Cellulitis in patients with chronic lower-limb lymphedema due to HIV-related Kaposi sarcoma.
Chronic Lower Limb Lymphedema (CL-LL) secondary to Kaposi sarcoma (KS) has not been recognized as a risk factor for cellulitis. The aim was to describe the clinical spectrum and use of antimicrobial prophylaxis in patients with cellulitis and CL-LL due to KS. HIV patients with KS, CL-LL, and at least one episode of cellulitis seen at the AIDS Cancer Clinic at INCan in Mexico from 2004 to 2019 were included. Demographic and clinical data were obtained from medical records. Thirty-nine men all with CL-LL were included. Clinical factors associated with cellulitis were groin and/or lymph-node KS infiltration (69.2%), onychomycosis and/or tinea pedis (44.7%), ulcerated lesions (38.4%), and obesity (2.5%). Eighteen (46.1%) were hospitalized in the first episode and eight (20.5%) in recurrence. Six (25.3%) died, two of toxic shock syndrome (TSS), and one of septic shock. Fourteen (35.8%) had at least one recurrent episode of cellulitis. Twenty-five (64.1%) received prophylaxis. Patients without prophylaxis had significantly more unfavorable outcomes (hospitalization and recurrences) than those with prophylaxis. CL-LL due to KS is a risk factor for cellulitis and severe complications in patients with a long life expectancy. Antimicrobial prophylaxis needs to be explored as it could prevent complications.


Glycosyltransferase activity of Fringe modulates Notch-Delta interactions.
Ligands that are capable of activating Notch family receptors are broadly expressed in animal development, but their activity is tightly regulated to allow formation of tissue boundaries. Members of the fringe gene family have been implicated in limiting Notch activation during boundary formation, but the mechanism of Fringe function has not been determined. Here we present evidence that Fringe acts in the Golgi as a glycosyltransferase enzyme that modifies the epidermal growth factor (EGF) modules of Notch and alters the ability of Notch to bind its ligand Delta. Fringe catalyses the addition of N-acetylglucosamine to fucose, which is consistent with a role in the elongation of O-linked fucose O-glycosylation that is associated with EGF repeats. We suggest that cell-type-specific modification of glycosylation may provide a general mechanism to regulate ligand-receptor interactions in vivo.


Crystal structure and functional analysis of an archaeal chromatin protein Alba from the hyperthermophilic archaeon Pyrococcus horikoshii OT3.
The crystal structure of the Alba protein (PhoAlba) from a hyperthermophilic archaeon, Pyrococcus horikoshii OT3, was determined at a resolution of 2.8 A. PhoAlba structurally belongs to the alpha/beta proteins and is similar not only to archaeal homologues but also to RNA-binding proteins, including the C-terminal half of initiation factor 3 (IF3-C) from Bacillus stearothermophilus, an Esherichia coli protein implicated in cell division (Yhhp), and an Arabidopsis protein of unknown function. We found by gel shift assay that PhoAlba interacts with both ribonuclease P (RNase P) RNA (PhopRNA) and precursor-tRNA(Tyr) (pre-tRNA(Tyr)) in P. horikoshii. However, the addition of PhoAlba to reconstituted particles composed of PhopRNA and four or five protein subunits had little influence on either the pre-tRNA processing activity or the optimum temperature for the processing activity. These results suggest that PhoAlba contributes little to the catalytic activity of P. horikoshii RNase P.


Transcarotid artery endovascular reconstruction of the aortic arch by modified bifurcated stent graft for Stanford type A dissection.
A 40-year-old man with Stanford type B dissection underwent his first endovascular repair (EVAR) in April 2004 by Talent thoracic stent graft. He had an uncomplicated recovery and maintained good blood pressure control. However, a new retrograde dissection appeared in September 2004. The new dissection involved his aortic arch and ascending thoracic aorta to the opening of the coronary arteries. To reconstruct the aortic arch, bypasses between the right common carotid artery (RCCA), left common carotid artery and left subclavian artery were performed before endovascular repair. A modified bifurcated Talent stent graft was deployed from the RCCA to the ascending thoracic aorta with a long limb in the innominate artery and a short limb in the aortic arch. A further two pieces of graft were deployed via the common femoral artery. The ascending thoracic aorta and aortic arch were reconstructed completely by the bifurcated stent graft. The final angiography confirmed that there was good stent graft configuration, normal blood flow, and stable haemodynamics. No endoleak or other major complications were encountered. This result indicated that it is possible to reconstruct the aortic arch with a bifurcated stent graft and could be a new endovascular repair model for complex thoracic aortic aneurysm and dissection.


[Influence of physicians born in Hungary on the development of medicine in Vienna].
The curricula vitae of Hungarian-born eminent physicians who worked in Vienna primarily during the 19th century were compiled. The reason for doing so was the 150th anniversary of the foundation of the Society of Physicians in Budapest.


A portion of the feline leukaemia virus genome is not endogenous in cat cells.
Although viral sequences closely related to feline leukaemia virus are represented in multiple copies in cellular DNA of all domestic cats, a specific fraction was present only in the virus-infected cells. This fraction was detected by viral cDNA enriched by a prior absorption of a total complementary DNA (cDNA) transcript with normal cat liver DNA. The recycled cDNA hybridized well with the cellular DNA of virus-infected cells, but to a lesser extent with DNA from uninfected cat cells. The probe was used to differentiate virus-positive from virus-negative tumour tissues of cats. The same approach with cDNA of another endogenous feline virus, RD114, failed to show any difference between a virus-infected cell line and normal cells, including both virus-inducible and non-inducible lines.


Effect of strontium substitution on the material properties and osteogenic potential of 3D powder printed magnesium phosphate scaffolds.
3D powder printing is a versatile method for the fabrication of individual bone implants and was used for the processing of in vivo degradable ceramic scaffolds based on ammonium magnesium phosphate hexahydrate (struvite). In this study, synergetic effects could be achieved by the substitution of magnesium phosphate cements with strontium carbonate. This substitution resulted in 8.2 wt%, 16.4 wt%, and 24.6 wt% Sr2+ doped scaffolds, with a 1.9-3.1 times increased radiopacity compared to pure struvite. The maximal compressive strength of (16.1 ± 1.1) MPa found for strontium substituted magnesium phosphate was in the range of cancelleous bone, which makes these 3D printed structures suitable for medical application in low-load-bearing bone areas. In an ion release study over a course of 18 days, the release of strontium, magnesium, calcium, and phosphate ions from scaffolds was analyzed by means of inductively coupled plasma mass spectrometry. Independent of the scaffold composition the Mg2+ concentrations (83-499 mg/l) continuously increased in the cell media. The Sr2+ release varied between 4.3 μg/day and 15.1 μg/day per g scaffold, corresponding to a Sr2+ concentration in media between 1.14 mg/l and 7.24 mg/l. Moreover, decreasing calcium and phosphate concentrations indicated the precipitation of an amorphous calcium phosphate phase. The superior osteogenic properties of strontium substituted magnesium phosphate, e.g. the increase of osteoblast activity and cell number and the simultaneous suppression of osteoclast differentiation could be verified in vitro by means of WST-assay, TRAP-staining, and SEM imaging.


Effect of PUVA on intestinal calcium absorption.
Intestinal calcium absorption increased significantly following 14 days of treatment with photochemotherapy (PUVA) in seven patients with chronic psoriasis. Irradiation with UVA alone over a similar period did not result in significant changes in calcium absorption in an additional seven psoriatic patients. These findings suggest that the increase in serum 25-OH vitamin D levels previously reported in patients treated by PUVA may have important biological consequences.


Protection by an antioxidant of rotenone-induced neuromotor decline, reactive oxygen species generation and cellular stress in mouse brain.
Exposure to environmental toxins, including rotenone, results in central nervous system and systemic toxicity. Rotenone is a widely used pesticide and a mitochondrial complex I (CI) inhibitor. This study reports effectiveness of a synthetic lipoylcarnitine antioxidant compound, lipoylcarnitine methyl ester iodide (PMX-500F), for treatment of chronic rotenone induced neurological deficits in mice. Mice (C57BL/6NTac; two months of age) received oral administration of rotenone (30 mg/kg/day) or vehicle, preceded by intraperitoneal injection of PMX-500F (19 mg/kg) or vehicle for four weeks. In the Rota-rod test, rotenone treatment had no effect (P>0.05); however, PMX-500F treatment improved locomotor coordination and endurance (latency to fall time; P<0.05). For neuromuscular strength (wire hang test), rotenone treated mice showed reduced latency to fall compared to control mice (P<0.05). PMX-500F treatment improved the outcome in both control and rotenone exposed mice (P<0.05). Rotenone administration increased ROS generation in the forebrain and midbrain regions, but not in the cerebellum (P<0.05). Co-treatment with PMX-500F normalized the ROS in forebrain and midbrain regions to that of the control concentrations. In rotenone administered mice, activated stress-activated protein kinase/c-Jun NH2-terminal kinase (pSAPK/JNK) was higher in forebrain and midbrain lysates than in control mice (P<0.05) and treatment with PMX-500F reduced pSAPK/JNK to control levels. The pSAPK/JNK levels in the cerebellum were similar in all four groups (P>0.05). Total SAPK/JNK was not altered by either rotenone or PMX-500F treatment (P>0.05). These results illustrate that an antioxidant, here PMX-500F, provides protection against rotenone induced decline in neuromotor function, reactive oxygen species (ROS) generation and cellular stress.


Large-scale selection and analysis of temperature-sensitive mutants for cell reproduction from BHK cells.
Temperature-sensitive (ts) mutant cells for cell reproduction were isolated from the Syrian hamster cell line BHK21/13 by multiple culturing in the presence of 5-fluoro-2'-deoxyuridine (FdU) at 37.5 degrees after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. A simple method for cell fusion was devised, which enabled us to perform complementation studies with a large number of ts mutants. By using the method we have analyzed 219 ts mutants and classified them into 18 complementation groups. Mutants that belonged to the same complementation groups tended to exhibit similar patterns of inhibition of DNA synthesis at 39.5 degrees; however, some mutants belonging to the same group showed somewhat different patterns, probably due to occurrence of different mutations in the same gene. Distribution of the ts mutants among the 18 complementation groups was uneven; more than 50% of the mutants examined were assigned to complementation group B and G. The mutations belonging to complementation group B and G were found to be linked to the X chromosome.


