Waiting and not knowing: the diagnosis of cancer in a child.
A subset of data from a longitudinal grounded theory study was analyzed to describe the experience families have during the period immediately surrounding the time of diagnosis of cancer in a child. A convenience sample consisted of 40 members of seven families with a child who was recently diagnosed with cancer with a favorable prognosis. All family members 5 years of age and older participated. Data collection consisted of three tape-recorded, semistructured interviews with family members in the home. It was found that the "waiting and not knowing" of this period was most distressing for family members. This period is further described and implications for nursing practice are discussed. Factors limiting generalizability of the findings include the small sample size, single site, and the short length of time families were followed.


The location of spinothalamic axons within spinal cord white matter in cat and squirrel monkey.
The locations of spinothalamic (STT) fibers in the spinal cord white matter have been identified in cat and squirrel monkey by light-microscopic visualization of labeled fibers following multiple thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase. Thalamic injections were combined with either a constricting dural tie or an intraspinal injection of colchicine to facilitate axonal labeling at more rostral spinal levels. In the cat, the ventral-to-dorsal distribution of labeled STT fibers was bimodal. In the ventrolateral white matter, labeled axons were coarse in nature and were primarily concentrated peripherally. In the dorsolateral white matter, labeled STT axons consisted of fine-caliber fibers concentrated in the ventral portion of the dorsolateral funiculus and were equally distributed throughout the medial and lateral white matter. In the squirrel monkey, the distribution of STT fibers was unimodal, extending from the ventral surface of the spinal white matter to the ventralmost portion of the dorsolateral funiculus. As in the cat, however, the ventrally located axons were large and coarse and were primarily located in the peripheral white matter, whereas the dorsalmost STT fibers were of fine caliber and were distributed equally in the medial and lateral white matter.


Androgen and estrogen receptors and co-regulators levels in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia.
To study if the endocrinological status of PCOS women affects the endometrial sensitivity to steroids by evaluating the expression of androgen receptor (AR), estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), co-activators AIB1 and ARA70, and co-repressor NCoR. Gene and/or protein expression of steroid receptors and co-regulators was measured in 17 samples of normal endometrium (NE), 23 PCOS endometrium without treatment (PCOSE), 11 endometria from PCOS women and with endometrial hyperplasia (HPCOSE), and 10 endometria from patients with endometrial hyperplasia (HE), using RT-PCR and/or immunohistochemistry and Western blot. Gene and protein expression of AR was relatively elevated in PCOSE and HPCOSE compared with NE. A significant increase in ERalpha protein expression was observed in PCOSE, preferentially in the nucleus of endometrial cells, whereas ERbeta gene and protein expression increased gradually from PCOSE to HPCOSE and HE, mainly in the epithelial compartment. Importantly, we found a gradual increase in the ERbeta/ERalpha gene and protein expression ratio in endometria from the four groups of women. AIB1 showed increased nuclear protein expression in PCOSE compared to NE, in the presence of a high expression of ARA70 in all groups. High expression of ARA70 together with a normal expression level of AIB1 was observed in HPCOSE. The cytoplasmic immunostaining of NCoR was similar between the four groups of patients. The PCOS endometrium exhibits a higher sensitivity to steroid action. We can inferred that these alterations could deregulate the transcription of genes involved in the cell cycle, which may lead to the development of endometrial hyperplasia in PCOS women.


[Effect of Staphylococcus aureus on the expressions of TLR2, IL-1β, TNF-α and NF-κB in Bcap-37 cells].
To observe the effects of Staphylococcus aureus (S.aureus) on the expressions of Toll-like receptor 2 (TLR2), proinflammatory cytokines (IL-1β, TNF-α) and nuclear factor κB(NF-κB) in human breast cancer Bcap-37 cells in vitro. At the different time points after Bcap-37 cells were challenged with S.aureus, the expressions of TLR2 mRNA and protein were respectively detected using RT-PCR and flow cytometry, the concentrations of IL-1β and TNF-α were examined by ELISA and NF-κB level by Western blotting. The mRNA and protein levels of TLR2 gradually increased in Bcap-37 cells since the stimulations of S.aureus and then dropped after the levels peaked at 4 and 6 hours, respectively (P<0.05). Meanwhile, the expressions of IL-1β and TNF-α was significantly elevated when Bcap-37 cells were exposed to S.aureus, and reached the maximal levels at 12 and 16 hours, respectively (P<0.05), and then IL-1β went down. Expression of NF-κB rose in a time-dependent manner after stimulated by S.aureus up to the maximum at 12 hours, and declined after 14 hours. In Bcap-37 cells, S.aureus exposure could up-regulate the expression of TLR2 at both mRNA and protein levels, increase the production of IL-1β and TNF-α, and stimulate the expression of NF-κB.


Computerized shade selection and the complex Class IV composite.
By utilizing digital shade mapping, a stratified composite technique, and the proper composite system, the dental practitioner stands a greater chance of meeting patient expectations. In the case presented, the use of the Clear-Match system helped simplify shade selection, which is the greatest variable in success of anterior composite restorations.


Prevalence of the HOXB13 G84E prostate cancer risk allele in men treated with radical prostatectomy.
To determine the prevalence and clinical correlates of the G84E mutation in the homeobox transcription factor, or HOXB13, gene using DNA samples from 9559 men with prostate cancer undergoing radical prostatectomy. DNA samples from men treated with radical prostatectomy at the University of Michigan and John Hopkins University were genotyped for G84E and this was confirmed by Sanger sequencing. The frequency and distribution of this allele was determined according to specific patient characteristics (family history, age at diagnosis, pathological Gleason grade and stage). Of 9559 patients, 128 (1.3%) were heterozygous carriers of G84E. Patients who possessed the variant were more likely to have a family history of prostate cancer than those who did not (46.0 vs 35.4%; P = 0.006). G84E carriers were also more likely to be diagnosed at a younger age than non-carriers (55.2 years vs 58.1 years; P < 0.001). No difference in the proportion of patients diagnosed with high grade or advanced stage tumours according to carrier status was observed. In the present study, carriers of the rare G84E variant in HOXB13 were both younger at the time of diagnosis and more likely to have a family history of prostate cancer compared with homozygotes for the wild-type allele. No significant differences in allele frequency were detected according to selected clinical characteristics of prostate cancer. Further investigation is required to evaluate the role of HOXB13 in prostate carcinogenesis.


Gular Cutaneous Fibrosarcoma and Anatomophysiological Considerations for Anaesthesia in a Saddled Bichir, Polypterus endlicheri endlicheri.
Bichirs (Polypterus spp.) have frequently been studied with regard to comparative and developmental anatomy; however, very little information has been published regarding diseases, aging changes, and medical and surgical management in these species. Neoplasia represents one such example of conditions for which a dearth of information in these species exists. There has been increasing recognition of various types of neoplasms, including cutaneous tumors, particularly in ornamental fish; some of which may be related to environmental or to infectious causes. When excision of such tumors is indicated, surgical anaesthesia is required. However, special considerations may be warranted when employing immersion anaesthesia protocols in facultative air-breathing fish that can utilise the lungs for respiration. This anatomophysiological feature of Polypterus spp. may not only influence induction and maintenance of surgical anaesthesia but may theoretically have implications for drowning. Herein, we describe the management of a case of a rapidly growing gular neoplasm in a juvenile saddled bichir and considerations for surgical anaesthesia in this "lunged" species. Induction and maintenance of surgical anaesthesia using tricaine methanesulfonate (MS-222) in this species were found to be effective at significantly lower concentrations than standard recommended doses. Histopathological analysis identified the mass as a fibrosarcoma. To the best of our knowledge, this is the first report of a cutaneous fibrosarcoma in a bichir, representing the first report of neoplasia in Polypterus spp. and the first description of surgical anaesthesia in this amphibious fish.


Comparison of Dorsal and Volar Percutaneous Approaches in Acute Scaphoid Fractures: A Meta-Analysis.
The dorsal approach allows better central screw placement along the long axis of the scaphoid compared with the volar approach in managing acute scaphoid fractures. However, it is unclear whether the dorsal approach leads to better clinical outcomes than the volar approach. This meta-analysis compared clinical outcomes, including the incidence of nonunion, postoperative complications, overall functional outcome, postoperative pain, grip strength, and range of wrist motion, between the dorsal and volar percutaneous approaches for the management of acute scaphoid fractures. Seven studies met the criteria for inclusion in the meta-analysis. The proportion of patients who developed nonunion (OR 0.74, 95% CI: 0.21 to 2.54; P = 0.63) and postoperative complications (OR 1.05, 95% CI: 0.45 to 2.44; P = 0.91) did not differ significantly between the dorsal and volar approaches. Both approaches also led to similar results in terms of overall functional outcome (95% CI: -0.39 to 0.22; P = 0.57), postoperative pain (95% CI: -0.52 to 0.46; P = 0.92), grip strength (95% CI: -4.56 to 1.02; P = 0.21), flexion (95% CI: -2.86 to 1.13; P = 0.40), extension (95% CI: -1.17 to 2.67; P = 0.44), and radial deviation (95% CI: -1.94 to 2.58; P = 0.78). However, ulnar deviation (95% CI: -7.48 to 0.05; P = 0.05) was significantly greater with the volar approach. Thus, orthopedic surgeons need to master both the dorsal and volar percutaneous approaches because not all acute scaphoid fractures can be dealt with completely with one approach.


Neuronal oscillations enhance stimulus discrimination by ensuring action potential precision.
Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and--at oscillation frequencies ranging from 3 to 65 Hz--permitted accurate discernment of up to 1,000 different stimuli. At low oscillation frequencies, stimulus discrimination showed a clear phase dependence whereby inputs arriving during the trough and the early rising phase of an oscillation cycle were most robustly discriminated. Thus, by ensuring AP precision, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems.


