improved, and she was discharged 18 days after the perforation. Histopathologically, the pancreatic tissue was consistent as autoimmune pancreatitis. Conclusion: Endoscopic closure using endoscopic clips may be a better therapeutic option for duodenal perforation caused by endoscopy.


Interactions between the Escherichia coli cyclic AMP receptor protein and RNA polymerase at class II promoters.
The effects of a number of mutations in crp have been measured at different cyclic AMP receptor protein (CRP)-dependent Class II promoters, where the CRP-binding site is centred around 41 1/2 base pairs upstream from the transcription start point. The amino acid substitutions HL159 and TA158 result in reduced CRP-dependent activation, but the reduction varies from one Class II promoter to another. Deletions in the C-terminus of the RNA polymerase alpha subunit suppress the effects of HL159 and TA158. The role of the C-terminus of alpha at these promoters is assessed. Other changes at E58, K52 and E96 affect CRP activity specifically at Class II promoters and their role is discussed.


Brexit is not only factor in EU nurse downturn.
Headlines have been screaming about European nurses 'giving up on the NHS'. This was triggered when the Nursing and Midwifery Council (NMC) reported that the number of EU nurses registering to work in the UK was down more than 90% since the Brexit vote in June last year.


Survival outcomes of different neoadjuvant treatment regimens in patients with locally advanced rectal cancer and MRI-detected extramural venous invasion.
MRI-detected extramural venous invasion (mrEMVI) is associated with poor survival outcomes in patients with locally advanced rectal cancer (LARC). An mrEMVI-positive status is considered a strong indication for neoadjuvant treatment, but the optimal regimen is unknown. We retrospectively compared pathological and survival outcomes of 584 patients diagnosed with mrEMVI-positive rectal cancer between January 2013 and October 2021, and receiving either neoadjuvant chemotherapy (NCT) alone, neoadjuvant chemoradiotherapy (nCRT) alone, or nCRT plus NCT, prior to total mesorectal excision. Propensity score matching (PSM) was used to balance clinical bias between groups, which were compared using chi-square testing and Kaplan-Meier curves. Median follow-up was 33.9 (range, 10.2-100.4) months. The 3-year overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) rates for all patients were 90.4%, 57.5%, 61.1%, and 85.7%, respectively. Of 584 mrEMVI-positive patients at the time of diagnosis, 457 (78.3%) were EMVI-negative on surgical pathology, and they had significantly better 3-year OS, DMFS, DFS, and LRFS rates (all p < 0.001) than patients who remained EMVI-positive. After PSM was applied, patients receiving nCRT alone had significantly better 3-year OS (96.8% vs. 86.5%, p = 0.005) and DMFS (67.1% vs. 53.5%, p = 0.03) rates than those receiving NCT alone. Patients receiving NCT plus nCRT had higher pathological complete response (PCR) (10.8% vs. 2.7%, p = 0.04) and downstaging (33.8% vs. 5.3%, p < 0.001) rates than those receiving nCRT alone, but survival rates did not differ (all p > 0.05). Most EMVI-positive patients with LARC converted to EMVI-negative after neoadjuvant treatment, resulting in improved OS and DFS. Patients receiving nCRT had more favorable survival outcomes than those receiving NCT, suggesting the importance of including neoadjuvant radiotherapy. Patients receiving NCT in addition to nCRT had higher rates of PCR and downstaging, but their survival rates were not better.