Cocaine washed out syndrome in a patient with acute myocardial infarction.
We present the case of a 34-year-old woman with cocaine-associated chest pain and hypersomnulence, who, because of her inability to report chest pain, and her comfortable appearance, was admitted to telemetry for a diagnosis of low-probability rule-out myocardial infarction. Her chest pain was incompletely relieved, and she subsequently was transferred to the intensive care unit and ruled in for myocardial infarction. We discuss the clinical syndrome of cocaine-related depressed level of consciousness, and its relationship to evaluation of cocaine-related chest pain.


The effects of mirror therapy on pain and motor control of phantom limb in amputees: A systematic review.
Phantom limb pain (PLP) is a major problem after limb amputation. Mirror therapy (MT) is a non-pharmacological treatment using representations of movement, the efficacy of which in reducing PLP remains to be clarified. Here, we present the first systematic review on MT efficacy in PLP and phantom limb movement (PLM) in amputees (lower or upper limb). A search on Medline, Cochrane Database and Embase, crossing the keywords "Phantom Limb" and "Mirror Therapy" found studies which were read and analyzed according the PRISMA statement. Twenty studies were selected, 12 on the subject of MT and PLP, 3 on MT and PLM, 5 on MT and both (PLP and PLM). Among these 20 studies, 5 were randomized controlled trials (163 patients), 6 prospective studies (55 patients), 9 case studies (40 patients) and methodologies were heterogeneous. Seventeen of the 18 studies reported the efficacy of MT on PLP, but with low levels of evidence. One randomized controlled trial did not show any significant effect of MT. As to the effect of MT on PLM, the 8 studies concerned reported effectiveness of MT: 4 with a low level of evidence and 4 with a high level of evidence. An alternative to visual illusion seems to be tactile or auditory stimulation. We cannot recommend MT as a first intention treatment in PLP. The level of evidence is insufficient. Further research is needed to assess the effect of MT on pain, prosthesis use, and body representation, and to standardize protocols.


Parafollicular C-cell hyperplasia. Report of three cases in primary thyroid lymphomas.
Three cases of C-cell hyperplasia were observed in a series of 21 cases of primary thyroid lymphoma (PTL). The association is not well understood, since PTL is not included in the group of thyroid diseases which are known to cause C-cell hyperplasia. It may be interpreted as a compensatory reaction to diffuse and rapid destruction of most of the gland, or a "stimulation" related to the production of "bio-humoral" factors by neoplastic cells.


Triglyceride to high-density lipoprotein cholesterol ratio is associated with increased mortality in older patients on peritoneal dialysis.
The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been suggested as a simple method to identify unfavorable cardiovascular (CV) outcomes in the general population. The aim of this study was to investigate the association between the TG/HDL-C ratio and all-cause and CV mortality in peritoneal dialysis (PD) patients. We retrospectively analyzed patients on PD from November 1, 2005, to February 28, 2017, with a follow-up period lasting until May 31, 2017. The main outcomes were all-cause and CV mortality. Among the 973 PD patients, the mean age was 49.67 ± 14.58 (y). During a median follow-up period of 27.2 months (IQR = 13.4-41.5 months), 229 (23.5%) patients died, with 120 (12.3%) dying as a result of CV diseases. The median serum TG/HDL-C ratio was 1.11 (IQR = 0.71-1.80). In a multivariate Cox regression analysis, patients with higher TG/HDL-C ratio levels (tertile 3) had a higher incidence of CV mortality (adjusted HR = 2.12; 95% CI: 1.21-3.72; P = 0.009) and all-cause mortality (adjusted HR = 2.08; 95% CI: 1.37-3.14; P = 0.001) compared to patients in tertile 1. These associations persisted after excluding the patients who have already taken lipid-lowering medications. For older patients (> 60 years), each 1-unit higher baseline TG/HDL-C level was associated with a 48% (95% CI: 1.06-2.07; P = 0.021) increased risk of all-cause mortality and a 59% (95% CI: 1.03-2.45; P = 0.038) increased risk of CV mortality; however, this association was not observed in patients ≤60 years of age. A higher serum TG/HDL-C ratio was an independent predictor of all-cause and CV mortality in PD patients. Furthermore, an elevated TG/HDL-C ratio was significantly associated with higher all-cause and CV mortality in older PD patients.


Health promotion in schools: a multi-method evaluation of an Australian School Youth Health Nurse Program.
Health promotion provides a key opportunity to empower young people to make informed choices regarding key health-related behaviours such as tobacco and alcohol use, sexual practices, dietary choices and physical activity. This paper describes the evaluation of a pilot School Youth Health Nurse (SYHN) Program, which aims to integrate a Registered Nurse into school communities to deliver health promotion through group education and individual sessions. The evaluation was guided by the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. The objectives were to explore: 1) whether the Program was accessible to the high school students; 2) the impacts of the Program on key stakeholders; 3) which factors affected adoption of the Program; 4) whether implementation was consistent with the Program intent; and 5) the long-term sustainability of the Program. Research included retrospective analysis of Program records, administration of a survey of student experiences and interviews with 38 stakeholders. This evaluation provided evidence that the SYHN Program is reaching students in need, is effective, has been adopted successfully in schools, is being implemented as intended and could be maintained with sustained funding. The nurses deliver an accessible and acceptable primary health care service, focused on health promotion, prevention and early intervention. After some initial uncertainty about the scope and nature of the role, the nurses are a respected source of health information in the schools, consulted on curriculum development and contributing to whole-of-school health activities. Findings demonstrate that the SYHN model is feasible and acceptable to the students and schools involved in the pilot. The Program provides health promotion and accessible primary health care in the school setting, consistent with the Health Promoting Schools framework.


Evaluation of the reliability, utility, and quality of the information in cardiopulmonary resuscitation videos shared on Open access video sharing platform YouTube.
The internet is a widely used source for obtaining medical information both by patients and physicians. YouTube is an essential source of information that may be a useful tool to inform the public and may improve the learning experience if used adequately. In this study, we aimed to estimate the quality and accuracy of videos about cardiopulmonary resuscitation videos aired on YouTube, which is the most popular video platform of the online world. We included the first 100 videos, in English, returned by the YouTube search engine in response to "cardiopulmonary resuscitation" keyword query to the study. The popularity of the videos was evaluated with an index called the video power index. The educational quality, accuracy, and transparency of the visual content were measured using the DISCERN questionnaire (DISCERN), Journal of American Medical Association (JAMA-BC) benchmark criteria, and Global Quality Score (GQS). The technical quality was measured by the Cardiopulmonary Resuscitation Scoring System (CPR-SS), which was utilized by three bariatric surgeons. The source in 7% of the videos was medical doctors. The content in 89% of the videos was cardiopulmonary resuscitation technique. According to sources, videos uploaded by physicians had significantly higher quality, transparency, educational and technical value. Unlike, videos uploaded by physicians had a lower video power index than videos uploaded by non-medical professionals. Cardiopulmonary resuscitation technique videos had significantly higher quality, transparency, educational and technical value. Cardiopulmonary resuscitation technique videos also had higher popularity scores than "information or lecture" videos. Also, negative correlations were found between the (popularity index and transparency, education and technical quality scores. Online information on cardiopulmonary resuscitation is of low quality, and its contents are of unknown source and accuracy. However, the educational potential of the online video platform, YouTube, cannot be neglected.


Homograft bone in revision acetabular arthroplasty. A clinical and radiographic study.
Thirty-seven patients with extensive acetabular defects due to loose implants had revisions with uncemented components, the acetabulum being augmented with homograft bone. In six of these, a histological study of graft incorporation was made. At a mean follow-up of 1.5 years 34 patients were free of pain and 35 could walk for 30 minutes or longer. No graft had obviously sequestrated. Two components had radiological evidence of migration but remain asymptomatic. We conclude that cementless revision surgery with homograft supplementation of the acetabulum is clinically successful in the short-term. The long-term outcome is unknown.


Short sequence in L1 region of human papillomaviruses correlates with clinical pictures and grouping by cross-hybridization.
A consensus primer-mediated polymerase chain reaction devised to amplify a short sequence in L1 region (L1-PCR) efficiently detected genital human papillomaviruses (HPVs) in clinical materials. Nucleotide sequencing of the amplified fragment showed that L1-PCR is also applicable to hitherto unsequenced HPVs. By comparing the amplified 210 nucleotides HPVs were classified into six groups, which are consistent with clinical pictures and a grouping based on cross-hybridization under the stringent condition.


Ethical Questions in Medical Electronic Adherence Monitoring.
Electronic adherence monitors (EAMs) record and report an array of health behaviors, ranging from taking daily medications to wearing medical devices. EAMs are utilized in research worldwide and are being investigated for clinical use. However, there is also growing popular concern about the extent to which electronic devices may be used to monitor individuals, including allegations in the media that EAMs represent a move towards "Big Brother" in medicine. Here, we highlight the unique benefits as well as the potential ethical challenges that electronic adherence monitoring generates. These challenges surround autonomy, privacy and confidentiality, trust, and ancillary care obligations. We describe key questions within each of these domains that warrant further investigation, and present potential solutions to many of the concerns raised.


The subjective amplitude of the diurnal rhythm matters - Chronobiological insights for neuroimaging studies.
Multiple aspects of human psychophysiology, including mood and cognition, are subjected to diurnal rhythms. While the previous magnetic resonance imaging (MRI) studies have focused solely on the morningness-eveningness (ME) preference dichotomy, i.e. the circadian phase, the second key dimension of the diurnal rhythms, i.e. the strength of these preferences (amplitude; AM), has been completely overlooked. Uncovering the neural correlates of AM is especially important considering its link with negative emotionality. Structural T1-weighted neuroimaging data from 79 early (EC) and 74 late (LC) chronotypes were analysed to compare grey matter (GM) volume and cortical thickness. The study aimed to elucidate whether the subjective AM and its interaction with ME was a significant predictor of individual brain structure. Both GM volume and cortical thickness of the left primary visual cortex was negatively correlated with AM scores across the entire sample. Furthermore, EC and LC differed in their association between AM scores and the GM volume in the right middle temporal gyrus, with the positive and negative correlations reported respectively in the two groups. The current study underlines the importance of the visual system in circadian rhythmicity and provides possible neural correlates for AM-related differences in negative affect processing. Furthermore, the presence of the opposite correlations between brain anatomy and AM in the two groups suggests that the behavioural and neuronal chronotype differences might become more pronounced in individuals with extreme diurnal differences in mood and cognition, highlighting the necessity to additionally account for AM in neuroimaging studies.


