Sequence conservation of homeologous bacterial artificial chromosomes and transcription of homeologous genes in soybean (Glycine max L. Merr.).
The paleopolyploid soybean genome was investigated by sequencing homeologous BAC clones anchored by duplicate N-hydroxycinnamoyl/benzoyltransferase (HCBT) genes. The homeologous BACs were genetically mapped to linkage groups C1 and C2. Annotation of the 173,747- and 98,760-bp BACs showed that gene conservation in both order and orientation is high between homeologous regions with only a single gene insertion/deletion and local tandem duplications differing between the regions. The nucleotide sequence conservation extends into intergenic regions as well, probably due to conserved regulatory sequences. Most of the homeologs appear to have a role in either transcription/DNA binding or cellular signaling, suggesting a potential preference for retention of duplicate genes with these functions. Reverse transcriptase-PCR analysis of homeologs showed that in the tissues sampled, most homeologs have not diverged greatly in their transcription profiles. However, four cases of changes in transcription were identified, primarily in the HCBT gene cluster. Because a mapped locus corresponds to a soybean cyst nematode (SCN) QTL, the potential role of HCBT genes in response to SCN is discussed. These results are the first sequenced-based analysis of homeologous BACs in soybean, a diploidized paleopolyploid.


Direct electrochemical synthesis of reduced graphene oxide (rGO)/copper composite films and their electrical/electroactive properties.
Electrical contact materials with excellent performances are crucial for the development and safe use of electrical contacts in different applications. In our work, reduced graphene oxide (rGO)/copper (Cu) composite films, as potential electrical contact materials, have been synthesized on copper foil with one-step electrochemical reduction deposition method. Cyclic voltammetry (CV) was used to define the deposition conditions, and confocal Raman microscopy (CRM), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) were used to characterize the chemical compositions, molecular and micro- and nano-structures of the composite films. Atomic force microscopy/scanning Kelvin probe force microscopy (AFM/SKPFM), conductive AFM (C-AFM) as well as impedance analysis were employed to evaluate the electroactive/electrical properties of the prepared composite films, respectively. The CRM and XPS results suggest that the rGO/Cu composite films can be synthesized through one-step electrochemical codeposition using suitable precursor solutions. Within a short deposition period, the growth of discrete nanograins in the composite film predominates, whereas pine-tree-leaf nanostructures are formed in the composite film when the deposition period is long, due to the chelating role of GO or rGO to regulate the growth rate of metallic copper nanograins. The electrical resistivity of the composite films is lower than the polished Cu foil and the electrodeposited Cu film, probably due to the higher conductivity (enhanced transfer of charge carriers) of the rGO incorporated in the composite films. The Volta potential variation in the rGO/Cu composite film is quite different from that in the electrodeposited Cu film. The electroactivity of the rGO/Cu composite films is higher than the electrodeposited Cu film, but lower than polished Cu foil, and the underlying mechanisms have been discussed.


Motivational factors in the careers of health care educators.
Little formal research attempts to relate personnel and job-role characteristics with motivations and satisfactions in the health care education field. This paper reports findings, based on a national multidisciplinary sample of health care educators (N = 229), that argue against cynical appraisals of motivations, job satisfactions, and job-role compatibility. A number of empirical hypotheses are derived that may serve as starting points for further inquiry. Instruments and methods useful for future research are described.


Superficial thrombophlebitis of lower limbs.
In the absence of malignancy, thrombophlebitis of the lower limb is invariably associated with pre-existent varicose veins. Not until pulmonary embolism was reported to occur in superficial phlebitis did the clinician introduce anticoagulants and/or surgery in the management of this condition. In an effort to reach an effective approach to this problem, 1,000 consecutive cases of varicose veins of the lower limbs were reviewed. Of these patients, 779 were admitted for elective vein ligation and stripping and 221 presented with thrombophlebitis. The latter group was subdivided into four categories according to the mode of management: (1) local heat and anti-inflammatory agents, 60 cases; (2) anticoagulants, 22 cases; (3) phlebotomy, high saphenous ligation and anticoagulation, 4 cases; and (4) ligation and stripping, 135 cases. In category 4 the saphenous is removed in a routine fashion together wih all its tributaries. All perforators are exposed, evacuated of thrombus when present, and ligated subfascially. Thrombi were encountered in one or more perforating veins in 10 patients, but no pulmonary embolism was observed in this group of patients. All instances of documented pulmonary embolism (10 cases) occurred in category 1 with one fatality. The incidence of pulmonary embolism in the elective group of ligation and stripping (without phlebitis) was 0.5%. The data indicate that the surgical approach is safe and preferable to the other modalities for several reasons: (1) It eliminates the varicosities and the phlebitic process simultaneously, (2) a single hospitalization is necessary (cost effectiveness), and (3) no anticoagulants are needed. If, for any reason, surgery cannot be undertaken, then anticoagulants should be employed in an effort to avoid thromboembolism.


Physiological Response to Cycling With Variable Versus Constant Power Output.
Introduction: Variable power output (VP) is one of the main characteristics of a road cycling mass-start. Tolerating VP during outdoor road cycling highly influences performance. There is a lack of continuous and comprehensive measurements during this power condition. Accordingly, the aim of the present study was to investigate physiological response to VP vs. constant power output (CP) as well as the perceived exertion of these two power conditions, and to investigate if variations in power output which span above lactate threshold (LT), differ from variations below LT. Methods: 15 elite competitive cyclists completed three test days, including 1 day of baseline testing and 2 days of main testing, consisting of four bouts of 28 min at two different intensities, "low" at 70% of LT and "high" at 95% of LT, with VP and CP. VP was performed with a 15% fluctuation of the average power output every second minute. Maximal oxygen uptake (VO2), respiratory exchange ratio (RER), heart rate (HR), blood lactate (LA), rating of perceived exertion (RPE), cadence (RPM) and power output (W) were measured. Results: At both low and high intensity, the VP condition induced a significantly higher VO2, HR and LA than the CP condition. Whole-bout RPE was similar between power conditions at high intensity. Additionally, at the high intensity, cycling with VP led to a greater increase in LA and lesser increase in RPE compared to cycling with CP. Discussion: The results of this study show that, despite considerable differences in the demand during the VP and CP bouts, there are minor differences in the perceptual and physiological response directly following these two power conditions in a cohort of elite competitive cyclists. A practical implication of these findings is that training with VP seems to be a viable alternative to training with CP, at least at high intensity.


Amniocytes can serve a dual function as a source of iPS cells and feeder layers.
Clinical barriers to stem-cell therapy include the need for efficient derivation of histocompatible stem cells and the zoonotic risk inherent to human stem-cell xenoculture on mouse feeder cells. We describe a system for efficiently deriving induced pluripotent stem (iPS) cells from human and mouse amniocytes, and for maintaining the pluripotency of these iPS cells on mitotically inactivated feeder layers prepared from the same amniocytes. Both cellular components of this system are thus autologous to a single donor. Moreover, the use of human feeder cells reduces the risk of zoonosis. Generation of iPS cells using retroviral vectors from short- or long-term cultured human and mouse amniocytes using four factors, or two factors in mouse, occurs in 5-7 days with 0.5% efficiency. This efficiency is greater than that reported for mouse and human fibroblasts using similar viral infection approaches, and does not appear to result from selective reprogramming of Oct4(+) or c-Kit(+) amniocyte subpopulations. Derivation of amniocyte-derived iPS (AdiPS) cell colonies, which express pluripotency markers and exhibit appropriate microarray expression and DNA methylation properties, was facilitated by live immunostaining. AdiPS cells also generate embryoid bodies in vitro and teratomas in vivo. Furthermore, mouse and human amniocytes can serve as feeder layers for iPS cells and for mouse and human embryonic stem (ES) cells. Thus, human amniocytes provide an efficient source of autologous iPS cells and, as feeder cells, can also maintain iPS and ES cell pluripotency without the safety concerns associated with xenoculture.


Full-Spectrum Responsive Naphthalimide/Perylene Diimide with a Giant Internal Electric Field for Photocatalytic Overall Water Splitting.
The co-assembly naphthalimide/perylene diimide (NDINH/PDINH) supramolecular photocatalysts were successfully synthesized via a rapid solution dispersion method. A giant internal electric field (IEF) in co-assembly structure was built by the larger local dipole. NDINH coated on PDINH could reduce the reflected electric field over PDINH to improve its responsive activity to ultraviolet light. Resultantly, an efficient full-spectrum photocatalytic overall water splitting activity with H2 and O2 evolution rate of 317.2 and 154.8 μmol g-1 h-1 for NDINH/PDINH together with optimized O2 evolution rate with 2.61 mmol g-1 h-1 using AgNO3 as a sacrificial reagent were achieved. Meanwhile, its solar-to-hydrogen efficiency was enhanced to 0.13%. The enhanced photocatalytic activity was primarily attributed to the IEF between NDINH and PDINH, significantly accelerating transfer and separation of photogenerated carriers. Additionally, a direct Z-scheme pathway of carriers contributed to a high redox potential. The strategy provided a new perspective for the design of supramolecular photocatalysts.