Intraperitoneal micro-organisms and the severity of peritonitis.
To find out if there was any correlation between the type or number of pathogenic bacteria in peritoneal exudate, the values of various prognostic scores, the inflammatory response, and the outcome, in patients with peritonitis. Prospective open study. University hospital, Germany. 51 Consecutive patients with secondary peritonitis. Laparotomy within 12 hours of admission or within 8 hours of diagnosis in 9 patients with postoperative peritonitis. Correlation between the severity of the disease (APACHE II score, Septic Severity Score, Mannheim Peritonitis Index, Peritonitis Index Altona II, and outcome), the intraperitoneal and the systemic inflammatory response, intraperitoneal and systemic endotoxin concentrations, and type and number of micro-organisms grown from peritoneal fluid. Intra-abdominal microbiological findings did not correlate with severity of illness judged by the scoring systems, the later incidence of infective complications, or the final outcome. The presence of intra-abdominal microbes was associated with signs of a systemic inflammatory response (median activation index 3 (range 1-3) compared with 2 (range 1-3)), the length of history (median 52 hours (range 3-72) compared with 16 hours (range 3-56), and local and systemic concentrations of endotoxin (peritoneal exudate: median 4800 EU/ml (range 0.06-136674) compared with 220 EU/ml (range 0.00-1800); plasma: median 0.05 EU/ml (range 0.00-1.32) compared with 0.04 EU/ml (range 0.00-0.13)). The sensitivity of the organisms to the antibiotics given (cefuroxime and metronidazole) did not influence the incidence of later infective complications or the outcome. These results do not suggest micro-organisms invading the peritoneal cavity and respective antibiotic treatment to be major determinants of the clinical course of peritonitis.


Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.
Substance P (SP) is an excitatory neurotransmitter in the central and peripheral nervous system. Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell transfer experimental autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically reduced clinical and histological signs of EAE if administered before disease onset. The protective effect of CP96,345 treatment was related to a reduced expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The cellular composition or activation status of splenocytes was not affected by CP-96,345 administration, while the secretion of proinflammatory Th1 cytokines was reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1 receptor antagonist treatment. In summary, our findings suggest that the protective effect of CP96,345 treatment is mediated by stabilization of the blood-brain barrier and suppression of Th1 immunity.


Total Synthesis of the Cardiotonic Steroid (+)-Cannogenol.
The total synthesis of (+)-cannogenol, an aglycon common to various biologically important cardiotonic glycosides, has been achieved. Synthesis of the versatile intermediate involves Mizoroki-Heck and intramolecular Diels-Alder reactions from the enantiomerically pure CD-ring segment, newly prepared in a multidecagram scale this time. Total synthesis by the site-selective transformations of the versatile intermediate demonstrated the applicability of our synthetic approach.


Randomized trial of laparoscopic cholecystectomy and mini-cholecystectomy.
Three hundred and ten patients having elective cholecystectomy were randomized to either laparoscopic cholecystectomy or mini-cholecystectomy. There were 155 patients in each group. Conversion to open cholecystectomy was significantly more common with laparoscopic cholecystectomy (13 versus 4 per cent) and complications were significantly more frequent with laparoscopic cholecystectomy (9 versus 3 per cent). If laparoscopic cholecystectomy was successful, hospital stay was significantly shorter than for mini-cholecystectomy (2 versus 3 days respectively), but overall the hospital stay was not significantly different. Postoperative analgesia requirements were reduced and return to normal activities and to work were faster after laparoscopic cholecystectomy. There was no significant cost difference between the two procedures.


Magnitude of Anemia and Its Associated Factors among Pregnant Women Attending Antenatal Care at Najo General Hospital, Northwest Ethiopia.
Anemia is one of the major causes of morbidity for pregnant women in resource-limited regions. Yet robust research-based evidence on this vital public health problem in remote areas where the problem could be massive is quite limited in Ethiopia, one of the developing countries. Thus, this study is aimed to assess the magnitude of anemia and its associated risk factors among pregnant women attending one of the health facilities in Ethiopia. A facility-based cross-sectional study design was employed in 2019. A total of 384 pregnant women attending the antenatal care (ANC) unit of Najo General Hospital, Northwest Ethiopia, were included in the study. Their sociodemographic characteristics, and medical, obstetric, and gynecological history were collected using pretested interview questionnaires. Blood samples were collected from each participant for the determination of malaria parasite and hemoglobin (Hb) level. In addition, stool samples were collected for examination of intestinal parasites. Data were analyzed using Statistical Package for Social Science (SPSS) software version 25. The overall magnitude of anemia among pregnant women was 37.8% (95% CI, 32.8%-42.3%). The proportion of mild anemia, moderate anemia, and severe anemia was 24%, 11%, and 2.3%, respectively. Some variables such as absence of malaria infection (AOR: 0.195, 95% CI: 0.066-0.576), lack of history of abortion (AOR: 0.469, 95% CI: 0.265-0.830), and absence of history of anemia (AOR: 0.227, 95% CI: 0.134-0.385) were identified as protective variables of anemia during pregnancy, while urban residence (AOR: 1.753, 95% CI: 1.013-3.034) was unexpectedly found as a predisposing factor. Despite the higher number of anemic pregnant women observed in the current study, pregnancy-associated anemia is moderate public health importance in the study area.


Multi-layer Shack-Hartmann wavefront sensing in the point source regime.
The Shack-Hartmann wavefront sensor (SHWS) is often operated under the assumption that the sensed light can be described by a single wavefront. In biological tissues and other multi-layered samples, secondary wavefronts from axially and/or transversely displaced regions can lead to artifactual aberrations. Here, we evaluate these artifactual aberrations in a simulated ophthalmic SHWS by modeling the beacons that would be generated by a two-layer retina in human and mouse eyes. Then, we propose formulae for calculating a minimum SHWS centroid integration area to mitigate these aberrations by an order of magnitude, potentially benefiting SHWS-based metrology and adaptive optics systems such as those used for retinal imaging and microscopy.


Dermal duct tumor with prominent ductal and sebaceous differentiation.
Dermal duct tumor is a rare, benign tumor. Clinically, dermal duct tumor presents as a firm papule, plaque or nodule, particularly on the lower limbs or head and neck region. Dermal duct tumor is been classified as poroma. Poroma can have divergent differentiation, but showing prominent ductal and sebaceous differentiation is rare. We present a case of dermal duct tumor with prominent ductal and sebaceous differentiation arising in the scalp. A 45-year-old man with a painless slow-growing, elevated, brownish nodule on his scalp of 7-year duration was admitted to our hospital. Histopathology revealed dermal duct tumor. The neoplasm also showed prominent ductal and sebaceous differentiation.


[Complications of palpebral epitheliomas: diagnostic, therapeutic, and prognostic implications].
To illustrate two cases of palpebral tumors that determined local complications, with consequences on the preoperative diagnosis and the surgical treatment (case 1) and on the functional prognosis of the eye (case 2). The history and evolution of the cases, the surgical techniques, the histopathological reports and the anatomical and functional results are described and analyzed. In case 1, the extension of the tumor led to a considerable tissular defect that claimed for a long and hard surgery for the anatomical and functional repair of the region. In case 2, the vegetant evolution of the tumor determined the irritation of the cornea and consecutive corneal ulcer that perforated, with the functional loss of the eye. The two cases are revealing aspects that are less frequent in the ophthalmic practice. They signalize, besides the deffisient adresability of the patient, the problem of the "territorial dispute" over the palpebral surgery between different specialties.


Electrophysiological recording from Drosophila larval body-wall muscles.
The Drosophila larval neuromuscular junction (NMJ) shares many structural and functional similarities to synapses in other animals, including humans. These include the basic feature of synaptic transmission, as well as the molecular mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy accessibility, and the well-characterized genetics, the fly NMJ remains an excellent model system for dissecting the cellular and molecular mechanisms of synaptic transmission. This protocol describes the steps for performing intracellular recording from fly larval body-wall muscles and explains how to record and analyze spontaneous and evoked synaptic potentials. Methods used include larval dissection ("filleting"), identification of muscle fibers and their innervating nerves, the use of a micromanipulator and microelectrode in penetrating the muscle membrane, and nerve stimulation to evoke synaptic potentials.


Phospholipid bilayers are viscoelastic.
Lipid bilayers provide the structural framework for cellular membranes, and their character as two-dimensional fluids enables the mobility of membrane macromolecules. Though the existence of membrane fluidity is well established, the nature of this fluidity remains poorly characterized. Three-dimensional fluids as diverse as chocolates and cytoskeletal networks show a rich variety of Newtonian and non-Newtonian dynamics that have been illuminated by contemporary rheological techniques. Applying particle-tracking microrheology to freestanding phospholipid bilayers, we find that the membranes are not simply viscous but rather exhibit viscoelasticity, with an elastic modulus that dominates the response above a characteristic frequency that diverges at the fluid-gel (L(α) - L(β)) phase-transition temperature. These findings fundamentally alter our picture of the nature of lipid bilayers and the mechanics of membrane environments.


Regioselective alkyl and alkynyl substitution reactions of epoxy alcohols by the use of organoaluminum ate complexes: regiochemical reversal of nucleophilic substitution reactions.
Unprecedented nucleophilic substitution reactions of 2,3-epoxy-1-alkanols with alkyl- and alkynylaluminum ate complexes have been studied and demonstrated to occur at the C2 position with extremely high stereoselectivity, i.e., with exactly reversed regioselectivity to that obtained in the substitution reactions by normal organoaluminum reagents, resulting in the formation of the C2-alkyl and C2-alkynyl substitution products in excellent yields.


Factors Associated With Medication Compliance in Elderly Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study.
The average age of patients with type 2 diabetes in Japan is over 70 years. Elderly patients tend to have poor medication compliance, therefore, it is important to understand their individual situations to improve medication compliance, the treatment of their diabetes, and their quality of life (QOL). This study aimed to identify factors associated with medication compliance in elderly type 2 diabetic patients. A cross-sectional study based on questionnaires was conducted on type 2 diabetes patients aged 65 years or older. The participants were recruited from patients who visited three dispensing pharmacies in the Shinagawa area of Tokyo between March 1 and September 30, 2019. The questionnaire consisted of patient information (sex, age, medication compliance status, knowledge of drug effects, and side effects), 12-Item Short Form Survey quality of life rating scale (SF-12), and Diabetes Treatment Satisfaction Questionnaire (DTSQ). Factors related to medication compliance were then evaluated. In all, there were 47 respondents: 31 males and 16 females. Four factors were found to be associated with medication compliance in elderly type 2 diabetic patients: medication storage (P = 0.01), knowledge of drug effects (P < 0.001), knowledge of side effects (P = 0.026), and physical functioning: (PF) (P = 0.045), a subscale of SF-12. Furthermore, the strength of the association between these four factors and medication compliance was calculated using Cramer's V coefficient of association. Knowledge of drug effects was the most strongly associated (knowledge of drug effects: V = 0.559; knowledge of side effects: V = 0.464; medication storage: V = 0.451; PF: V = 0.334). Because diabetes mellitus has no subjective symptoms and treatment effects are not felt to a great extent, it is difficult to motivate patients to consistently adhere to medication. When pharmacists provide medication guidance to elderly patients with type 2 diabetes mellitus, it is important to provide sufficient information to ensure they fully understand the drug effects to maintain medication compliance.