Parturient paresis and hypocalcemia in ruminant livestock.
Parturient paresis (hypocalcemia) is most likely to affect dairy cattle around the time of parturition. It causes progressive neuromuscular dysfunction and flaccid paralysis. Older dairy cows, cows with a history of parturient paresis during a previous lactation, high-producing cows, and cows from the Jersey and Guernsey breeds are at highest risk for developing parturient paresis. Nonparturient hypocalcemia may also occur and is related to events other than parturition, such as severe stress, that temporarily overwhelm the mechanisms of calcium homeostasis. Beef cattle, sheep, and goats are affected less frequently by hypocalcemia than are dairy cows. Because these species are not as stressed for milk production as dairy cattle, nonparturient hypocalcemia makes up a higher proportion of cases in nondairy ruminants. Clinical signs of hypocalcemia in beef cattle, sheep, and goats tend toward hyperesthesia and tetany rather than the classic flaccid paralysis that occurs in dairy cattle with parturient hypocalcemia. Prompt and effective treatment of hypocalcemia helps to reduce the incidence of secondary complications, such as muscle damage or mastitis. The standard treatment regimen of 500 ml of 23 per cent calcium gluconate, administered intravenously, will elicit a favorable response in approximately 75 per cent of recumbent cows within 2 hours of treatment. Relapses following successful initial therapy are common and may be prevented in part by supplementation of intravenous treatment with an additional 500 ml of 23 per cent calcium gluconate administered subcutaneously. Proper nursing care following treatment speeds recovery and reduces the incidence of secondary complications owing to hypocalcemia.


Treatment selection for cancer patients: application of statistical decision theory to the treatment of advanced ovarian cancer.
Optimal treatment selection for patients with chronic disease, especially advanced cancer, requires careful consideration in weighing risks and benefits of each therapy. The application of statistical decision theory to such problems provides an explicit and systematic means of combining information on risks and benefits with individual patient preferences on quality-of-life issues. This paper evaluates the strengths and weaknesses of this methodology by using, as an example, treatment selection in advanced ovarian cancer. Possible treatment options and the major consequences of each are first outlined on a decision tree. The probability of various outcomes is estimated from the literature and methods for assessing the relative value or utility of each outcome are illustrated by interviews with 9 volunteers. Based on decision analysis, the recommended treatment for advanced ovarian cancer is found to be highly dependent on survival estimates but far less dependent on other probability estimates or the method of obtaining utilities. Individual preferences are also found to influence the treatment choice. The analysis illustrates that an important strength in using decision theory is its ability to identify key factors in the decision through sensitivity analysis. This may help both the physician selecting treatment and the investigator planning clinical trials which compare these therapies. In addition, this method can help in planning a trial's sample size by determining what survival difference between therapeutic strategies is worth detecting. Some problems identified with this methodology include the need for several simplifying assumptions and the difficulties in assessing individual preferences. On balance, we believe decision theory in this setting can play a useful role in complementing the physician's clinical judgement.


Evaluation of a leukotriene receptor antagonist in prevention of hyperoxic lung injury in newborn rabbits.
Prolonged exposure to hyperoxia can result in significant lung injury and has been associated with the development of bronchopulmonary dysplasia. Leukotrienes (LT) recruit polymorphonuclear leukocytes (PMN) to the lung, increase vascular permeability, and have therefore been postulated to play a role in the pathogenesis of hyperoxic lung injury. This study investigates ICI 198,615 (ICI), an LTD4 and LTE4 receptor antagonist in preventing hyperoxic lung injury in newborn rabbits. Matched littermates of 7-day-old rabbits received ICI (0.1 or 1.0 microM/kg/h) or vehicle alone, were exposed to greater than 95% O2, and sacrificed after 48, 72, 84 and 96 h of exposure. Bronchoalveolar alveolar lavage fluid (BAL) of the left lung was analyzed for white cell count, differential, absolute number of PMNs, total protein, and cyclooxygenase products 6-keto-PGF1 alpha, and thromboxane B2. Lung water was quantified utilizing the right lung. Results demonstrated no significant differences between the ICI groups or between the ICI groups and controls. In conclusion, the administration of the LTD4 and LTE4 receptor antagonist ICI 198,615 was insufficient to reduce the formation of pulmonary edema, reduce mortality or attenuate hyperoxic lung injury. These experiments suggest that a number of other mediators may be involved in the hyperoxic lung injury process and that the functional inhibition of a portion of the arachidonic acid cascade was not sufficient to either prevent or attenuate hyperoxic lung injury in newborn rabbits.


Multidetector computed tomography diagnosis of splenic flexure volvulus: usefulness of multiplanar reformats.
Splenic flexure volvulus is the least common form of colonic volvulus. Preoperative radiological diagnosis is usually made presumptively, based on plain radiographs and/or barium contrast enema study in patients presenting with acute large bowel obstruction. We report a case in which multidetector computer tomography (CT) findings were diagnostic of this condition, thus highlighting the usefulness of multiplanar reformatting.


Sedation Practice Outside the Operating Room for Pediatric Gastrointestinal Endoscopy.
Medical records of the 575 children who underwent gastrointestinal endoscopy outside the operating room were investigated retrospectively. The most frequently used combinations were propofol-midazolam-fentanyl in 83.2% of the procedures and propofol-midazolam in 13.8% of the procedures. 24 (3.4%) of 703 procedures had complications due to sedation anesthesia; 11 had hypoxia and 8 had pain in the injection area. Sedation anesthesia practice provided by an anesthesiologist outside the operating room enables gastrointestional endoscopic procedures to be carried out more safely.


Antigenic specificity in the E-rosette augmentation reaction.
The antigen reactivity of murine T-lymphocytes can be detected by their formation of a lymphokine that augments the formation of E-rosettes by normal human lymphocytes and sheep erythrocytes. Aspects of the specificity of E-rosette augmentation (ERA) were investigated with spleen cells of mice immunized with proteins or contact-sensitizers. The antigen dose-response curves in ERA were bell-shaped, with peak reactivity at optimal antigen concentrations and complete inhibition with moderate antigen excesses of 5-10 times the optimum. Optimal ERA was antigen-specific, spleen cells reacting only with molecules containing the immunizing determinant. Inhibition with moderate excess was also antigen-specific but great excess of antigen (100 times the optimum) was non-specifically suppressive. The mechanism of specific suppression by moderate excess of antigen appears to be related to the mode of its presentation to lymphocytes by accessory cells. The property of T-lymphocytes, reacting with a single defined determinant, to be inhibited specifically by moderate excess of any antigen containing this determinant, suggests a method of analysis of complex antigens.


[The concurrence of bronchial carcinoma and anthracosilicosis in the lung (concomitantly a contribution to "silicotic carcinoma in scar tissue of the lung")].
Among 4608 evaluated post mortem records (3452 miners with silicosis and 1156 miners without silicosis or nonminers resp.) 501 cases had developed a bronchial carcinoma. 425 of these observed cases showed a bronchial carcinoma together with silicosis, 76 cases were without anthracosilicosis. The occurrence of the bronchial carcinoma in case of anthracosilicosis did not depend on the time of employment in the underground mining industry. Neither was there a correlation between the determined grade of anthracosilicosis and the frequency of bronchial carcinoma. The diagnosis for 2,8% of these combined cases of anthracosilicosis and bronchial carcinoma was silicotic carcinoma of scar tissue. Statistically no signficant differences could be detected between the two groups of bronchial carcinomata with and without silicosis regarding age structure, kind of propagation and histological type of the bronchial carcinoma.


Cleavage of the C(O)-S Bond of Thioesters by Palladium/Norbornene/Copper Cooperative Catalysis: An Efficient Synthesis of 2-(Arylthio)aryl Ketones.
A Pd/norbornene/Cu cooperative catalysis for the efficient synthesis of 2-(arylthio)aryl ketones from aryl halides and thioesters has been developed. The first example of cooperative catalysis by palladium, norbornene, and copper, wherein the C(O)-S bond of thioesters is cleaved by a Pd(II) palladacycle with the assistance of CuI, has been observed.


Atypical Temporal Dynamics of Resting State Shapes Stimulus-Evoked Activity in Depression-An EEG Study on Rest-Stimulus Interaction.
Major depressive disorder (MDD) is a complex psychiatric disorder characterized by changes in both resting state and stimulus-evoked activity. Whether resting state changes are carried over to stimulus-evoked activity, however, is unclear. We conducted a combined rest (3 min) and task (three-stimulus auditory oddball paradigm) EEG study in n=28 acute depressed MDD patients, comparing them with n=25 healthy participants. Our focus was on the temporal dynamics of both resting state and stimulus-evoked activity for which reason we measured peak frequency (PF), coefficient of variation (CV), Lempel-Ziv complexity (LZC), and trial-to-trial variability (TTV). Our main findings are: i) atypical temporal dynamics in resting state, specifically in the alpha and theta bands as measured by peak frequency (PF), coefficient of variation (CV) and power; ii) decreased reactivity to external deviant stimuli as measured by decreased changes in stimulus-evoked variance and complexity-TTV, LZC, and power and frequency sliding (FS and PS); iii) correlation of stimulus related measures (TTV, LZC, PS, and FS) with resting state measures. Together, our findings show that resting state dynamics alone are atypical in MDD and, even more important, strongly shapes the dynamics of subsequent stimulus-evoked activity. We thus conclude that MDD can be characterized by an atypical temporal dynamic of its rest-stimulus interaction; that, in turn, makes it difficult for depressed patients to react to relevant stimuli such as the deviant tone in our paradigm.