Inkjet-Printed High-Q Nanocrystalline Diamond Resonators.
Diamond is a highly desirable material for state-of-the-art micro-electromechanical (MEMS) devices, radio-frequency filters and mass sensors, due to its extreme properties and robustness. However, the fabrication/integration of diamond structures into Si-based components remain costly and complex. In this work, a lithography-free, low-cost method is introduced to fabricate diamond-based micro-resonators: a modified home/office desktop inkjet printer is used to locally deposit nanodiamond ink as ∅50-60 µm spots, which are grown into ≈1 µm thick nanocrystalline diamond film disks by chemical vapor deposition, and suspended by reactive ion etching. The frequency response of the fabricated structures is analyzed by laser interferometry, showing resonance frequencies in the range of ≈9-30 MHz, with Q-factors exceeding 104 , and (f0 × Q) figure of merit up to ≈2.5 × 1011 Hz in vacuum. Analysis in controlled atmospheres shows a clear dependence of the Q-factors on gas pressure up until 1 atm, with Q ∝ 1/P. When applied as mass sensors, the inkjet-printed diamond resonators yield mass responsivities up to 981 Hz fg-1 after Au deposition, and ultrahigh mass resolution up to 278 ± 48 zg, thus outperforming many similar devices produced by traditional top-down, lithography-based techniques. In summary, this work demonstrates the fabrication of functional high-performance diamond-based micro-sensors by direct inkjet printing.


Hopping or Tunneling? Tailoring the Electron Transport Mechanisms through Hydrogen Bonding Geometry in the Boron-Doped Diamond Molecular Junctions.
Mechanisms of charge transport in molecular junctions involving hydrogen bonds are complex and remain mostly unclear. This study is focused on the elucidation of the electron transfer in a molecular device consisting of two boron-doped diamond interfaces bound with an aromatic linker and a hydrogen bonding surrogating molecule. The projected local density of states (PLODS) analysis coupled with transmission spectra and current-voltage (I-V) simulations show that hydrogen bonding through electron-donating hydroxyl groups in the aromatic linker facilitates electron transfer, while the electron-withdrawing carboxyl group inhibits electron transfer across the junction. Moreover, slight variations in the geometry of hydrogen bonding lead to significant changes in the alignment of the energy levels and positions of the transmission modes. As a result, we observe the switching of the electron transport mechanism from tunneling to hopping accompanied by a change in the shape of the I-V curves and current magnitudes. These results give important information on the tailoring of the electronic properties of molecular junctions.


Selective nonoperative management of low-grade blunt pancreatic injury: are we there yet?
Nonoperative management (NOM) of low-grade blunt pancreatic injuries (LGBPI) diagnosed by computed tomographic (CT) abnormalities of the pancreas in the adult hemodynamically stable (HDS) patient has not been previously defined. We report our experience of patients with LGBPI at a single Level I Trauma Center. Adult HDS patients during a 5-year period with blunt pancreatic injuries with an abbreviated injury score of </=2 were identified through the hospital trauma registry. Management, complications, and outcome were reviewed. Patients who underwent initial emergency laparotomy, died on hospital day one, or had a Glasgow Coma Scale of three were excluded. Failure of NOM was defined by need for subsequent exploratory laparotomy or development of a pancreatic complication. Data are reported as mean +/- SEM. A total of 120 patients were identified as having blunt pancreatic injury of which 35, with pancreatic abbreviated injury score of </=2, were blunt HDS patients with abdominal CT evidence of pancreatic injury. Amylase elevation was noted in 23 of 35 (68.5%) patients with positive CT scan findings of LGBPI. Study population consisted of 20 male patients and 15 female patients, age 32 +/- 13.22, injury severity score 21 +/- 10.08, systolic pressure 123 +/- 27.06 with mean base deficit -3.78 +/- 2. Of these 12 (34.28%) patients had an associated intra-abdominal solid organ injury. Five patients failed NOM (F-NOM), one had missed small bowel injury, three had pancreatic abscess, of which one developed a pancreatic fistula which resolved with medical management, and one F-NOM for blunt liver injury with missed bowel injury. No death in the F-NOM group and two deaths (5.71%) in the successful NOM (S-NOM) group unrelated to the pancreas. The average length of stay was 11 days +/- 9.71 days. NOM of LGBPI diagnosed by CT was successful in the majority of HDS patients, with low morbidity and mortality. We propose a management algorithm for NOM of LGBPI in which the role for early ductal injury detection with endoscopic retrograde cholangio-pancreatogram or magnetic retrograde cholangio-pancreatogram should be incorporated to better analyze the most appropriate treatment.


MBC and ECBL libraries: outstanding tools for drug discovery.
Chemical libraries have become of utmost importance to boost drug discovery processes. It is widely accepted that the quality of a chemical library depends, among others, on its availability and chemical diversity which help in rising the chances of finding good hits. In this regard, our group has developed a source for useful chemicals named Medicinal and Biological Chemistry (MBC) library. It originates from more than 30 years of experience in drug design and discovery of our research group and has successfully provided effective hits for neurological, neurodegenerative and infectious diseases. Moreover, in the last years, the European research infrastructure for chemical biology EU-OPENSCREEN has generated the European Chemical Biology library (ECBL) to be used as a source of hits for drug discovery. Here we present and discuss the updated version of the MBC library (MBC v.2022), enriched with new scaffolds and containing more than 2,500 compounds together with ECBL that collects about 100,000 small molecules. To properly address the improved potentialities of the new version of our MBC library in drug discovery, up to 44 among physicochemical and pharmaceutical properties have been calculated and compared with those of other well-known publicly available libraries. For comparison, we have used ZINC20, DrugBank, ChEMBL library, ECBL and NuBBE along with an approved drug library. Final results allowed to confirm the competitive chemical space covered by MBC v.2022 and ECBL together with suitable drug-like properties. In all, we can affirm that these two libraries represent an interesting source of new hits for drug discovery.


Economic risk criteria for dams considering the relative level of economy and industrial economic contribution.
When a dam breaks, huge floods will be generated that may inundate urban areas, enterprises, farmlands, and infrastructure and cause giant economic losses. Economic risk criteria are a kind of basis for determining dam risk levels and to decide whether risk control measures should be taken or not. However, compared to loss-of-life risk criteria, much fewer economic risk criteria for dams have been proposed and implemented for two main reasons: (a) The ability of most areas to endure economic losses caused by dam breach changes over time because of the constant development of their economic levels; and (b) Economic development levels in an area are distinct from the levels in other areas, resulting in significant differences in the ability of different areas to endure economic losses caused by a dam breach. Therefore, an equivalent economic scale (EES) that indicates the relative economic level of an area to the whole country in a given period of time is a preferred measure. It was shown in this paper that EES has much more stable values than do ordinary economic measures; therefore, it was taken as the basic index for establishing economic risk criteria. Furthermore, due to the distinct economic loss rates of different industries, the index of industrial economic contribution (IEC) was introduced to determine the correction coefficient to modify the ESS to reflect the potential economic loss of the area to be evaluated. This is the first research that pays careful attention to the change of ability to endure economic losses, in which the established economic risk criteria are applicable over a relatively long time and for different areas based on the consideration of the relative level of the economy and the industrial economic contribution.


Immunohistochemistry and mass spectrometry for highly multiplexed cellular molecular imaging.
The role of immunohistochemistry (IHC) in the management of cancer has expanded to provide improved diagnostic classification, as well as guidance on disease prognosis, therapy, and relapse. These new tasks require evaluation of an increasing number of protein targets; however, conventional multiplexing, usually achieved using serial tissue sections stained for a single analyte per slide, can exhaust small biopsy specimens, complicate slide-to-slide protein expression correlation, and leave insufficient material for additional molecular assays. A new approach, mass spectrometry immunohistochemistry (MSIHC), compatible with high levels of target multiplexing and suitable for use on formalin-fixed, paraffin-embedded samples can circumvent many of these issues. The strategy employs antibodies that are labeled with elemental mass tags, such as isotopically pure lanthanides not typically found in biological specimens, rather than with typical fluorophores or chromogens. The metal-labeled antibodies are then detected in tissue using lasers or ion beams to liberate the tags for subsequent mass spectrometry detection. Within a given multiplexed IHC panel, the metal labels are selected so that their respective masses do not overlap. More than 30 antibodies have been imaged simultaneously, and up to 100 antibodies could potentially be detected at once if the full available mass spectrum is deployed. MSIHC has a number of advantages over conventional IHC techniques. Background due to autofluorescence is absent and the dynamic range is 10(5), exceeding immunofluorescence and chromogenic IHC by 100-fold and 1000-fold, respectively. Detection of labeled primary antibodies improves assay linearity over both chromogenic and fluorescent IHC. Multiplexed mass-tagged antibodies incubated simultaneously with tissue do not appear to cross-interfere, and because the mass tags do not degrade, samples are stable indefinitely. The imaging resolution of multiplexed ion-beam imaging can be better than light microscopy. With appropriate instrumentation, MSIHC has the potential to transform research and clinical pathology practice.


Do quaternary ammonium monomers induce drug resistance in cariogenic, endodontic and periodontal bacterial species?
Antibacterial monomers were developed to combat oral biofilm acids and caries; however, little is known on whether quaternary ammonium monomers (QAMs) would induce drug resistance in oral bacteria. The objective of this study was to investigate the effects of new antimicrobial monomers dimethylaminohexadecyl methacrylate (DMAHDM) and dimethylaminododecyl methacrylate (DMADDM) on the induction of drug resistance in eight species of cariogenic, endodontic and periodontal bacteria for the first time. Streptococcus mutans (S. mutans), Streptococcus sanguis, Streptococcus gordonii, Enterococcus faecalis (E. faecalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), Porphyromonas gingivalis (P. gingivalis), and Prevotella intermedia (P. intermedia) were tested. Minimum inhibitory concentration (MIC) was assessed using chlorhexidine (CHX) as control. Minimal bactericidal concentration (MBC), bacterial growth and membrane permeability properties were also investigated. CHX induced drug resistance in four species. DMAHDM did not induce any resistance. DMADDM induced drug resistance in only one benign species S. gordonii. The DMADDM-resistant and CHX-resistant S. gordonii had the same MIC and MBC values as S. gordonii parental strain against DMAHDM (p>0.1), hence DMAHDM effectively inhibited the resistant strains. The resistant strains had slower growth metabolism than parental strain. DMAHDM induced no drug resistance, and DMADDM had much less drug resistance than the commonly-used CHX in the eight common oral species. With its potent antimicrobial functions shown previously, the new DMAHDM is promising for applications in restorative, preventive, periodontal and endodontic treatments to combat cariogenic and pathological bacteria with no drug resistance in all tested species.