Inhaled hypertonic saline+hyaluronic acid in cystic fibrosis with asthma-like symptoms: a new therapeutic chance.
The aim of the paper is to report the case of a boy affected by cystic fibrosis, with non-ABPA-related recurrent wheezing and frequent pulmonary exacerbation during childhood, who had been inhaling 7% NaCl+0.1% hyaluronic acid (HA) as a maintenance therapy. We reviewed patient database and, analysing a 7-year follow-up, considered pulmonary exacerbation, antibiotic and steroid courses, pulmonary function (forced expiratory volume in one second; FEV1) and microbiological data. After starting 7% NaCl+0.1% HA treatment, we observed a dramatic decrease of oral antibiotic need (0.55 courses/month during the pretreatment period against 0.10 courses/month in the treatment period), associated with a good initial recovery and a stability of FEV1. In our opinion this case could suggest an extended indication for inhaled 7% NaCl+0.1% HA use in CF, not only in patients who did not tolerate hypertonic saline, but also in patients with coexistent asthma-like symptoms.


The "patient as care partner" approach is nowadays considered as a major lever for the optimization of health care systems. Although patients must undeniably represent major stakeholders of a healthcare system, this field of practice on partnership requires to be better documented in order to improve effectiveness and efficiency and to establish good practices. This article raises three main research issues in the field of partnership in health : conceptual clarification, evaluation and understanding of practices. This article aims to initiate a dialogue on the construction of a research agenda on the theme of partnership.


Sense of coherence and health among home-dwelling older people.
Sense of coherence (SOC) is important for maintaining health. The aim of this study was to investigate if the SOC experience among home-dwelling physically active older people differs from that of hospital patients with the same age and sex. Data were collected with questionnaires and structured interviews containing Antonovsky's SOC scale in an age- and sex-matched study group (n=160). Non-parametric statistical analyses were performed. No differences were found in SOC between home-dwelling individuals and patients. Ninety-five percent of the home-dwelling individuals perceived themselves as being in good health and 42.5% among the patients (p<0.001). SOC and disease were predictors for health in the total study group. Among the home-dwelling individuals, SOC, disease and being single were predictors for health and among the patients solely SOC. When using the components of the SOC concept, comprehensibility and disease predicted health for the home-dwelling individuals and meaningfulness predicted health for the patients.


Alcohol early intervention: a nursing model for screening and intervention strategies.
This paper presents the background policy directions in Australia that are encouraging nurses to initiate alcohol early intervention strategies. The current clinical initiatives that are supporting screening and early intervention strategies are critically reviewed and presented in the form of an Alcohol Early Intervention Model to guide nursing practice. The model is compatible with current directions in nursing which encourage more independent, empowering and educationally focused strategies. This model also provides direction for undergraduate and graduate nursing curricula and offers opportunities for future research.


NMR studies of the backbone protons and secondary structure of pentapeptide and heptapeptide substrates bound to bovine heart protein kinase.
The conformations of enzyme-bound pentapeptide (Arg-Arg-Ala-Ser-Leu) and heptapeptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly) substrates of protein kinase have been studied by NMR in quaternary complexes of the type (Formula: see text). Paramagnetic effects of Mn2+ bound at the inhibitory site of the catalytic subunit on the longitudinal relaxation rates of backbone Ca protons, as well as on side-chain protons of the bound pentapeptide and heptapeptide substrates, have been used to determine Mn2+ to proton distances which range from 8.2 to 12.4 A. A combination of the paramagnetic probe-T1 method with the Redfield 2-1-4-1-2 pulse sequence for suppression of the water signal has been used to measure distances from Mn2+ to all of the backbone amide (NH) protons of the bound pentapeptide and heptapeptide substrates, which range from 6.8 to 11.1 A. Paramagnetic effects on the transverse relaxation rates yield rate constants for peptide exchange, indicating that the complexes studied by NMR dissociate rapidly enough to participate in catalysis. Model-building studies based on the Mn2+-proton distances, as well as on previously determined distances from Cr3+-AMPPCP to side-chain protons [Granot, J., Mildvan, A.S., Bramson, H. N., & Kaiser, E. T. (1981) Biochemistry 20, 602], rule out alpha-helical, beta-sheet, beta-bulge, and all possible beta-turn conformations within the bound pentapeptide and heptapeptide substrates. The distances are fit only by extended coil conformations for the bound peptide substrates with a minor difference between the pentapeptides and heptapeptides in the phi torsional angle at Arg3C alpha and in psi at Arg2C alpha. An extended coil conformation, which minimizes the number of interactions within the substrate, would facilitate enzyme-substrate interaction and could thereby contribute to the specificity of protein kinase.


Nuclear co-translocation of myotrophin and p65 stimulates myocyte growth. Regulation by myotrophin hairpin loops.
Myotrophin, a 12-kDa ankyrin repeat protein, stimulates protein synthesis and cardiomyocyte growth to initiate cardiac hypertrophy by activating the NF-kappaB signaling cascade. We found that, after internalization into myocytes, myotrophin cotranslocates into the nucleus with p65 to stimulate myocyte growth. We used structure-based mutations on the hairpin loops of myotrophin to determine the effect of the loops on myotrophin and p65 localization, induction of protein synthesis, and cardiac hypertrophy. Loop mutants, most prominently glutamic acid 33-->alanine (E33A), stimulated protein synthesis much less than wild type. Myotrophin-E33A internalized into myocytes but did not translocate into the nucleus and failed to promote nuclear translocation of p65. In addition, two cardiac hypertrophy marker genes, atrial natriuretic factor and beta-myosin heavy chain, were not up-regulated in E33A-treated cells. Myotrophin-induced myocyte growth and initiation of hypertrophy thus require nuclear co-translocation of myotrophin and p65, in a manner that depends crucially on the myotrophin hairpin loops.


Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response.
ABSTRACT Dermal exposure to JP-8 petroleum jet fuel leads to toxicological responses in humans and rodents. Serum profiling is a molecular analysis of changes in the levels of serum proteins and other molecules in response to changes in physiology. This present study utilizes serum profiling approaches to examine biomolecular changes in the sera of rats exposed to dermal applications of JP-8 (jet propulsion fuel-8). Using gel electrophoresis and electrospray ionization (ESI) mass spectrometry (MS), levels of serum proteins as well as low-mass constituents were found to change after dermal exposures to JP-8. The serum protein levels altered included the acute-phase response proteins haptoglobin, ceruloplasmin, alpha(1)-inhibitor III, and apolipoprotein A-IV. Haptoglobin levels increased after a 1-day JP-8 dermal exposure and continued to increase through 7 days of exposure. Ceruloplasmin levels increased after 5 days of exposure. Serum alpha(1)-inhibitor III was reduced after a 1-day exposure and the depletion continued after 7 days of exposure. Apolipoprotein A-IV increased after a 1-day exposure and then returned to basal levels after 3- and 5-day exposures of JP-8. Levels of the acute-phase protein alpha(2)-macroglobulin were found to not vary over these time course studies. Using ESI-MS analysis directly on the sera from rats exposed to dermal JP-8, low-mass sera constituents were found to correlate with control (acetone) or JP-8 exposure.


[Vascular malformations associated with Marfan syndrome, Ehlers-Danlos syndrome and neurofibromatosis 1 and their surgical treatment].
The Marfan syndrome, vascular type Ehlers-Danlos syndrome and neurofibromatosis 1 are associated with vascural complications that may be fatal. Therefore, referral to treatment should be properly timed, followed by therapy taking special features of the disease into consideration. When treating a vascular malformation related to an inherited disorder, it is important to collaborate with clinical geneticists in order to obtain genetic counseling and DNA diagnostics as well as to elucidate the status of close relatives.


Do analgesics improve functioning in patients with chronic low back pain? An explorative triple-blinded RCT.
TREATMENT of patients with chronic low back pain (CLBP) aims to reduce disability, improve functional capacity, and participation. Time contingent prescription of analgesics is a treatment modality in CLBP. The impact of analgesics on functional capacity is unknown. Aim of the study was to explore the effect of analgesics on functioning measured by functional capacity evaluation, and self-reported disability in patients with CLBP. Explorative Randomized Placebo-Controlled Clinical Trial was performed in an outpatient pain rehabilitation setting on patients waiting for rehabilitation. Included patients had low back pain lasting >3 months, visual analogue scale worst pain ≥4.0 cm, and age >18 years. Outcome measures before (T0) and after treatment (T1): functional capacity, pain intensity, Roland Morris Disability Questionnaire. T1: global perceived pain relief. Patient characteristics and psychological questionnaires were assessed. Fifty patients were included in this study and were randomly assigned to 2 weeks treatment or placebo. acetaminophen/tramadol 325 mg/37.5 mg per capsule. Dose: maximum acetaminophen 1,950 mg and tramadol 225 mg per day; treatment and placebo titrated identically. Compliance and side-effects were monitored. TREATMENT effects between groups over time were compared. One patient (treatment group) was lost to follow-up. Forty-nine patients remained in the study. TREATMENT effects in primary outcomes did not differ significantly between groups. A subgroup of 10 (42%) patients (treatment group) reported global pain relief (responders) who reduced self-reported disability (p < 0.05). Responders had significantly lower catastrophizing scores. Overall treatment effects were small and non-significant. A subgroup, however, reported improved functioning as a result of treatment. Responders had lower catastrophizing scores.