Essential Oil Variation within Warburgia salutaris-A Coveted Ethnomedicinal Aromatic Tree.
Warburgia salutaris, known as 'Pepper bark', is an ethnomedicinally important tree found in the southern regions of Africa. A total of 75 fresh leaf specimens of W. salutaris (n=40 wild and 35 cultivated) were collected from the Limpopo (wild) and KwaZulu-Natal provinces (cultivated), two distinct locations in South Africa. In this study, the leaf essential oils obtained by hydrodistillation were characterized using gas chromatography coupled to mass spectrometry/flame ionization detection (GC/MS/FID). More than 15 compounds, accounting for 90-99 % of the total oil composition were identified. The analysis revealed that myrcene (0.6-65.3 %), (E)-β-ocimene (nd-56.9 %), (Z)-β-ocimene (nd-19.1 %), α-pinene (nd-19.1 %) and limonene (nd-11.7 %) are major constituents of W. salutaris essential oils. Chemometric analysis revealed two major chemotypes within the essential oils with a modeled variation of approximately 60 %. Linalool and germacrene D were revealed as markers associated with the wild-harvested oils, while cultivated oils were distinguished by higher levels of limonene and α-humulene. The intra-population variation indicated two chemically distinct chemotypes from three different populations, however, the season of harvest did not have a direct influence on the chemical profiles of the essential oils.


Epidemiology and antimicrobial resistance of Escherichia coli in broiler chickens, farmworkers, and farm sewage in Bangladesh.
Antimicrobial resistance (AMR) has become an emerging threat worldwide, and developing countries such as Bangladesh are considered to be at greater risk of disseminating the resistant bacteria between human-animal interfaces. The present study was carried out to determine the prevalence and AMR profile of Escherichia coli isolated from broiler chickens, the environment, and farmworkers. This study also aimed to identify the risk factors associated with multidrug-resistant (MDR) E. coli infection in broiler chickens. In addition, the presence of carbapenem resistance gene (NDM-1) was assessed. A total of 114 E. coli isolates, recovered from 150 samples (cloacal swabs = 50, farm sewage = 50, and hand washed water of farmworkers = 50) collected from 50 broiler farms, were identified by biochemical examination and polymerase chain reaction (PCR) assay. Antimicrobial susceptibility test was performed for 10 antibiotics by disk diffusion test. Carbapenem resistance gene (NDM-1) was detected by PCR. Risk factors were identified through multivariable logistic regression. The highest prevalence of E. coli was recorded in broiler chickens (86%) and the lowest in farmworkers (66%). For MDR E. coli infection, 'winter season', 'absence of specific shoes for staff', and 'use of antibiotics without veterinarian's prescription' were the significant risk factors. High resistance of the E. coli isolates was observed against levofloxacin (81.6%), doxycycline (78.1%), cefotaxime (78.1%), and ciprofloxacin (70.2%). About 76% of the isolates demonstrated MDR. None of the isolates were positive for the NDM-1 gene. The high level and similar pattern of antibiotic resistance in E. coli isolates from broiler chickens, farmworkers, and sewage in poultry farms indicates a good possibility of spreading the antibiotic-resistant E. coli in such settings.


Enhanced reductive degradation of methyl orange in a microbial fuel cell through cathode modification with redox mediators.
A model azo dye, methyl orange (MO), was reduced through in situ utilization of the electrons derived from the anaerobic conversion of organics in a microbial fuel cell (MFC). The MO reduction process could be described by a pseudo first-order kinetic model with a rate constant of 1.29 day(-1). Electrochemical impedance spectroscopic analysis shows that the cathode had a high polarization resistance, which could decrease the reaction rate and limit the electron transfer. To improve the MO reduction efficiency, the cathode was modified with redox mediators to enhance the electron transfer. After modification with thionine, the polarization resistance significantly decreased by over 50%. As a consequence, the MO decolorization rate increased by over 20%, and the power density was enhanced by over three times. Compared with thionine, anthraquinone-2, 6-disulfonate modified cathode has less positive effect on the MFC performance. These results indicate that the electrode modification with thionine is a useful approach to accelerate the electrochemical reactions. This work provides useful information about the key factors limiting the azo dye reduction in the MFC and how to improve such a process.


Graphene Quantum Dots: Molecularly Designed, Nitrogen-Functionalized Graphene Quantum Dots for Optoelectronic Devices (Adv. Mater. 23/2016).
H. Tetsuka and co-workers develop a versatile technique to tune the energy levels and energy gaps of nitrogen-functionalized graphene quantum dots (NGQDs) continuously through molecular structure design, as described on page 4632. The incorporation of layers of NGQDs into the structures markedly improves the performance of optoelectronic devices.


[Lymphomatoid papulosis in childhood: six case reports and a literature review].
Lymphomatoid papulosis (LyP) is a rare lymphoproliferative disorder. It is now included in the World Health Organisation (WHO) classification of cutaneous lymphomas. Although frequently described in adults, there have been only a few reported cases of LyP in children; diagnosis is often difficult in this population and no clear guidelines have been established regarding management or monitoring. In this article we report six new cases of LyP in children. This is a retrospective study of six children, aged between two and 11 years, seen at the Hôtel-Dieu Hospital in Lyon and at the Grenoble Hospital Centre between 2005 and 2008. Each child underwent skin biopsy for histological and immunohistochemical analysis. All six children presented papulonodular lesions on the limbs and trunk, in some cases necrotic, present for different times and developing in episodes. Histology and immunolabelling announces in all six cases militated in favour of LyP type A, with large CD30+ and CD15- cells dispersed in an inflammatory dermal infiltrate made up for the most part of lymphocytes, polynuclear neutrophils, eosinophils and a small number of histiocytes. Only around 60 cases of LyP have so far been reported in children, principally type A. Association with malignant lymphoma occurs, with high risk in relation to the general population of the same age. Clinical diagnosis is confirmed histopathology and immunolabelling. There is currently no consensus regarding therapeutic management. First-line treatment generally comprises therapeutic abstention or dermal corticosteroids. Methotrexate and phototherapy constitute possible alternatives but should be used only in very disseminate or debilitating forms of the disease. The presentation and course of LyP of childhood differs very little from the adult form. Cases of associated lymphoma have been reported. Although regular clinical monitoring is recommended, there is no call for routine laboratory testing.


Silk flow diverter in the treatment of complex intracranial aneurysms: a single-center experience with 60 patients.
Flow diverters are used to treat complex aneurysms that are not amenable to coiling. The aim of the present work was to retrospectively evaluate our experience with the Silk flow diverter. Technical nuances and complications are specifically discussed. Retrospectively data was collected on patients treated with Silk between October 2008 and October 2013. Sixty patients harboring 67 aneurysms were treated using the Silk. Fifteen aneurysms were located in the posterior circulation and 52 in the anterior. A good angiographic result was achieved in 88 % (53/60) of the aneurysms available for imaging follow-up. There were ten treatment-related complications, 80 % were ischemic. Risk of complications increased with aneurysm size and in aneurysms of the posterior circulation. Silk flow diverters are a good treatment option for aneurysms of the anterior circulation. Additional stents may be required in specific cases due to the Silk's low radial resistance. Treatment of giant fusiform aneurysms of the posterior circulation with Silk flow diverters is associated with a high rate of severe complications.


Outcomes of knee replacement patients using autotransfusion.
More than 500,000 total knee replacements are performed annually in the United States, of which approximately 30% to 50% utilized autotransfusion. The purpose of the study was to describe the difference in patient outcomes between autotransfusion and allogenic blood recipients who have a total knee replacement. A descriptive study using retrospective chart review (N = 115) was conducted. Those receiving autotransfusion had a significant shorter length of stay. No difference in hemoglobin or discharge site was found between those receiving autotransfusion and those receiving allogenic blood. Lower weight and increased age were associated with discharge to an inpatient rehabilitation unit.


Venous anomaly analogous to vertical embryonic positioning of the straight sinus associated with atretic cephalocele at the suboccipital region.
The coexistence of venous anomalies, such as vertical embryonic positioning of the straight sinus (VEP of SS), has been reported in patients with atretic cephalocele (AC). VEP of SS has been exclusively encountered when the AC is found above the torcular. We report a patient with suboccipital AC associated with venous anomalies analogous to VEP of SS, consisted of the Galenic venous system which did not drain into the straight sinus in the tentorium, but into the falcine sinus instead. Differences with VEP of SS in our case had no anatomical relationship between the falcine sinus and the suboccipital AC and no large cerebrospinal fluid space around the falcine sinus. A detailed neuroradiological examination was helpful for detecting these minute anomalies.


Diimidazo[1,2-c:4',5'-e]pyrimidines: adenosine agonist activity demonstrated by microphysiometry.
Silicon-based microphysiometry, measuring extracellular acidification rate of cells in culture, demonstrated that a series of diimidazo[1,2-c:4',5'-e]pyrimidines were agonists at the human adenosine A1 receptor. 5-amino-7,8-dihydro-3-ribofuranose-8-(R)-(phenyl)-3H-diimidazo [1,2-c:4',5'-e]pyrimidine (2a) had an EC50 of 100 microM and reached 90% of the Emax produced by R-PIA.


Structural insights into human serum albumin-mediated prostaglandin catalysis.
Previous studies have shown that many arachidonic acid metabolites bind to human serum albumin (HSA) and that the metabolism of these molecules is altered as a result of binding. The present study attempted to gain insights into the mechanisms by which prostaglandins bound to subdomain 2A of HSA are metabolized by catalytic processes. The breakdown of the prostaglandin 15-keto-PGE(2) to 15-keto-PGA(2) and 15-keto-PGB(2) in the presence of wild-type HSA and a number of subdomain 2A mutants was examined using a previously validated spectroscopic method which monitors absorbance at 505 nm. The species examined using this method were wild-type HSA, K195M, K199M, F211V, W214L, R218M, R218P, R218H, R222M, H242V, R257M, and bovine serum albumin. Previous studies of HSA-mediated catalysis indicated that the breakdown of HSA-bound prostaglandins results from an alkaline microenvironment in the binding site. Our results show that the catalytic breakdown of HSA-bound 15-keto-PGE(2) to 15-keto-PGB(2) results from two specific processes which are modulated by specific amino acid residues. Specifically, some amino acid residues modulate the rate of step 1, the conversion of 15-keto-PGE(2) to 15-keto-PGA(2), while other residues modulate the rate of step 2, the conversion of 15-keto-PGA(2) to 15-keto-PGB(2). Some residues modulate the rate of steps 1 and 2. In total, while our results support the involvement of certain basic amino acid residues in the catabolism of HSA-bound 15-keto-PGE(2), our data suggest that metabolism of HSA-bound prostaglandins may be a more complex and specific process than previously thought.


