Full-scale biofilter reduction efficiencies assessed using portable 24-hour sampling units.
Portable 24-hr sampling units were used to collect air samples from eight biofilters on four animal feeding operations. The biofilters were located on a dairy, a swine nursery, and two swine finishing farms. Biofilter media characteristics (age, porosity, density, particle size, water absorption capacity, pressure drop) and ammonia (NH3), hydrogen sulfide (H2S), sulfur dioxide (SO2), methane (CH4), and nitrous oxide (N2O) reduction efficiencies of the biofilters were assessed. The deep bed biofilters at the dairy farm, which were in use for a few months, had the most porous media and lowest unit pressure drops. The average media porosity and density were 75% and 180 kg/m3, respectively. Reduction efficiencies of H2S and NH3 (biofilter 1: 64% NH3, 76% H2S; biofilter 2: 53% NH3, 85% H2S) were close to those reported for pilot-scale biofilters. No N2O production was measured at the dairy farm. The highest H2S, SO2, NH3, and CH4 reduction efficiencies were measured from a flat-bed biofilter at the swine nursery farm. However, the highest N2O generation (29.2%) was also measured from this biofilter. This flat-bed biofilter media was dense and had the lowest porosity. A garden sprinkler was used to add water to this biofilter, which may have filled media pores and caused N2O production under anaerobic conditions. Concentrations of H2S and NH3 were determined using the portable 24-hr sampling units and compared to ones measured with a semicontinuous gas sampling system at one farm. Flat-bed biofilters at the swine finishing farms also produced low amounts of N2O. The N2O production rate of the newer media (2 years old) with higher porosity was lower than that of older media (3 years old) (P = 0.042).


Gain of an axially slotted cylinder covered with a chiral coating and embedded in a chiral medium.
The gain characteristics of an axially slotted cylinder coated with a chiral layer and placed in another chiral background have been investigated using numerical simulations. The effects of various types of chiral coatings and chiral backgrounds upon the gain pattern have been studied. It is shown that an increase in the chirality of the coating enhances the gain in the forward direction and reduces the gain in the backward direction for the fixed chirality of the background. It is also studied that, by increasing the chirality of the background medium, the gain in the backward direction also increases. It is further found that the chiral nihility coating makes the gain pattern nearly isotropic, and this gain is almost independent of the chirality of the background chiral medium.


Recovery of Endothelium-dependent vascular relaxation impairment in convalescent COVID-19 patients: Insight from a pilot study.
Endothelial dysfunction is a key-feature in acute COVID-19. However, follow-up data regarding endothelial dysfunction and injury after COVID-19 infection are lacking. We aimed to investigate the changes in endothelium-dependent vasorelaxation at baseline and four months after hospital discharge in COVID-19 patients. Twenty COVID-19 patients were compared to 24 healthy controls. Clinical and morphological data were collected after hospital admission for SARS-CoV-2 infection and reactive hyperaemia index (RHI) measurement was performed with a delay between 24 and 48 h after hospital admission and four months after hospital discharge in the outpatient clinics. Blood tests including inflammatory markers and measurement of post-occlusive vasorelaxation by digital peripheral arterial tonometry were performed at both visits. At baseline, COVID-19 patients exhibited reduced RHI compared to controls (p < 0.001), in line with an endothelial dysfunction. At four months follow-up, there was a 51% increase in the RHI (1.69 ± 0.32 to 2.51 ± 0.91; p < 0.01) in favor of endothelium-dependent vascular relaxation recovery. RHI changes were positively correlated with baseline C-reactive protein (r = 0.68; p = 0.02). Compared to COVID-19 patients with a decrease in RHI, COVID-19 patients with an increase in RHI beyond the day-to-day variability (i.e. >11%) had less severe systemic inflammation at baseline. Convalescent COVID-19 patients showed a recovery of systemic artery endothelial dysfunction, in particular patients with lower inflammation at baseline. Further studies are needed to decipher the interplay between inflammation and endothelial dysfunction in COVID-19 patients.


Driving towards obesity: a systematized literature review on the association between motor vehicle travel time and distance and weight status in adults.
Higher levels of sedentary behavior are associated with adverse health outcomes. Over-reliance on private motor vehicles for transportation is a potential contributor to the obesity epidemic. The objective of this study was to review evidence on the relationship between motor vehicle travel distance and time and weight status among adults. Keywords associated with driving and weight status were entered into four databases (PubMed Medline Transportation Research Information Database and Web of Science) and retrieved article titles and abstracts screened for relevance. Relevant articles were assessed for their eligibility for inclusion in the review (English-language articles a sample ≥ 16 years of age included a measure of time or distance traveling in a motor vehicle and weight status and estimated the association between driving and weight status). The database search yielded 2781 articles, from which 88 were deemed relevant and 10 studies met the inclusion criteria. Of the 10 studies included in the review, 8 found a statistically significant positive association between time and distance traveled in a motor vehicle and weight status. Multilevel interventions that make alternatives to driving private motor vehicles more convenient, such as walking and cycling, are needed to promote healthy weight in the adult population.


The role of epigenetics and long noncoding RNA MIAT in neuroendocrine prostate cancer.
Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm. NEPC is thought to originate from the transdifferentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/noncoding interactome (ENI) orchestrates cancer cells' plasticity, thereby allowing the emergence of metastatic, drug-resistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, miRNAs) play a key role in NEPC initiation and progression. Long noncoding RNAs represent vast and largely unexplored component of the ENI. Their role in NEPC has not been investigated. We show preliminary evidence indicating that a lncRNA (MIAT) is selectively upregulated in NEPCs and might interact with Polycomb genes. Our results indicate that long noncoding RNAs can be exploited as new biomarkers and therapeutic targets for NEPC.


A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee.
To investigate the efficacy and tolerability of a course of 5 injections of hyaluronan (HA) given at intervals of one week in patients with symptomatic, mild to moderate osteoarthritis (OA) of the knee. A double blind, randomized, parallel group, multicenter (17 centers), saline vehicle-controlled study was conducted over 18 weeks. Patients received either 25 mg (2.5 ml) HA in a phosphate buffered solution or 2.5 ml vehicle containing only the buffer by intraarticular injection. Five injections were given at one week intervals and the patients were followed for a further 13 weeks. The Western Ontario McMaster (WOMAC) OA instrument was used as the primary efficacy variable and repeated measures analysis of covariance was used to compare the 2 treatments over Weeks 6, 10, 14, and 18. Of 240 patients randomized for inclusion in the study, 223 were evaluable for the modified intention to treat analysis. The active treatment and control groups were comparable for demographic details, OA history, and previous treatments. Scores for the pain and stiffness subscales of the WOMAC were modestly but significantly lower in the HA-treated group overall (Weeks 6 to 18; p < 0.05) and the statistically significant difference from the control was not apparent until after the series of injections was complete. The physical function subscale did not reach statistical significance (p = 0.064). Tolerability of the procedure was good and there were no serious adverse events that were considered to have a possible causal relationship with the study treatment. Intraarticular HA treatment was significantly more effective than saline vehicle in mild to moderate OA of the knee for the 13 week postinjection period of the study.


Enantioselective synthesis of 8-azabicyclo[3.2.1]octanes via asymmetric 1,3-dipolar cycloadditions of cyclic azomethine ylides using a dual catalytic system.
The first example of asymmetric 1,3-dipolar cycloadditions between diazo imine-derived cyclic azomethine ylides and acryloylpyrazolidinone using a rhodium(ii) complex/chiral Lewis acid binary system is reported. The asymmetric cycloadditions afforded optically active 8-oxabicyclo[3.2.1]octanes with high diastereo- and enantioselectivities (up to >99 : 1 dr, 99% ee). A switch of exo/endo-selectivity was observed depending on the diazo substrates.


A protracted mumps outbreak in Western Australia despite high vaccine coverage: a population-based surveillance study.
In 2007-08, a genotype J mumps outbreak occurred among Aboriginal people in northern Western Australia, despite high vaccine coverage. In March, 2015, a second protracted mumps outbreak occurred in northern Western Australia and spread widely across rural areas of the state. This time the outbreak was caused by a genotype G virus and again primarily affected Aboriginal people. We aimed to describe the epidemiology of this outbreak. In this population-based surveillance study, we analysed statutory notifications and public health case follow-up data from the Western Australia Notifiable Infectious Diseases Database and vaccination information from the Australian Childhood Immunisation Register. An outbreak case of mumps was notified if the affected person was living in or visiting a community in Western Australia where there was active mumps transmission, and if mumps infection was confirmed by laboratory diagnosis or by an epidemiological link. We analysed case demographics, vaccination status, and age-standardised attack rates in Aboriginal and non-Aboriginal people by region of notification. Laboratory diagnoses were made by real-time RT-PCR, serology, or both, and carried out by the sole public pathology provider in Western Australia. Between March 1, 2015, and December 31, 2016, 893 outbreak cases were notified. 798 (89%) of 893 outbreak cases were reported in Aboriginal people. 40 (4%) of 893 people were admitted to hospital, and 33 (7%) of 462 men reported orchitis. Mumps attack rates increased sharply with age, peaking in the 15-19 age group. 371 (89%) of 419 people aged 1-19 years were fully vaccinated and 29 (7%) were partly vaccinated. Of the 240 people who tested positive by real-time RT-PCR and had also been tested for mumps-specific IgG and IgM, 165 (69%) were positive for IgG but negative for IgM, indicating the importance of RT-PCR testing for diagnosis in vaccinated populations. None of the cases from the 2007-08 genotype J outbreak were re-notified. The number of mumps outbreaks reported in recent years among highly vaccinated populations, including Indigenous populations, has been growing. More widespread and pre-emptive use of the third dose of measles, mumps, and rubella vaccine might be required to control and prevent future outbreaks in high-risk populations. Research should explore the benefit of increasing the intervals between vaccine doses to strengthen the durability of vaccine protection. None.