Hydroxyapatite, a multifunctional material for air, water and soil pollution control: A review.
Hydroxyapatite (Ca10(PO4)6(OH)2), a calcium phosphate biomaterial, is a very promising candidate for the treatment of air, water and soil pollution. Indeed, hydroxyapatite (Hap) can be extremely useful in the field of environmental management, due in one part to its particular structure and attractive properties, such as its great adsorption capacities, its acid-base adjustability, its ion-exchange capability and its good thermal stability. Moreover, Hap is able to constitute a valuable resource recovery route. The first part of this review will be dedicated towards presenting Hap's structure and defining properties that result in its viability as an environmental remediation material. The second will focus on its use as adsorbent for wastewater and soil treatment, while indicating the mechanisms involved in this remediation process. Finally, the last part will impart all findings on Hap's applications in the field of catalysis, whether it be as catalyst, as photocatalyst, or as active phase support. Hence, all of the above will have served in showcasing the benefits gained by employing hydroxyapatite in air, water and soil clean-up.


[Expression of IGF-IR and IR in children with acute lymphoblastic leukemia].
This study was aimed to investigate the mRNA expression levels of insulin-like growth factor-I receptor (IGF-IR) and insulin receptor (IR) in peripheral blood lymphocytes of childhood ALL and their relationship with clinical features. The expression levels of IR and IGF-IR in peripheral blood lymphocytes of ALL children and healthy children were analysed. Peripheral blood samples were obtained from 43 ALL patients and 14 healthy children. The mRNA expression of IGF-IR and IR was measured by RT-PCR. The results showed that IGF-IR was widely expressed on peripheral blood lymphocytes of ALL children and healthy controls, mRNA level of IGF-IR significantly increased in ALL children of newly diagnosed, relapsed and hyperglycemia groups (P = 0.000, P = 0.002 and P = 0.05)as compared with the normal control group. mRNA level of IGF-IR in CR group was significantly lower than that in newly diagnosed and relapsed groups (P = 0.000 and P = 0.018); mRNA level of IR in newly diagnosed and relapsed groups were significantly lower than that in the normal control group (P = 0.001 and P = 0.018). mRNA level of IR in CR group was significantly higher than that in newly diagnosed and relapsed groups (P = 0.000 and P = 0.001); mRNA levels of IGF-IR and IR correlated with the clinical stages of the disease, while they had no association with the sex, age and white blood cell counts at new diagnosis. It is concluded that IGF-IR positively correlates with the stages of the disease, indicating that IGF-IR plays a leading role in the proliferation of tumor cells, and its increased expression levels may reflect the malignant proliferation of ALL cells.


Efficacy of a Proteus mirabilis outer membrane protein vaccine in preventing experimental Proteus pyelonephritis in a BALB/c mouse model.
A BALB/c mouse model of nonobstructive, ascending Proteus mirabilis pyelonephritis was characterized bacteriologically, histologically, and serologically from 3 to 28 days. Intravesicular administration of 2 X 10(8) P. mirabilis K7 resulted in the septic death of 9 (16%) of 57 mice by day 15. Among the survivors, K7 colonized the kidneys in great numbers until day 21. Histological examination of the kidneys revealed acute inflammation which was characterized by neutrophil infiltration by day 3, renal necrosis by day 7, and fibroblastic infiltration by day 14 which persisted at least until day 28. The immunoglobulin G response to the outer membrane proteins (OMP) was assessed by enzyme-linked immunosorbent assay and Western blotting (immunoblotting). Anti-OMP immunoglobulin G antibodies were detected as early as day 7, and the reciprocals of their titers rose progressively up to day 28 (i.e., greater than or equal to 500). This model was also used to assess the efficacy of OMP and lipopolysaccharide (LPS) immunization in preventing renal infection. K7 OMP or LPS (100 micrograms) preparations were administered intramuscularly in Freund's complete adjuvant. After 2 weeks, mice were intravesicularly challenged with 2 X 10(8) bacteria of the homologous K7 strain or one of four heterologous strains. Compared with the saline-immunized control group and K7 LPS-immunized mice, K7 OMP recipients were protected from death when challenged by homologous or heterologous strains. In addition, K7 OMP recipients were protected (P less than 0.003) from subsequent renal infection when challenged by the K7 strain and had more rapid bacterial renal clearance when challenged by three of four heterologous strains. OMP recipients produced antibodies which bound major OMP moieties (viz., 36- to 39-kDa cell wall constituents) as assessed by Western blotting. These results support the concept that immunization with selected bacterial protein surface coat constituents can prevent uromucosal infection by interfering with colonization or renal injury.


Gianturco Z-stent placement for the treatment of chronic central venous occlusive disease: implantation of 208 stents in 137 symptomatic patients.
To report the technical successes, adverse events, and long-term stent patency rates of Gianturco Z-stents for management of chronic central venous occlusive disease. Overall, 137 patients, with mean age 48.6±16.1 years (range, 16-89 years), underwent placement of Gianturco Z-stents for chronic central venous occlusions. Presenting symptoms included lower extremity edema (n=66, 48.2%), superior vena cava syndrome (n=30, 21.9%), unilateral upper extremity swelling (n=20, 14.6%), hemodialysis fistula or catheter dysfunction (n=11, 8.0%), ascites (n=8, 5.8%), and both ascites and lower extremity edema (n=2, 1.5%). Most common etiologies of central venous occlusion were prior central venous access placement (n=58, 42.3%), extrinsic compression (n=29, 21.2%), and post-surgical anastomotic stenosis (n=27, 19.7%). Number of stents placed, stent implantation location, stent sizes, technical successes, adverse events, need for re-intervention, follow-up evaluation, stent patencies, and mortality were recorded. Technical success was defined as recanalization and stent reconstruction with restoration of in-line venous flow. Adverse events were defined by the Society of Interventional Radiology Adverse Event Classification criteria. Primary and primary-assisted stent patencies were analyzed using Kaplan-Meier analysis. In total, 208 Z-stents were placed. The three most common placement sites were the inferior vena cava (n=124, 59.6%), superior vena cava (n=44, 21.2%), and brachiocephalic veins (n=27, 13.0%). Technical success was achieved in 133 patients (97.1%). There were two (1.5%) severe adverse events (two cases of stent migration to the right atrium), one (0.7%) moderate adverse event, and one (0.7%) mild adverse event. Mean follow-up was 43.6±52.7 months. Estimated 1-, 3-, and 5-year primary stent patency was 84.2%, 84.2%, and 82.1%, respectively. Estimated 1-, 3-, and 5-year primary-assisted patency was 92.3%, 89.6%, and 89.6%, respectively. The 30- and 60- day mortality rates were 2.9% (n=4) and 5.1% (n=7), none of which were directly attributable to Z-stent placement. Gianturco Z-stent placement is safe and effective for the treatment for chronic central venous occlusive disease with durable short- and long-term patencies.


Adsorption and Electrochemical Detection of Bovine Serum Albumin Imprinted Calcium Alginate Hydrogel Membrane.
In this paper, bovine serum albumin (BSA)-imprinted calcium alginate (CaAlg) hydrogel membrane was prepared using BSA as a template, sodium alginate (NaAlg) as a functional monomer, and CaCl₂ as a cross-linker. The thickness of the CaAlg membrane was controlled by a glass rod enlaced with brass wires (the diameter was 0.1, 0.2, 0.3, 0.4, and 0.5 mm). The swelling properties of the CaAlg membranes prepared with different contents of NaAlg were researched. Circular dichroism indicated that the conformation of BSA did not change during the preparing and eluting process. The thinner the CaAlg hydrogel membrane was, the larger the adsorption capacity and the higher the imprinting efficiency of the CaAlg. The maximum adsorption capacity of molecularly imprinted polymer (MIP) and non-imprinted CaAlg hydrogel membrane (NIP) was 38.6 mg·g-1 and 9.2 mg·g-1, respectively, with an imprinting efficiency of 4.2. The MIP was loaded on the electrode to monitor the selective adsorption of BSA by voltammetry curve.


Study on the Clinical Implications of NLR and PLR for Diagnosing Frailty in Maintenance Hemodialysis Patients and Their Correlations with Patient Prognosis.
To explore the clinical implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for diagnosing frailty in patients with maintenance hemodialysis (MHD) and their correlations with patient prognosis. A total of 185 patients with MHD admitted to the hemodialysis center of our hospital were selected, 72 of whom were diagnosed with frailty according to the Chinese version of Tilburg Frailty Indicator (TFI). The relevant data were collected, and the influencing factors of frailty in MHD patients were analyzed by one-way analysis of variance (ANOVA) and multivariate logistic regression. The value of NLR and PLR in diagnosing frailty in MHD patients was observed, and patients' all-cause mortality was compared during the 3-year follow-up. The influences of different levels of NLR and PLR on the survival of MHD patients were investigated. Multivariate regression analysis identified that serum albumin, dialysis adequacy, NLR, and PLR are independent risk factors for frailty in MHD patients (P < 0.05). The area under the receiver operating characteristic (ROC) curve of NLR and PLR in diagnosing frailty in MHD patients was 0.859 and 0.799, respectively. Compared with the nonfrailty group, the 3-year mortality was higher, and the 3-year survival rate assessed by survival analysis was lower in the frailty group (P < 0.05). Patients with high NLR and PLR levels showed a lower 3-year survival rate. Dialysis adequacy, serum albumin, NLR, and PLR are independently associated with frailty in MHD patients. NLR and PLR are of a certain diagnostic value for frailty in MHD patients. MHD patients with frailty have an unfavorable prognosis, as of those with high NLR and PLR levels.


Field-induced anti-nematic and biaxial ordering in binary mixtures of discotic mesogens and spherical magnetic nanoparticles.
Using computer simulations we explore the equilibrium structure and response to external stimuli of complex magnetic hybrids consisting of magnetic particles in discotic liquid crystalline matrices. We show that the anisotropy of the liquid crystalline matrix (either in the nematic or in the columnar phase) promotes the collective orientational ordering of self-assembled magnetic particles. Upon applying an external homogeneous magnetic field in an otherwise isotropic state, the magnetic particles self-assemble into linear-rodlike-chains. At the same time structural changes occur in the matrix. The matrix transforms from an isotropic to a non-conventional anti-nematic state in which the symmetry axis of the discs is, on average, perpendicular to the magnetic field. In addition, a stable biaxial nematic state is found upon applying an external field to an otherwise uniaxial discotic nematic state. These observed morphologies constitute an appealing alternative to binary mixtures of rigid rod-disc system and indicate that non-trivial biaxial ordering can be obtained in the presence of a uniaxial external stimulus.