Culture-Based Quantification with Molecular Characterization of Non-O157 and O157 Enterohemorrhagic Escherichia coli Isolates from Rectoanal Mucosal Swabs of Feedlot Cattle.
Enterohemorrhagic Escherichia coli (EHEC) strains are foodborne pathogens carried in the intestinal tracts of ruminants and shed in the feces. High concentrations (≥104 colony-forming units [CFU]/g) of EHEC in cattle feces are associated with contamination of hides, and subsequently, carcasses and beef. Several studies using agar media have quantified O157 but few have quantified non-O157 EHEC in samples from cattle. Thus, the objective of this study was to determine the concentration of O157 and non-O157 EHEC in cattle, and to characterize the associated EHEC isolates for their virulence potential. Two hundred feedlot steers were sampled by rectoanal mucosal swab (RAMS) every 35 days over four sampling periods, and a spiral plating method using modified Possé differential agar was used to quantify EHEC organisms in these samples. Bacterial colonies from agar plates were tested by multiplex PCR for Shiga toxin and intimin genes (stx and eae, respectively), and confirmed EHEC isolates (i.e., positive for both stx and eae) were serotyped and characterized for virulence genes using a microarray. Organisms detected in this study included O26, O101, O103, O109, O121, O145, O157, and O177 EHEC, with all except O121 quantifiable and measuring within a range from 9.0 × 102 to 3.0 × 105 CFU/g of RAMS sample. Organisms of the same EHEC serogroup were not detected in quantifiable concentrations from a single animal more than once. EHEC organisms most commonly detected at quantifiable levels were O26, O157, and O177. Interestingly, O26 EHEC isolates tested negative for stx1 but positive for stx2a. High concentrations of EHEC were detected in 11 (5.5%) of the steers at least once over the sampling period. These results indicate that in addition to O157, non-O157 EHEC are transiently present in high concentrations in the rectoanal mucosal region of cattle.


The dynamics of honesty: modelling the growth of costly, sexually-selected ornaments.
The handicap principle suggests that individuals of superior quality can more easily bear the cost of developing extravagant ornaments. Consequently, ornament size should provide reliable information about quality or condition. Previous models have largely ignored the process of ornament growth, focusing only on final ornament size. We model ornament growth schedules for individuals of different qualities, where higher quality individuals experience lower costs of carrying energy reserves of a given size, but where all individuals pay a net cost of carrying ornaments of a given size. If the costs of ornament production ensure that final ornament size reliably signals quality, the information conveyed by the signal can change dramatically during growth. Higher quality individuals should delay growth until closer to breeding. Taking a snapshot of partially developed ornaments prior to breeding would show them to be larger in poorer quality individuals. The claim that costly ornaments honestly signal quality thus needs to be understood in a dynamic context, and may only hold during some phases of growth.


Propolis extract promotes translocation of glucose transporter 4 and glucose uptake through both PI3K- and AMPK-dependent pathways in skeletal muscle.
It is well known that propolis has the ability to prevent hyperglycemia. However, the underlying mechanism is not yet fully understood. We therefore investigated whether a Brazilian propolis ethanol extract affects glucose uptake and translocation of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle cells. In L6 myotubes, the extract at 1 μg/mL significantly promoted GLUT4 translocation and glucose uptake activity. Regarding the mechanism of GLUT4 translocation, propolis extract induced both PI3K and AMPK phosphorylation in a dose-dependent manner in L6 myotubes. However, we could not define which pathway was preferentially associated with GLUT4 translocation, because both PI3K and AMPK inhibitors revealed off-target effects to each other. The main polyphenols found in the propolis extract, artepillin C, coumaric acid, and kaempferide, promoted GLUT4 translocation in L6 myotubes. Additionally, these compounds activated both PI3K- and AMPK-dependent dual-signaling pathways. However, only kaempferide increased glucose uptake activity under our experimental conditions. Single oral administrations of propolis extract, at 250 mg/kg body weight, lowered postprandial blood glucose levels in ICR mice. The extract promoted GLUT4 translocation in skeletal muscle of rats and mice, but did not inhibit α-glucosidase activity in the small intestine under our experimental conditions. It was confirmed that propolis extract promoted phosphorylation of both PI3K and AMPK in rat skeletal muscle. In conclusion, we show that Brazilian propolis has the potential to prevent hyperglycemia through the promotion of GLUT4 translocation in skeletal muscle and that kaempferide is one of the candidates for active compound in propolis.


Reduced cranial parasympathetic tone during the remission phase of cluster headache.
Cluster headache (CH) attacks are accompanied by cranial autonomic symptoms indicative of parasympathetic hyperactivity and sympathetic dysfunction ipsilateral to the pain. We aimed to assess cranial autonomic function in CH patients during the remission phase of cluster headache. During a remission phase, 38 episodic CH patients underwent the following: dynamic pupillometry, measurement of the superficial temporal artery diameter by ultrasound, and measurement of the retinal vessel diameters from digital retinal photographs. Pupillometry was also performed on 30 age- and sex-matched healthy controls. Thirty patients were included (27 men, three women, mean age 50.2 years ± 12.6). Seven patients reported occasional side shift of their headache, but with a clear predominating side. Significantly reduced average pupillary constriction velocity and retinal venular diameter on the CH pain side were found. There was no asymmetry of the superficial temporal artery diameters. Compared to healthy controls, cluster patients displayed bilaterally reduced pupillary average and maximum constriction velocities, reduced constriction in percentage and increased latency of the light reflex. The present findings indicate a bilaterally reduced cranial parasympathetic tone in CH patients in remission phase, with significant lateralization to the CH pain side. This implies a central origin, and a central pathophysiological model of CH is discussed.


United States Special Operations Command fatality study of subcommands, units, and trends.
Death from injury occurs predominantly in prehospital settings. Injury prevention and prehospital care of military forces is the responsibility of combatant commanders. Medical examiner and trauma systems should routinely study fatalities and inform commanders of mortality trends. Data reported on US Special Operations Command (USSOCOM) fatalities who died while performing duties from September 11, 2001, to September 10, 2018, were reevaluated to compare subcommands, units, and trends. Injury was assessed by mechanism, severity, operational posture, and survivability. Death was assessed by manner, cause, classification, mechanism, and preventability. Of 614 USSOCOM fatalities (median age, 30 years; male, 98.5%), 67.6% occurred in the Army command, of which 49.2% occurred in the Special Forces command. Battle injury accounted for 60.1% of USSOCOM fatalities. Most battle-injured fatalities in each subcommand had nonsurvivable injuries and nonpreventable deaths. For each subcommand except Marine Corps, fatalities with nonsurvivable injuries sustained injuries primarily while mounted. By subcommand, the primary cause of death for fatalities with nonsurvivable injuries was blast for Army (57.6%), multiple/blunt force for Navy (60.0%), gunshot wound for Air Force (55.6%), and split between blast (50.0%) and gunshot wound (50.0%) for Marine Corps. For each subcommand except Air Force, fatalities with potentially survivable-survivable injuries sustained injuries primarily while dismounted, and the mechanism of death was primarily hemorrhage plus other mechanism or hemorrhage alone. Hemorrhage only mechanism of death was surpassed over time by complex multimechanism death. Potential for injury survivability and death preventability was greatest during early and later years of conflict. Organizational differences in mortality characteristics and trends were identified from which commanders can refine efforts to prevent and treat injury and improve survival. Fatality analyses inform operational risk matrices and advance casualty prevention and response efforts. Prevention, assessment, and treatment strategies must evolve to reduce death from hemorrhage plus coexisting mechanisms. Performance Improvement and Epidemiological, level IV.


Cell-cultured meat: Lessons from GMO adoption and resistance.
This article discusses the choices and strategies that can hasten or delay the adoption of novel food technologies. We start by examining how genetically-modified food became an object of controversy in the United States and Europe. Then, we present lessons suggested by the history of GMOs for cell-cultured meat adoption. The history of GMOs suggests at least eleven concrete lessons for cultured meat adoption that remain under-discussed in the literature. This paper's findings diverge in several ways from received wisdom on cultured meat adoption. We argue, among other things, that genetic engineering firms understood their work to be humanitarian and environmentally-friendly and so were unprepared for popular backlash, that technology adoption is more readily affected by consumer activism when buyers in a supply chain exert more pressure on sellers than the reverse, and that focusing on the positive aspects of a technology is more successful for encouraging its adoption than responding to negative perceptions.