Survival and quality of life after extracorporeal life support for refractory cardiac arrest: A case series.
Extracorporeal life support (ECLS) is an emerging option to treat selected patients with cardiac arrest refractory to cardiopulmonary resuscitation (CPR). Our primary objective was to determine the mortality at 30 days and at hospital discharge among adult patients receiving veno-arterial ECLS for refractory cardiac arrest. Our secondary objectives were to determine the 1-year survival and the health-related quality of life, and to examine factors associated with 30-day mortality. In a retrospective, single-center investigation within a tertiary referral center, we analyzed the prospectively collected data of 49 patients rescued from refractory cardiac arrest through emergent implantation of ECLS (E-CPR) (18.1% of our overall ECLS activity, 2005-2013), implanted in-hospital and during ongoing external cardiac massage in all cases. A prospective follow-up with administration of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) questionnaire was performed. The mean age was 47.6 ± 1.6 years; out-of-hospital cardiac arrest occurred in 12% of cases; average low-flow time was 47.2 ± 33 minutes; causes of cardiac arrest were heart disease (61.2%), trauma (14.3%), respiratory disease (4.1%), sepsis (2%), and miscellaneous (18.4%). Rates of survival at E-CPR explantation and at 30 days were 42.9% and 36.7%, respectively; brain death occurred in 24.5% of cases. Increased simplified acute physiology score; higher serum lactate levels and lower body temperature at the time of implantation were associated with 30-day mortality. Bridge to heart transplantation or implantation of a long-term ventricular assist device was performed in 8.2%. No deaths occurred during the follow-up after discharge (36.7% survival; average follow-up was 15.6 ± 19.2 months). The average Physical Component Summary and Mental Component Summary scores (SF-36 questionnaire) were, respectively, 45.2 ± 6.8 and 48.3 ± 7.7 among survivors. Extracorporeal cardiopulmonary resuscitation is a viable treatment for selected patients with cardiac arrest refractory to CPR. In our series, approximately one third of rescued patients were alive at 6 months and presented quality-of-life scores comparable to those previously observed in patients treated with ECLS.


CDP-Diacylglycerol Synthases (CDS): Gateway to Phosphatidylinositol and Cardiolipin Synthesis.
Cytidine diphosphate diacylglycerol (CDP-DAG) is a key intermediate in the synthesis of phosphatidylinositol (PI) and cardiolipin (CL). Both PI and CL have highly specialized roles in cells. PI can be phosphorylated and these phosphorylated derivatives play major roles in signal transduction, membrane traffic, and maintenance of the actin cytoskeletal network. CL is the signature lipid of mitochondria and has a plethora of functions including maintenance of cristae morphology, mitochondrial fission, and fusion and for electron transport chain super complex formation. Both lipids are synthesized in different organelles although they share the common intermediate, CDP-DAG. CDP-DAG is synthesized from phosphatidic acid (PA) and CTP by enzymes that display CDP-DAG synthase activities. Two families of enzymes, CDS and TAMM41, which bear no sequence or structural relationship, have now been identified. TAMM41 is a peripheral membrane protein localized in the inner mitochondrial membrane required for CL synthesis. CDS enzymes are ancient integral membrane proteins found in all three domains of life. In mammals, they provide CDP-DAG for PI synthesis and for phosphatidylglycerol (PG) and CL synthesis in prokaryotes. CDS enzymes are critical for maintaining phosphoinositide levels during phospholipase C (PLC) signaling. Hydrolysis of PI (4,5) bisphosphate by PLC requires the resynthesis of PI and CDS enzymes catalyze the rate-limiting step in the process. In mammals, the protein products of two CDS genes (CDS1 and CDS2) localize to the ER and it is suggested that CDS2 is the major CDS for this process. Expression of CDS enzymes are regulated by transcription factors and CDS enzymes may also contribute to CL synthesis in mitochondria. Studies of CDS enzymes in protozoa reveal spatial segregation of CDS enzymes from the rest of the machinery required for both PI and CL synthesis identifying a key gap in our understanding of how CDP-DAG can cross the different membrane compartments in protozoa and in mammals.


Temporal allocation of foraging effort in female Australian fur seals (Arctocephalus pusillus doriferus).
Across an individual's life, foraging decisions will be affected by multiple intrinsic and extrinsic drivers that act at differing timescales. This study aimed to assess how female Australian fur seals allocated foraging effort and the behavioural changes used to achieve this at three temporal scales: within a day, across a foraging trip and across the final six months of the lactation period. Foraging effort peaked during daylight hours (57% of time diving) with lulls in activity just prior to and after daylight. Dive duration reduced across the day (196 s to 168 s) but this was compensated for by an increase in the vertical travel rate (1500-1600 m·h(-1)) and a reduction in postdive duration (111-90 s). This suggests physiological constraints (digestive costs) or prey availability may be limiting mean dive durations as a day progresses. During short trips (<2.9 d), effort remained steady at 55% of time diving, whereas, on long trips (>2.9 d) effort increased up to 2-3 d and then decreased. Dive duration decreased at the same rate in short and long trips, respectively, before stabilising (long trips) between 4-5 d. Suggesting that the same processes (digestive costs or prey availability) working at the daily scale may also be present across a trip. Across the lactation period, foraging effort, dive duration and vertical travel rate increased until August, before beginning to decrease. This suggests that as the nutritional demands of the suckling pup and developing foetus increase, female effort increases to accommodate this, providing insight into the potential constraints of maternal investment in this species.


The last decade of symptom-oriented research in emergency medicine: triage, work-up, and disposition.
As a result of the ever-increasing use of imaging and clinical chemistry, symptom-oriented research has lost ground in many areas of clinical medicine. In emergency medicine, the importance of symptom-oriented research is obvious, as the three major tasks (triage, work-up and disposition) are still under-investigated. Scientific progress is closely linked to the analysis of readily available information, such as the patients' symptoms. A decade ago, there were more questions than answers. Therefore, we describe the state of the evidence and the importance of symptoms for decisions at triage, during work-up and for disposition. Recent advances in each field focusing on symptoms as predictors of outcome and/or diagnosis are shown. Finally, future directions of research regarding novel triage tools, efficient work-up and evidence-based disposition are discussed. Symptom-oriented research has been a driver for medical progress for centuries, and re-focusing on patient-centred clinical research will strengthen this field in the future in order to support smarter medicine.


Epithelioid Trophoblastic Tumour: A Case with Genetic Linkage to a Child Born over Seventeen Years Prior, Successfully Treated with Surgery and Pembrolizumab.
Epithelioid trophoblastic tumours are rare neoplasms showing differentiation towards the chorion leave-type intermediate cytotrophoblast, with only a handful of cases being reported in the literature. These tumours are slow-growing and are typically confined to the uterus for extended periods of time. While the pathogenesis is unclear, they are thought to arise from a remnant intermediate trophoblast originating from prior normal pregnancies or, less frequently, gestational trophoblastic tumours. A protracted time period between the gestational event and tumour development is typical. This case describes a 49-year-old previously healthy female who presented with a completely asymptomatic uterine mass, discovered incidentally during a routine gynaecological assessment. The pathological analysis of the hysterectomy specimen confirmed an epithelioid trophoblastic tumour, involving the uterus and cervix. This is a rare gynaecological tumour. A comparative short tandem repeat analysis revealed genetic similarities to a previous healthy gestation seventeen years prior. She was successful treated with adjuvant pembrolizumab, with no evidence of disease recurrence to date.


Sialendoscopy for Improvement of Salivary Flow in Patients with Sjögren Syndrome - Comparative Analysis of Intraglandular Washing Solutions.
Introduction Among the potential diseases that present altered salivary flow and activity is Sjögren syndrome. Sialendoscopy seems to be an important therapeutic option. Objective To compare the results obtained with sialendoscopy for improving salivary flow measured by scintigraphy in patients with primary Sjögren syndrome to those obtained with other intraglandular washing solutions. Methods Patients from our institution's rheumatology clinic diagnosed with primary Sjögren syndrome underwent parotid scintigraphy prior to the sialendoscopy procedure. During the sialendoscopy procedure, one of the parotid glands was randomized to receive a wash with saline while the other was washed with a corticosteroid solution. After 1 month, a new scintigraphy examination of the parotid glands was performed to observe the salivary flow for comparison. Results A total of 13 female patients with mean age of 53.38 years (range, 27-76 years) were included in this study. After sialendoscopy, 10 patients (76.92%) were observed to have improvement in salivary excretion with radiopharmaceutical during scintigraphy. When analyzing each gland that was treated separately (26 glands), after sialendoscopy, improvement was observed in 18 glands (69.23%), 8 treated with dexamethasone and 10 with saline solution in the wash. There was no improvement in 8 glands (30.77%). Conclusion This study demonstrates that sialendoscopy is as an important tool to improve salivary flow measured by scintigraphy in patients with primary Sjogren syndrome, increasing salivary excretion through dilation and consequent unblocking of the ducts. These data suggest that there is no statistically significant difference between intraductal washing solutions using saline or dexamethasone solution.