Primary central nervous system extranodal nasal-type natural killer/T-cell lymphoma with CD20 expression.
We report a unique case of primary CNS extranodal natural killer/T-cell lymphoma (PCNS ENKTCL) with CD20 expression and the monoclonal rearrangement of Ig heavey chain (IgH) gene. Resection specimens were evaluated using HE-stained sections, immunohistochemistry, in situ hybridization and PCR. Histopathologic examination, immunohistochemistry and molecular studies showed the intermediate-sized lymphoma cells expressing CD2, CD3ε, granzyme B, TIA-1, CD20 and Epstein-Barr virus-encoded RNA, with germline T-cell receptor gene and the monoclonal rearrangement of IgH gene. Clinicopathologic and radiographic evaluation indicated the lesion was of exclusive left cerebellar localization. Thus, PCNS ENKTCL with the CD20 expression was diagnosed. ENKTCL with both CD20-positive expression and the monoclonal rearrangement of IgH gene may be mistaken for B-cell lymphoma; thus, the comprehensive evaluation of histomorphology, more extensive immunoprofiles and molecular studies is essential to reach the correct diagnosis. The rare PCNS ENKTCL shows a highly aggressive nature and a poorer prognosis.


CBCT: a revolutionary diagnostic aid for endodontic dilemmas.
Successful management of endodontic problems is reliant on diagnostic imaging techniques to provide critical information about the teeth under investigation, and their surrounding anatomy. Until recently, most of this core information was obtained from conventional radiographs. The introduction of cone-beam computed tomography (CBCT) specifically dedicated to imaging the maxillofacial region heralds a true paradigm shift from a two dimensional (2D) to a three dimensional (3D) approach to data acquisition and image reconstruction. CBCT systems provide small field of view images at low dose with sufficient spatial resolution for applications in endodontic diagnosis, treatment guidance, and post treatment evaluation. CBCT has been the subject of unparalleled levels of independent research in dental imaging in the area of endodontics. It gives the edge of 3D imaging at lower radiation level in comparison to conventional CT and has helped to treat endodontic cases with external resoption, root canal variations and apical periodontitis providing the size, site and extent accurately. This paper reviews the fundamentals of CBCT and presents the applications of this imaging system in contemporary endodontic practice.


Effect of physiologic perfusion-fixation on the morphometrically evaluated dimensions of the term placental cotyledon.
To estimate the in vivo dimensions of the fetal villous tree of the normal term placenta. Dual-circuit perfusion-fixation of a cotyledon from eight normal term placentas was performed with random intra-cotyledon tissue sampling. Stereologic methods were used to derive estimates of villous (intermediate and terminal) surface area and volume, and star volume (a measure of villous volume). Villous surface area (mean 20.9 m2 [standard deviation 1.8]), capillary surface area (12.8 m2 [1.5]), villous volume (469 mL [40]), and capillary volume (80 mL [10]) values were all approximately 50% higher than reported previously. Star volume estimates ranged from 480 to 1350 microns 3. Tissue perfusion-fixation more accurately reconstructs the in vivo state, resulting in higher reference values than previously thought for the fetal villous tree dimensions. Up to one-quarter of fetoplacental blood volume is likely to be accommodated within the placenta at term.


Organization and topology of photosystem I subunits.
Intact spinach (Spinacia oleracea) thylakoid membranes were treated with various proteases and photosystem I (PSI) complexes were isolated from these membranes to define the membrane topology of specific PSI subunits. Trypsin treatment caused cleavage of the PSI-D and E subunits. Thermolysin treatment cleaved the PSI-D, E, H, and K subunits, and also caused limited degradation of the reaction center core PSI-A and B subunits. Pronase treatment produced the most dramatic results as the PSI-A and B subunits were cleaved to 47-, 45-, 26-, and 24-kilodalton products. In addition, pronase degraded the PSI-D, E, H, K, and L subunits. Proteolytic cleavage sites for several of the products were identified by amino acid sequencing. The results indicate that PSI-A, B, D, E, H, K, and L subunits all have stroma-exposed regions, and these findings are summarized in a model describing the subunit organization of PSI.


MCM-22/silica selective flake nanocomposite membranes for hydrogen separations.
MCM-22/silica composite films were fabricated using layer-by-layer deposition toward a nanoscale realization of the selective flake concept first proposed by Cussler in (J. Membr. Sci. 1990, 52 (3), 275-288). According to this concept, considerable zeolitic transport selectivity can be harvested if plate-like zeolite particles were oriented flat within an appropriate thin film matrix. c-Out-of-plane oriented MCM-22 flakes were chosen because of the expected H(2)-selective (over other permanent gases) molecular sieving action through their c-axis-transport-limiting aperture defined by six SiO(4) tetrahedra. To fill the gaps between MCM-22 particles the evaporation induced self-assembled (EISA) mesoporous silica, introduced by Brinker et al. in (Nature 1997, 389 (6649), 364-368), was selected as a tunable matrix, through which Knudsen diffusion would be the dominant transport mechanism for permanent gases. The repetition of appropriate deposition cycles (i.e., particle deposition and subsequent silica coating) led to the gradual increase of separation performance achieving H(2)/N(2) ideal selectivity as high as 120.


Wintertime haze and ozone at Dinosaur National Monument.
Dinosaur National Monument (DINO) is located near the northeastern edge of the Uinta Basin and often experiences elevated levels of wintertime ground-level ozone. Previous studies have shown that high ozone mixing ratios in the Uinta Basin are driven by elevated levels of volatile organic compounds (VOCs) and nitrogen oxides (NOx) from regional oil and gas development coupled with temperature inversions and enhanced photochemistry from persistent snow cover. Here, we show that persistent snow cover and temperature inversions, along with abundant ammonia, also lead to wintertime haze in this region. A study was conducted at DINO from November 2018 through May 2020 where ozone, speciated fine and coarse aerosols, inorganic gases, and VOCs were measured. Three National Ambient Air Quality Standards (NAAQS) ozone exceedances were observed in the first winter, and no exceedances were observed in the second winter. In contrast, elevated levels of particulate matter were observed both winters, with 24-h averaged particle light extinction exceeding 100 Mm-1. These haze events were dominated by ammonium nitrate, and particulate organics were highly correlated with ammonium nitrate. Ammonium nitrate formation was limited by nitric acid in winter. As such, reductions in regional NOx emissions should reduce haze levels and improve visibility at DINO in winter. Long-term measurements of particulate matter from nearby Vernal, Utah, suggest that visibility impairment is a persistent issue in the Uinta Basin in winter. From April through October 2019, relatively clean conditions occurred, with average particle extinction of ~10 Mm-1. During this period, ammonium nitrate concentrations were lower by more than an order of magnitude, and contributions from coarse mass and soil to haze levels increased. VOC markers indicated that the high levels of observed pollutants in winter were likely from local sources related to oil and gas extraction activities.Implications: Elevated ground-level ozone and haze levels were observed at Dinosaur National Monument in winter. Haze episodes were dominated by ammonium nitrate, with 24-h averaged particle light extinction exceeding 100 Mm-1, reducing visual range near the surface to ~35 km. Despite elevated ammonium nitrate concentrations, additional gas-phase ammonia was available, such that any increase in NOx emissions in the region is likely to lead to even greater haze levels.


Glyphosate effects on carbon assimilation, ribulose bisphosphate carboxylase activity, and metabolite levels in sugar beet leaves.
Application of a 17-millimolar solution of glyphosate (GLP) to sugarbeet (Beta vulgaris L.) leaves resulted in an immediate and rapid decline in the level of ribulose bisphosphate (RuBP). Phosphoglyceric acid level began to decrease about 2 hours following the decline in RuBP level. Photosynthesis rate declined linearly with RuBP level, but only when the RuBP level had decreased to about twice the RuBP carboxylase active site concentration. This occurred about 4 hours following GLP-application. At this time starch synthesis also declined abruptly. The activation state of RuBP carboxylase did not change for 8 hours following GLP application and then decreased slightly from 70 to 50% when the RuBP level fell below the RuBP carboxylase active-site concentration. Triose-phosphate, hexose-phosphate, and adenylate energy charge did not change for 8 hours following GLP-application. These data indicate that GLP induced a depletion of carbon or phosphate or both from the photosynthetic carbon reduction cycle, reducing the rate of regeneration of RuBP, photosynthesis, and starch synthesis, while having little effect upon the rate of sucrose synthesis and transport.


Oral exposure to polyethylene microplastics induces inflammatory and metabolic changes and promotes fibrosis in mouse liver.
Accumulating evidence shows widespread contamination of water sources and food with microplastics. Although the liver is one of the main sites of bioaccumulation within the human body, it is still unclear whether microplastics produce damaging effects. In particular, the hepatic consequences of ingesting polyethylene (PE) microplastics in mammals are unknown. In this study, female mice were fed with food contaminated with 36 and 116 µm diameter PE microbeads at a dosage of 100 µg/g of food for 6 and 9 weeks. Mice were exposed to each type of microbead, or co-exposed to the 2 types of microbeads. Mouse liver showed altered levels of genes involved in uptake, synthesis, and β-oxidation of fatty acids. Ingestion of PE microbeads disturbed the detoxification response, promoted oxidative imbalance, increased inflammatory foci and cytokine expression, and enhanced proliferation in liver. Since relative expression of the hepatic stellate cell marker Pdgfa and collagen deposition were increased following PE exposure, we assessed the effect of PE ingestion in a mouse model of CCl4-induced fibrosis and showed that PE dietary exposure exacerbated liver fibrogenesis. These findings provide the first demonstration of the adverse hepatic effects of PE ingestion in mammals and highlight the need for further health risk assessment in humans.