Isolation and characterization of a novel single-chain variable fragment (scFv) against Lymphocyte function-associated antigen-1 (LFA-1) using phage display method.
Lymphocyte function-associated antigene-1 (LFA-1) is a well-described integrin found on lymphocytes and other leukocytes, which is known to be overexpressed in leukemias and lymphomas. This receptor plays a significant role in immune responses such as T-cell activation, leukocyte cell-cell interactions, and trafficking of leukocyte populations. Subsequently, binders of LFA-1 emerge as potential candidates for cancer and autoimmune therapy. This study used the phage display technique to construct and characterize a high-affinity single-chain fragment variable (scFv) antibody against LFA-1. After expression, purification, dialysis, and concentration of the recombinant LFA-1 protein, four female BALB/c mice were immunized, splenocyte's mRNA was extracted, and cDNA was synthesized. A scFv library was constructed by linking the amplified VH/Vκ fragments through a 72-bp linker using SOEing PCR. Next, the scFv gene fragments were cloned into the pComb-3XSS phagemid vector; thus, the phage library was developed. The selection process involved three rounds of phage-bio-panning, polyclonal, and monoclonal phage ELISA. AF17 was chosen and characterized among the positive clones through SDS-PAGE, Western blotting, indirect ELISA, and in-silico analyses. The results of the study showed the successful construction of a high-affinity scFv library against LFA-1. The accuracy of the AF17 production and its ability to bind to the LFA-1 were confirmed through SDS-PAGE, Western blot, and ELISA. This study highlights the potential application of the high-affinity AF17 against LFA-1 for targeting T lymphocytes for therapeutic purposes.


Management of stage D1 adenocarcinoma of the prostate: the Johns Hopkins experience 1974 to 1987.
There is no consensus on the proper management of men with stage D1 adenocarcinoma of the prostate. Although cure is unlikely, many men survive for long intervals apparently free of metastatic disease. Thus, effective palliation of the local lesion with low morbidity is desirable. From 1974 to 1987, 120 consecutive men with stage D1 prostate cancer were treated with 3 primary modes of therapy (mean followup 48 months): 1) expectant therapy (35), 2) external beam radiotherapy (21) and 3) radical prostatectomy (64). These patients were statistically homogeneous as determined by Gleason grade but not by extent of metastatic disease. The over-all 5 and 10-year projected actuarial survival rates for the radical prostatectomy patients were 97 and 62%, respectively, and the apparent clinical survival free of disease at 5 years and 80 months, respectively, was 83 and 68%. The direct disease-specific 10-year survival free of disease was 46%. However, only 3 of 27 patients followed for 3 years or longer had undetectable levels of prostate specific antigen. Using a Cox univariate proportional hazards model several factors appeared to have significant prognostic value including volume of lymph node metastases (macroscopic greater than 2 mm.), percentage of positive lymph nodes sampled and frozen section diagnosis. Gleason grade, clinical stage and the number of positive nodes did not have significant prognostic value. Local recurrence requiring an operation was noted in 8 of 35 patients (23%) treated expectantly, 5 of 21 (24%) treated with radiotherapy and 2 of 64 (3%) treated with radical prostatectomy. Significant gastrointestinal or genitourinary complications occurred in 33% of the men treated with radiotherapy and 1.5% of those undergoing radical prostatectomy. Since the introduction of nerve-sparing radical prostatectomy in 1982, potency resumed in 55% of the 33 patients who were potent preoperatively and have been followed 1 year or longer. These data suggest that in properly selected patients radical prostatectomy, although not curative, can provide excellent palliation of the local lesion with acceptable morbidity and that symptomatic local recurrence of prostatic cancer achieved with radiation therapy is identical to the results in men who were managed expectantly.


[In situ diffuse reflectance FTIR spectroscopy study of the selective catalytic reduction reaction of NO over Ag/SAPO-34 catalysis].
An in situ diffuse reflectance FTIR spectroscopy (DRIFTS) study of the selective catalytic reduction (SCR) of NO with propene in the presence of excess O2 was carried out over Ag/SAPO-34 catalyst. The SCR reaction was investigated at temperatures from 573 to 773 K, and the role of oxygen in the NO reduction process was determined by comparing experiments using an initial reaction mixture containing oxygen and without oxygen. The results show that both NO and propene are easily activated in oxygen. Furthermore, the presence of oxygen is necessary to form organo-NOx adsorbed species. Based on these experiments, a reaction mechanism is proposed that NO, propene and oxygen react to form organo-nitro and organo-nitrito adsorbed species as key intermediates, and then these intermediates decompose to nitrogen.


[Significance of local factors for the development of contact allergic reactions in patients with chronic venous insufficiency].
There are a number of local factors which might contribute to the induction and persistence of contact allergies in patients with chronic venous insufficiency of the lower leg and their sequelae such as stasis dermatitis and leg ulcers. Thus, the acanthotic epidermis might have a certain "reservoir function" for potential contact allergens. Furthermore, the density of epidermal Langerhans' cells is increased in areas of stasis dermatitis, and the dermis contains a high number of cells bearing HLA-DR antigens, which might act as antigen-presenting cells.


The oral mucosal surface and blood vessels.
Detailed information about the size of the oral mucosa is scarce in the literature, and those studies that do exist do not take into account the size of the tongue or the enlargement of the surface by the papillae. Because of the various functions of the oral mucosa in the maintenance of oral health, knowledge of its true size may provide a better understanding of the physiology of the oral cavity and some oral diseases and direct future therapeutic strategies. The aim of this study was to determine the total size of the oral mucosa. Five human adult cadaver heads were cut in the median sagittal plane, and the total area of the oral surface was determined using silicon casts. The surface of the tongue was measured with quantitative profilometry. Photographs of oral blood vessels were taken in different areas of the oral mucosa of adult test subjects using intravital microscopy, and the pictures were compared with vessel casts of the oral mucosal capillaries of a maccaca fasciculrais monkey, which was studied using a scanning electron microscope. The results showed that the dorsal side of the tongue comprises a large proportion of the total oral mucosal surface. The surface area of the epithelium increases moving from anterior to posterior on the tongue, and the number of underlying blood vessels increases proportionally. It can be concluded that the back of the tongue plays an important role in the oral resorption of drugs. The results may be of relevance for the delivery and development of oral drug application.


An overview of statistical learning theory.
Statistical learning theory was introduced in the late 1960's. Until the 1990's it was a purely theoretical analysis of the problem of function estimation from a given collection of data. In the middle of the 1990's new types of learning algorithms (called support vector machines) based on the developed theory were proposed. This made statistical learning theory not only a tool for the theoretical analysis but also a tool for creating practical algorithms for estimating multidimensional functions. This article presents a very general overview of statistical learning theory including both theoretical and algorithmic aspects of the theory. The goal of this overview is to demonstrate how the abstract learning theory established conditions for generalization which are more general than those discussed in classical statistical paradigms and how the understanding of these conditions inspired new algorithmic approaches to function estimation problems. A more detailed overview of the theory (without proofs) can be found in Vapnik (1995). In Vapnik (1998) one can find detailed description of the theory (including proofs).


Adult prostate sarcoma: the Memorial Sloan Kettering experience.
To present our institutional experience with adult prostate sarcoma over 30 years. We reviewed 38 cases of adult prostate sarcoma diagnosed and treated at our institution between 1982 and 2012. Univariate Cox proportional hazards regression was used to determine if there was an association between specific disease characteristics (tumor size, histology, American Joint Committee on Cancer stage, and metastasis at diagnosis) and cancer-specific survival (CSS). A total of 38 patients were included, with a median age of 50 years (range, 17-73 years). Most men presented with lower urinary tract symptoms (45%), hematuria (24%), or acute urinary retention (21%). Diagnosis was established with prostate needle biopsy (68%) or transurethral resection of the prostate (18%). The predominant histologic subtypes were leiomyosarcoma (13 cases, 34%) and rhabdomyosarcoma (12 cases, 32%). Rhabdomyosarcoma was associated with poorer CSS (hazard ratio, 3.00; 95% confidence interval [CI], 1.13-7.92; P = .027) compared with leiomyosarcoma. We did not observe a significant relationship between tumor size and CSS. Overall, median CSS was 2.9 years (95% CI, 1.5-5.4), with 7.7 years for clinically localized disease (95% CI 2.5; upper bound not reached) and 1.5 years for metastatic disease (95% CI 1.1, 2.7). Adult prostate sarcoma has a poor prognosis, especially in cases of metastatic disease at the time of diagnosis. Surgery remains the standard of care, but it provides limited benefit to those with metastatic disease or as a consolidation therapy after partial response to systemic therapy.


Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review.
To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.


Revalidation of the RACE scale after its regional implementation in Catalonia: a triage tool for large vessel occlusion.
Our aim was to revalidate the RACE scale, a prehospital tool that aims to identify patients with large vessel occlusion (LVO), after its region-wide implementation in Catalonia, and to analyze geographical differences in access to endovascular treatment (EVT). We used data from the prospective CICAT registry (Stroke Code Catalan registry) that includes all stroke code activations. The RACE score evaluated by emergency medical services, time metrics, final diagnosis, presence of LVO, and type of revascularization treatment were registered. Sensitivity, specificity, and area under the curve (AUC) for the RACE cut-off value ≥5 for identification of both LVO and eligibility for EVT were calculated. We compared the rate of EVT and time to EVT of patients transferred from referral centers compared with those directly presenting to comprehensive stroke centers (CSC). The RACE scale was evaluated in the field in 1822 patients, showing a strong correlation with the subsequent in-hospital evaluation of the National Institute of Health Stroke Scale evaluated at hospital (r=0.74, P<0.001). A RACE score ≥5 detected LVO with a sensitivity 0.84 and specificity 0.60 (AUC 0.77). Patients with RACE ≥5 harbored a LVO and received EVT more frequently than RACE <5 patients (LVO 35% vs 6%; EVT 20% vs 6%; all P<0.001). Direct admission at a CSC was independently associated with higher odds of receiving EVT compared with admission at a referral center (OR 2.40; 95% CI 1.66 to 3.46), and symtoms onset to groin puncture was 133 min shorter. This large validation study confirms RACE accuracy to identify stroke patients eligible for EVT, and provides evidence of geographical imbalances in the access to EVT to the detriment of patients located in remote areas.