A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling.
Mannose 6-phosphate receptors (MPRs) deliver newly synthesized lysosomal enzymes to endosomes and then recycle to the Golgi. MPR recycling requires Rab9 GTPase; Rab9 recruits the cytosolic adaptor TIP47 and enhances its ability to bind to MPR cytoplasmic domains during transport vesicle formation. Rab9-bearing vesicles then fuse with the trans-Golgi network (TGN) in living cells, but nothing is known about how these vesicles identify and dock with their target. We show here that GCC185, a member of the Golgin family of putative tethering proteins, is a Rab9 effector that is required for MPR recycling from endosomes to the TGN in living cells, and in vitro. GCC185 does not rely on Rab9 for its TGN localization; depletion of GCC185 slightly alters the Golgi ribbon but does not interfere with Golgi function. Loss of GCC185 triggers enhanced degradation of mannose 6-phosphate receptors and enhanced secretion of hexosaminidase. These data assign a specific pathway to an interesting, TGN-localized protein and suggest that GCC185 may participate in the docking of late endosome-derived, Rab9-bearing transport vesicles at the TGN.


The index of microcirculatory resistance (IMR) in takotsubo cardiomyopathy.
We report a patient who presents with acute chest pain and positive cardiac enzymes clinically consistent with an acute coronary syndrome (ACS). Coronary angiography revealed normal epicardial arteries and the left ventriculogram was notable for apical ballooning. This was strongly suggestive of takotsubo cardiomyopathy. Pressure wire measurements of Fractional flow reserve (FFR) and IMR demonstrated a normal FFR, but significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR, which unlike CFR is specific for the microcirculation and reproducible through a range of hemodynamic states.


During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter.
CD11c is a member of the beta(2) integrin family of adhesion molecules that, together with CD18, forms a heterodimeric receptor on the surface of myeloid, NK, dendritic, and certain leukemic, lymphoma, and activated lymphoid cells. Monocytic differentiation is associated with an induction of both CD11c and CD18 gene expression. The resulting CD11c/CD18 receptor mediates firm adhesion to the vascular endothelium, transendothelial migration, chemotaxis, and phagocytosis. Monocytic differentiation can be mimicked in vitro by treatment of the promonocytic cell line U937 with PMA. Recently, we reported that in U937 cells, expression of the CD11c gene is controlled by an unidentified transcription factor that binds ssDNA. This finding suggested that DNA secondary structure plays an important role in controlling the CD11c gene and prompted us to search for additional ssDNA-binding activities with which this gene interacts. In this study, we report that in U937 cells, expression of the CD11c gene is mediated by the ssDNA-binding protein Puralpha. During PMA-induced differentiation, the ability of Puralpha to activate the CD11c promoter in U937 cells increases, as does that of Sp1. Together, these increases in the functional activity of both Puralpha and Sp1 combine to induce CD11c expression.


Synthesis and sorption properties of hexa-(peri)-hexabenzocoronene-based porous organic polymers.
In this communication, we report the synthesis of several novel hexa-(peri)-hexabenzocoronene (HBC) containing microporous polymers. These polymers exhibit good adsorption properties for H2, N2 and CO2 gases. Based on fluorescence quenching studies, we have shown that the highly conjugated π-surfaces may be accessible by guests in solution.


Distribution and retention of spermatozoa with acrosomal and nuclear abnormalities in the cow genital tract.
Two experiments were conducted to evaluate the fate of sperm following uterine insemination. In Exp. I, five pairs of Holstein cows were inseminated with egg yolk-Tris extended semen (approximately 1.0 X 10(9) sperm; .5 ml) from five ejaculates from a single bull that had high levels (approximately 70%) of morphologically abnormal sperm. Cows were slaughtered 12 h after insemination. The genital tracts were removed and promptly clamped into defined regions. Sperm were recovered by flushing with 2.9% sodium citrate buffer. Proportions of abnormal sperm in the various regions were compared with those in the inseminate. Sperm numbers were also determined from each region. Regions of the tract varied in number of sperm (P less than .001), proportions of knobbed acrosomes (P less than .001), tapered heads (P less than .001), protoplasmic droplets (P less than .001), tail abnormalities (P less than .029) and total abnormalities (P less than .002). A total of 63.5 +/- 6.4 X 10(6) sperm was recovered. These sperm were distributed throughout the tract as follows: vagina, 91.8%; cervix, 5.4%; uterine horns, 2.7%, and uterotubal junctions-isthmi, .04%. No sperm were recovered from ampullae. Because retrograde movement of sperm from the uterus occurred in Exp. I, we conducted Exp. II to determine the extent of sperm loss from the genital tract following insemination. Three pairs of Holstein cows were inseminated with .42 X 10(9) sperm (.5 ml; egg yolk-Tris extender) from the same bull used in Exp. I (three ejaculates). All discharged mucus and urine was collected for 12 h after insemination for recovery of sperm. Aspirates (approximately 1 ml) of mucus from the vagina were evaluated during the 12-h post-insemination period for numbers of sperm and leucocytes. Sperm were also recovered from the tract following slaughter (approximately 12 h) to determine retention. Overall, 73 +/- 3.7% of inseminated sperm were recovered. Components were: inseminate lost from the genital tract in discharged mucus, 60 +/- 4.6%; lost in urine, .06 +/- .02%; aspirated from the vagina, 4.4 +/- 1%; adhered to equipment, 1.3 +/- .3%, and retained in the genital tract, 6.5 +/- 1.6%. Predicted numbers of sperm contained in discharged mucus 2 h post-insemination were greater (P less than .009) than at subsequent hours.(ABSTRACT TRUNCATED AT 400 WORDS)


Geographical variation of shoeprint comparison class correspondences.
The underlying principles involved in the interpretation of shoeprint comparisons have become a topical subject due to criticisms in the 2009 National Academy of Science (NAS) report on forensic sciences[1]. Difficulties in the application and understanding of these principles were also highlighted in a recent court ruling [2-5] and subsequent discussion of the ruling. We report here a survey that may inform some aspects of this interpretation and discuss the implications of findings from this survey in the light of that court ruling and more importantly the NAS report. 1,511 shoeprints were taken from student volunteers in Auckland, Wellington and Dunedin, New Zealand. 500 shoeprints were sampled from student volunteers at Australian universities. 100 from each of the University of Technology in Sydney, University of Queensland in Brisbane, University of Newcastle, Charles Sturt University in Bathurst and University of Canberra, Australia. These cities are distributed along the east coast of Australia. The shoeprints, taken from each country, were compared against each other for the presence of any pattern correspondences However shoeprints have not been compared between countries. In all locations the pattern of some common and many rare outsole patterns was repeated, with Converse Chuck Taylor All Stars and Vans Canvas Era common in all locations.


Functional poly(ε-caprolactone) based materials: preparation, self-assembly and application in drug delivery.
Recent advances in synthesis of functional poly-ε-caprolactone (PCL) and its self-assembly behavior, as well as application in drug delivery have been reviewed. Three strategies including end group functionalization, postpolymerization modification and new monomer preparation have been summarized to show possibilities for PCL derivatives. Complex architectures like cyclic and multi-arm PCL have been emphasized. Both chemical composition and topology have coordinately affected the property of PCL-based materials on the molecular level. A large variety of PCLs with sophisticated topology like block, graft, cyclic, and star have displayed versatile morphologies in solutions. These selfassembly aggregates have been applied as nano-scaled drug carries either to physically encapsulate or covalently conjugate drugs for controlled release. In particular, PCL with pendant groups has been extensively studied to illustrate the noncovalent interaction with drugs and the influence on the release profile. In general, functional PCL has shown great potential in construct of complicated supramolecular structures, and thus as ideal drug carriers for sustainable and targeted delivery.


Association of Lactase Persistence Genotypes (rs4988235) and Ethnicity with Dairy Intake in a Healthy U.S. Population.
Lactase persistence (LP) is a trait in which lactose can be digested throughout adulthood, while lactase non-persistence (LNP) can cause lactose intolerance and influence dairy consumption. One single nucleotide polymorphism (SNP ID: rs4988235) is often used as a predictor for dairy intake, since it is responsible for LP in people in European descent, and can occur in other ethnic groups. The objective of this study was to determine whether rs4988235 genotypes and ethnicity influence reported dairy consumption in the United States (U.S.). A food frequency questionnaire (FFQ) and multiple Automated Self-Administered 24-h recalls (ASA24®) were used to measure habitual and recent intake, respectively, of total dairy, cheese, cow's milk, plant-based alternative milk, and yogurt in a multi-ethnic U.S. cohort genotyped for rs4988235. Within Caucasian subjects, LP individuals reported consuming more recent total dairy and habitual total cow's milk intake. For subjects of all ethnicities, LP individuals consumed more cheese (FFQ p = 0.043, ASA24 p = 0.012) and recent total dairy (ASA24 p = 0.005). For both dietary assessments, Caucasians consumed more cheese than all non-Caucasians (FFQ p = 0.036, ASA24 p = 0.002) independent of genotype, as well as more recent intake of yogurt (ASA24 p = 0.042). LP subjects consumed more total cow's milk than LNP, but only when accounting for whether subjects were Caucasian or not (FFQ p = 0.015). Fluid milk and alternative plant-based milk consumption were not associated with genotypes or ethnicity. Our results show that both LP genotype and ethnicity influence the intake of some dairy products in a multi-ethnic U.S. cohort, but the ability of rs4988235 genotypes to predict intake may depend on ethnic background, the specific dairy product, and whether intake is reported on a habitual or recent basis. Therefore, ethnicity and the dietary assessment method should also be considered when determining the suitability of rs4988235 as a proxy for dairy intake.