Implementation of a chest pain management service improves patient care and reduces length of stay.
Chest pain is one of the most common complaints in patients presenting to an emergency department. Delays in management due to a lack of readily available objective tests to risk stratify patients with possible acute coronary syndromes can lead to an unnecessarily lengthy admission placing pressure on hospital beds or inappropriate discharge. The need for a co-ordinated system of clinical management based on enhanced communication between departments, timely and appropriate triage, clinical investigation, diagnosis, and treatment was identified. An evidence-based Chest Pain Management Service and clinical pathway were developed and implemented, including the introduction of after-hours exercise stress testing. Between November 2005 and March 2013, 5662 patients were managed according to a Chest Pain Management pathway resulting in a reduction of 5181 admission nights by more timely identification of patients at low risk who could then be discharged. In addition, 1360 days were avoided in high-risk patients who received earlier diagnosis and treatment. The creation of a Chest Pain Management pathway and the extended exercise stress testing service resulted in earlier discharge for low-risk patients; and timely treatment for patients with positive and equivocal exercise stress test results. This service demonstrated a significant saving in overnight admissions.


Pelvic organ prolapse and relationship with skeletal integrity.
Health burden related to osteoporotic fractures in an aging female population far exceeds that imposed by other chronic disorders such as cardiovascular disease and breast cancer. Bone mineral density assessment and clinical risk factors provide independent insights into fracture risk in individuals. A finite list of clinical risk factors are identified as prognostic of fracture risk, namely among aging women, including low body mass, compromised reproductive physiology (e.g., prolonged periods of amenorrhea and early menopause), parental and personal histories of fracture, and alcohol and tobacco use. Pelvic organ prolapse is a common gynecologic entity and a contributor to age-related morbidities. The purpose of this review is to communicate data identifying pelvic organ prolapse as another clinical risk factor for fracture risk in postmenopausal women and to increase the caregiver's vigilance in anticipating and instituting preventive care strategies to a population (i.e., postmenopausal women with clinically appreciable pelvic organ prolapse) that may be at an enhanced lifetime risk for skeletal fractures.


The response of water voles, Arvicola terrestris, to the odours of predators.
We investigated the response of water voles to the odours of predators in outdoor enclosures. Water voles were given access to two food cages, one containing the odour of a predator and the other containing no odour, and were videotaped for 22 h. Sheep odour was also used as a control for novel odour. The predators were American mink, Mustela vison, and brown rat, Rattus norvegicus. There was no difference in the voles' response to sheep odour and no odour. The voles entered the treatment cages containing the mink's odour significantly fewer times than they entered the control cages, indicating avoidance of the former. They also gathered less food from, and stayed a shorter time inside, the treatment cages. The voles avoided the mink's odour more than the rat's odour. The fact that the experimental animals had not had previous contact with American mink suggests that the response is innate. These results also suggest that water voles perceived mink as a greater risk than rats, although they avoided odours of both these species. Copyright 1999 The Association for the Study of Animal Behaviour.


Probing Electrode Heterogeneity Using Fourier-Transformed Alternating Current Voltammetry: Application to a Dual-Electrode Configuration.
Quantitative studies of electron transfer processes at electrode/electrolyte interfaces, originally developed for homogeneous liquid mercury or metallic electrodes, are difficult to adapt to the spatially heterogeneous nanostructured electrode materials that are now commonly used in modern electrochemistry. In this study, the impact of surface heterogeneity on Fourier-transformed alternating current voltammetry (FTACV) has been investigated theoretically under the simplest possible conditions where no overlap of diffusion layers occurs and where numerical simulations based on a 1D diffusion model are sufficient to describe the mass transport problem. Experimental data that meet these requirements can be obtained with the aqueous [Ru(NH3)6]3+/2+ redox process at a dual-electrode system comprised of electrically coupled but well-separated glassy carbon (GC) and boron-doped diamond (BDD) electrodes. Simulated and experimental FTACV data obtained with this electrode configuration, and where distinctly different heterogeneous charge transfer rate constants (k0 values) apply at the individual GC and BDD electrode surfaces, are in excellent agreement. Principally, because of the far greater dependence of the AC current magnitude on k0, it is straightforward with the FTACV method to resolve electrochemical heterogeneities that are ∼1-2 orders of magnitude apart, as applies in the [Ru(NH3)6]3+/2+ dual-electrode configuration experiments, without prior knowledge of the individual kinetic parameters (k01 and k02) or the electrode size ratio (θ1:θ2). In direct current voltammetry, a difference in k0 of >3 orders of magnitude is required to make this distinction.


Binding characteristics of GYKI-46 903, a non-competitive ligand at 5-HT3 receptors.
GYKI-46903 [(+)-(5S,6R)-4-(4-fluorophenyl)-6-propionyloxy-1-aza-bicyclo[3.3.1]-non-3-ene-hydrochloride], a cognition enhancer identified as a non-competitive antagonist of 5-HT3receptors in isolated guinea-pig ileum, was investigated for allosteric action at 5-HT3 receptors in rat cortical membranes by using [3H]granisetron. Equilibrium and kinetic protocols were applied and the competitive antagonist granisetron was included as a negative control. In competition studies, both granisetron and GYKI-46 903 displaced the radioligand with K(i) values of 0.20 +/- 0.02 and 79.84 +/- 0.28 nM, respectively. The inhibition curve for GYKI-46 903 resulted in a Hill slope significantly greater than unity ( 1.37 +/- 0.11), whereas the slope for granisetron was 0.88 +/- 0.08, not different from unity. These results indicate non-competitive and competitive interactions, respectively. Scatchard analysis yielded a linear plot, suggesting a single population of binding sites with a Kd of 0.13 +/- 0.01 nM and a Bmax) of 13.15 +/- 0.34 fmol per mg of protein. Scatchard plots obtained in the absence and presence of granisetron (0.1-3 nM) or GYKI-46 903 (30-1000 nM) revealed a concentration-dependent increase in Kd values by either of these compounds. Granisetron left the Bmax unchanged, but there was a significant increase in the Bmax by GYKI-46 903, which could point to an atypical allosteric interaction. The Schild plot derived from the Kd shifts induced by granisetron was linear with a slope of 1.02, not different from unity, as expected from a competitive interaction. The Schild regression for GYKI-46 903 was linear with a slope of 1.20, deviating significantly from unity, which may also indicate an allosteric interaction. Both the association and dissociation curves of [3H]granisetron were monoexponential. The dissociation rate constant (K(-1)) and the association rate constant (K(+1)) were 0.32 +/- 0.01 min(-1) and 1.15 min(-1) x nM(-1), respectively. The dissociation driven by an excess concentration of ondansetron ( 1 microM) in the absence and presence of granisetron (0.1-3 nM) or GYKI-46 903 (30-10 000 nM) was not influenced by the compounds under study, as compared with the control, indicating the lack of an allosteric effect on the dissociation. Summing up, the binding profile of GYKI-46 903 may reflect a mixed type of action, including a negative allosteric interaction.


Prosthetic Joint Infections in Patients Undergoing Carpal Tunnel Release.
Little information is available regarding the rate of prosthetic joint infections (PJIs) in patients undergoing carpal tunnel release (CTR) without antibiotic prophylaxis. Hand surgeons should be aware of patients' history of arthroplasty. All patients who underwent CTR at our institution between 2012 and 2014 were identified and their charts were reviewed to identify those who had a history of total hip, knee, and/or shoulder arthroplasty. Further chart review consisted of identifying a history of PJI, use of perioperative antibiotics, and surgeon awareness of prior arthroplasty. Two hundred seventy-five CTR surgeries were performed in patients who had previously undergone total joint arthroplasty (TJA). There were no PJIs in any group of patients (P = 0.01). Hand surgeon awareness of the presence of an arthroplasty history had no discernable effect on the choice to use antibiotics. There was a 0% rate of PJI in our series of patients with a history of TJA who underwent CTR. Overall hand surgeon awareness of TJA status was poor or poorly documented. Routine prophylactic antibiotics may not be indicated in patients undergoing CTR, even with the presence of a prosthetic joint. IV.


The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a benefit-risk review.
Heavy menstrual bleeding (HMB) is a common problem in women of reproductive age and can cause irritation, inconvenience, self-consciousness and fear of social embarrassment. Our objective was to review and appraise literature identified from the MEDLINE and EMBASE databases to evaluate the clinical evidence and provide an update on the risks and benefits of using the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of HMB. The LNG-IUS consistently reduces menstrual blood loss (MBL) in women with HMB, including those with underlying uterine pathology or bleeding disorders. The available data suggest that it reduces MBL to a greater extent than other medical therapies, including combined oral contraceptives, oral progestogens (both short- or long-cycle regimens), tranexamic acid and oral mefenamic acid. In addition, the LNG-IUS and endometrial ablation appear to reduce MBL to a similar extent. The adverse effects reported with the LNG-IUS in women with HMB are similar to those typically observed in women using the system for contraception. Uterine perforations were not reported in any of the studies reviewed, but expulsion rates may be higher than in the general population of LNG-IUS users. Overall, the LNG-IUS has a positive effect on most quality-of-life domains, at least comparable to those achieved with hysterectomy or endometrial ablation, and is consistently a cost-effective option across a variety of countries and settings. In conclusion, the LNG-IUS is an effective treatment option for women with HMB, including those with underlying organic pathology or bleeding disorders.


Immersive Virtual Reality for the Cognitive Rehabilitation of Stroke Survivors.
We present the results of a double-blind phase 2b randomized control trial that used a custom built virtual reality environment for the cognitive rehabilitation of stroke survivors. A stroke causes damage to the brain and problem solving, memory and task sequencing are commonly affected. The brain can recover to some extent, however, and stroke patients have to relearn how to carry out activities of daily living. We have created an application called VIRTUE to enable such activities to be practiced using immersive virtual reality. Gamification techniques enhance the motivation of patients such as by making the level of difficulty of a task increase over time. The design and implementation of VIRTUE is described together with the results of the trial conducted within the Stroke Unit of a large hospital. We report on the safety and acceptability of VIRTUE. We have also observed particular benefits of VR treatment for stroke survivors that experienced more severe cognitive impairment, and an encouraging reduction in time spent in the hospital for all patients that received the VR treatment.