[New anaesthetic technique in diode laser treatment of retinopathy of prematurity].
Anaesthesia in premature infants can have many complications. Although the application of diode laser is less painful than cryotherapy, there has to be adequate immobilization of the patient to provide a correct focus of the spot. At Hospital Infantil de Zaragoza, the same standard anaesthetic technique has been applied since 1999, obtaining sedation with inhaled anaesthetic agents combined with topical anaesthesia. We analyse the results obtained on the application of this technique. The study included 72 consecutive premature infants treated with diode laser for retinopathy of prematurity (ROP), using an anaesthetic technique combining inhalatory sedation and topical anaesthesia. The personal data of each patient was collected (gestational age, birth weight, postconceptional age at the time of initial treatment, associated systemic disorders) together with information related to the surgical intervention (duration, intraoperative and postoperative complications). Intraoperative complications occurred in 12 cases (16.66%). These were self-limited in 9 cases and only 3 cases required orotracheal intubation (4.16%). Postoperative complications occurred in 4 cases (5.55%) during the 48 h following treatment. No statistically significant relationship was found between the presence of intraoperative complications and the mean gestational age and birth weight, and the presence of apnoea, intraventricular haemorrhage or a permeable ductus. A statistically significant relationship was found between the presence of postoperative complications and significant intraventricular haemorrhage. This anaesthetic technique combining inhalatory gases and topical anaesthesia is safe, with few complications and comfortable for the surgeon.


A retrospective study of peanut and tree nut allergy: Sensitization and correlations with clinical manifestations.
Peanut (PN) and tree nut (TN) allergies are among the leading causes of fatal food-induced anaphylaxis and are increasing in prevalence, especially in children. Their cosensitization and concurrent clinical allergy have been understudied. This retrospective study investigated the correlation between PN and TN allergy, both in terms of in vitro sensitization (IVS) and clinical allergic manifestations. We conducted a retrospective medical record review at the Allergy Clinic at University Hospital of Brooklyn. Fourteen hundred six charts were reviewed, of which 76 (5.4%) had documented relevant clinical allergy: PN allergy but not TN allergy (n = 29) or TN allergy but not PN allergy (n = 11) or both (n = 30). Six patients with PN allergy but no TN exposure history were not included in the analysis. The majority of patients (67/76, 88.1%) had a concurrent history of asthma, rhinoconjunctivitis, or AD. Sensitivity of TN IVS predicting PN IVS was 38/39 (97%). Similarly, sensitivity of PN IVS predicting TN IVS was 38/42 (91%). Sensitivity of TN clinical allergy predicting PN allergy was 30/59 (51%). Sensitivity of PN clinical allergy predicting TN allergy was 30/41 (73%). The total number of organ systems involved in reported clinical reactions correlated with IVS to TN (p = 0.004) but not IVS to PN (p = 0.983). In summary, we found PN sensitization predicts TN sensitization in vitro, with lower predictability for clinical reactions.


Parcellating connectivity in spatial maps.
A common goal in biological sciences is to model a complex web of connections using a small number of interacting units. We present a general approach for dividing up elements in a spatial map based on their connectivity properties, allowing for the discovery of local regions underlying large-scale connectivity matrices. Our method is specifically designed to respect spatial layout and identify locally-connected clusters, corresponding to plausible coherent units such as strings of adjacent DNA base pairs, subregions of the brain, animal communities, or geographic ecosystems. Instead of using approximate greedy clustering, our nonparametric Bayesian model infers a precise parcellation using collapsed Gibbs sampling. We utilize an infinite clustering prior that intrinsically incorporates spatial constraints, allowing the model to search directly in the space of spatially-coherent parcellations. After showing results on synthetic datasets, we apply our method to both functional and structural connectivity data from the human brain. We find that our parcellation is substantially more effective than previous approaches at summarizing the brain's connectivity structure using a small number of clusters, produces better generalization to individual subject data, and reveals functional parcels related to known retinotopic maps in visual cortex. Additionally, we demonstrate the generality of our method by applying the same model to human migration data within the United States. This analysis reveals that migration behavior is generally influenced by state borders, but also identifies regional communities which cut across state lines. Our parcellation approach has a wide range of potential applications in understanding the spatial structure of complex biological networks.


Logical analysis of timing-dependent receptor signalling specificity: application to the insulin receptor metabolic and mitogenic signalling pathways.
We present a method for logical analysis of signal-transduction networks, focusing on metabolic and mitogenic signalling by the insulin receptor, with specific emphasis on dependence of the signalling properties on the timing of binding events. We discuss a basic model which demonstrates this dependence (hormone binding leads to activation of the receptor which can lead to a commitment to mitogenic signalling), and show how residence time of the hormone on the receptor can determine the specificity of signalling between the alternative metabolic or mitogenic pathways. The method gives conditions for the selection of specific branches in the signalling pathway expressed in terms of inequalities among the characteristic activation or deactivation times of components of that pathway. In this way, the conditions for mitogenic signalling can be given in terms of a required range of values of the hormone residence time on the receptor, which is directly related to the kinetic dissociation rate.


Emissions, Transport, and Fate of Emerging Per- and Polyfluoroalkyl Substances from One of the Major Fluoropolymer Manufacturing Facilities in China.
Fluoropolymer manufacturing is a major historical source of perfluorooctanoic acid (PFOA) on a global scale, but little is known about the emissions, transport, and fate of emerging per- and polyfluoroalkyl substances (PFASs). Here, we performed a comprehensive spatial trend and interyear comparison of surface water and sediment samples from the Xiaoqing River, which receives water discharge from one of the major fluoropolymer manufacturing facilities in China. A suspect screening identified 42 chemical formulas, including the tetramer acid of hexafluoropropylene oxide (HFPO-TeA) and numerous tentatively detected isomers of C9-C14 per- or polyfluoroalkyl ether carboxylic acids (PFECAs). As revealed by the spatial trends and peak area-based sediment-water distribution coefficients, emerging PFASs with 3-9 perfluorinated carbons were transported unimpededly with the bulk water flow having no measurable degradation. Emerging PFASs with >9 perfluorinated carbons displayed more rapidly decreasing spatial trends than shorter-chain homologues in surface water due to increasing sedimentation rates. The presence of HFPO oligomers, monoether PFECAs, monohydrogen-substituted perfluoroalkyl carboxylic acids (PFCAs) and monochlorine-substituted PFCAs could partly be explained by the active use of polymerization aids or the impurities therein. However, further research is encouraged to better characterize the emissions of low-molecular-weight PFASs from fluoropolymers throughout their life-cycle.


The Cognitive Dimension and the Affective Dimension in the Patient's Experience.
This article deals with the experience of the specific client of health services, that is, the patient. Satisfaction questionnaires are usually applied to assess patient experience. However, this tool provides only a cognitive evaluation; it does not afford an affective dimension of the experience. The objective of the present study is to verify the relationship between the cognitive dimension of patient experience, collected through questionnaires, and the affective dimension, derived from the analysis of neurophysiological data. We propose a novel methodology that integrates physiological data collected by facial expression analysis to identify patients' emotions. A first, qualitative procedure was carried out to define the patient journey. This was recorded on video and later used in the experiment. The experiment collected information from the participants using two techniques. First, as they viewed the videos, facial expression analysis (FEA) was applied to assess their responses. Second, after they watched the videos, traditional questionnaires were presented. The results provided by the two techniques were then compared. The results show that there is no relationship between the emotional valence reported by questionnaires and the neurophysiological data. This reflects the two different dimensions of the experience, one cognitive and the other affective. Both facilitate the understanding of patient satisfaction.


A Novel Chromosomal Translocation Identified due to Complex Genetic Instability in iPSC Generated for Choroideremia.
Induced pluripotent stem cells (iPSCs) have revolutionized the study of human diseases as they can renew indefinitely, undergo multi-lineage differentiation, and generate disease-specific models. However, the difficulty of working with iPSCs is that they are prone to genetic instability. Furthermore, genetically unstable iPSCs are often discarded, as they can have unforeseen consequences on pathophysiological or therapeutic read-outs. We generated iPSCs from two brothers of a previously unstudied family affected with the inherited retinal dystrophy choroideremia. We detected complex rearrangements involving chromosomes 12, 20 and/or 5 in the generated iPSCs. Suspecting an underlying chromosomal aberration, we performed karyotype analysis of the original fibroblasts, and of blood cells from additional family members. We identified a novel chromosomal translocation t(12;20)(q24.3;q11.2) segregating in this family. We determined that the translocation was balanced and did not impact subsequent retinal differentiation. We show for the first time that an undetected genetic instability in somatic cells can breed further instability upon reprogramming. Therefore, the detection of chromosomal aberrations in iPSCs should not be disregarded, as they may reveal rearrangements segregating in families. Furthermore, as such rearrangements are often associated with reproductive failure or birth defects, this in turn has important consequences for genetic counseling of family members.


Why are medical students 'checking out' of active learning in a new curriculum?
The University of Virginia School of Medicine recently transformed its pre-clerkship medical education programme to emphasise student engagement and active learning in the classroom. As in other medical schools, many students are opting out of attending class and others are inattentive while in class. We sought to understand why, especially with a new student-centred curriculum, so many students were still opting to learn on their own outside of class or to disengage from educational activities while in class. Focus groups were conducted with students from two classes who had participated in the new curriculum, which is designed to foster small-group and collaborative learning. The sessions were audio-recorded and then transcribed. The authors read through all of the transcripts and then reviewed them for themes. Quotes were analysed and organised by theme. Interview transcripts revealed candid responses to questions about learning and the learning environment. The semi-structured nature of the interviews enabled the interviewers to probe unanticipated issues (e.g. reasons for choosing to sit with friends although that diminishes learning and attention). A content analysis of these transcripts ultimately identified three major themes embracing multiple sub-themes: (i) learning studio physical space; (ii) interaction patterns among learners, and (iii) the quality of and engagement in learning in the space. Students' reluctance to engage in class activities is not surprising if classroom exercises are passive and not consistently well designed or executed as active learning exercises that students perceive as enhancing their learning through collaboration. Students' comments also suggest that their reluctance to participate regularly in class may be because they have not yet achieved the developmental level compatible with adult and active learning, on which the curriculum is based. Challenges include helping students better understand the nature of deep learning and their own developmental progress as learners, and providing robust faculty development to ensure the consistent deployment of higher-order learning activities linked with higher-order assessments.