What you say and what I hear-Investigating differences in the perception of the severity of psychological and physical violence in intimate partner relationships.
The correct communication of the severity of violence is essential in the context of legal trials, custody cases, support of victims, etc., for providing fair treatment. A narrator that communicates their experiences of interpersonal violence may rate the seriousness of the incident differently than a rater reading the narrator's text, suggesting that there exist perceptual differences (PD) in severity ratings between the narrator and the rater. We propose that these perceptual differences may depend on whether the narrative is based on physical or psychological violence, and on gender differences. Physical violence may be evaluated as more serious by the receiver of the narrative than by the narrator (Calibration PD), whereas the seriousness of psychological violence may be difficult to convey, leading to a discrepancy in the seriousness ratings between the narrator and the rater (Accuracy PD). In addition, gender stereotypes may influence the seriousness rating (Gender PD), resulting in violence against women being perceived as more serious than the same violence against men. These perceptual differences were investigated in 3 phases using a new experimental procedure. In Phase 1, 113 narrators provided descriptions and seriousness ratings of self-experienced physical and psychological violence in relationships. In Phase 2, 340 independent raters rated the seriousness of 10 randomly selected narrations from Phase 1. In Phase 3, the genders in the narrations were changed to the opposite gender, and seriousness ratings were collected from 340 different raters. Our results confirmed the hypothesized perceptual differences. Violence to male victims was considerably more likely to be seen as severe when the raters were misled to believe the victim was a woman. We propose that these data provide practical guidelines for how to deal with misinformation in the communication of violence. The data also show that mean values and the confidence of such severity ratings need to be adjusted for several factors, such as whether it is self-experienced or communicated, the type of violence, and the gender of the victims and raters.


Altered regulation of insulin-like growth factor binding protein-1 in patients with polycystic ovary syndrome.
Insulin-like growth factor (IGF-I) action is influenced by circulating as well as tissue levels of its binding proteins. Because serum IGF binding protein-1 (IGFBP-1) levels have been found to be decreased in patients with polycystic ovary syndrome (PCOS), we tested the hypothesis that regulation of IGFBP-1 secretion may be different in patients with PCOS compared with normal women. We studied 15 normal ovulatory women and 15 women with PCOS of similar age (21 +/- 1 and 22 +/- 1 years, respectively). All subjects were studied after an overnight fast between days 5-8 after spontaneous or progestin-induced menses. Perturbations included the administration of insulin intravenously, maintenance of a euglycemic clamp, and, in a subsequent cycle, the administration of a long-acting somatostatin analogue (octreotide, 100 micrograms) given subcutaneously. Blood samples were collected before treatment, every 15 minutes for 6 hours after insulin, and every 30 minutes for 3 hours after octreotide administration. Serum levels of IGF-I, IGFBP-1, IGFBP-3, and insulin were measured by specific immunoassays. Compared with the controls, patients with PCOS had significantly higher insulin levels, similar IGF-I and IGFBP-3 levels, and significantly lower IGFBP-1. Insulin did not change serum IGF-I levels in either group, although a significant decrease in IGFBP-1 levels occurred in normal women but not in patients with PCOS. Octreotide treatment also did not change serum IGF-I levels in either group, but serum insulin levels decreased significantly and IGFBP-1 levels increased significantly in both groups; this response was significantly greater in controls. Our data are compatible with the notion that regulation of IGFBP-1 is altered in women with PCOS and that several factors may be involved.


Rodeo Thumb: To Replant or Not.
This study investigated patient-reported outcomes after surgical treatment of rodeo thumb amputation to guide clinical decision-making. A retrospective review was performed for rodeo thumb amputations from 2009 to 2019. Patient-reported outcomes were collected and compared by injury level, age, and treatment. Two-sided t test was used to compare continuous variables, and Pearson chi-square test was used to compare categorical data. The study included 37 patients. Patients with interphalangeal injuries treated with replantation had Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores similar to those treated with amputation (1 versus 8; p = 0.07). There was no significant difference in percentage of patients with similar or better roping ability after treatment (40 percent versus 79 percent; p = 0.26), and similar percentages were satisfied (80 percent versus 71 percent; p = 1.00). Patients with metacarpophalangeal injuries treated with replantation and those treated with amputation had similar questionnaire scores (7 versus 10; p = 0.47). Both groups had similar roping ability after treatment (67 percent versus 56 percent; p = 1.00), and there was no statistically significant difference in satisfaction (79 percent versus 44 percent; p = 0.34). Pediatric patients had questionnaire scores similar to those of adults (6 versus 8; p = 0.42). A significantly higher percentage of pediatric patients had similar roping ability following injury than adults (100 percent versus 54 percent; p = 0.02). Most patients in both groups were satisfied (89 percent versus 61 percent; p = 0.22). For both interphalangeal and metacarpophalangeal injuries, patient-reported outcomes were similar regardless of treatment. Children were able to return to roping and perform at a similar or higher level at a greater rate than adults, but had similar questionnaire scores and satisfaction.


Summer diatom blooms in the eastern North Pacific gyre investigated with a long-endurance autonomous surface vehicle.
Satellite chlorophyll a (chl a) observations have repeatedly noted summertime phytoplankton blooms in the North Pacific subtropical gyre (NPSG), a region of open ocean that is far removed from any land-derived or Ekman upwelling nutrient sources. These blooms are dominated by N2-fixing diatom-cyanobacteria associations of the diatom genera Rhizosolenia Brightwell and Hemiaulus Ehrenberg. Their nitrogen fixing endosymbiont, Richelia intracellularis J.A. Schmidt, is hypothesized to be critical to the development of blooms in this nitrogen limited region. However, due to the remote location and unpredictable duration of the summer blooms, prolonged in situ observations are rare outside of the Station ALOHA time-series off of Hawai'i. In summer, 2015, a proof-of-concept mission using the autonomous vehicle, Honey Badger (Wave Glider SV2; Liquid Robotics, a Boeing company, Sunnyvale, CA, USA), collected near-surface (<20 m) observations in the NPSG using hydrographic, meteorological, optical, and imaging sensors designed to focus on phytoplankton abundance, distribution, and physiology of this bloom-forming region. Hemiaulus and Rhizosolenia cell abundance was determined using digital holography for the entire June-November mission. Honey Badger was not able to reach the 30°N subtropical front region where most of the satellite chl a blooms have been observed, but near-real time navigational control allowed it to transect two blooms near 25°N. The two taxa did not co-occur in large numbers, rather the blooms were dominated by either Hemiaulus or Rhizosolenia. The August 2-4, 2015 bloom was comprised of 96% Hemiaulus and the second bloom, August 15-17, 2015, was dominated by Rhizosolenia (75%). The holograms also imaged undisturbed, fragile Hemiaulus aggregates throughout the sampled area at ∼10 L-1. Aggregated Hemiaulus represented the entire observed population at times and had a widespread distribution independent of the summer export pulse, a dominant annual event suggested to be mediated by aggregate fluxes. Aggregate occurrence was not consistent with a density dependent formation mechanism and may represent a natural growth form in undisturbed conditions. The photosynthetic potential index (Fv:Fm) increased from ∼0.4 to ∼0.6 during both blooms indicating a robust, active phytoplankton community in the blooms. The diel pattern of Fv:Fm (nocturnal maximum; diurnal minimum) was consistent with macronutrient limitation throughout the mission with no evidence of Fe-limitation despite the presence of nitrogen fixing diatom-diazotroph assemblages. During the 5-month mission, Honey Badger covered ∼5,690 km (3,070 nautical miles), acquired 9,336 holograms, and reliably transmitted data onshore in near real-time. Software issues developed with the active fluorescence sensor that terminated measurements in early September. Although images were still useful at the end of the mission, fouling of the LISST-Holo optics was considerable, and appeared to be the most significant issue facing deployments of this duration.


[Reconstruction of the anterior eye segment in children based on penetrating rotary autokeratoplasty].
The paper describes the technique of reconstruction of the anterior segment of the eye used in 46 children, aged from 3 to 14 years, with coarse adherent corneal leukomas, adhesions and obliterations of the pupil, cataracts of mainly (89.2%) posttraumatic etiology. Besides rotatory penetrating autokeratoplasty, the complex surgical intervention included iridoplasty in 91.3%, cataract extraction in 82.6%, anterior vitrectomy in 17.4%, intraocular lens implantation in 2.2% of cases. The complex surgical intervention allowed to achieve transparency of the central zone of the cornea thanks to avoidance of tissue incompatibility, harmless manipulations on the tissues of the anterior segment of the eye, prevention of recurrent adhesions in the anterior chamber. A rise of visual acuity was recorded in 33 persons (71.7%), of them to 0.3-0.7 with correction in 30.8% of cases in remote terms of follow-up. Improvement of cosmetic appearance was achieved in all of the patients operated on.


A Scoping Review on College Student Physical Activity: How Do Researchers Measure Activity and Examine Inequities?
The purpose of this scoping review was to critically examine the design and quality of contemporary research involving college student physical activity participation, focusing on physical activity measurement, assessment of sociodemographic characteristics, and examination of inequities based on sociodemographic characteristics. Systematic searches were conducted in 4 electronic databases. From 28,951 sources screened, data were extracted from 488 that met the inclusion criteria. The majority of the studies were cross-sectional in design (91.4%) and employed convenience sampling methods (83.0%). Based on the subsample of studies that reported the percentage of students meeting aerobic (n = 158; equivalent of 150 min/wk of moderate physical activity) and muscle-strengthening activity recommendations (n = 8; ≥2 times/wk), 58.7% and 47.8% of students met aerobic and muscle-strengthening recommendations, respectively. With the exception of age and sex, sociodemographic characteristics were rarely assessed, and inequities based upon them were even more scarcely examined-with no apparent increase in reporting over the past decade. College student physical activity levels remain concerningly low. The generalizability of findings from the contemporary literature is limited due to study design, and acknowledgement of the influence that sociodemographic characteristics have on physical activity has largely been overlooked. Recommendations for future research directions and practices are provided.