In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys.
Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. Similar to cocaine, other local anesthetics bind to the dopamine transporter (DAT) and inhibit DA uptake in rodent and monkey brain. Additionally, local anesthetics are self-administered in rhesus monkeys, indicative of abuse liability. The present study examined the reinforcing and DAT effects of the local anesthetics dimethocaine, procaine and cocaine using in vivo techniques. Monkeys were trained to respond under a second-order schedule for i.v. cocaine administration (0.10 or 0.30 mg/kg/infusion). When responding was stable, dimethocaine (0.030-1.7 mg/kg/ infusion) or procaine (0.10-10 mg/kg/ infusion) was substituted for the cocaine training dose. Dimethocaine administration produced higher response rates compared with that of procaine, and was a more potent reinforcer. Drug effects on behavior were related to DAT occupancy in monkey striatum during neuroimaging with positron emission tomography (PET). DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 66 and 82% and <10-41% for doses of dimethocaine and procaine that maintained maximum response rates, respectively. Finally, in vivo microdialysis in awake subjects determined drug-induced changes in extracellular DA in the caudate nucleus. There was close correspondence between peak increases in DA and DAT occupancy. Overall, reinforcing effects were consistent with DAT effects determined with in vivo techniques. The results further support a role for the DAT in the abuse liability of local anesthetics.


[Annual epidemics of hepatitis A in four large cities related to holiday travel among immigrant children].
Analysis of the transmission pattern of hepatitis A in relation to ethnicity and travel behaviour in Amsterdam. Utrecht, Rotterdam and The Hague. Descriptive study of notified cases. Municipal Health Services of the four major cities in the Netherlands. Notification data of hepatitis A in Amsterdam, Utrecht, Rotterdam and The Hague were analysed over the period 1992-1995. Cases were analysed according to age (0-19 years or > 19 years), whether or not they travelled abroad in the period of six weeks before the onset of the first symptoms of disease, and endemicity of hepatitis A in the country of ethnic origin. The strong increase of hepatitis A after the summer holidays could be divided into several smaller epidemics starting with an epidemic among children of Moroccan and Turkish descent who had spent the summer holidays in these countries, among children of the same ethnic background who had not travelled abroad, followed by epidemics among non-travelling children and adults of mainly Dutch descent, respectively. A strong correlation was found in Amsterdam between the incidence in the former two groups and the latter two groups (Pearsons r = 0.68; p = 0.004). Children who spent the summer holidays in a hepatitis A endemic country, particularly Morocco and Turkey, appeared to be the main importers of hepatitis A in the four major cities. Active immunization of all children born in the Netherlands of Moroccan and Turkish descent is the most preferable intervention.


Occurrence of dolichol in human tissues.
The concentration of dolichol has been determined in various human tissues obtained at autopsy. The highest levels ( 3000 microgram/g wet weight) were found in testes. Liver and several other endocrine tissues contained about 1000 microgram/g. Lower levels were present in other tissues examines. Only a small proportion of the total dolichol in human tissues was esterified to fatty acids.


The deep medial femoral sulcus sign: does it exist?
To determine the normal depth of the medial femoral sulcus on lateral radiographs of the knee and determine if abnormal deepening of the medial femoral sulcus exists as a radiographic indicator of intra-articular knee abnormalities. A retrospective search was performed over a period of 10 years to identify all individuals with a bone contusion of the anterior medial femoral condyle at MR imaging. Study patients had documented acute knee injuries and radiographs 6 weeks or less prior to their MR. A control group had normal MR exams and radiographs 6 weeks or less prior to their MR. Two fellowship-trained musculoskeletal radiologists independently measured the depth of the medial femoral sulcus on lateral radiographs blinded to control or study individuals. The study group consisted of 76 patients (57 men, 19 women; age range, 18-50 years; mean age, 27 years) and 92 control patients (33 men, 59 women; age range, 18-46 years; mean age 26 years). Sulcus depth was (0-2.3 mm reader 1 and 0-1.7 mm reader 2 for controls; 0-2.2 mm reader1 and 0-1.8 mm reader 2 for study patients). No significant difference in sulcus depth was identified between the control and study groups. Inter-reader agreement was very strong. The most common cause of injury in the study group was motor vehicle accidents followed by hyperextension and twisting injuries of the knee. The normal medial femoral sulcus ranges in depth from 0 to 2.3 mm. Although impaction of the sulcus does occur following knee injuries, the sulcus does not deepen.


Experimental validation of a novel spine model demonstrates the large contribution of passive muscle to the flexion relaxation phenomenon.
When an individual enters a maximally flexed spine position, their largest extensor muscles become electrically inactive despite a substantial extensor moment demand being placed on the low back; this is termed flexion relaxation. Stresses within intervertebral discs, ligaments, and passive muscles are thought to support this moment thereby allowing the extensor muscles to 'turn off'. While the mechanical behaviour of the intervertebral disc and ligaments have been studied extensively, less is known regarding the moment supported by passive muscle tissue during spine flexion. Here we estimated the L4/L5 moment supported by the passive musculature during spine flexion based on experimentally derived architectural and material properties. We then tested the validity of the passive muscle prediction by determining whether the cumulative passive tissue moment (including passive muscle, intervertebral discs, and ligaments) would support the extensor moment demand-calculated with inverse dynamics-near maximum spine flexion. The model predicted that the passive tissues were able to support the entire extensor moment demand, indicating that muscle activity was not required to support the weight of the upper body, consistent with the mechanism of flexion relaxation. The model further demonstrated that despite being inactive, spine muscles still greatly contribute to flexion relaxation by passively supporting ~47% of the extensor moment demand on the spine. Finally, there was strong agreement between the predicted active muscle moments and the recorded spine muscle activity (EMG); this strong agreement persisted when the external moment was manipulated using a pulley-system. These findings provide additional confidence that the estimated passive muscle moments are reasonably accurate throughout spine flexion.


Fat content of the diet among pre-school children in Britain; relationship with food and nutrient intakes.
To investigate the relationship between the percentage of energy from fat and food and nutrient intakes at 18 and 43 months of age. Diet was assessed using a 3 day unweighed food record. The children were divided into quartiles of fat intake as a percentage of energy (QFI), and food and nutrient intakes in the different QFIs were compared. A total of 1026 children at 18 months and 863 children at 43 months, taking part in the Avon Longitudinal Study of Pregnancy and Childhood, participated. At 18 months the mean (s.d.) fat intake was 31.2 (2.8) % of energy in the lowest QFI and 43.1 (2.2) % in the highest. Energy intake increased slightly with increasing QFI. The percentage of energy derived from total sugar, and in particular non-milk extrinsic sugar fell as QFI increased, as did the ratio of polyunsaturated to saturated fatty acids. Intakes of retinol equivalents and zinc increased significantly with increasing QFI, while intakes of iron and most water soluble vitamins fell. There was a particularly marked fall in vitamin C intake as fat intake increased, from 11.8 mg/MJ in the lowest QFI, to 6.0 mg/MJ in the highest (P<0.001). Consumption of whole milk increased substantially with percentage energy from fat, from 51 g/MJ in the lowest QFI to 116 g/MJ in the highest (P<0.001), while consumption of fruit and fruit juice fell. The results obtained at 43 months were very similar. The chances of a suboptimal intake of zinc and retinol were higher at lower fat intakes. However, intakes of the fat-soluble vitamins E and D were unrelated to fat intake and intakes of iron and vitamin C fell as fat intakes increased. Some suggestions for improving diet in this age group have been given. University of Bristol.


A method for collecting semithin epoxy serial sections for light microscopy and 3-D reconstruction.
In the three-dimensional reconstruction of neuronal structure, it is imperative that ribbons of semithin or ultrathin sections be obtained. Resin-embedded semithin sections display better structural details than paraffin-embedded sections. The cutting and collecting of long ribbons of resin-embedded semithin sections using a microtome, requires the use of large troughs on glass knives. A simple plastic trough has been described which facilitates the collection of ribbons directly onto a coverslip. As the ribbons are formed, they are floated on a coverslip. The water in the trough is slowly drained through a tubing which is attached to a syringe. The ribbons settle on the coverslip, which is easily removed and placed on a hotplate to dry the sections.


Spontaneous separation of epiretinal membrane in a child with Stargardt macular dystrophy.
We demonstrate optical coherence tomography findings of spontaneous separation of an epiretinal membrane associated with Stargardt macular dystrophy in a child. A period of observation seems appropriate in eyes with an epiretinal membrane associated with Stargardt's disease, as the membrane may show spontaneous release and the macular area may improve.


Transfer of maternal colostral leukocytes promotes development of the neonatal immune system I. Effects on monocyte lineage cells.
Although it has been established that maternal leukocytes traffic from colostrum into the neonatal circulation, the effects of these cells on neonatal immunity are only beginning to be understood. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal antigen presenting cells. At birth, groups of neonatal calves received whole or cell-free colostrum (CFC) from their respective dams. Peripheral blood samples were obtained over the first 4 weeks of life, and expression of surface markers associated with cellular activation and physiological stress were monitored on monocyte lineage cells. Calves receiving cell-free colostrum at birth expressed elevated levels of CD11a, CD11c, and CD14, compared to calves receiving whole colostrum (C). Calves receiving cell-free colostrum had an elevated number of monocytes in the peripheral blood during the first 2 weeks of life, however, these cells expressed lower levels of expression of CD25 and MHC class I compared to calves receiving whole colostrum. The most significant differences in marker expression occurred within the first 7 days of life.