Fetal alcohol-exposed rats exhibit differential response to cholinergic drugs on a delay-dependent memory task.
Fetal alcohol exposure in human and rodents produces a number of cognitive deficits including impairments in learning and memory. Recent evidence in our laboratory has shown that fetal alcohol-exposed (FAE) rats respond differently to systemic administration of cholinergic drugs when tested for vigilance and locomotor activity. The present study examined the effects of muscarinic and nicotinic agonists and antagonists on memory performance in a delayed alternation task. Subjects were male offspring of Sprague-Dawley rats fed a 35% ethanol-derived caloric diet, pair-fed with sucrose, or chow-fed with lab chow during the last 2 weeks of gestation. Rats (3 months old) were food-deprived prior to training in the T-maze. Rats were first trained in the alternation task at no delay for five sessions. Rats were then trained at longer delays (20, 60, 180 s) until all groups showed similar performance for two consecutive sessions. Each animal was then tested following systemic injections of the cholinergic antagonists scopolamine and mecamylamine (60-s delay) and the cholinergic agonists pilocarpine and nicotine (180-s delay). Rats received saline injections on alternate days of testing. The results revealed that FAE rats exhibited no impairments in alternation performance at the no delay and 20-s delay, but showed impairments on both the 60- and 180-s delays during the initial sessions. However, with additional training, FAE rats showed performance similar to that of control groups at these delays. Following both pilocarpine and nicotine injections, control groups, but not the FAE group, showed significant memory enhancement in the alternation task. Following scopolamine injections, the FAE rats showed a significant impairment, while control groups showed a nonsignificant decrease in performance. All three groups showed impairments in the alternation task following administration of mecamylamine compared to saline treatment. These findings suggest that alterations in the cholinergic system in FAE rats may underlie some of the cognitive deficits observed with prenatal alcohol exposure.


[some features of nuclear genome transcription at early stages of liver regeneration. RNA-polymerase activity of isolated nuclei].
The RNA-polymerase activity of isolated nuclei after 1, 3, 6, 12 and 24 hrs following partial hepatectomy was studied. The enzyme activity showed almost a 2-fold decrease after the first post-operative hour, followed by an increase of activity which reached its maximum after 6 hrs. A decrease of nuclear hepatocyte RNA-polymerase sensitivity to alpha-amanitine after 1 and 3 hrs following the surgery was found. After 6 hrs the enzyme was activated by alpha-amanitine. Using selective incorporation of four labelled ribonucleoside triphosphates, it was shown that alpha-amanitine causes a shift in the nucleotide composition of RNA synthesized in the regenerating liver towards the AU-type RNA.


Adaptive color reduction.
The paper proposes an algorithm for reducing the number of colors in an image. The proposed adaptive color reduction (ACR) technique achieves color reduction using a tree clustering procedure. In each node of the tree, a self-organized neural network classifier (NNC) is used which is fed by image color values and additional local spatial features. The NNC consists of a principal component analyzer (PCA) and a Kohonen self-organized feature map (SOFM) neural network (NN). The output neurons of the NNC define the color classes for each node. The final image not only has the dominant image colors, but its texture also approaches the image local characteristics used. Using the adaptive procedure and different local features for each level of the tree, the initial color classes can be split even more. For better classification, split and merging conditions are used in order to define whether color classes must be split or merged. To speed up the entire algorithm and reduce memory requirements, a fractal scanning subsampling technique is used. The method is independent of the color scheme, it is applicable to any type of color images, and it can be easily modified to accommodate any type of spatial features and any type of tree structure. Several experimental and comparative results, exhibiting the performance of the proposed technique, are presented.


99mTc-MIBI SPECT/CT imaging had high sensitivity in accurate localization of parathyroids before parathyroidectomy for patients with secondary hyperparathyroidism.
Purpose: Accurate preoperative parathyroid localization is important for successful parathyroidectomy (PTX). The aim of our study was to investigate whether SPECT/CT has enhanced effect in preoperative localization of parathyroids. Methods: In our retrospective cohort study, we evaluated the effects of technetium-99m methoxyisobutylisonitrile-single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) on preoperative parathyroid localization for 645 secondary hyperparathyroidism (SHPT) patients. Among them, 569 successful PTX patients were divided into group A (received 99mTc-MIBI scintigraphy, n = 175) and group B (received 99mTc-MIBI scintigraphy and SPECT/CT imaging, n = 394). Sensitivity, specificity, and consistency of two imaging methods in preoperative localization of parathyroids were compared. Results: Overall sensitivity and consistency were higher in group B, while there was no difference in specificity between the two groups. In group A, the sensitivity of 99mTc-MIBI was 50.00%, 77.11%, 61.76%, and 76.54% in the right upper gland (RU), right lower gland (RL), left upper gland (LU), and left lower gland (LL) subgroups, while the consistency was 52.00%, 76.57%, 61.71%, and 75.43%, respectively. In group B, the sensitivity of 99mTc-MIBI with SPECT/CT was 69.39%, 90.03%, 78.07%, and 84.27%, and the consistency was 69.54%, 88.32%, 78.43%, and 84.26%, respectively. The sensitivity and consistency in lower glands were higher than in upper glands in both groups. Sensitivity for eutopic parathyroid was higher in group B, while there was no difference for ectopic parathyroid. Conclusions: 99mTc-MIBI SPECT/CT can increase the sensitivity and consistency of preoperative localization of eutopic parathyroid glands, and it can accurately locate ectopic parathyroid without sensitivity improvement.


Alterations in urinary metabolites due to unilateral ureteral obstruction in a rodent model.
Urinary tract obstruction (UTO) results in renal compensatory mechanisms and may progress to irrecoverable functional loss and histologic alterations. The pathophysiology of this progression is poorly understood. We identified urinary metabolite alterations in a rodent model of partial and complete UTO using (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy. Principal component analysis (PCA) was used for classification and discovery of differentiating metabolites. UTO was associated with elevated urinary levels of alanine, succinate, dimethylglycine (DMG), creatinine, taurine, choline-like compounds, hippurate, and lactate. Decreased urinary levels of 2-oxoglutarate and citrate were noted. The patterns of alteration in partial and complete UTO were similar except that an absence of elevated urinary osmolytes (DMG and hippurate) was noted in complete UTO. This pattern of metabolite alteration indicates impaired oxidative metabolism of the mitochondria in renal proximal tubules and production of renal protective osmolytes by the medulla. Decreased production of osmolytes in complete obstruction better elucidates the pathophysiology of progression from renal compensatory mechanisms to irrecoverable changes. Further confirmation of these potential biomarkers in children with UTO is necessary.


Cervical Total Disc Replacement and Anterior Cervical Discectomy and Fusion: Reoperation Rates, Complications, and Hospital Resource Utilization in 72 688 Patients in the United States.
Healthcare readmissions are important causes of increased cost and have profound clinical impact. Thirty-day readmissions in spine surgery have been well documented. However, rates, causes, and outcomes are not well understood outside 30 d. To analyze 30- and 90-d readmissions for a retrospective cohort of anterior cervical discectomy and fusions (ACDF) and total disc replacement (TDR) for degenerative cervical conditions. The Nationwide Readmissions Database approximates 50% of all US hospitalizations with patient identifiers to track patients longitudinally. Patients greater than 18 yr old were identified. Rates of readmission for 30 and 90 d were calculated. Predictor variables, complications, outcomes, and costs were analyzed via univariate and multivariable analyses. Between January and September 2013, 72 688 patients were identified. The 30- and 90-d readmission rates were 2.67% and 5.97%, respectively. The most prevalent reason for 30-d readmission was complication of medical/surgical care (20.3%), whereas for 90-d readmission it was degenerative spine etiology (19.2%). Common risk factors for 30- and 90-d readmission included older age, male gender, Medicare/Medicaid, prolonged initial length of stay, and various comorbidities. Unique risk factors for 30- and 90-d readmissions included adverse discharge disposition and mechanical implant-related complications, respectively. When comparing ACDF and TDR, ACDFs were associated with increased 90-d readmissions (6.0% vs 4.3%). The TDR cohort had a shorter length of stay, lower complication rate, and fewer adverse discharge dispositions. Identification of readmission causes and predictors is important to potentially allow for changes in periperative management. Decreasing readmissions would improve patient outcomes and reduce healthcare costs.


Quench Analyses of the MIT 1.3-GHz LTS/HTS NMR Magnet.
The MIT 1.3-GHz LTS/HTS NMR magnet is currently under development. The unique features of this magnet include a 3-nested formation for an 800-MHz REBCO insert (H800) and the no-insulation (NI) winding technique for H800 coils. Because when it is driven to the normal state, an NI REBCO magnet will respond electromagnetically, thermally, and mechanically that may result in permanent magnet damage, analysis of a quenching magnet is a key aspect of HTS magnet protection. We have developed a partial element equivalent circuit method coupled to a thermal and stress finite element method to analyze electromagnetic and mechanical responses of a nested-coil REBCO magnet each a stack of NI pancake coils. Using this method, quench simulations of the MIT 1.3-GHz LTS (L500)/HTS (H800) NMR magnet (1.3G), we have evaluated currents, strains, and torques of H800 Coil 1 to Coil 3 and L500, and center fields of 1.3G, L500, and H800. Our analyses show H800 is vulnerable to mechanical damage.