Cocaine- and amphetamine-regulated transcript peptide immunoreactivity in the brain of the CCK-1 receptor deficient obese OLETF rat.
Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in homeostatic regulation and reward. CART has been shown to reduce food intake, but the underlying mechanisms and the relevance of this effect on obesity yet remain unknown. Therefore, we used immunohistochemistry to investigate the expression of CART peptide in various brain regions of the obese Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking the CCK-1 receptor. Analysis revealed that whereas the distribution of CART-peptide immunoreactive neurons and axonal networks was identical in OLETF rats and lean controls, the intensity of CART immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens (p < 0.01), the basolateral complex of the amygdala (p < 0.05) and the rostro-medial nucleus of the solitary tract (p < 0.001) of the OLETF rats. These areas are involved in reward and integration of taste and viscerosensory information and have been previously associated with altered functions in this strain. The findings suggest that in addition to previously described deficits in peripheral satiety signals and augmented orexigenic regulation, the anorectic effect of CART peptide may also be diminished in OLETF rats.


Effectiveness of thiazides on serum and urinary calcium levels and bone mineral density in patients with osteoporosis: a systematic review and meta-analysis.
Osteoporosis is the most common metabolic bone disease and a major public health problem worldwide. Thiazides are widely used as antihypertensive agents with good tolerability and efficacy. Furthermore, thiazides have long been regarded as candidates for the prevention of postmenopausal bone loss. However, there is insufficient evidence that thiazides have a sustained beneficial effect on preserving bone mass and preventing osteoporosis to date. We searched the PubMed, the Cochrane Library, and Embase in June 2018 for randomized controlled trials on the use of thiazides to treat osteoporosis. Continuous outcomes are presented as the standardized mean difference (SMD) and 95% CI. Furthermore, P-values <0.05 were considered significant. Five trials with 756 patients were randomly assigned in the five trials included in this meta-analysis. Serum calcium level was higher in the thiazide group than in the control group (SMD 0.33, 95% CI [0.16, 0.50]), and urinary calcium level was significantly lower in the thiazide group (SMD -0.35, 95% CI [-0.52, -0.17]). There was no significant difference in bone mineral density between the two groups (SMD 0.19, 95% CI [-0.16, 0.54]). Thiazides might play a role in preserving bone mass and be effective in the prevention and treatment of osteoporosis. Future high-quality trials are needed to confirm our findings in the future.


Studies on the mechanisms of neurulation in the chick: morphometric analysis of the relationship between regional variations in cell shape and sites of motive force generation.
Microfilaments, which are organized into bundles in the apical ends of neuroepithelial cells, are generally thought to play a major role in generating the driving forces for neural tube closure. Because of their proximity to the luminal surface, the contractile activity of these microfilament bundles results in conspicuous changes in the overall shape of neuroepithelial cells, most notably apical constriction and apical surface folding. In the present study, we have used morphometric methods and computer-assisted image analysis to reveal the distribution of microfilament-mediated forces in the developing midbrain during initial contact of apposing neural folds in chick embryos at Hamburger and Hamilton stage 8+ of development (Hamburger and Hamilton (1951) J. Morphol., 88:49-92). The degree of apical constriction, apical surface folding, and bending of the neuroepithelium was used as a barometer of local microfilament activity. Results indicate that cells forming the floor and midlateral walls of the developing midbrain consistently show a higher degree of apical constriction and surface folding than those at other locations. These same regions of the neuroepithelium also exhibit the greatest degree of bending. We conclude that the principal driving forces for closure of the neural tube, at the level of the midbrain, are concentrated in certain regions of the neuroepithelium (i.e., the floor and midlateral walls of the forming neural tube) rather than uniformly distributed.


Immunomodulating activity of analogs of noninflammatory fragment 163-171 of human interleukin-1beta.
The synthetic nonapeptide Val-Gln-Gly-Glu-Glu-Ser-Asn-Asp-Lys corresponding to the amino acid sequence 163-171 of human interleukin-1beta (IL-1beta) has been reported to retain considerable immunostimulatory activity of the native protein without the induction of the inflammatory or pyrogenic responses. Two lipophilic derivatives of this nonapeptide, one having a lauroyl residue (1) and the other having a palmitoyl residue (2) at the N-terminus of the peptide, and a more stable analog carrying D-Val residue at position 1 of the peptide (3) were synthesized with a view to find out if these structural modifications had a favorable effect on in vitro mouse thymocyte proliferation and IL-1 dependent inhibition of A375 cells. We have found that analogs (1) and (2) are active in both the tests like the parent nonapeptide. The lipophilic analog (2) is in fact, effective at a lower dose as compared to the parent nonapeptide in mouse thymocyte proliferation assay. Although the analog (3) has the ability to inhibit A375 cells, it does not stimulate mouse thymocyte proliferation in vitro. The IL-1beta fragment (163-171) and the analog (2) were further compared for their effects on pyrogenicity, blood glucose level, acute phase response and radioprotection. Unlike IL-1beta, its fragment (163-171) and the analog (2) do not induce pyrogenicity and any of the acute phase related changes such as the increase in C-reactive protein and hypoglycemia following their administration in Balb/c mice. We have found that 40% of animals treated with analog (2) survive more than 21 days after lethal irradiation as compared to 20% survivors in groups treated with recombinant IL-1beta or its nonapeptide fragment (163-171), under conditions when all the control animals died within 10 days. This study may help in designing small peptides which may be more effective and stable.


Use of permitted drugs in Italian professional soccer players.
To assess the frequency and quantity of usage of permitted drugs by Italian professional soccer players. A cohort of 1041 professional soccer players from the two Italian major leagues was assembled during the season 2003-4; 743 of the 785 (94.6%) subjects available on the day of the interview answered an epidemiological questionnaire, which included questions on the type and frequency of use of several permitted drugs. 92.6% of players reported having used oral anti-inflammatory products in the previous year, and most of them were current users (86.1%). 36% of the players, mostly current users, reported the use of analgesics. 82.8% of the players reported current use of supplements, and 28% reported using vitamins. The regular use of several permitted drugs is very high among professional soccer players. The description of players' behaviour is the first step towards regular monitoring of the players' need for, and use of, vitamins, supplements and other permitted drugs.


Mitotic spindle: kinetochore fibers hold on tight to interpolar bundles.
When a cell starts to divide, it forms a spindle, a micro-machine made of microtubules, which separates the duplicated chromosomes. The attachment of microtubules to chromosomes is mediated by kinetochores, protein complexes on the chromosome. Spindle microtubules can be divided into three major classes: kinetochore microtubules, which form k-fibers ending at the kinetochore; interpolar microtubules, which extend from the opposite sides of the spindle and interact in the middle; and astral microtubules, which extend towards the cell cortex. Recent work in human cells has shown a close relationship between interpolar and kinetochore microtubules, where interpolar bundles are attached laterally to kinetochore fibers almost all along their length, acting as a bridge between sister k-fibers. Most of the interpolar bundles are attached to a pair of sister kinetochore fibers and vice versa. Thus, the spindle is made of modules consisting of a pair of sister kinetochore fibers and a bundle of interpolar microtubules that connects them. These interpolar bundles, termed bridging fibers, balance the forces acting at kinetochores and support the rounded shape of the spindle during metaphase. This review discusses the structure, function, and formation of kinetochore fibers and interpolar bundles, with an emphasis on how they interact. Their connections have an impact on the force balance in the spindle and on chromosome movement during mitosis because the forces in interpolar bundles are transmitted to kinetochore fibers and hence to kinetochores through these connections.


Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer.
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.


Intellectual disabilities and dementia: New tasks and experiences of Austrian formal caregivers.
In Austria, due to its history, only relatively little research on the topic of intellectual disabilities and dementia has been conducted to date. The present study thus aims to explore the challenges and tasks currently facing formal caregivers, together with assessing their wishes for further development. Ten semi-structured interviews were held with formal caregivers. Interviews were transcribed and analysed by means of structured qualitative content analysis. Caregivers must deal with conflicts between residents, and with increasing demands for care and emotional support. Education and training on dementia and intellectual disability are mostly of high quality, but still remain insufficient. Caregivers would like to see suitable adaptation of care premises, smaller groups, more staff and better training on dementia and intellectual disability. To ensure quality care and 'ageing in place', caregivers and providers need to pay greater attention to dementia-related changes when planning and adapting services.


Toll-Like Receptor 4 (TLR4) Stimulates Synovial Injury of Temporomandibular Joint in Rats Through the Activation of p38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.
BACKGROUND Synovitis is an important disease that cause intractable pain in temporomandibular joint (TMJ), and the inflammation process played a crucial role in the initiation and development of temporomandibular joint disorder. A series of investigations suggested that the increasing expression of interleukin-(IL) 1β secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In this present study, we investigated the signaling pathways which regulate the expression of IL-1β. MATERIAL AND METHODS The occlusal interference animal model was created to induce synovial injury. Forty-eight rats were divided into 4 groups: 1) control group, 2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor targeting the p38) group. The inflammation changes were observed, and the expression of p38 and IL-1β in the synovial membranes were assayed. RESULTS The results showed that downstream p38 MAPK (mitogen-activated protein kinase) signaling was triggered following the activation of TLR4. Moreover, the injection of SB203580 could inhibit the inflammatory reactions and the increased expression of IL-1β at both mRNA and protein levels. CONCLUSIONS The results prompted us that TLR4 may stimulates synovial inflammatory reactions and increased expression of IL-1β in rats through the activation of p38 MAPK signaling pathway, p38 was an important mediator in the mechanisms of the initiation and development of synovial injury by regulating the expression of IL-1β in synovial membranes.