Fibre-optic transillumination of the sinuses: a comparison of the value of radiography and transillumination in antral disease.
The development of transillumination of the paranasal sinuses is reviewed. A technique of transillumination with a fibre-optic source is described. In acute sinusitis there was a very significant correlation between radiography and transilluminometry.


Parent-assisted group treatment for friendship problems of children with autism spectrum disorders.
Children with Asperger's Disorder or High Functioning Autism are included in regular education classes but find themselves excluded from the social lives of their classmates. This paper briefly reviews studies which attempt to provide them with training to overcome their social difficulties. These interventions have had limited success and have not systematically incorporated the child's parents into the intervention. Children's Friendship Training is a manualized parent-assisted group treatment which teaches social skill through learning and practicing sets of rules of etiquette for key social situations. The treatment approach has been demonstrated to have success in improving friendships of children with autism spectrum disorders. The content of Children's Friendship Training is briefly described and results of controlled studies are reviewed. Limitations of previous research and future directions are also described.


Adsorption of As(V) and Ni(II) by Fe-Biochar composite fabricated by co-pyrolysis of orange peel and red mud.
This study aimed to compare the adsorption performance of Fe-biochar composites (Fe-C-N2 and Fe-C-CO2), fabricated by co-pyrolysis of red mud and orange peel in N2 and CO2, for As(V) and Ni(II). By the syngas production comparison test, it was confirmed that CO2 was more advantageous than N2 as a pyrolytic medium gas to produce more CO. The resulting Fe-biochar composite showed the aggregate morphology consisting of different Fe phases (magnetite or metal Fe) from the inherent hematite phase in red mud and carbonized carbon matrix, and there was no distinct difference between the structural shapes of two Fe-biochar composites. Adsorption experiments showed that the adsorption capacities for As(V) and Ni(II) in single mode were almost similar with 7.5 and 16.2 mg g-1 for Fe-C-N2 and 5.6 and 15.1 mg g-1 for Fe-C-CO2, respectively. The adsorption ability of Fe-C-CO2 for both As(V) and Ni(II) was further enhanced in binary adsorption mode (As(V): 13.4 mg g-1, Ni(II):17.6 mg g-1) through additional removal of those ions by Ni(II)-As(V) complexation. The overall results demonstrated CO2-assisted pyrolysis can provide a viable platform to convert waste materials into fuel gases and environmental media for co-adsorption of cationic and anionic heavy metals.


Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts.
Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome. Post hoc analysis of two prospective cohort studies conducted in two ICUs. In patients mechanically ventilated for at least 24 h undergoing a first spontaneous breathing trial, severe ICU-DD was defined as diaphragm twitch pressure < 7 cmH2O and ICU-AW was defined as Medical Research Council Score < 48. One hundred sixteen patients were assessed. Factors independently associated with severe ICU-DD were age, longer duration of MV, and exposure to sufentanil, and those factors associated with ICU-AW were longer duration of MV and exposure to norepinephrine. Severe ICU-DD (OR 3.56, p = 0.008), but not ICU-AW, was independently associated with weaning failure (59%). ICU-AW (OR 4.30, p = 0.033), but not severe ICU-DD, was associated with ICU mortality. Weaning failure and mortality rate were higher in patients with both severe ICU-DD and ICU-AW (86% and 39%, respectively) than in patients with either severe ICU-DD (64% and 0%) or ICU-AW (63% and 13%). Severe ICU-DD and ICU-AW have different risk factors and different impacts on weaning failure and mortality. The impact of the combination of ICU-DD and ICU-AW is more pronounced than their individual impact.


Dual action of androgen on calcium signaling and luteinizing hormone secretion in pituitary gonadotrophs.
An increase in serum androgen levels associated with a suppression of cyclic gonadotropin secretion is frequently observed in females with impaired ovarian function. Here, we addressed the hypotheses that androgens (testosterone and dihydrotestosterone) alter gonadotropin secretion by modulating agonist-induced Ca2+ signaling and/or Ca(2+)-controlled exocytosis. In mixed populations of pituitary cells from female rats, addition of testosterone reduced basal and agonist (GnRH)-induced gonadotropin secretion in a concentration- and time-dependent manner. The suppressive actions of this androgen on gonadotropin secretion were observed over the full GnRH concentration range. Reduction in agonist-induced gonadotropin secretion was also observed after addition of dihydrotestosterone, indicating that the inhibitory action of testosterone is not mediated by its conversion to estradiol. Both the extracellular Ca(2+)-independent spike phase and extracellular Ca(2+)-dependent sustained phase of GnRH-induced gonadotropin secretions were affected by testosterone. In part, the inhibitory action of testosterone was mediated by attenuation of GnRH-induced InsP3 production and InsP3-dependent Ca2+ mobilization. In addition, testosterone exhibited a Ca(2+)-independent action on gonadotropin secretion, as documented by attenuation of high potassium-induced secretion without an affect on depolarization-induced Ca2+ signals. These results suggest that androgen inhibition of gonadotropin secretion occurs at two distinct steps in the secretory pathway, one prior to and one after elevation in cytosolic Ca2+ concentration.


Muscle synergism during isometric plantarflexion in achilles tendon rupture patients and in normal subjects revealed by velocity-encoded cine phase-contrast MRI.
The triceps surae muscle is often considered to be the sole contributor to the plantarflexion torque although the deeper plantarflexor muscles may also be activated in the plantarflexion task. We measured coordinative strategies and muscle synergism during isometric plantarflexion task from 11 volunteers. Velocities from the distal end of the medial gastrocnemius, soleus, and flexor hallucis longus muscles were encoded in the superior-inferior direction using cine phase-contrast magnetic resonance imaging. Eight of the subjects were healthy and served as controls for subject to subject variability. Three of the subjects had experienced an Achilles tendon rupture followed by surgical repair and they were measured up to 8 weeks of rehabilitation. There were marked individual differences in the use of the different muscles during plantarflexion task in control subjects. Soleus to flexor hallucis longus displacement ratio during contraction varied from 0.4 to 9.6 while the moment arm ratio between Achilles tendon and flexor hallucis longus tendons was 1.9 (standard deviation 0.2). In Achilles tendon rupture patients the relative contribution of flexor hallucis longus was very high both in their injured and uninjured leg. This coordinative strategy remained throughout rehabilitation. The findings suggest that early recovery of plantarflexion torque after Achilles tendon rupture may be due to compensation by flexor hallucis longus as well as to normalization of the triceps surae muscle function. Also, this study suggests that the individual differences in coordinative strategies in addition to moment arms and muscle-tendon properties can influence the calculation of forces produced by individual muscles.


Centrally located lung cancer and risk of occult nodal disease: an objective evaluation of multiple definitions of tumour centrality with dedicated imaging software.
Current guidelines recommend invasive mediastinal staging in patients with centrally located radiographic stage T1N0M0 nonsmall cell lung cancer (NSCLC). The lack of a specific definition of a central tumour has resulted in discrepancies among guidelines and heterogeneity in practice patterns. Our objective was to study specific definitions of tumour centrality and their association with occult nodal disease. Pre-operative chest computed tomography scans from patients with clinical (c) T1N0M0 NSCLC were processed with a dedicated software system that divides the lungs in thirds following vertical and concentric lines. This software accurately assigns tumours to a specific third based both on the location of the centre of the tumour and its most medial aspect, creating eight possible definitions of central tumours. 607 patients were included in our study. Surgery was performed for 596 tumours (98%). The overall pathological (p) N disease was: 504 (83%) N0, 56 (9%) N1, 47 (8%) N2 and no N3. The prevalence of N2 disease remained relatively low regardless of tumour location. Central tumours were associated with upstaging from cN0 to any N (pN1/pN2). Two definitions were associated with upstaging to any N: concentric lines, inner one-third, centre of the tumour (OR 3.91, 95% CI 1.85-8.26; p<0.001) and concentric lines, inner two-thirds, most medial aspect of the tumour (OR 1.91, 95% CI 1.23-2.97; p=0.004). We objectively identified two specific definitions of central tumours. While the rate of occult mediastinal disease was relatively low regardless of tumour location, central tumours were associated with upstaging from cN0 to any N.


Sex differences in minor psychiatric morbidity: a survey of a homogeneous population.
Epidemiological methods of psychiatric assessment were used to examine whether there is a sex difference in the constitutional vulnerability of the male and female phenotype to minor psychiatric morbidity. In order to minimise the effect of environment and of sex roles and stereotypes as far as possible, a sample of relatively homogeneous employed men and women are studied. No sex difference in prevalence of minor psychiatric morbidity or its outcome was found in this population of men and women of similar age, education, occupation and social environment. However, women did report significantly more somatic symptoms of psychogenic origin.


Evaluation of the Potential Pharmacokinetic Interactions Between Vixotrigine and an Oral Contraceptive.
Vixotrigine is a voltage- and use-dependent sodium channel blocker in development for neuropathic pain management. This study evaluated the effect of coadministration of vixotrigine (metabolized primarily via uridine diphosphate-glucuronosyltransferases) and an oral contraceptive containing ethinyl estradiol (uridine diphosphate-glucuronosyltransferase inducer) and levonorgestrel on the pharmacokinetics and safety of all three compounds. In this phase I, open-label, fixed-sequence, multiple-dose study, 36 healthy women received oral vixotrigine 150 mg three times daily for 6 days and once on day 7. This was followed by a washout period, days 8-11. The oral contraceptive was administered alone on days 12-25 and with vixotrigine 150 mg three times daily on days 26-32. Serial blood samples were collected for pharmacokinetic analysis. Safety was assessed. The geometric least-squares mean ratios (90% confidence intervals) for the area under the concentration-time curve over 8 h and maximum concentration of vixotrigine co-administered with an oral contraceptive vs vixotrigine alone were 0.85 (0.82-0.89) and 0.91 (0.87-0.96), respectively. The geometric least-squares mean ratios (90% confidence interval) for area under the concentration-time curve over 24 h and maximum concentration of ethinyl estradiol with vixotrigine vs ethinyl estradiol alone were 0.94 (0.91-0.97) and 0.89 (0.84-0.94), respectively; the ratios for levonorgestrel with vixotrigine vs levonorgestrel alone were 1.06 (0.98-1.16) and 1.05 (0.98-1.13), respectively. No adverse events occurring with vixotrigine alone were deemed related to the study drug by the investigators. Coadministration of vixotrigine and an oral contraceptive containing ethinyl estradiol and levonorgestrel had no clinically relevant effect on exposure of all three compounds. ClinicalTrials.gov registration number: NCT03324685 (registered 25 October, 2017).


Cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries: a modelling study.
Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence. In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya, $750 in South Africa, $3000 in Colombia, and $1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective. Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya, $260 in South Africa, $2207 in Colombia, and $205 in Ukraine). Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis. WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation.


Organomediated Enantioselective (18)F Fluorination for PET Applications.
The first organomediated asymmetric (18)F fluorination has been accomplished using a chiral imidazolidinone and [(18)F]N-fluorobenzenesulfonimide. The method provides access to enantioenriched (18)F-labeled α-fluoroaldehydes (>90% ee), which are versatile chiral (18)F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2S,4S)-4-[(18)F]fluoroglutamic acid.


Ni-Doped CsPbBr3 Perovskite: Synthesis of Highly Stable Nanocubes.
A nanocube of Ni-doped CsPbBr3nanocrystals (NCs) has been successfully synthesized and characterized by various spectroscopy techniques such as High-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), etc. The optoelectronic properties of NCs have been investigated with different solvents. HR-TEM and FE-SEM reveal that the obtained Ni-doped CsPbBr3NCs exhibit cubic-rectangular morphologies with different sizes. Furthermore, the radiative exciton kinetics of NCs was examined using the time-correlated single photon counting (TCSPC) technique. The present study ravels that synthesized nanocubes are highly stable.


Pure primary testicular carcinoid: a case report and discussion.
We report a case of pure primary testicular carcinoid tumor and review the literature. Distinctions are emphasized among the 3 subgroups of testicular carcinoids and their clinical significance. Criteria to establish the diagnosis of pure primary testicular carcinoid are offered.


A UHPLC-MS/MS bioanalytical assay for the determination of BMS-911543, a JAK2 inhibitor, in human plasma.
Herein we report a rapid, accurate and robust UHPLC-MS/MS assay for the quantitation of BMS-911453, a Janus kinase 2 inhibitor under clinical development for the treatment of myeloproliferative disorders, in human plasma. A systematic method development approach was used to optimize the mass spectrometry, chromatography, and sample extraction conditions, and to minimize potential bioanalytical risks. The validated method utilizes stable-isotope labeled (13)C4-BMS-911543 as the internal standard. Liquid-liquid extraction was used for sample preparation. Chromatographic separation was achieved within 2min on a Zorbax Extend-C18 column with an isocratic elution. BMS-911543 and its internal standard were detected by positive ion electrospray tandem mass spectrometry. The assay range was from 1 to 500ng/mL, and the standard curve was fitted with 1/x(2) weighted linear regression. The intra-assay precision was within 5.0% CV and the inter-assay precision was within 2.6% CV. The inter-assay mean accuracy, expressed as percents of theoretical, was between 99.8% and 102.3%. The assay has high recovery (∼80%) and minimal matrix effect (0.95-1.00). BMS-911543 was stable in human plasma for at least 24h at room temperature, 90 days at -20°C, and following three freeze-thaw cycles. The validated method was successfully applied to sample analysis in clinical studies.


T lymphocytes (CD3) may participate in the recurrence of cervical intraepithelial neoplasia grade III.
Data from the literature demonstrate that the local and systemic immune responses seem to play an important role in the progression of cervical intraepithelial neoplasia (CIN). Our aim was to investigate whether recurrences among CIN III patients might be related to the presence of local lymphocytes, macrophage and enzyme iNOS. We analyzed 35 patients with CIN III who underwent conization and followed up for a minimum of 4 years. Using immunohistochemistry, the presence of T lymphocytes (CD3, CD8 and CD45RO), B lymphocytes (CD20), macrophages (CD68) and the expression of the enzyme iNOS were investigated. The quantity of marked cells is graded as: 0, absence of cells; 1, rare cells; 2, moderate number of cells; 3, many cells. For statistical purposes, we took the scores 0 and 1 to indicate weak marking and the scores 2 and 3 to indicate strong marking. We found strong positive expression of CD3-positive T lymphocytes among CIN III patients with recurrence following conization (100 vs. 50% without recurrence, p=0.02). We did not find any statistical differences in the expression of CD20, CD68, CD45RO, CD8 or iNOS. It is concluded that strong positive findings of CD3 T lymphocytes were related to recurrence following conization due to CIN III.


Collagen adhesin-nanoparticle interaction impairs adhesin's ligand binding mechanism.
Pathogenic bacteria specifically recognize extracellular matrix (ECM) molecules of the host (e.g. collagen, fibrinogen and fibronectin) through their surface proteins known as MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) and initiate colonization. On implantation, biomaterials easily get coated with these ECM molecules and the MSCRAMMs mediate bacterial adherence to biomaterials. With the rapid rise in antibiotic resistance, designing alternative strategies to reduce/eliminate bacterial colonization is absolutely essential. The Rhusiopathiae surface protein B (RspB) is a collagen-binding MSCRAMM of Erysipelothrix rhusiopathiae. It also binds to abiotic surfaces. The crystal structure of the collagen-binding region of RspB (rRspB31-348) reported here revealed that RspB also binds collagen by a unique ligand binding mechanism called "Collagen Hug" which is a common theme for collagen-binding MSCRAMMs of many Gram-positive bacteria. Here, we report the interaction studies between rRspB31-348 and silver nanoparticles using methods like gel shift assay, gel permeation chromatography and circular dichroism spectroscopy. The "Collagen Hug" mechanism was inhibited in the presence of silver nanoparticles as rRspB31-348 was unable to bind to collagen. The total loss of binding was likely because of rRspB31-348 and silver nanoparticle protein corona formation and not due to the loss of the structural integrity of rRspB31-348 on binding with nanoparticles as observed from circular dichroism experiments. Interaction of rRspB31-348 with silver nanoparticle impaired its ligand binding mechanism. Details of this inhibition mechanism may be useful for the development of antimicrobial materials and antiadhesion drugs.


Intracellular antioxidant enzymes are not globally upregulated during hibernation in the major oxidative tissues of the 13-lined ground squirrel Spermophilus tridecemlineatus.
Hibernating mammals exhibit oxidative stress resistance in brain, liver and other tissues. In many animals, cellular oxidative stress resistance is associated with enhanced expression of intracellular antioxidant enzymes. Intracellular antioxidant capacity may be upregulated during hibernation to protect against oxidative damage associated with the ischemia-reperfusion that occurs during transitions between torpor and arousal. We tested the hypothesis that the 13-lined ground squirrel (Spermophilus tridecemlineatus), upregulates intracellular antioxidant enzymes in major oxidative tissues during hibernation. The two major intracellular isoforms of superoxide dismutase (MnSOD and CuZnSOD), which catalyze the first step in superoxide detoxification, were quantified in heart, brain and liver tissue using immunodetection and an in-gel activity assay. However, no differences in SOD protein expression or activity were found between active and hibernating squirrels. Measurements of glutathione peroxidase and glutathione reductase, which catalyze hydrogen peroxide removal, were not broadly upregulated during hibernation. The activity of catalase, which catalyzes an alternative hydrogen peroxide detoxification pathway, was higher in heart and brain of torpid squirrels, but lower in liver. Taken together, these data do not support the hypothesis that hibernation is associated with enhanced oxidative stress resistance due to an upregulation of intracellular antioxidant enzymes in the major oxidative tissues.


Gene editing of a human gene in yeast artificial chromosomes using modified single-stranded DNA and dual targeting.
A single-nucleotide polymorphism (SNP) in a human gene can alter the behavior of the corresponding protein, and thereby affect an individual's response to drug therapy. Here, we describe a novel dual-targeting approach for introducing an SNP of choice into virtually any gene, through the use of modified single-stranded oligonucleotides (MSSOs). We use this strategy to create SNPs in a human gene contained in a yeast artificial chromosome (YAC). In the dual-targeting protocol, two different MSSOs are designed to edit two different bases in the same cell. A change in one of these genes is selective while the other is non-selective. We show that the population identified by selective pressure is enriched for cells that bear an edited base at the nonselective site. YACs with human genomic inserts containing particular SNPs or haplotypes can be used for pharmacogenomic applications, in cell lines and in transgenic animals.


Pseudopregnancy in Saanen goats (Capra hircus) raised in Northeast Brazil.
The prevalence of pseudopregnancy over 44 months was investigated in 23 Saanen goats raised in Northeast Brazil during continuous oestrous cycling (cyclic group) or after synchronization of oestrus (synchronized group). The goats were monitored by ultrasonography and their plasma progesterone profile. The overall prevalence of pseudopregnancy was 30.4% (7/23). In the cyclic group, 28.6% (4/14) of goats showed pseudopregnancy, while in the synchronized group the prevalence was 33.3% (3/9). There was no significant difference between the groups (p>0.05). The mean (+/- SD) length of pseudopregnancy, as shown by the progesterone profile, was 121.6 +/- 33.5 days, ranging from 70 to 155 days. The study defined the prevalence of pseudopregnancy in Saanen goats raised in Northeast Brazil for the first time. This finding identified a major problem for this breed, as without treatment such animals remain unproductive until the spontaneous resolution of the condition. More research seems desirable to ascertain the prevalence of this condition in other breeds in this region of Brazil.


Black esophagus as an uncommon cause of gastrointestinal bleeding.
Black esophagus (BE) or Acute esophageal necrosis (AEN) is rare clinical entity with an estimated incidence of 0.01-0.2% of patiens undergoing esophagogastroduodenoscopy (EGD). BE is characterized by circumferential blackish coloration of the mucosa, with abrupt interruption at the esophagogastric junction level, secondary to hypoperfusion and ischemia. Upper gastrointestinal hemorrhage is the most common presentation (70-90%), being a rare cause of it. We present 3 cases that were admitted in our center for hematemesis.


[Mucocutaneous lymph node syndrome (author's transl)].
Authors present the case of a two year old spanish girls with mucocutaneous lymph node syndrome such as described by Kawasaki.