[An increase of plasma cells in the regenerated mucous membrane of maxillary sinus. Experimental study].
In ten albino New Zealand rabbits we studied in the regenerated mucosa of the maxillary sinus what happens after three months of radical removal of sinus mucosa. The study was realized by light and electronic microscopy, with special attention to the plasma cells around the submucosal glands. There is an increased of plasma cells, in a proportion of 10:1.


The RSNA International COVID-19 Open Radiology Database (RICORD).
The coronavirus disease 2019 (COVID-19) pandemic is a global health care emergency. Although reverse-transcription polymerase chain reaction testing is the reference standard method to identify patients with COVID-19 infection, chest radiography and CT play a vital role in the detection and management of these patients. Prediction models for COVID-19 imaging are rapidly being developed to support medical decision making. However, inadequate availability of a diverse annotated data set has limited the performance and generalizability of existing models. To address this unmet need, the RSNA and Society of Thoracic Radiology collaborated to develop the RSNA International COVID-19 Open Radiology Database (RICORD). This database is the first multi-institutional, multinational, expert-annotated COVID-19 imaging data set. It is made freely available to the machine learning community as a research and educational resource for COVID-19 chest imaging. Pixel-level volumetric segmentation with clinical annotations was performed by thoracic radiology subspecialists for all COVID-19-positive thoracic CT scans. The labeling schema was coordinated with other international consensus panels and COVID-19 data annotation efforts, the European Society of Medical Imaging Informatics, the American College of Radiology, and the American Association of Physicists in Medicine. Study-level COVID-19 classification labels for chest radiographs were annotated by three radiologists, with majority vote adjudication by board-certified radiologists. RICORD consists of 240 thoracic CT scans and 1000 chest radiographs contributed from four international sites. It is anticipated that RICORD will ideally lead to prediction models that can demonstrate sustained performance across populations and health care systems.


Therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation in rats.
To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation. 108 Wistar rats weighing (200 g+/-30 g) were randomly divided into a sham shock (SS) group (n=36), a hemorrhagic shock resuscitation (HS) group (n=36) and a hemorrhagic shock cisapride treated (HSC) group (n=36). Sampling at 1, 2 and 4 hours after resuscitation was done and 6 samples for each observation item were taken. The gastric blood flow volume was measured by isotope label biological microglobulin. Gastric pHi, gastric emptying, MDA and Na+-K+-ATPase of gastric mucosa were measured. In the HSC group, the relative residual rate of gastric pigment decreased significantly, the gastric blood flow volume elevated; gastric pHi increased significantly at 2 hours; the level of mucosal MDA decreased at 4 hours, the activity of Na+-K+-ATPase increased and the lactic acid level in the portal vein decreased significantly compared to the HS group. After hemorrhagic shock resuscitation, cisapride contained the following functions, 1) promoting gastric emptying, 2) increasing the blood flow of gastric blood flow volume and gastric pHi, 3) depressing the lactic acid concentration of the portal vein and improving MDA volume and Na+-K+-ATPase activity of gastric mucosa. It suggests that after complementing effective circulating blood volume for hemorrhagic shock resuscitation, early use of cisapride for gastric motility is helpful for an improvement of lasting ischemia and hypoxia in stomach.


A global calibration model for a-Si EPIDs used for transit dosimetry.
Electronic portal imaging devices (EPIDs) are not only applied for patient setup verification and detection of organ motion but are also increasingly used for dosimetric verification. The aim of our work is to obtain accurate dose distributions from a commercially available amorphous silicon (a-Si) EPID for transit dosimetry applications. For that purpose, a global calibration model was developed, which includes a correction procedure for ghosting effects, field size dependence and energy dependence of the a-Si EPID response. In addition, the long-term stability and additional buildup material for this type of EPID were determined. Differences in EPID response due to photon energy spectrum changes have been measured for different absorber thicknesses and field sizes, yielding off-axis spectrum correction factors based on transmission measurements. Dose measurements performed with an ionization chamber in a water tank were used as reference data, and the accuracy of the dosimetric calibration model was determined for a large range of treatment conditions. Gamma values using 3% as dose-difference criterion and 3 mm as distance-to-agreement criterion were used for evaluation. The field size dependence of the response could be corrected by a single kernel, fulfilling the gamma evaluation criteria in case of virtual wedges and intensity modulated radiation therapy fields. Differences in energy spectrum response amounted up to 30%-40%, but could be reduced to less than 3% using our correction model. For different treatment fields and (in)homogeneous phantoms, transit dose distributions satisfied in almost all situations the gamma criteria. We have shown that a-Si EPIDs can be accurately calibrated for transit dosimetry purposes.


Choline: essential for brain development and function.
Pregnancy and lactation are periods when maternal reserves of choline are depleted. At the same time, the availability of choline for normal development of brain is critical. Variations in choline intake by mothers influence memory performance in their offspring. The mechanisms for this potent effect of choline are not yet elucidated but may involve changes in acetylcholine synthesis, transmembrane signal transduction, or regulation of apoptosis. These observations are important for the obstetrician and pediatrician as they consider the ideal dietary intake for mothers and their children.


Mass Spectrometry-Based Multiomics Identifies Metabolic Signatures of Sarcopenia in Rhesus Monkey Skeletal Muscle.
Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in "omics" technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offers new insights into the molecular mechanisms underlying sarcopenia for the evaluation and monitoring of a therapeutic treatment of sarcopenia.


Validity and reliability of the Turkish version of the Self-reported Foot and Ankle Score in patients with foot or ankle pain.
The aim of this study was to translate the Self-Reported Foot and Ankle Score (SEFAS) into Turkish and to determine the validity and reliability of the translated version in patients with foot or ankle pain. A total of 98 patients (65 females, 33 males, mean age=39 years, age range 18-65 years) who presented with foot or ankle pain for at least one week were included in the study. SEFAS was translated into Turkish (SEFAS-T) and then back-translated into English by two bilingual translators to ensure the accuracy of translation. To determine the validity of the translated version, SEFAS-T, The Foot and Ankle Outcome Score (FAOS), and the Short Form 36 (SF-36) were administered at the first assessment on the same day. SEFAS-T was repeated five days later (Spearman's rho). Intra-class correlation coefficients (ICCs) were used for assessment of the test re-test reliability, while the Cronbach's alpha coefficient was used to assess the internal consistency of the questionnaire Results: SEFAS-T showed good test-retest reliability (ICC: 0.887). Item 4 showed poor item-total correlation and inter-item correlations. When item 4 was excluded, the Cronbach's alpha value was found as 0.906. SEFAS-T total scores showed correlation with all the FAOS sub-scores (p<0.001) and all the SF-36 components (p≤0.001) except mental health (rho: 0.149, p: 0.143). The highest correlation was found between SEFAS-T Total Score and the Sports and Recreations subscale of FAOS (rho: 0.796, p<0.001). SEFAS-T seems to be valid and reliable as a measure for foot or ankle pain in Turkish patients. Level II, Diagnostic study.


Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro.
The endothelial blood-brain barrier (BBB) has a critical role in controlling lymphocyte traffic into the central nervous system (CNS), both in physiological immunosurveillance, and in its pathological aberrations. The intercellular signals that possibly could induce lymphocytes to cross the BBB include immunogenic presentation of protein (auto-)antigens by BBB endothelia to circulating T lymphocytes. This concept has raised much, though controversial, attention. We approached this problem by analyzing in vitro immunospecific interactions between clonal rat T lymphocyte lines with syngeneic, stringently purified endothelial monolayer cultures from adult brain micro-vessels. The rat brain endothelia (RBE) were established from rat brain capillaries using double collagenase digestion, density gradient fractionation and selective cytolysis of contaminating pericytes by anti-Thy 1.1 antibodies and complement. Incubation with interferon-gamma in most of the brain-derived endothelial cells induced Ia-antigens in the cytoplasm and on the cell surface in some of the cells. Before the treatment, the cells were completely Ia-negative. Pericytes were unresponsive to IFN-gamma treatment. When confronted with syngeneic T cell lines specific for protein (auto-)antigens (e.g., ovalbumin and myelin basic protein, MBP), RBE were completely unable to induce antigen-specific proliferation of syngeneic T lymphocytes irrespective of pretreatment with IFN-gamma and of cell density. RBE were inert towards the T cells, and did not suppress T cell activation induced by other "professional" antigen presenting cells (APC) such as thymus-derived dendritic cells or macrophages. IFN-gamma-treated RBE were, however, susceptible to immunospecific T cell killing. They were lysed by MBP-specific T cells in the presence of the specific antigen or Con A. Antigen dependent lysis was restricted by the appropriate (MHC) class II product. We conclude that the interaction of brain endothelial cells with encephalitogenic T lymphocytes may involve recognition of antigen in the molecular context of relevant MHC products, but that this interaction per se is insufficient to initiate the full T cell activation program.


Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic.
Epidemiological studies link arsenic exposure to increased risks of cancers of the skin, kidney, lung, bladder and liver. Additionally, a variety of non-cancerous conditions such as diabetes mellitus, hypertension, and cardiovascular disease have been associated with chronic ingestion of low levels of arsenic. However, the biological and molecular mechanisms by which arsenic exerts its effects remain elusive. Here we report increased renal hexokinase II (HKII) expression in response to arsenic exposure both in vivo and in vitro. In our model, HKII was up-regulated in the renal glomeruli of mice exposed to low levels of arsenic (10 ppb or 50 ppb) via their drinking water for up to 21 days. Additionally, a similar effect was observed in cultured renal mesangial cells exposed to arsenic. This correlation between our in vivo and in vitro data provides further evidence for a direct link between altered renal HKII expression and arsenic exposure. Thus, our data suggest that alterations in renal HKII expression may be involved in arsenic-induced pathological conditions involving the kidney. More importantly, these results were obtained using environmentally relevant arsenic concentrations.