Degloving injury to the penis.
A case of reconstruction after penile skin avulsion is described in an eight-year-old boy. Penile coverage was gained by use of the avulsed skin flap itself, without a graft or local tissue flap. The procedure avoids any valuable time delay; thus, enhancing the chances to obtain adequate flap viability, avoids patient discomfort caused by perineal expansion, gives a satisfactory cosmetic appearance, and taking into account his age, avoids future psychosomatic and psychosexual problems.


Safety and effectiveness of secukinumab in psoriasis vulgaris and psoriatic arthritis: Real-world evidence in Japan.
Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, has been available for the treatment of moderate to severe psoriasis and psoriatic arthritis since February 2015 in Japan. Because there was a time gap after the previous approval of biologics for psoriatic disease indication, it was suggested that patients to be treated with secukinumab at its launch might have refractory disease symptoms. In order to assess the safety and effectiveness of secukinumab in those patients, a 52-week, open-label, multicenter, observational cohort study was conducted. In total, 306 and 250 patients were included in the safety and effectiveness analysis sets, respectively. Over half of patients had previously received biologics (56.9%). Adverse events, serious adverse events and adverse reactions were reported in 41.2%, 7.2% and 24.2% of patients, respectively. The most commonly reported adverse reactions were oral candidiasis (2.9%), consistent with those reported in clinical studies. In addition, none of the patient characteristics assessed for the effect on safety of secukinumab increased the occurrence of adverse reactions. Psoriasis Area and Severity Index score (mean ± standard deviation) improved from baseline (14.7 ± 12.3) to week 12 (1.78 ± 3.3), which was maintained up to week 24 (1.59 ± 3.0). The proportion of patients with a Dermatology Life Quality Index score of 0/1 improved from baseline (2.2%) to week 12 (64.7%) and sustained up to week 24 (71.4%). In addition to the skin symptoms, improvement was observed in all psoriatic arthritis disease-related assessments. The current study reaffirmed the safety and effectiveness of secukinumab with broader patients than those in the clinical studies.


Calorific content of certain bacteria and fungi.
Calorific contents of dried cells of several representative species of bacteria (gram-negative rods and gram-positive rods and cocci), two species of yeasts, and a filamentous fungus were determined by bomb calorimetry. The grand mean was 5,383 cal per g of ash-free dry weight. This value was then used to determine quantity of energy assimilated (E(a)) during growth. Subsequently, E(a) was employed in the equation: Y(kcal) = Y/(E(a) + E(d)), where Y(kcal) is the yield of cells per kilocalorie of energy taken from a culture medium, Y is the yield per mole of substrate utilized, E(a) is Y times caloric content of the cells, and E(d) is the energy expended by oxidative dissimilation. An estimate of E(d) was obtained for a number of experiments by multiplying the moles of oxygen consumed per mole of substrate utilized during growth by the average quantity of energy utilized to reduce a mole of oxygen with electrons from organic compounds (106 kcal). From previous studies in our laboratories, a value for Y(kcal) of 0.118 g/kcal was predicted. The mean value for data from five studies of aerobic growth of prototrophic heterotrophs was found to be 0.111.


Convergent and Distinct Effects of Multisensory Combination on Statistical Learning Using a Computer Glove.
Learning to play a musical instrument involves mapping visual + auditory cues to motor movements and anticipating transitions. Inspired by the serial reaction time task and artificial grammar learning, we investigated explicit and implicit knowledge of statistical learning in a sensorimotor task. Using a between-subjects design with four groups, one group of participants were provided with visual cues and followed along by tapping the corresponding fingertip to their thumb, while using a computer glove. Another group additionally received accompanying auditory tones; the final two groups received sensory (visual or visual + auditory) cues but did not provide a motor response-all together following a 2 × 2 design. Implicit knowledge was measured by response time, whereas explicit knowledge was assessed using probe tests. Findings indicate that explicit knowledge was best with only the single modality, but implicit knowledge was best when all three modalities were involved.


The Effect of Nutritional Status on Outcome of Hospitalization in Paediatric Liver Disease Patients.
Liver is an important organ for metabolism. It has a major role in integrating the various biochemical pathways of metabolism. Thus, children with chronic liver disease are at high risk for developing undernutrition, with important prognostic implications. To evaluate the nutritional status of hospitalized paediatric liver disease patients and its effect on outcome. We prospectively analysed the nutritional status of 59 consecutive patients during their first 24 hours of admission, at the Hepatology Unit, using the following indices: weight/age, height/age, weight/height, Body Mass Index (BMI), arm circumference and triceps skinfold, subcapular skinfold, and mid upper arm circumference. According to the measurements: 35.6% were underweight, 49% were stunted, 10% were wasted by weight for length/height percentile and 5% were wasted by body mass index, 49% had percentage of ideal body weight below normal, 27% had head circumference below 3rd percentile, 59.4% had triceps skinfold thickness below 5th percentile, 66% had subscapular skinfold thickness below 5th percentile; 56% had arm circumference below 5th percentile. There was no correlation between these growth parameters and mortality. However, we found a positive correlation between decreased triceps skinfold thickness and prolonged hospital stay. Malnourished patients, according to triceps skinfold thickness, were significantly younger and they were the ones who suffered from cholestatic disorders of infancy. Only triceps skinfold thickness was found to be a useful predictor for a prolonged hospital stay. Serial measurements may be more effective.


The nature of selection. (Written circa 1971, published posthumously)
A model that unifies all types of selection (chemical, sociological, genetical, and every other kind of selection) may open the way to develop a general "Mathematical Theory of Selection" analogous to communication theory. [Note added by S. A. Frank: This previously unpublished manuscript was found among Dr. Price's papers when he died in 1975. In this paper Dr. Price did not provide a complete, general theory of selection. Rather, he argued why such a theory is needed and what some of its properties might be. The accompanying article provides commentary on this paper and describes Dr. Price's significant contributions to evolutionary genetics (S. A. Frank, 1995, J. theor. Biol. 175, 373-388).]


Effect of radiation quality on mutagenic joining of enzymatically-induced DNA double-strand breaks in previously irradiated human cells.
Previous work has shown that high charge and energy particle irradiation of human cells evokes a mutagenic repair phenotype, defined by increased mutagenic repair of new double-strand breaks that are introduced enzymatically, days or weeks after the initial irradiation. The effect was seen originally with 600 MeV/u (56)Fe particles, which have a linear energy transfer (LET) value of 174 keV/μm, but not with X rays or γ rays (LET ≤ 2 keV/μm). To better define the radiation quality dependence of the phenomenon, we tested two ions with intermediate LET values, 1,000 MeV/u (48)Ti (LET = 108 keV/μm) and 300 MeV/u (28)Si (LET = 69 keV/μm). These experiments used a previously validated assay, where a rare-cutting nuclease introduces double-strand breaks in two reporter transgene cassettes, which are located on different chromosomes. Deletions of a block of sequence in one of the cassettes, or translocations between cassettes, are measured independently using a multicolor fluorescence assay. The results showed that (48)Ti was a potent, but transient, inducer of mutagenic repair, based on increased frequency of nuclease-induced translocations. The (48)Ti ions did not affect the frequency of nuclease-induced deletions. The (28)Si ions had no measurable effect on either endpoint. There was a close correlation between the induction of the mutagenic repair phenomenon and the frequency of micronuclei in the targeted population (R(2) = 0.74), whereas there was no apparent correlation with radiation-induced cell inactivation. Together, these results better define the radiation quality dependence of the mutagenic repair phenomenon and establish its correlation, or lack of correlation, with other endpoints.


Lewis acid-catalyzed ring-opening reactions of methylenecyclopropanes with alcoholic or acidic nucleophiles.
[reaction: see text] Methylenecyclopropanes can react with various nucleophiles such as alcohols, phenols, carboxylic acids, and thiols to give the corresponding homoallylic esters or ethers in good yields with good stereoselectivities in the presence of Lewis acids.


Cost-Effectiveness Analysis of Inguinal Hernia Repair With Mesh Performed by Surgeons and Medical Doctors in Ghana.
Task-sharing is the pragmatic sharing of tasks between providers with different levels of training. To our knowledge, no study has examined the cost-effectiveness of surgical task-sharing of hernia repair in a low-resource setting. This study has aimed to evaluate and compare the cost-effectiveness of mesh repair performed by Ghanaian surgeons and medical doctors (MDs) following a standardized training program. This cost-effectiveness analysis included data for 223 operations on adult men with primary reducible inguinal hernia. Cost per surgery was calculated from the healthcare system perspective. Disability weights were calculated using pre- and postoperative pain scores and benchmarks from the Global Burden of Disease Study 2017. The mean cost/disability-adjusted life-year (DALY) averted in the surgeon group was 444.9 United States dollars (USD) (95% confidence interval [CI] 221.2-668.5) and 278.9 USD (95% CI 199.3-358.5) in the MD group (P = .168), indicating that the operation is very cost-effective when performed by both providers. The incremental cost/DALY averted showed that task-sharing with MDs is also very cost-effective (95% bootstrap CI -436.7 to 454.9). The analysis found that increasing provider salaries is cost-effective if productivity remains high. When only symptomatic cases were analyzed, the mean cost/DALY averted reduced to 232.0 USD (95% CI 17.1-446.8) for the surgeon group and 129.7 USD (95% CI 79.6-179.8) for the MD group (P = .348), and the incremental cost/DALY averted increased by 45% but remained robust. Elective inguinal hernia repair with mesh performed by Ghanaian surgeons and MDs is a low-cost procedure and very cost-effective in the context of the study. To maximize cost-effectiveness, symptomatic patients should be prioritized over asymptomatic patients and a high level of productivity should be maintained.


Platelet activation during preparation and storage of concentrates: detection by flow cytometry.
This paper describes a rapid, whole blood micro-method for assessing the activation status of platelets that can be used to monitor changes occurring during the preparation and storage of platelet concentrates. Platelets are examined for the expression of markers of early activation (fibrinogen binding) and of degranulation (GP53 and GMP-140 expression), using flow cytometry. Fibrinogen binding can be detected in a number of blood packs even before processing. Platelet concentrates prepared by the washed platelet method become further activated during centrifugation and separation. More than 90% of platelets in freshly prepared concentrates carried bound fibrinogen (90.9 +/- 7.7%) whilst the GP53 and GMP-140 antigens were expressed on 11.3 +/- 3.3% and 13.7 +/- 5.1 of these cells respectively (mean +/- SD). Fibrinogen binding fell on storage of the platelets for four days, attributed to shedding of the fibrinogen molecule.