Effectiveness of acupuncture in the management of restless leg syndrome: a systematic review and meta-analysis.
Acupuncture is an important component of traditional Chinese medicine which is used to treat an array of health conditions. This study evaluates the effectiveness of acupuncture in the management of restless leg syndrome (RLS). A comprehensive literature survey was conducted in electronic databases to identify studies evaluating the effectiveness of acupuncture in the treatment of RLS. Cure, marked effect, effective, ineffective, and total effective rates of individual studies were pooled to achieve their respective overall estimates and a meta-analysis of mean change from baseline in International Restless Legs Syndrome Rating Scale (IRLSRS) was performed. A total of 18 studies were included in this meta-analysis, among which 640 RLS patients were treated with acupuncture alone or combined with other therapies (acupuncture group) and 447 RLS patients were treated with non-acupuncture therapies (control group). Cure, marked effect, and effective rates were 47.8% [95% confidence interval (CI): 38.3% to 57.3%], 27.4% (95% CI: 20.3% to 34.8%), and 24.2% (95% CI: 16.9% to 31.5%) in patients treated with acupuncture either alone or combination with other treatments, and 21.7% (95% CI: 20.7% to 22.7%), 28.0% (95% CI: 20.0% to 32.9%), and 22.3% (95% CI: 17.0% to 27.6%) in patients treated with non-acupuncture therapies, respectively. The ineffective rate was 4.7% (95% CI: 4.3% to 5.0%) in the acupuncture group and 32.9% (95% CI: 22.2% to 43.7%) in non-acupuncture groups. IRLSRS scores improved significantly after acupuncture treatment [mean change from baseline -9.45 (95% CI: -18.42 to -0.49); P=0.04]. Although the overall quality of the included studies was low, the results of this meta-analysis suggested that acupuncture is an effective treatment option for RLS. Well-designed randomized controlled trials especially those involving a sham-acupuncture arm are needed to confirm these outcomes.


A novel intramolecular hydrogen bonding between a side-chain pyridine ring and an amide hydrogen of the peptide backbone in tripeptides containing the new amino acid, alpha,alpha-di(2-pyridyl)glycine.
Four tripeptides (Z-AA1-2Dpy-AA3-OMe; AA1, AA3 = Gly, Aib) containing a novel amino acid, alpha, alpha-di(2-pyridyl)glycine (2Dpy), were synthesized by the modified Ugi reaction. NMR analysis clearly indicated that the 2Dpy-containing tripeptides except the peptide in which AA1, AA3 = Aib, adopt a unique conformation with two intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen and between AA3-NH and another pyridine nitrogen. This conformation has so far not been reported. On the other hand, the peptide Z-Aib-2Dpy-Aib-OMe probably adopts a beta-turn structure which is stabilized by two intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen and between AA3-NH and the C=O of the Z group.


Infection of normal human epithelial cells by Epstein-Barr virus.
Primary cultures of epithelial cells were grown from the tonsils and adenoids of patients with diseases not related to Epstein-Barr virus. The cells could not be infected by Epstein-Barr virus. Fluorescein-labeled Epstein-Barr virus and a cytofluorograph were then used to show that the epithelial cells do not have detectable receptors for the virus. However, implantation with Epstein-Barr virus receptors gave the cells the ability to bind the labeled virus. One to 5 percent of receptor-implanted cells exposed to the transforming B95-8 substrain of the virus expressed Epstein-Barr nuclear antigen. The early and viral capsid Epstein-Barr virus-determined antigens were not detected in the virus-infected cultures. The results show that normal human epithelial cells from the nasopharynx become susceptible to infection by Epstein-Barr virus when the membrane barrier resulting from the lack of viral receptors is overcome by receptor implantation.


Introduction Imaging experience made us suspect an overrepresentation of ponytails in riders admitted as polytrauma after falling from their horse. Methods In a single-centre case-control study conducted over three months, we reviewed the records of all admitted polytraumatised patients for trauma mechanism and presence of ponytail on CT. Cerebral CTs were reviewed in the three standard imaging planes using a bone or lung window. Ponytail was diagnosed if most or all of the hair on the head was gathered and secured at the back of the head with a hair tie. Data were analysed with Fisher's exact test. Results Seven female riders (mean age 22 years) were admitted after falling from their horse (study group); six of these riders wore a ponytail. No male riders were admitted. Therefore, only female polytraumatised patients having suffered any other trauma were selected as controls. The control group consisted of 13 patients (mean age 33,5 years), two of whom wore a ponytail. In three controls, all without ponytails, the trauma also had been related to a horse. Thus, horses were involved in 50% of the traumas included in this study. Ponytail was found more frequently in riders admitted after falling from their horse, p less-than 0,005. Conclusion Having an almost circumferential vision, horses may be scared by the sideways swaying of a ponytail worn by their own rider. In riders, ponytails can trigger a sensation of tightness or even headache which may impair focus. Thus, while female riders most likely wear ponytails for practicality, ponytails may increase the risk of accident by affecting rider and horse. Further studies are required to determine if the observed association between ponytails and trauma is causal. Funding none. Trial registration not applicable.


Dementia Friendly Care: Methods to Improve Stakeholder Engagement and Decision Making.
Dementia friendly (DF) is a term that has been increasingly used in the international literature to describe approaches that include and involve people living with dementia within their communities and wider society. How to support the involvement of people living with dementia to achieve dementia friendly care or support outcomes is an area that has begun to receive attention. We begin by introducing the concept of dementia friendly, the policy context and what has already been evidenced via prior reviews and conceptual discussions. We conducted a systematic review following PRISMA guidelines, resulting in the inclusion of nineteen papers that reported on the methods and approaches used to involve people living with dementia in achieving dementia friendly or supportive care outcomes. Five primary themes were identified: the potential of group-based activities to facilitate inclusion and engagement; achieving engagement in decision making; the value of developing tools to help service providers to engage those living with dementia in care decisions; the role of awareness raising and education to support the inclusion of a range of stakeholders in achieving DF support and care outcomes; the need for cultural and contextual sensitivity when seeking to engage stakeholders to achieve positive care outcomes. We conclude by considering how both the underpinning ethos of social citizenship and social inclusion need to be in place alongside a range of approaches that are adapted to fit local contexts and needs to enable the involvement of people living with dementia in achieving dementia friendly care outcomes.


MicroRNA166 Modulates Cadmium Tolerance and Accumulation in Rice.
MicroRNAs (miRNAs) are 20- to 24-nucleotide small noncoding RNAs that regulate gene expression in eukaryotic organisms. Several plant miRNAs, such as miR166, have vital roles in plant growth, development and responses to environmental stresses. One such environmental stress encountered by crop plants is exposure to cadmium (Cd), an element highly toxic to most organisms, including humans and plants. In this study, we analyzed the role of miR166 in Cd accumulation and tolerance in rice (Oryza sativa). The expression levels of miR166 in both root and leaf tissues were significantly higher in the reproductive stage than in the seedling stage in rice. The expression of miR166 in the roots of rice seedlings was reduced after Cd treatment. Overexpression of miR166 in rice improved Cd tolerance, a result associated with the reduction of Cd-induced oxidative stress in transgenic rice plants. Furthermore, overexpression of miR166 reduced both Cd translocation from roots to shoots and Cd accumulation in the grains. miR166 targets genes encoding the class-III homeodomain-Leu zipper (HD-Zip) family proteins in plants. In rice, HOMEODOMAIN CONTAINING PROTEIN4 (OsHB4) gene (Os03g43930), which encodes an HD-Zip protein, was up-regulated by Cd treatment but down-regulated by overexpression of miR166 in transgenic rice plants. Overexpression of OsHB4 increased Cd sensitivity and Cd accumulation in the leaves and grains of transgenic rice plants. By contrast, silencing OsHB4 by RNA interference enhanced Cd tolerance in transgenic rice plants. These results indicate a critical role for miR166 in Cd accumulation and tolerance through regulation of its target gene, OsHB4, in rice.


Consuming cassava as a staple food places children 2-5 years old at risk for inadequate protein intake, an observational study in Kenya and Nigeria.
Inadequate protein intake is known to be deleterious in animals. Using WHO consensus documents for human nutrient requirements, the protein:energy ratio (P:E) of an adequate diet is > 5%. Cassava has a very low protein content. This study tested the hypothesis that Nigerian and Kenyan children consuming cassava as their staple food are at greater risk for inadequate dietary protein intake than those children who consume less cassava. A 24 hour dietary recall was used to determine the food and nutrient intake of 656 Nigerian and 449 Kenyan children aged 2-5 years residing in areas where cassava is a staple food. Anthropometric measurements were conducted. Diets were scored for diversity using a 12 point score. Pearson's Correlation Coefficients were calculated to relate the fraction of dietary energy obtained from cassava with protein intake, P:E, and dietary diversity. The fraction of dietary energy obtained from cassava was > 25% in 35% of Nigerian children and 89% of Kenyan children. The mean dietary diversity score was 4.0 in Nigerian children and 4.5 in Kenyan children, although the mean number of different foods consumed on the survey day in Nigeria was greater than Kenya, 7.0 compared to 4.6. 13% of Nigerian and 53% of Kenyan children surveyed had inadequate protein intake. The fraction of dietary energy derived from cassava was negatively correlated with protein intake, P:E, and dietary diversity. Height-for age z score was directly associated with protein intake and negatively associated with cassava consumption using regression modeling that controlled for energy and zinc intake. Inadequate protein intake was found in the diets of Nigerian and Kenyan children consuming cassava as a staple food. Inadequate dietary protein intake is associated with stunting in this population. Interventions to increase protein intake in this vulnerable population should be the focus of future work.