Daunomycin-bands are similar to Q-bands on chromosomes of Vicia faba.
Lin et al.2 discovered fluorescent bands on human chromosomes stained with daunomycin (D-bands). These bands looked like Q-bands. We demonstrate D-bands, which look like respective Q-bands, in Vicia faba and infer that the similarity between D and Q banding is general.


Editors' roundup: October 2022.
This commentary constitutes the October edition of the 'Editors' roundup'-a multi-author omnibus of personal recommendations to interesting biophysics-related articles contributed by members of the editorial boards of leading international biophysics journals. The present commentary contains contributions from Progress in Biochemistry and Biophysics (an official journal of the Biophysical Society of China), European Biophysics Journal (the official journal of the European Biophysical Societies Association), Biophysical Reviews (the official IUPAB journal), and Biophysics (an official journal of the Russian Academy of Sciences). This edition of the Editors' Roundup also contains a new section from an editor at large who has provided selections from a number of journals on a single thematic topic.


miR319 and its target TCP4 involved in plant architecture regulation in Brassica napus.
Plant architecture is a collection of genetically controlled crop productivity and adaptation. MicroRNAs (miRNAs) have been proved to function in various biological processes, but little is known about how miRNA regulates plant architecture in rapeseed (Brassica napus L.). In this study, four small RNA libraries and two degradome libraries from shoot apex of normal and rod-like plants were sequenced. A total of 639 miRNA precursors and 16 differentially expressed miRNAs were identified in this study. In addition, 322 targets were identified through degradome sequencing. Among them, 14 targets were further validated via RNA ligase-mediated 5' rapid amplification of cDNA ends. Transgenic approach showed that increased TCP4 activity in Arabidopsis resulted in premature onset of maturation and reduced plant size along with early flowering and shortened flowering time. miR319-OE lines in Brassica napus exhibited serrated leaves and abnormal development of shoot apical meristem (SAM), which led to the deformed growth of stem and reduced plant height. In conclusion, our study lays the foundation for elucidating miRNA regulate plant architecture and provides new insight into the miR319/TCP4 module regulates plant architecture in rapeseed.


The skeleton: a multi-functional complex organ: the role of key signalling pathways in osteoclast differentiation and in bone resorption.
Osteoclasts are the specialised cells that resorb bone matrix and are important both for the growth and shaping of bones throughout development as well as during the process of bone remodelling that occurs throughout life to maintain a healthy skeleton. Osteoclast formation, function and survival are tightly regulated by a network of signalling pathways, many of which have been identified through the study of rare monogenic diseases, knockout mouse models and animal strains carrying naturally occurring mutations in key molecules. In this review, we describe the processes of osteoclast formation, activation and function and discuss the major transcription factors and signalling pathways (including those that control the cytoskeletal rearrangements) that are important at each stage.


Normalization of protein intake by body weight and the associations of protein intake with nutritional status and survival.
To examine the associations of total protein intake (TPI) and dietary protein intake (DPI) with baseline nutrition and subsequent mortality. Retrospective analysis of incident dialysis patients. National cohort from The United States Renal Data System data. Incident dialysis patients (n = 5,059) with blood urea nitrogen (BUN) and urea clearances reported on form 2728. TPI was calculated from BUN and urea clearance. DPI was defined as TPI divided by weight. Urinary creatinine (UCr) calculated from creatinine clearance and serum creatinine was used as a marker of muscle mass. The associations of TPI and DPI with each of serum albumin < or = 3.3 g/dL (50th percentile), UCr < or = 0.56 g/d (25th percentile), body mass index < 18.5, and death were examined. Compared with patients in the highest quartile of TPI (> 60.2 g/d), those in the lowest quartile (< or = 32.4 g/d) had 1.89-fold higher odds (P < .001) of low serum albumin, 10.22-fold higher odds (P < .001) of low UCr, and 3.83-fold higher odds (P < .001) of low body mass index in multivariable logistic regression models, and an 18% increase (P < .001) in hazard of death. Compared with patients with DPI > 1.2 g/kg/d, those with DPI < 0.8 g/kg/d had nonsignificantly higher odds of low serum albumin, 2.38-fold higher odds (P < .001) of low UCr, and 0.44-fold lower odds (P < .001) of low body mass index, and a 15% (P = .04) decrease in hazard of death. Higher TPI is associated with better nutrition at baseline and subsequent survival. Normalization of TPI by body weight provides contradictory information on nutritional status as well as survival.


Characteristics of gastric cancer according to Helicobacter pylori infection status.
The definition and incidence of gastric cancer (GC) without Helicobacter pylori (Hp) infection varies between studies. The aim of our study was to compare the characteristics of GC according to Hp infection status. We evaluated the presence of Hp infection in 1833 GC patients with rapid urease tests, serology examinations, and histological evaluations. GC was classified as GC with current Hp infection (HpC-GC), GC with past Hp infection (HpP-GC), and GC not associated with Hp infection (HpN-GC). HpP-GC was defined as GC without current infection but with a positive serology test, glandular atrophy, and/or intestinal metaplasia. HpN-GC was defined as GC with negative Hp test results and no histological changes. The numbers of HpC-GC, HpP-GC, and HpN-GC were 1378 (75.2%), 412 (22.5%), and 43 (2.3%), respectively. Among GCs without current infection, 90.5% (412/455) were associated with HpP-GC. HpP-GCs were more common in older and male patients, had an increased incidence of synchronous cancer, and less frequently had a diffuse-type histology than HpC-GCs. HpN-GCs were more common in younger, female patients; had a higher proportion of diffuse-type cancers; and more frequently showed distant metastasis than HpP-GCs. In the 40s, the proportion of HpP-GCs with diffuse-type histology (41.9%) was lower than that of HpC-GCs (60.3%) (P = 0.016). The difference was also significant in the 50s (29.1% vs 40.1%, respectively, P = 0.004). Most GCs in Korea without current Hp infection showed evidence of past Hp infection. The proportion of GCs with diffuse-type histology decreased in patients with past infection.


Review of probiotics for use in bivalve hatcheries.
The aquaculture of bivalve molluscs has attained a considerable level of production but it is not enough to cover the demand of worldwide consumers. In the development of this sector, hatcheries play an important role, as suppliers of competent spat of different bivalves, including species with an aquaculture based on natural extraction present. Besides, these installations may help in the recovery of exhausted natural beds and in the obtaining of populations under genetic selection. Unfortunately, the disease outbreaks caused by bacterial pathogens are frequent, with the loss of complete batches, compromising the regular production and the economic viability of the industry. There are many descriptive studies about these outbreaks, but only a few focused on the control of microbiota. The particularities of bivalve aquaculture in hatchery must be taken into account to design methods of control. A common environment is shared by larvae and bacteria, including both beneficial and potentially pathogenic. The filter-feeding behaviour of larvae increases the strong influence of these populations. The classical treatments are directed toward to the complete elimination of bacteria from culture seawater. That objective is unfeasible, because the cultures are not axenic, and undesirable, since some bacteria enhance larval development. Taking into account these considerations, the most promising alternative is the use of probiotic bacteria. In this review we summarize the scientific literature about this subject, considering the particularities of bivalve larval cultures and the need to adapt the concept of probiotic and the strategies to use in marine bivalve hatcheries.


Sociodemographic characteristics associated with self-care and quality of life among community-dwelling older adults with type 2 diabetes.
To assess how well community-dwelling older adults in Singapore were coping with their diabetes, and the sociodemographic characteristics that were associated with their level of coping. This was a cross-sectional study involving 257 older adults. Multiple regression was used to assess the associations between various sociodemographic characteristics and coping measures of present quality of life and level of self-care. Older adults mainly sought care in the primary care setting. They were not coping well given their mean scores for diabetes-dependent quality of life and the self-care index were -3.57 and 3.55 respectively. Compared to those with post-secondary education, individuals who had no formal (adjusted B -0.92, p 0.003), primary level (adjusted B -0.76, p < 0.001) and secondary level (adjusted B -0.50, p < 0.02) education reported lower present quality of life. Those with prior lowest skill level occupations were less likely to consume a healthy diet per week than those with prior highest skill level occupations (adjusted B -1.48, p 0.004). There should be provision of diabetes self-care interventions targeting older adults in Singapore especially for those with lower education and work skill levels. As the first line of contacts, primary care providers should advocate for diabetes self-care and develop community-based interventions for these priority groups.


Digital Transformation in Medical Affairs Sparked by the Pandemic: Insights and Learnings from COVID-19 Era and Beyond.
A number of developments, including increasing regulatory and compliance scrutiny, increased transparency expectations, an increasingly vocal patient, patient centricity and greater requirements for real-world evidence, have driven the growth and importance of medical affairs as a trusted, science-driven partner over the past decade. The healthcare environment is shifting towards a digital, data-driven and payor-focused model. Likewise, medical affairs as a function within the pharmaceutical industry has become more "patient-centric" with strategic engagements embracing payers and patients apart from clinicians. The pandemic has impacted the healthcare industry as well as the function of medical affairs in numerous ways and has brought new challenges and demands to tackle. There is indeed a silver lining due to intense digital transformation within this crisis. The emerging digital innovation and new technologies in healthcare, medical education and virtual communications are likely to stay and advance further. In this review, we discuss how the digital transformation sparked by the pandemic has impacted the medical affairs function in pharmaceuticals and provide further insights and learnings from the COVID-19 era and beyond. Based on the learning and insights, digital innovation in three key strategic imperatives of medical affairs-HCP engagement, external partnerships and data generation will enable medical affairs to become future-fit as a strategic leadership function.


Lithium disilicate occlusal surfaces on acrylic resin denture teeth in a mandibular implant-retained overdenture opposed by a maxillary removable complete denture: A clinical report.
Decreased masticatory efficiency, loss of vertical dimension of occlusion, and loss of maxillomandibular relationships are common in relation to the wear experienced by the artificial teeth in removable complete dentures and implant-retained overdentures. To prevent early surface loss, the occlusal surfaces of acrylic resin denture teeth were replaced with adhesively luted lithium disilicate onlays in this patient's prostheses.