Polyethylenimine and chitosan carriers for the delivery of RNA interference effectors.
Manipulating gene activity represents a promising approach for the treatment of cancer and other diseases. The relatively recent discovery of RNA interference (RNAi) revolutionized therapeutic approaches in this field. RNA effectors can now be used to modify the activity of genes and theoretically control any biological process. However, the clinical application of RNAi has been limited by the inefficient delivery of RNA. Challenges associated with the in vivo use of RNAi mediators, include rapid degradation, uptake by the reticular endothelial system and inefficient cellular internalization. To date, various strategies have been developed in order to overcome these pitfalls. Among these approaches, non-viral delivery systems have gained increasing popularity, as they are generally considered safer than their viral counterparts. The use of cationic polymers, especially polyethylenimine and chitosan, for the in vivo delivery of doubled-stranded RNAs is discussed in this review.


[Reproducible marginal gap measurements of partial ceramic crowns].
Aim of this research was to test the hypothesis that marginal gap measurements by a digital microscopic image processing computer are reproducible. Light microscopic images of the margins of Artglass partial crowns on stone dies were obtained with a 3CCD color video camera, digitized and processed. Ten measuring points were painted on a 0.5 mm section of the finish line of the preparation. The opposite corresponding measuring points on the margin of the partial crown were painted as well. The distance (marginal gap) between two corresponding points was painted and calculated by the computer. Reproducibility (precision) is reflected in the ability to reproduce the same measurement results in repeated measurements (n = 5). The reproducibility error was expressed as the coefficient of variation (CV) in percent (%). The localization of the corresponding measurement points and the calculation of the marginal gap were performed without errors. For a marginal gap between 15-50 microns the average measurement error was 3% or 0.45-1.5 microns. It was concluded that the measurement of the gap between two points by the digital image processing computer was reproducible. The measurement error was neglectable given that a clinically acceptable marginal gap is 100 microns.


Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study).
Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient's risk category and improve targeted prophylactic strategies. (Clinicaltrial.gov: NCT01315925)


Misuses and misunderstandings of boundary theory in clinical and regulatory settings.
This paper outlines a number of misapplications of boundary theory in both regulatory settings and clinical situations. The authors review clinical vignettes that illustrate the difference between boundary crossings, which lead to productive work in psychotherapy, and boundary violations, which are harmful to the patient and exploit the patient's vulnerable position. They also discuss developments in the field that have led to an excessively rigid and defensive posture on the part of some clinicians that may lead to less than optimal psychiatric treatment. They survey recent developments in the wording of state statutes that broadly define sexual misconduct in psychotherapy. This review of the current status of boundary theory in both the law and clinical practice suggests that an overreaction has occurred that requires corrections. The critical role of context must be considered whenever a boundary problem has been alleged, and boundaries must be regarded as flexible standards of good practice rather than lists of generically forbidden behavior.


Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia.
Mutations in a group of genes that contribute to ciliary function cause Bardet-Biedl syndrome (BBS). Most studies of BBS have focused on primary, sensory cilia. Here, we asked whether loss of BBS proteins would also affect motile cilia lining the respiratory tract. We found that BBS genes were expressed in human airway epithelia, and BBS2 and BBS4 localized to cellular structures associated with motile cilia. Although BBS proteins were not required for ciliogenesis, their loss caused structural defects in a fraction of cilia covering mouse airway epithelia. The most common abnormality was bulges filled with vesicles near the tips of cilia. We discovered this same misshapen appearance in airway cilia from Bbs1, Bbs2, Bbs4, and Bbs6 mutant mice. The structural abnormalities were accompanied by functional defects; ciliary beat frequency was reduced in Bbs mutant mice. Previous reports suggested BBS might increase the incidence of asthma. However, compared with wild-type controls, neither airway hyperresponsiveness nor inflammation increased in Bbs2(-/-) or Bbs4(-/-) mice immunized with ovalbumin. Instead, these animals were partially protected from airway hyperresponsiveness. These results emphasize the role of BBS proteins in both the structure and function of motile cilia. They also invite additional scrutiny of motile cilia dysfunction in patients with this disease.


Exercise Intensity and Technical Demands of Small-Sided Soccer Games for Under-12 and Under-14 Players: Effect of Area per Player.
The aim of this study was to evaluate the effects of 6 different areas per player (AP) on exercise intensity (EI) measured during small-sided games (SSGs) and expressed as percentage of maximal heart rate (%MHR) and technical actions (TAs) involvement with the ball, crosses, headers, tackles, shots on goal, dribbling, passing, and target passing-in U-12 and U-14 soccer players during SSGs. Seventeen male U-12 soccer players (age 10.0 ± 0.5 years, body mass 39.3 ± 5.3 kg, and height 143.8 ± 4.6 cm) and 16 male U-14 soccer players (age 13.2 ± 0.3 years, body mass 46.6 ± 11.9 kg, and height 154.8 ± 8.5 cm) performed SSGs with different AP: 40, 50, 66.7, 90, 112.5, and 150 m. Our results indicate that at larger AP, the U-12 group's mean EI values were significantly higher than those at smaller AP (p ≤ 0.05); in addition, intergroup comparison showed that EI was higher in U-12 than that in U-14 players when AP of 112.5 and 150 m were considered (p ≤ 0.05). Technical action analysis evidenced that moving from smaller to larger AP, U-14 players adapted better to AP changes. In conclusion, these results suggest that AP influences differently EI and TAs in U-12 and U-14 players. Our results could be taken into account by conditioning coaches to better tailor the physiological and technical training in young players through the modulation of AP.


Social and family factors in childhood hospital admission.
The relation between social, economic, and family life event measures and rates of hospital admission during the period from birth to 5 years was studied in a birth cohort of New Zealand children. Both family social background and family life events made a significant contribution to the variability in the risk of hospital admission. However, economic factors made no significant contribution to rates of admission when the correlated effects of family social background and life events were taken into account. In addition, the effects of family life events on risks of admission appeared to be far more marked than the effects of family social background. Possible explanations of the consistent association between life events and rates of morbidity during early childhood are discussed.


Observations on neurophysiological pattern and behavioural traits as death-feigning mechanism in Eucryptorrhynchus scrobiculatus (Coleoptera: Curculionidae).
In adaptation to surrounding environmental stimuli, most insects exhibit defense behaviour (death feigning) to improve survival rates in the wild. However, the underlying mechanism of death feigning remains largely unknown. Here, we tested the neurophysiological pattern and behavioural traits of the death-feigning mechanism in the forestry pest Eucryptorrhynchus scrobiculatus. Using neuroanatomy, LC-MS/MS target metabolomics detection technology and qRT-PCR, we investigated the effects of neurochemicals and metabolic pathways in experimental weevils. Excision and drug tests were conducted to verify the key regulatory body parts involved in regulating the central nervous system in death feigning. Our results reconstructed the death-feigning mechanism of E. scrobiculatus: when the effective stimuli point of arousal weevils received mechanical stimulation, the thoracoabdominal ganglion transmitted signals into the brain through the ventral nerve cord, and then the brain regulated dopamine (DA) and serotonin (5-HT) metabolic pathways, reducing the expression of dopamine (dar2) and octopamine (oar1, oab2) receptor genes, finally inducing death feigning. Our study suggests that the variation of neurotransmitters in the brain is an important indicator of the physiological response of death feigning, and the results provide ecological and theoretical information for future investigations to reveal key behaviour and target genes for pest control.


Virtual histology intravascular ultrasound analysis of non-culprit attenuated plaques detected by grayscale intravascular ultrasound in patients with acute coronary syndromes.
Noncalcific attenuated plaques identified by grayscale intravascular ultrasound (IVUS) are often seen in patients with acute coronary syndromes and have been associated with no reflow and creatine kinase-MB elevation after percutaneous coronary intervention. Histopathology has shown cholesterol clefts, microcalcification, or organized thrombus. One hundred twenty-four vessels in 64 patients with acute coronary syndromes from the PROSPECT trial were identified for inclusion in the present analysis. After excluding 4 vessels with severe calcification, 9 vessels with <40% plaque burden, and 3 vessels with too few (<3) virtual histology (VH)-IVUS frames for analysis, complete grayscale IVUS and VH-IVUS was available for 108 vessels in 64 patients that contained 39 VH-IVUS thin-capped fibroatheromas (VH-TCFA), 40 thick-capped fibroatheromas (VH-ThFA), and 33 pathologic intimal thickening but no fibrotic or fibrocalcific plaques. Overall, there were 47 grayscale IVUS attenuated plaques in 43 vessels. Compared to the minimum luminal sites of the remaining 65 vessels (controls), attenuated plaques contained larger necrotic core areas (1.5 +/- 0.9 vs 0.9 +/- 0.8 mm(2) in controls, p = 0.001). Fibroatheromas (VH-TCFA or VH-ThFA) were more common at the sites of attenuated plaques than at control sites (VH-TCFA 42.5% vs 29.2%, VH-ThFA 53.2% vs 23.1%, pathologic intimal thickening 4.3% vs 47.7%, p <0.0001). In conclusion, grayscale IVUS attenuated plaques are associated with a large amount of VH-IVUS necrotic core and are markers of the presence of fibroatheromas (VH-TCFA or VH-ThFA). This may explain the biologic instability of these lesions.