Pathophysiology of blepharospasm and oromandibular dystonia.
The pathophysiology of reflexes mediated by the fifth and seventh cranial nerves has been studied in 16 patients with blepharospasm and oromandibular dystonia compared with normal age-matched subjects. The EMG activity of the dystonic spasms in the periocular and jaw muscles was similar to that described in other muscles in patients with generalized torsion dystonia. The latency of the R1 and R2 components of the blink reflex and of the corneal reflex was normal. However, the amplitude and the duration of the R1 and R2 and the duration of the corneal reflex were increased. In some patients the R1 component was also present on the side contralateral to the stimulus, while in normal subjects it was present only on the ipsilateral side. The excitability cycle of recovery of the R2 component of the blink reflex after a prior conditioning shock was enhanced in the patients. There were no EEG potentials preceding blepharospasms in the patients, although a Bereitschaftspotential was seen beginning some 500 ms prior to voluntary blinks in the same individuals. Exteroceptive suppression in the contracting masseter and orbicularis oculi muscles was absent in 40 to 50 per cent of the patients. The jaw jerk was present in all the patients with normal latency. These results indicate that the neuronal arcs of the facial reflexes in blepharospasm and oromandibular dystonia are normal. However, there is an abnormal excitatory drive, perhaps from the basal ganglia, to the facial motoneurons and the interneurons which mediate the facial reflexes in the brainstem.


Use of information and communication technology in the support of viral hepatitis patients in Japan.
In Ishikawa Prefecture, Japan, the regional core center for hepatitis care coordination (Kanazawa University Hospital, the only regional core center in the prefecture) conducts follow-ups with people who tested positive for viral hepatitis at screenings organized primarily by municipal governments. This program, called the Ishikawa Hepatitis Follow-up Program, has been operating since 2010. The regional core center has conventionally verified the status of program participants using a paper-based system of "examination letters" which specialized institutes mail to the regional core center when a program participant visits a physician there. However, only a low 40% to 50% of examination letters were returned to the regional core center. The program is now using the information and communication technology tool ID-Link to help the regional core center participate in care and provide support through mutual sharing of clinical information with specialized institutes. Currently, 1,632 of the 3,202 people who had tested positive for hepatitis testing since 2002 have consented to participate in the Ishikawa Hepatitis Follow-up Program, and as of the end of March 2021, information about 132 among those 1,632 people is being shared between specialized institutes and the regional core center using ID-link. Sharing of clinical information between the regional core center and specialized institutes enabled by ID-Link provided a more accurate picture of how many people who tested positive for viral hepatitis had visited a specialized institute compared with the previous paper-based system of examination letters, making follow-up more efficient.


Increased and mistimed sex hormone production in night shift workers.
Night shift work has been associated with an increased risk for breast and prostate cancer. The effect of circadian disruption on sex steroid production is a possible underlying mechanism, underinvestigated in humans. We have assessed daily rhythms of sex hormones and melatonin in night and day shift workers of both sexes. We recruited 75 night and 42 day workers, ages 22 to 64 years, in different working settings. Participants collected urine samples from all voids over 24 hours on a working day. Urinary concentrations of 16 sex steroid hormones and metabolites (estrogens, progestagens, and androgens) and 6-sulfatoxymelatonin were measured in all samples. Mean levels and peak time of total and individual metabolite production were compared between night and day workers. Night workers had higher levels of total progestagens [geometric mean ratio (GMR) 1.65; 95% confidence intervals (CI), 1.17-2.32] and androgens (GMR: 1.44; 95% CI, 1.03-2.00), compared with day workers, after adjusting for potential confounders. The increased sex hormone levels among night shift workers were not related to the observed suppression of 6-sulfatoxymelatonin. Peak time of androgens was significantly later among night workers, compared with day workers (testosterone: 12:14 hours; 10:06-14:48 vs. 08:35 hours; 06:52-10:46). We found increased levels of progestagens and androgens as well as delayed peak androgen production in night shift workers compared with day workers. The increase and mistiming of sex hormone production may explain part of the increased risk for hormone-related cancers observed in night shift workers.


Mutual regulation of decapentaplegic and hedgehog during the initiation of differentiation in the Drosophila retina.
Neuronal differentiation in the Drosophila retinal primordium, the eye imaginal disc, begins at the posterior tip of the disc and progresses anteriorly as a wave. The morphogenetic furrow (MF) marks the boundary between undifferentiated anterior cells and differentiating posterior cells. Anterior progression of differentiation is driven by Hedgehog, synthesized by cells located posterior to the MF. We report here that hedgehog (hh), which is expressed prior to the start of differentiation along the disc's posterior margin, also plays a crucial role in the initiation of differentiation. Using a temperature-sensitive allele we show that hh is normally required at the posterior margin to maintain the expression of decapentaplegic (dpp) and of the proneural gene atonal. In addition, we find that ectopic differentiation driven by ectopic dpp expression or loss of wingless function requires hh. Consistent with this is our observation that ectopic dpp induces the expression of hh along the anterior margin even in the absence of differentiation. Taken together, these data reveal a novel positive regulatory loop between dpp and hh that is essential for the initiation of differentiation in the eye disc.


Aligned multilayered electrospun scaffolds for rotator cuff tendon tissue engineering.
The rotator cuff consists of several tendons and muscles that provide stability and force transmission in the shoulder joint. Whereas most rotator cuff tears are amenable to suture repair, the overall success rate of repair is low, and massive tears are prone to re-tear. Extracellular matrix (ECM) patches are used to augment suture repair, but they have limitations. Tissue-engineered approaches provide a promising solution for massive rotator cuff tears. Previous studies have shown that, compared to nonaligned scaffolds, aligned electrospun polymer scaffolds exhibit greater anisotropy and exert a greater tenogenic effect. Nevertheless, achieving rapid cell infiltration through the full thickness of the scaffold is challenging, and scaling to a translationally relevant size may be difficult. Our goal was to evaluate whether a novel method of alignment, combining a multilayered electrospinning technique with a hybrid of several electrospinning alignment techniques, would permit cell infiltration and collagen deposition through the thickness of poly(ε-caprolactone) scaffolds following seeding with human adipose-derived stem cells. Furthermore, we evaluated whether multilayered aligned scaffolds enhanced collagen alignment, tendon-related gene expression, and mechanical properties compared to multilayered nonaligned scaffolds. Both aligned and nonaligned multilayered scaffolds demonstrated cell infiltration and ECM deposition through the full thickness of the scaffold after only 28days of culture. Aligned scaffolds displayed significantly increased expression of tenomodulin compared to nonaligned scaffolds and exhibited aligned collagen fibrils throughout the full thickness, the presence of which may account for the increased yield stress and Young's modulus of cell-seeded aligned scaffolds along the axis of fiber alignment. Rotator cuff tears are an important clinical problem in the shoulder, with over 300,000 surgical repairs performed annually. Re-tear rates may be high, and current methods used to augment surgical repair have limited evidence to support their clinical use due to inadequate initial mechanical properties and slow cellular infiltration. Tissue engineering approaches such as electrospinning have shown similar challenges in previous studies. In this study, a novel technique to align electrospun fibers while using a multilayered approach demonstrated increased mechanical properties and development of aligned collagen through the full thickness of the scaffolds compared to nonaligned multilayered scaffolds, and both types of scaffolds demonstrated rapid cell infiltration through the full thickness of the scaffold.


Large Stokes-shifted NIR-emission from nanospace-induced aggregation of perylenemonoimide-doped polymer nanoparticles: imaging of folate receptor expression.
The development of a water-soluble, perylenemonoimide (PMI) dye-doped polymer nanoparticle (PNP) with NIR emission for live-cell imaging is demonstrated. The large Stokes-shifted NIR emission is due to confined nanospace-induced aggregation offered by the polymer matrix. Later, folic acid functionalised PNP (PNP-FA) is successfully employed to differentiate folate receptor positive and negative cancer cells.


Thin adsorbed films of a strong cationic polyelectrolyte on silica substrates.
The adsorption of poly(diallyldimethyl ammonium chloride) (DADMAC) on planar silica substrates was examined as a function of ionic strength and pH. The study was carried out with reflectometry in an impinging-jet cell and complemented by atomic force microscopy (AFM) and ellipsometry investigations. The adsorption process is initially transport limited, whereby the adsorption rate increases somewhat with increasing ionic strength. This effect is caused by a simultaneous decrease of the hydrodynamic radius of the polymer. After a transient period, the adsorption process saturates and leads to an adsorption plateau. The plateau value increases strongly with increasing ionic strength. This increase can be explained by progressive screening of the electrostatic repulsion between the adsorbing polyelectrolyte chains, as can be rationalized by a random sequential adsorption (RSA) model. The adsorbed amount further increases with increasing pH, and this effect is probably caused by the corresponding increase of the surface charge of the silica substrate.