The appropriateness of use of coronary artery bypass graft surgery in New York State.
To determine the appropriateness of use of coronary artery bypass graft surgery in New York State. Retrospective randomized medical record review. Fifteen randomly selected hospitals in New York State that provide coronary artery bypass graft surgery. Random sample of 1338 patients undergoing isolated coronary artery bypass graft surgery in New York State in 1990. Percentage of patients who had bypass surgery for appropriate, inappropriate, or uncertain indications; operative (30-day) mortality; and complications. Nearly 91% of the bypass operations were rated appropriate; 7%, uncertain; and 2.4%, inappropriate. This low inappropriate rate differs substantially from the 14% rate found in a previous study of patients operated on in 1979, 1980, and 1982. The difference in rates was not due to more lenient criteria but to changes in practice, the most important being that the fraction of patients receiving coronary artery bypass grafts for one- and two-vessel disease fell from 51% to 24%. Individual hospital rates of inappropriateness (0% to 5%) did not vary significantly. Rates of appropriateness also did not vary by hospital location, volume, or teaching status. Operative mortality was 2.0%; 17% of patients suffered a complication. Complication rates varied significantly among hospitals (P < .01) and were higher in downstate hospitals. The rates of inappropriate and uncertain use of coronary artery bypass graft surgery in New York State were very low. Rates of inappropriate use did not vary significantly among hospitals, or according to region, volume of bypass operations performed, or teaching status.


Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution.
Lower prevalence rates of allergic diseases in rural as compared with urban populations have been interpreted as indicating an effect of air pollution. However, little is known about other factors of the rural environment which may determine the development of atopic sensitization and related diseases. The authors tested the hypothesis that children growing up on a farm were less likely to be sensitized to common aerollergens and to suffer from allergic diseases than children living in the same villages but in nonfarming families. Three age groups of schoolchildren (6-7 years, 9-11 years, 13-15 years) living in three rural communities were included in the analyses. An exhaustive questionnaire was filled in by 1620 (86.0%) parents. A blood sample was provided by 404 (69.3%) of the 13-15 year olds to determine specific IgE antibodies against six common aeroallergens. Farming as parental occupation was reported for 307 children (19.0%). After adjustment for potential covariates such as family history of asthma and allergies, parental education, number of siblings, maternal smoking, pet ownership, indoor humidity and heating fuels, farming as parental occupation was significantly associated with lower rates of sneezing attacks during pollen season (adjusted OR 0.34, 95% CI 0.12-0.89) and atopic sensitization (adjusted OR 0.31, 95% CI 0.13-0.73) whereas the association with wheeze (adjusted OR 0.77 95% CI 0.38-1.58) and itchy skin rash (adjusted OR 0.86, 95% CI 0.49-1.50) was not statistically significant. The risk of atopic sensitization was lower in children from full-time farmers (adjusted OR 0.24, 95% CI 0.09-0.66) than from part-time farmers (adjusted OR 0.54, 95% CI 0.15-1.96). Factors directly or indirectly related to farming as parental occupation decrease the risk of children becoming atopic and developing symptoms of allergic rhinitis.


[Apoptosis and carcinogenesis in aging: oxygen-peroxide aspect].
New facts are given by the author for the general oxygen-peroxide concept of aging, cancerogenesis and apoptosis. The idea is confirmed that the cell breath dysfunction leads to the oxidative stress firstly in mitochondria, then in cytoplasm and in the cell in general is the starting moment for the induction of the named processes. The superfluous formation of the active oxygen forms, peroxides of lipids and proteins as signal molecules creates disbalance between pro- and antioxidants, which size increases in aging cells and even more in tumor's and apoptosis cells. In the limits of these specialized "disbalanses" the named signal molecules play key role not only on starting "mitochondrial" stages of aging process, carcinogenesis and apoptosis, but also on following "performing" stages. They influence on the work of performing links (telomerase, oncoproteins, transcription factors, proteinkinase, endonuclease, caspase and so on).


BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer.
Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC. This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type. There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis. BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.


Revisiting the Americans with Disabilities Act after two decades.
This article examines the Americans with Disabilities Act (ADA) 20 years after its passage. It provides an overview of the history and major components of the ADA, examines who has disabilities and how they are faring, and traces how the ADA has evolved through court cases that have limited its scope. In addition, the article investigates abuse of the ADA, its economic impact, and the problems in defining a disability. Although the ADA is continuing to evolve, it requires significant change to live up to its magnificent promise.


[Bariatric surgery on children and adolescents].
Morbid obesity in teenagers has become an increasing problem. Conventional diet has not yet shown effective long-term weight loss. Alternatively, bariatric surgery on adolescents has resulted in substantial weight loss, recovery from diabetes, improvement of cardiovascular risk factors and improvement in psychosocial status. Still, surgery performed on adolescents provides ethical challenges such as the unknown long-term prognosis after surgery. Despite these challenges, in cases of severe intractable obesity or development of life-threatening complications due to obesity, surgery should be considered.


Clinical application of the hanover classification for iatrogenic bile duct lesions.
Background. There is only limited evidence available to justify generalized clinical classification and treatment recommendations for iatrogenic bile duct lesions. Methods. Data of 93 patients with iatrogenic bile duct lesions was evaluated retrospectively to analyse the variety of encountered lesions with the Hanover classification and its impact on surgical treatment and outcomes. Results. Bile duct lesions combined with vascular lesions were observed in 20 patients (21.5%). 18 of these patients were treated with additional partial hepatectomy while the majority were treated by hepaticojejunostomy alone (n = 54). Concomitant injury to the right hepatic artery resulted in additional right anatomical hemihepatectomy in 10 of 18 cases. 8 of 12 cases with type A lesions were treated with drainage alone or direct suture of the bile leak while 2 patients with a C2 lesion required a Whipple's procedure. Observed congruence between originally proposed lesion-type-specific treatment and actually performed treatment was 66-100% dependent on the category of lesion type. Hospital mortality was 3.2% (n = 3). Conclusions. The Hannover classification may be helpful to standardize the systematic description of iatrogenic bile duct lesions in order to establish evidence-based and lesion-type-specific treatment recommendations.


Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis.
Background: Sodium-glucose cotransporter 2 (SGLT2), also known as solute carrier family 5 member 2 (SLC5A2), is a promising target for a new class of drugs primarily established as kidney-targeting, effective glucose-lowering agents used in diabetes mellitus (DM) patients. Increasing evidence indicates that besides renal effects, SGLT2 inhibitors (SGLT2i) have also a systemic impact via indirectly targeting the heart and other tissues. Our hypothesis states that the pleiotropic effects of SGLT2i are associated with their binding force, location of targets in the SGLT2 networks, targets involvement in signaling pathways, and their tissue-specific expression. Methods: Thus, to investigate differences in SGLT2i impact on human organisms, we re-created the SGLT2 interaction network incorporating its inhibitors and metformin and analyzed its tissue-specific expression using publicly available datasets. We analyzed it in the context of the so-called key terms ( autophagy, oxidative stress, aging, senescence, inflammation, AMPK pathways, and mTOR pathways) which seem to be crucial to elucidating the SGLT2 role in a variety of clinical manifestations. Results: Analysis of SGLT2 and its network components' expression confidence identified selected organs in the following order: kidney, liver, adipose tissue, blood, heart, muscle, intestine, brain, and artery according to the TISSUES database. Drug repurposing analysis of known SGLT2i pointed out the influence of SGLT1 regulators on the heart and intestine tissue. Additionally, dapagliflozin seems to also have a stronger impact on brain tissue through the regulation of SGLT3 and SLC5A11. The shortest path analysis identified interaction SIRT1-SGLT2 among the top five interactions across six from seven analyzed networks associated with the key terms. Other top first-level SGLT2 interactors associated with key terms were not only ADIPOQ, INS, GLUT4, ACE, and GLUT1 but also less recognized ILK and ADCY7. Among other interactors which appeared in multiple shortest-path analyses were GPT, COG2, and MGAM. Enrichment analysis of SGLT2 network components showed the highest overrepresentation of hypertensive disease, DM-related diseases for both levels of SGLT2 interactors. Additionally, for the extended SGLT2 network, we observed enrichment in obesity (including SGLT1), cancer-related terms, neuroactive ligand-receptor interaction, and neutrophil-mediated immunity. Conclusion: This study provides comprehensive and ranked information about the SGLT2 interaction network in the context of tissue expression and can help to predict the clinical effects of the SGLT2i.


Identification of haptoglobin as a natural inhibitor of trypanocidal activity in human serum.
Trypanosomes are protozoan parasites of medical and veterinary importance. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense infect humans, causing African sleeping sickness. However, Trypanosoma brucei brucei can only infect animals, causing the disease Nagana in cattle. Man is protected from this subspecies of trypanosomes by a toxic subtype of high density lipoproteins (HDLs) called the trypanosome lytic factor (TLF). The toxic molecule in TLF is believed to be the haptoglobin-related protein that when bound to hemoglobin kills the trypanosome via oxidative damage initiated by its peroxidase activity. The amount of lytic activity in serum varies widely between different individuals with up to a 60-fold difference in activity. In addition, an increase in the total amount of lytic activity occurs during the purification of TLF, suggesting that an inhibitor of TLF (ITLF) exists in human serum. We now show that the individual variation in trypanosome lytic activity in serum correlates to variations in the amount of ITLF. Immunoblots of ITLF probed with antiserum against haptoglobin recognize a 120-kDa protein, indicating that haptoglobin is present in partially purified ITLF. Haptoglobin involvement is further shown in that it inhibits TLF in a manner similar to ITLF. Using an anti-haptoglobin column to remove haptoglobin from ITLF, we show that the loss of haptoglobin coincides with the loss of inhibitor activity. Addition of purified haptoglobin restores inhibitor activity. This indicates that haptoglobin is the molecule responsible for inhibition and therefore causing the individual variation in serum lytic activity.