Preparative purification of peoniflorin and albiflorin from peony rhizome using macroporous resin and medium-pressure liquid chromatography.
Peoniflorin (PF) and albiflorin (AF) are two principal components of Paeonia species, which exhibit various biological activities such as improvement of blood circulation and immunoregulating function. To further utilization of waste parts of peony plants, an efficient method for preparative purification of these two ingredients from white peony rhizome was developed based on macroporous resin (MAR) and medium-pressure liquid chromatography (MPLC). The separation characteristics of nine typical MARs were investigated by static adsorption/desorption experiments, and LX38 was revealed as optimal one. Further static experiments with LX38 resin indicated that the adsorbents fitted well to the pseudo-second-order kinetics model and both Langmuir and Freundlich isotherm models. Based on the optimal process parameters, a large-scale preparation was successfully applied. After one run treatment with LX38, the contents of PF and AF were increased 15-fold to 24.5 and 16.8% in the refined extract, respectively. Both purified compounds were obtained from refined extract by reversed-phase MPLC at second-stage separation. The process developed is better because of its low cost, high efficiency, and procedural simplicity making it a potential approach for large-scale production of PF and AF for their further applications in functional foods and pharmaceuticals.


Analysis of the differential gene and protein expression profile of the rolled leaf mutant of transgenic rice (Oryza sativa L.).
The importance of leaf rolling in rice (Oryza sativa L.) has been widely recognized. Although several studies have investigated rice leaf rolling and identified some related genes, knowledge of the molecular mechanism underlying rice leaf rolling, especially outward leaf rolling, is limited. Therefore, in this study, differential proteomics and gene expression profiling were used to analyze rolled leaf mutant of transgenic rice in order to investigate differentially expressed genes and proteins related to rice leaf rolling. To this end, 28 differentially expressed proteins related to rolling leaf traits were isolated and identified. Digital expression profiling detected 10 genes related to rice leaf rolling. Some of the proteins and genes detected are involved in lipid metabolism, which is related to the development of bulliform cells, such as phosphoinositide phospholipase C, Mgll gene, and At4g26790 gene. The "omics"-level techniques were useful for simultaneously isolating several proteins and genes related to rice leaf rolling. In addition, the results of the analysis of differentially expressed proteins and genes were closely consistent with those from a corresponding functional analysis of cellular mechanisms; our study findings might form the basis for further research on the molecular mechanisms underlying rice leaf rolling.


Evaluation of ανβ3-mediated tumor expression with a 99mTc-labeled ornithine-modified RGD derivative during glioblastoma growth in vivo.
In this study, a novel way of distinguishing the intrinsic relationship between ανβ3 integrin targeting and detection of tumor growth by using a radiolabeled tracer based on a cyclic Arg-Gly-Asp (RGD) peptide was provided. The potential of the in vivo scintigraphic imaging of the developing vasculature from the early stage of tumor growth was evaluated. Alongside with the scintigraphic images, biodistribution studies were performed at distinct time points to validate this noninvasive imaging approach. The ability to noninvasively assess the tumor growth of ανβ3 integrin-positive glioblastoma tumors provides a method to better understand tumor angiogenesis in vivo and allows for a direct assessment of anti-integrin treatment efficacy.


Verbal Communication with the Patient Is Not Enough: The Six Languages of the Sick.
Evidence shows that verbal communication is just one of the ways patients indicate their wishes. For a sufficiently careful communication, we should also grasp other five unusual though evident languages: (a) body language, (b) the way patients manage their environment, (c) unconscious language, (d) lab-evidenced language, and (e) the way they master technology. So, we have six languages that should be intertwined to understand the real language of the sick. Grasping these languages helps health professionals frame the patient's mood, their level of suffering or mental growth, and understand what words alone cannot express. Words cannot express completely what a patient senses: for subjection, shyness, because some patients are still non-verbal or because verbal communication is just a useful way of freezing concept but has not the same fluidity and liberty of the other above-described languages. It is mandatory for caregivers to wonder how many of these languages they are actually decrypting during an interview with the patient. On the other hand, caregivers unconsciously communicate much through two unexpected languages: the architectural language and the language of medical procedures. The way they welcome or obstruct the patient, their hesitations across a treatment, or in showing a serene collegiality are forms of subtle communication. A paradigmatic scenario where all these languages should be implemented is the "informed consent" process, which should be turned into a "shared therapeutic pathway", summing up all the communicative modes illustrated in the text.