Urban environment adherence to the Mediterranean diet and prevalence of asthma symptoms among 10- to 12-year-old children: The Physical Activity, Nutrition, and Allergies in Children Examined in Athens study.
Epidemiological studies have revealed several associations between asthma symptoms and environmental and dietary factors, but the potential environment- diet interactions on asthma incidence have rarely been investigated. The aim of this work was to evaluate the interrelationships between urban/rural environment, adherence to a healthy dietary pattern, the Mediterranean diet, and childhood asthma. A cross-sectional survey was performed and 1125 (529 boys), 10- to 12-year-old children were selected from 18 schools located in urban Athens area (n = 700) and from 10 schools located in rural areas of Ilia and Viotia (n = 425), Greece. Children and their parents completed standardized questionnaires, which evaluated, among others, environmental factors and dietary habits. Asthma was defined according to Phase II of the International Study on Allergies and Asthma in Childhood criteria. Adherence to the Mediterranean diet was assessed using the Mediterranean and Diet Quality Index for children and adolescents (KIDMED) score. Living in urban areas was associated with higher odds of ever had asthma symptoms by 1.78 times (95% confidence interval [CI], 1.25-2.54) when compared with rural areas. In contrast, 1-unit increase in the KIDMED score was associated with 16% lower likelihood of having asthma symptoms (95% CI, 0.77-0.91), after adjusting for various confounders. When stratifying the analysis by area of living it was observed that adherence to the Mediterranean diet was associated with lower likelihood of asthma in both urban and rural areas (urban, odds ratio [OR] = 0.81, 95% CI, 0.73-0.91; rural, OR = 0.87, 95% CI, 0.75-1.00). Urban environment seems to increase the likelihood of childhood asthma, whereas adherence to the healthy Mediterranean dietary pattern could mediate the aforementioned association and confers significant protection.


The long-term restoration of ecosystem complexity.
Multiple large-scale restoration strategies are emerging globally to counteract ecosystem degradation and biodiversity loss. However, restoration often remains insufficient to offset that loss. To address this challenge, we propose to focus restoration science on the long-term (centuries to millennia) re-assembly of degraded ecosystem complexity integrating interaction network and evolutionary potential approaches. This approach provides insights into eco-evolutionary feedbacks determining the structure, functioning and stability of recovering ecosystems. Eco-evolutionary feedbacks may help to understand changes in the adaptive potential after disturbance of metacommunity hub species with core structural and functional roles for their use in restoration. Those changes can be studied combining a restoration genomics approach based on whole-genome sequencing with replicated space-for-time substitutions linking changes in genetic variation to functions or traits relevant to the establishment of evolutionarily resilient communities. This approach may set the knowledge basis for future tools to accelerate the restoration of ecosystems able to adapt to ongoing global changes.


Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial.
Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity. FPSK_Mac [13]04. The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults. Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day. In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found. Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.


Occurrence of cytosolic protein and phosphoprotein changes in human colon tumor cells with the development of resistance to mitomycin C.
The cytosolic proteins and phosphoproteins of a mitomycin C-sensitive cell line were examined as progressively greater doses of mitomycin C were administered over a period of 44 weeks. Resistance of the human colon carcinoma cell line increased from a 50% inhibitory concentration of 1 to 6 microM over this time period. Changes in cytosolic protein patterns included increases in the amounts of three proteins with molecular weight X 10(-3)/apparent isoelectric point (Mr/pl) values of 56/6.2, 37/7.3, and 27/6.1. Analysis of in vitro 32P-labeled phosphoprotein patterns revealed reductions in the amounts of four proteins with Mr/pl values of 42/6.3, 40/6.7, 31/6.3, and 25/6.1. One increase was detected in a phosphoprotein with a Mr/pl value of 33/6.1. These changes in cytosolic components paralleled the development of resistance to mitomycin C and may reflect changes in the clonal composition of the cell line as it becomes progressively more resistant to mitomycin C or changes in critical proteins or enzymes involved in the activation or biotransformation of the drug.


A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy.
Specific immunotherapy is a common treatment of allergic diseases and could potentially be applied to other immunologic disorders. Despite its use in clinical practice, more defined and safer allergy vaccine preparations are required. Differences between epitopes of IgE that recognize the 3-dimensional structure of allergens and T cells that recognize linear amino acid sequences provide a suitable tool for novel vaccine development for specific immunotherapy. The aim of the study was to delete B-cell epitopes and prevent IgE crosslinking, but to preserve T-cell epitopes by fusion of 2 major allergens of bee venom because of a change in the conformation. By genetic engineering, we produced a fusion protein composed of the 2 major bee venom allergens: phospholipase A 2 (Api m 1) and hyaluronidase (Api m 2). The Api m [1/2] fusion protein induced T-cell proliferation and both T H 1-type and T H 2-type cytokine responses. In contrast, IgE reactivity was abolished, and profoundly reduced basophil degranulation and type 1 skin test reactivity was observed. Pretreatment of mice with Api m [1/2] fusion protein significantly suppressed the development of specific IgE as well as other antibody isotypes after immunization with the native allergen. The novel fusion protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE FcepsilonRI crosslinking and protects from IgE development.


Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern.
Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.


Micro-array versus nano-array platforms: a comparative study for ODN detection based on SPR enhanced ellipsometry.
The rapid and sensitive detection of DNA has recently attracted worldwide attention for a variety of disease diagnoses and detection of harmful bacteria in food and drink. In this paper, we carried out a comparative study based on surface plasmon resonance enhanced ellipsometry (SPREE) for the detection of oligodeoxynucleotides (ODNs) using micro- and nano-array platforms. The micro-arrayed surfaces were fabricated by a photolithography approach using different types of mask having varying size and shape. Well-ordered arrays of high aspect ratio polymeric nanotubes were also obtained using high molecular weight polystyrene (PS) and anodic aluminum oxide (AAO) membranes having 200 nm pore diameters. The SPREE sensors were then prepared by direct coupling of thiolated probe-ODNs, which contain suitable spacer arms, on gold-coated micro- and nano-arrayed surfaces. We experimentally demonstrated that, for the first time, gold-coated free standing polymeric nano-arrayed platforms can easily be produced and lead to a significant sensor sensitivity gain compared to that of the conventional SPREE surfaces of about four times. We believe that such an enhancement in sensor response could be useful for next generation sensor systems.


Fifteen-minute consultation: stabilisation of the high-risk newborn infant beside the mother.
Paediatric and adult resuscitation is often performed with family present. Current guidelines recommend deferred umbilical cord clamping as part of immediate neonatal care, requiring neonatal assessment next to the mother. This paper describes strategies for providing care beside the mother using both standard resuscitation equipment and a trolley designed for this purpose.


Polyamine homoeostasis.
The polyamines are essential for a variety of functions in the mammalian cell. Although their specific effects have not been fully elucidated, it is clear that the cellular polyamines have to be kept within certain levels for normal cell function. Polyamine homoeostasis in mammalian cells is achieved by a complex network of regulatory mechanisms affecting synthesis and degradation, as well as membrane transport of polyamines. The two key enzymes in the polyamine biosynthetic pathway, ODC (ornithine decarboxylase) and AdoMetDC (S-adenosylmethionine decarboxylase), are strongly regulated by feedback mechanisms at several levels, including transcriptional, translational and post-translational. Some of these mechanisms have been shown to be truly unique and include upstream reading frames and ribosomal frameshifting, as well as ubiquitin-independent proteasomal degradation. SSAT (spermidine/spermine N1-acetyltransferase), which is a crucial enzyme for degradation and efflux of polyamines, is also highly regulated by polyamines. A cellular excess of polyamines rapidly induces SSAT, resulting in increased degradation/efflux of the polyamines. The polyamines appear to induce both transcription and translation of the SSAT mRNA. However, the major part of the polyamine-induced increase in SSAT is caused by a marked stabilization of the enzyme against degradation by the 26S proteasome. In addition, active transport of extracellular polyamines into the cell contributes to cellular polyamine homoeostasis. Depletion of cellular polyamines rapidly induces an increased uptake of exogenous polyamines, whereas an excess of polyamines down-regulates the polyamine transporter(s). However, the protein(s) involved in polyamine transport and the exact mechanisms by which the polyamines regulate the transporter(s) are not yet known.


[Alloplasty of cranial defects in children].
In 52 patients whose ages ranged from 2 to 15 years skull defects 6 to 8 cm2 in size were closed with cold-stored grafts of the skull bone of an adult donor. Resorption of the graft in the late period occurred in one patient who underwent a second alloplasty with good results. Alloplasty of defects in the skull of children may be accomplished with a graft taken from an adult donor. In children, allotransplantation has advantages over explantation because the skull defect is repaired with bone of full biological value and an allograft may be used for closure of a defect of any size and in a child of any age, a young child among others.


Gut-derived endotoxin elicits hepatotrophic factor secretion for liver regeneration.
The influence of exogenous endotoxin pretreatment on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats with midline laparotomy and liver manipulation as the sham control. Animals were pretreated with endotoxin at a dose of 33 micrograms/100 g sc or iv 24 h before surgery and then fasted. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA, and plasma levels of hepatotrophic factors were measured by radioimmunoassay or radioreceptor assay. Systemic endotoxemia occurred after exogenous endotoxin administration as well as after partial hepatectomy due to absorption of exogenous endotoxin from the gut into the portal circulation as determined by quantitative chromogenic lysate assay of perchloric acid-extracted plasma samples. Alterations in putative hepatotrophic factors, including insulin, glucagon, epidermal growth factor, vasopressin, and triiodothyronine, were remarkable similar in response to endotoxemia by exogenous endotoxin administration and by endogenous endotoxin absorption from the gut after partial hepatectomy. Our hypothesis purports that gut-derived systemic endotoxemia elicits hepatotrophic factor secretion for liver regeneration after partial hepatectomy and that endotoxin pretreatment expedites the hepatotrophic factor response, thus accelerating DNA synthesis in the proliferating liver after 67% resection.